Jennie Smith

ROME – Bacterial vaginosis and hormonal contraception may increase the risk that HIV-positive women will pass on the infection to their partners, according to two studies presented at the International AIDS Society Conference on HIV Pathogenesis and Treatment.

In addition, a third, small study suggested that measurable HIV RNA may remain in the genital tracts of some women taking antiretroviral therapy.

Dr. Craig R. Cohen of the University of California, San Francisco, presented research exploring the potential association between bacterial vaginosis (BV) and HIV transmission, from a 2-year study of 2,236 HIV-negative men with HIV-positive female partners.

While previous studies had demonstrated that women with BV are at a higher risk of acquiring HIV, Dr. Cohen and his colleagues showed for the first time that BV also makes them more likely to transmit it.

HIV incidence in men whose infected female partner had BV 3 months prior to detecting seroconversion was 2.87/100 person-years (hazard ratio, 3.09), Dr. Cohen and his colleagues found, compared with 0.88/100 person-years in men whose female partners had normal vaginal flora.

After they controlled for sociodemographic factors, sexual behavior, male circumcision, sexually transmitted infections, pregnancy and plasma HIV in female partners, Dr. Cohen and his colleagues still found an elevated risk associated with BV, with an adjusted hazard ratio of 2.83.

The reasons for that were unclear, Dr. Cohen said, though he added it was unlikely that BV increases concentrations of HIV RNA in women. However, BV might affect male partners’ susceptibility, he said.

Bacterial vaginosis affects between 15% and 20% of women in North America and as many as half of women in sub-Saharan Africa, Dr. Cohen said, nothing that 40% of women in his study had vaginosis at enrollment. Normalization of vaginal flora in HIV-positive women could mitigate female-to-male transmission, he said.

Hormonal Contraception Upped Risk

In a second study, the use of hormonal contraception was shown not only to increase women’s susceptibility to acquiring HIV but also to increase their chances of transmitting it.

Renee Heffron of the University of Washington, Seattle, presented a prospective cohort study using data from two trials enrolling 3,750 HIV-discordant couples in seven African countries.

Ms. Heffron and her colleagues found HIV acquisition rates and transmission rates alike to be twofold higher among women using hormonal contraception. Previous studies had demonstrated only higher acquisition rates for women.

Among 2,476 couples in which the women were HIV positive, acquisition rates were 2.61/100 person-years for male partners of women using hormonal contraception, compared with 1.51 for partners of women who did not (HR 1.97, P = .02).

Acquisition incidence was 6.61/100 person-years among women using injected or oral hormonal contraception, compared with 3.78 for those not using the methods (HR 1.98, P = .03). Most of the women in the study were using injectable methods. The number of women using oral contraceptives was not high enough for the findings regarding oral contraceptives to reach statistical significance.

Ms. Heffron and her colleagues also found significantly more HIV-RNA in the genital tracts of infected women on hormonal contraception, suggesting a mechanism for transmission.

The study used data collected between 2004 and 2010, and none of the enrolled seropositive women were eligible for antiretroviral therapy, according to their countries’ guidelines, at the time of enrollment.

Measurable HIV RNA Remains

The results of a third study presented at the meeting suggested that even women taking antiretroviral therapy (ART) have measurable HIV RNA in their genital tracts.

Dr. Anandi N. Sheth of Emory University, Atlanta, presented findings from a small study in which she and colleagues analyzed serum and cervicovaginal lavage (CLV) samples collected twice weekly for 3 weeks from 20 HIV-positive women in the United States.

Though all the women in the study were taking combination antiretroviral therapy (tenofovir, emtricitabine, atazanavir/ritonavir) for at least 6 months and had undetectable serum viral loads at enrollment, HIV-1 RNA was detected at low levels in CLV samples from nine women (45%).

The results suggest that the standard combination ART "does not completely inhibit local viral replication and may not completely block sexual transmission," Dr. Sheth said.

Dr. Sheth said that only one of the women in her study was using hormonal contraception; another was using an intrauterine device. An analysis of vaginal infections among the enrolled women during the study period was in progress, she said, and could shed more light on the findings.

The study presenters did not provide conflict of interest information.

ROME – Bacterial vaginosis and hormonal contraception may increase the risk that HIV-positive women will pass on the infection to their partners, according to two studies presented at the International AIDS Society Conference on HIV Pathogenesis and Treatment.

In addition, a third, small study suggested that measurable HIV RNA may remain in the genital tracts of some women taking antiretroviral therapy.

Dr. Craig R. Cohen of the University of California, San Francisco, presented research exploring the potential association between bacterial vaginosis (BV) and HIV transmission, from a 2-year study of 2,236 HIV-negative men with HIV-positive female partners.

While previous studies had demonstrated that women with BV are at a higher risk of acquiring HIV, Dr. Cohen and his colleagues showed for the first time that BV also makes them more likely to transmit it.

HIV incidence in men whose infected female partner had BV 3 months prior to detecting seroconversion was 2.87/100 person-years (hazard ratio, 3.09), Dr. Cohen and his colleagues found, compared with 0.88/100 person-years in men whose female partners had normal vaginal flora.

After they controlled for sociodemographic factors, sexual behavior, male circumcision, sexually transmitted infections, pregnancy and plasma HIV in female partners, Dr. Cohen and his colleagues still found an elevated risk associated with BV, with an adjusted hazard ratio of 2.83.

The reasons for that were unclear, Dr. Cohen said, though he added it was unlikely that BV increases concentrations of HIV RNA in women. However, BV might affect male partners’ susceptibility, he said.

Bacterial vaginosis affects between 15% and 20% of women in North America and as many as half of women in sub-Saharan Africa, Dr. Cohen said, nothing that 40% of women in his study had vaginosis at enrollment. Normalization of vaginal flora in HIV-positive women could mitigate female-to-male transmission, he said.

Hormonal Contraception Upped Risk

In a second study, the use of hormonal contraception was shown not only to increase women’s susceptibility to acquiring HIV but also to increase their chances of transmitting it.

Renee Heffron of the University of Washington, Seattle, presented a prospective cohort study using data from two trials enrolling 3,750 HIV-discordant couples in seven African countries.

Ms. Heffron and her colleagues found HIV acquisition rates and transmission rates alike to be twofold higher among women using hormonal contraception. Previous studies had demonstrated only higher acquisition rates for women.

Among 2,476 couples in which the women were HIV positive, acquisition rates were 2.61/100 person-years for male partners of women using hormonal contraception, compared with 1.51 for partners of women who did not (HR 1.97, P = .02).

Acquisition incidence was 6.61/100 person-years among women using injected or oral hormonal contraception, compared with 3.78 for those not using the methods (HR 1.98, P = .03). Most of the women in the study were using injectable methods. The number of women using oral contraceptives was not high enough for the findings regarding oral contraceptives to reach statistical significance.

Ms. Heffron and her colleagues also found significantly more HIV-RNA in the genital tracts of infected women on hormonal contraception, suggesting a mechanism for transmission.

The study used data collected between 2004 and 2010, and none of the enrolled seropositive women were eligible for antiretroviral therapy, according to their countries’ guidelines, at the time of enrollment.

Measurable HIV RNA Remains

The results of a third study presented at the meeting suggested that even women taking antiretroviral therapy (ART) have measurable HIV RNA in their genital tracts.

Dr. Anandi N. Sheth of Emory University, Atlanta, presented findings from a small study in which she and colleagues analyzed serum and cervicovaginal lavage (CLV) samples collected twice weekly for 3 weeks from 20 HIV-positive women in the United States.

Though all the women in the study were taking combination antiretroviral therapy (tenofovir, emtricitabine, atazanavir/ritonavir) for at least 6 months and had undetectable serum viral loads at enrollment, HIV-1 RNA was detected at low levels in CLV samples from nine women (45%).

The results suggest that the standard combination ART "does not completely inhibit local viral replication and may not completely block sexual transmission," Dr. Sheth said.

Dr. Sheth said that only one of the women in her study was using hormonal contraception; another was using an intrauterine device. An analysis of vaginal infections among the enrolled women during the study period was in progress, she said, and could shed more light on the findings.

The study presenters did not provide conflict of interest information.

ROME – Bacterial vaginosis and hormonal contraception may increase the risk that HIV-positive women will pass on the infection to their partners, according to two studies presented at the International AIDS Society Conference on HIV Pathogenesis and Treatment.

In addition, a third, small study suggested that measurable HIV RNA may remain in the genital tracts of some women taking antiretroviral therapy.

Dr. Craig R. Cohen of the University of California, San Francisco, presented research exploring the potential association between bacterial vaginosis (BV) and HIV transmission, from a 2-year study of 2,236 HIV-negative men with HIV-positive female partners.

While previous studies had demonstrated that women with BV are at a higher risk of acquiring HIV, Dr. Cohen and his colleagues showed for the first time that BV also makes them more likely to transmit it.

HIV incidence in men whose infected female partner had BV 3 months prior to detecting seroconversion was 2.87/100 person-years (hazard ratio, 3.09), Dr. Cohen and his colleagues found, compared with 0.88/100 person-years in men whose female partners had normal vaginal flora.

After they controlled for sociodemographic factors, sexual behavior, male circumcision, sexually transmitted infections, pregnancy and plasma HIV in female partners, Dr. Cohen and his colleagues still found an elevated risk associated with BV, with an adjusted hazard ratio of 2.83.

The reasons for that were unclear, Dr. Cohen said, though he added it was unlikely that BV increases concentrations of HIV RNA in women. However, BV might affect male partners’ susceptibility, he said.

Bacterial vaginosis affects between 15% and 20% of women in North America and as many as half of women in sub-Saharan Africa, Dr. Cohen said, nothing that 40% of women in his study had vaginosis at enrollment. Normalization of vaginal flora in HIV-positive women could mitigate female-to-male transmission, he said.

Hormonal Contraception Upped Risk

In a second study, the use of hormonal contraception was shown not only to increase women’s susceptibility to acquiring HIV but also to increase their chances of transmitting it.

Renee Heffron of the University of Washington, Seattle, presented a prospective cohort study using data from two trials enrolling 3,750 HIV-discordant couples in seven African countries.

Ms. Heffron and her colleagues found HIV acquisition rates and transmission rates alike to be twofold higher among women using hormonal contraception. Previous studies had demonstrated only higher acquisition rates for women.

Among 2,476 couples in which the women were HIV positive, acquisition rates were 2.61/100 person-years for male partners of women using hormonal contraception, compared with 1.51 for partners of women who did not (HR 1.97, P = .02).

Acquisition incidence was 6.61/100 person-years among women using injected or oral hormonal contraception, compared with 3.78 for those not using the methods (HR 1.98, P = .03). Most of the women in the study were using injectable methods. The number of women using oral contraceptives was not high enough for the findings regarding oral contraceptives to reach statistical significance.

Ms. Heffron and her colleagues also found significantly more HIV-RNA in the genital tracts of infected women on hormonal contraception, suggesting a mechanism for transmission.

The study used data collected between 2004 and 2010, and none of the enrolled seropositive women were eligible for antiretroviral therapy, according to their countries’ guidelines, at the time of enrollment.

Measurable HIV RNA Remains

The results of a third study presented at the meeting suggested that even women taking antiretroviral therapy (ART) have measurable HIV RNA in their genital tracts.

Dr. Anandi N. Sheth of Emory University, Atlanta, presented findings from a small study in which she and colleagues analyzed serum and cervicovaginal lavage (CLV) samples collected twice weekly for 3 weeks from 20 HIV-positive women in the United States.

Though all the women in the study were taking combination antiretroviral therapy (tenofovir, emtricitabine, atazanavir/ritonavir) for at least 6 months and had undetectable serum viral loads at enrollment, HIV-1 RNA was detected at low levels in CLV samples from nine women (45%).

The results suggest that the standard combination ART "does not completely inhibit local viral replication and may not completely block sexual transmission," Dr. Sheth said.

Dr. Sheth said that only one of the women in her study was using hormonal contraception; another was using an intrauterine device. An analysis of vaginal infections among the enrolled women during the study period was in progress, she said, and could shed more light on the findings.

The study presenters did not provide conflict of interest information.

ROME – The latest World Health Organization guidelines for combination antiretroviral therapy in low- and middle-income countries recommend four triple-drug combinations (all including tenofovir) for first-line HIV treatment.

However, in a July 20 presentation at the International AIDS Society Conference on HIV Pathogenesis and Treatment, Dr. Michele Tang, of Stanford (Calif.) University, offered a meta-analysis showing that one of these combinations – tenofovir, lamivudine, and nevirapine (TDF/3TC/NVP) – appears to control HIV less effectively than do the three others.

Dr. Tang and her colleagues conducted a systematic review that included 29 studies evaluating tenofovir combined with lamivudine plus nevirapine; emtricitabine and nevirapine; emtricitabine and efavirenz; and/or lamivudine and efavirenz.

The TDF/3TC/NVP combination was the least well studied of the four tenofovir-containing regimens, occurring in only three of the studies Dr. Tang’s group looked at, which were an open-label pilot study, a randomized controlled trial, and a 2010 retrospective cohort study. In the open-label pilot study without a comparator, the regimen was associated with a 30% rate of virologic failure. In the two others, it was associated with 25% and 21% rates of failure, whereas the failure rates of the comparator regimens were 3% and 10%, respectively.

The U.S. Department of Health and Human Services guidelines already classify TDF/3TC/NVP as a regimen to be used "with caution," Dr. Tang noted.

Antiretroviral regimens "are more than the sum of their parts," she said.

"3TC and FTC [emtricitabine] are not interchangeable. As clinicians, we tend to think of them as interchangeable, but there are some differences."

Further study is "urgently required before this regimen is widely deployed for initial ARV [antiretroviral] therapy," Dr. Tang said.

She did not offer any financial disclosures.

ROME – The latest World Health Organization guidelines for combination antiretroviral therapy in low- and middle-income countries recommend four triple-drug combinations (all including tenofovir) for first-line HIV treatment.

However, in a July 20 presentation at the International AIDS Society Conference on HIV Pathogenesis and Treatment, Dr. Michele Tang, of Stanford (Calif.) University, offered a meta-analysis showing that one of these combinations – tenofovir, lamivudine, and nevirapine (TDF/3TC/NVP) – appears to control HIV less effectively than do the three others.

Dr. Tang and her colleagues conducted a systematic review that included 29 studies evaluating tenofovir combined with lamivudine plus nevirapine; emtricitabine and nevirapine; emtricitabine and efavirenz; and/or lamivudine and efavirenz.

The TDF/3TC/NVP combination was the least well studied of the four tenofovir-containing regimens, occurring in only three of the studies Dr. Tang’s group looked at, which were an open-label pilot study, a randomized controlled trial, and a 2010 retrospective cohort study. In the open-label pilot study without a comparator, the regimen was associated with a 30% rate of virologic failure. In the two others, it was associated with 25% and 21% rates of failure, whereas the failure rates of the comparator regimens were 3% and 10%, respectively.

The U.S. Department of Health and Human Services guidelines already classify TDF/3TC/NVP as a regimen to be used "with caution," Dr. Tang noted.

Antiretroviral regimens "are more than the sum of their parts," she said.

"3TC and FTC [emtricitabine] are not interchangeable. As clinicians, we tend to think of them as interchangeable, but there are some differences."

Further study is "urgently required before this regimen is widely deployed for initial ARV [antiretroviral] therapy," Dr. Tang said.

She did not offer any financial disclosures.

ROME – The latest World Health Organization guidelines for combination antiretroviral therapy in low- and middle-income countries recommend four triple-drug combinations (all including tenofovir) for first-line HIV treatment.

However, in a July 20 presentation at the International AIDS Society Conference on HIV Pathogenesis and Treatment, Dr. Michele Tang, of Stanford (Calif.) University, offered a meta-analysis showing that one of these combinations – tenofovir, lamivudine, and nevirapine (TDF/3TC/NVP) – appears to control HIV less effectively than do the three others.

Dr. Tang and her colleagues conducted a systematic review that included 29 studies evaluating tenofovir combined with lamivudine plus nevirapine; emtricitabine and nevirapine; emtricitabine and efavirenz; and/or lamivudine and efavirenz.

The TDF/3TC/NVP combination was the least well studied of the four tenofovir-containing regimens, occurring in only three of the studies Dr. Tang’s group looked at, which were an open-label pilot study, a randomized controlled trial, and a 2010 retrospective cohort study. In the open-label pilot study without a comparator, the regimen was associated with a 30% rate of virologic failure. In the two others, it was associated with 25% and 21% rates of failure, whereas the failure rates of the comparator regimens were 3% and 10%, respectively.

The U.S. Department of Health and Human Services guidelines already classify TDF/3TC/NVP as a regimen to be used "with caution," Dr. Tang noted.

Antiretroviral regimens "are more than the sum of their parts," she said.

"3TC and FTC [emtricitabine] are not interchangeable. As clinicians, we tend to think of them as interchangeable, but there are some differences."

Further study is "urgently required before this regimen is widely deployed for initial ARV [antiretroviral] therapy," Dr. Tang said.

She did not offer any financial disclosures.

ROME – Game-changing evidence that antiretroviral agents can be used by HIV-infected and uninfected populations to prevent transmission is pushing the issue of how much broader use of antiretrovirals will fit into clinical practice.

"In the United States, only 19% of those who are HIV positive have an undetectable viral load," said Dr. Julio Montaner, director of the British Columbia Center for Excellence in HIV/AIDS (Clin. Infect. Dis. 2011;52:793-800). That means that a majority of people currently eligible for antiretroviral therapy are not receiving enough of it, even in developed-world settings, he said at the International AIDS Society Conference on HIV Pathogenesis and Treatment.

Photo credit: Marcus Rose/Worker's Photos

In sub-Saharan Africa, a maximum of 35% of people who are eligible for antiretroviral therapy (ART) under conservative eligibility guidelines are receiving it now, said Dr. Wafaa El-Sadr, of Columbia University in New York. Evidence from randomized controlled trials shows that early treatment prevents transmission in serodiscordant heterosexual couples, a majority of them married. However, serodiscordant married couples might not be the ideal – or only – targets for expanded ART. "ART is not a simple intervention," she said, adding, "retention in ART is suboptimal."

Issues of broader testing, therapy adherence, possible resistance, and the cost of such prophylactic interventions all remain to be worked out.

It’s not clear if and how oral antiretrovirals currently in use will be licensed for pre-exposure prophylaxis (PrEP) and Treatment as Prevention (TasP), said Tim Farley, Ph.D., head of microbicide research at the World Health Organization. Whether broad or narrow extensions of indications for tenofovir and tenofovir/emtricitabine will be sought remains to be addressed.

The broadest indication would allow these medications to be prescribed to anyone deemed at risk of contracting HIV; narrower indications might limit them to members of groups shown to benefit in randomized controlled trials, such the HIV-negative member of a serodiscordant couple. Licensing that targets specific groups, such as men who have sex with men, could be problematic in many countries, he said.

Off-label use of oral antiretrovirals was an immediate possibility in developing countries, said Dr. Farley, who added that WHO was considering issuing guidelines that would promote their use in prevention as an interim measure in advance of extended indications.

The U.S. Food and Drug Administration was meeting with drug manufacturers in an effort to get started on an extension of agents’ indications, Dr. Farley said, and the European Medicines Agency has said that it might make use of its legal ability to endorse indications for use outside the European community in order to promote the adoption of the antiretrovirals as a preventive strategy in African countries.

The issue of fast, broad access was of critical concern given that another proven HIV prevention intervention – tenofovir gel – languishes in regulatory limbo. At the conference, women advocates marched through the site with signs shouting: "Where the hell is our gel?"

The presenters did not disclose whether or not they had conflicts of interest.

ROME – Game-changing evidence that antiretroviral agents can be used by HIV-infected and uninfected populations to prevent transmission is pushing the issue of how much broader use of antiretrovirals will fit into clinical practice.

"In the United States, only 19% of those who are HIV positive have an undetectable viral load," said Dr. Julio Montaner, director of the British Columbia Center for Excellence in HIV/AIDS (Clin. Infect. Dis. 2011;52:793-800). That means that a majority of people currently eligible for antiretroviral therapy are not receiving enough of it, even in developed-world settings, he said at the International AIDS Society Conference on HIV Pathogenesis and Treatment.

Photo credit: Marcus Rose/Worker's Photos

In sub-Saharan Africa, a maximum of 35% of people who are eligible for antiretroviral therapy (ART) under conservative eligibility guidelines are receiving it now, said Dr. Wafaa El-Sadr, of Columbia University in New York. Evidence from randomized controlled trials shows that early treatment prevents transmission in serodiscordant heterosexual couples, a majority of them married. However, serodiscordant married couples might not be the ideal – or only – targets for expanded ART. "ART is not a simple intervention," she said, adding, "retention in ART is suboptimal."

Issues of broader testing, therapy adherence, possible resistance, and the cost of such prophylactic interventions all remain to be worked out.

It’s not clear if and how oral antiretrovirals currently in use will be licensed for pre-exposure prophylaxis (PrEP) and Treatment as Prevention (TasP), said Tim Farley, Ph.D., head of microbicide research at the World Health Organization. Whether broad or narrow extensions of indications for tenofovir and tenofovir/emtricitabine will be sought remains to be addressed.

The broadest indication would allow these medications to be prescribed to anyone deemed at risk of contracting HIV; narrower indications might limit them to members of groups shown to benefit in randomized controlled trials, such the HIV-negative member of a serodiscordant couple. Licensing that targets specific groups, such as men who have sex with men, could be problematic in many countries, he said.

Off-label use of oral antiretrovirals was an immediate possibility in developing countries, said Dr. Farley, who added that WHO was considering issuing guidelines that would promote their use in prevention as an interim measure in advance of extended indications.

The U.S. Food and Drug Administration was meeting with drug manufacturers in an effort to get started on an extension of agents’ indications, Dr. Farley said, and the European Medicines Agency has said that it might make use of its legal ability to endorse indications for use outside the European community in order to promote the adoption of the antiretrovirals as a preventive strategy in African countries.

The issue of fast, broad access was of critical concern given that another proven HIV prevention intervention – tenofovir gel – languishes in regulatory limbo. At the conference, women advocates marched through the site with signs shouting: "Where the hell is our gel?"

The presenters did not disclose whether or not they had conflicts of interest.

ROME – Game-changing evidence that antiretroviral agents can be used by HIV-infected and uninfected populations to prevent transmission is pushing the issue of how much broader use of antiretrovirals will fit into clinical practice.

"In the United States, only 19% of those who are HIV positive have an undetectable viral load," said Dr. Julio Montaner, director of the British Columbia Center for Excellence in HIV/AIDS (Clin. Infect. Dis. 2011;52:793-800). That means that a majority of people currently eligible for antiretroviral therapy are not receiving enough of it, even in developed-world settings, he said at the International AIDS Society Conference on HIV Pathogenesis and Treatment.

Photo credit: Marcus Rose/Worker's Photos

In sub-Saharan Africa, a maximum of 35% of people who are eligible for antiretroviral therapy (ART) under conservative eligibility guidelines are receiving it now, said Dr. Wafaa El-Sadr, of Columbia University in New York. Evidence from randomized controlled trials shows that early treatment prevents transmission in serodiscordant heterosexual couples, a majority of them married. However, serodiscordant married couples might not be the ideal – or only – targets for expanded ART. "ART is not a simple intervention," she said, adding, "retention in ART is suboptimal."

Issues of broader testing, therapy adherence, possible resistance, and the cost of such prophylactic interventions all remain to be worked out.

It’s not clear if and how oral antiretrovirals currently in use will be licensed for pre-exposure prophylaxis (PrEP) and Treatment as Prevention (TasP), said Tim Farley, Ph.D., head of microbicide research at the World Health Organization. Whether broad or narrow extensions of indications for tenofovir and tenofovir/emtricitabine will be sought remains to be addressed.

The broadest indication would allow these medications to be prescribed to anyone deemed at risk of contracting HIV; narrower indications might limit them to members of groups shown to benefit in randomized controlled trials, such the HIV-negative member of a serodiscordant couple. Licensing that targets specific groups, such as men who have sex with men, could be problematic in many countries, he said.

Off-label use of oral antiretrovirals was an immediate possibility in developing countries, said Dr. Farley, who added that WHO was considering issuing guidelines that would promote their use in prevention as an interim measure in advance of extended indications.

The U.S. Food and Drug Administration was meeting with drug manufacturers in an effort to get started on an extension of agents’ indications, Dr. Farley said, and the European Medicines Agency has said that it might make use of its legal ability to endorse indications for use outside the European community in order to promote the adoption of the antiretrovirals as a preventive strategy in African countries.

The issue of fast, broad access was of critical concern given that another proven HIV prevention intervention – tenofovir gel – languishes in regulatory limbo. At the conference, women advocates marched through the site with signs shouting: "Where the hell is our gel?"

The presenters did not disclose whether or not they had conflicts of interest.

ROME – In a conference abuzz about new strategies for preventing HIV infection with antiretroviral medications, excitement about the potential for a vaccine was comparably subdued.

With so much success at preventing the transmission of the virus by using antiretroviral therapy prophylactically, one might ask, "Do we still need a vaccine?" The answer is an unequivocal ‘yes,’ according to Dr. Gary J. Nabel of the Vaccine Research Center at the National Institutes of Health.

Dr. Myron S. Cohen of the University of North Carolina Chapel Hill, agreed. Though Dr. Cohen presented the conference’s most celebrated finding – that early initiation of antiretroviral therapy was associated with a 96% reduction in transmission to an uninfected partner in heterosexual serodiscordant couples – he cautioned that transmission can occur at "any CD4 count. ... The bottom line: Make a vaccine and that will solve the problem."

Concerns about the costs and logistics of scaling up antiretroviral therapy for use in prevention, particularly in settings where eligible HIV-infected people have limited access to such agents in the first place, further underscored the urgency to produce a durable, effective vaccine.

"We need to maintain our devotion to an HIV vaccine. ... We mustn’t forget how cost effective an HIV vaccine is," Dr. Nabel said at the International AIDS Society Conference on HIV Pathogenesis and Treatment.

While many were disappointed by 2009 results from a Phase III trial in Thailand (n = 16,402) of a prime-boost vaccine that lowered the risk of HIV infection by less than a third compared to placebo (N. Engl. J. Med. 2009;361:2209-20), Dr. Nabel asserted that opportunities for vaccine development have never been more promising. The past year has seen a surge of optimism about vaccines thanks to the discovery of VRCO2 and VRCO1, two potent antigens that neutralize more than 90% of all known HIV strains, he noted.

The pre-VRCO1 era, Dr. Nabel said, should now be regarded as "the dark ages" for HIV vaccine development.

Further, a better understanding of HIV-1 entry "has provided an opportunity for AIDS vaccine development through the definition of highly conserved invariant viral structures" that can be targeted by broadly neutralizing antibodies, he said.

Several scientists presented an overview and update of the more than 40 ongoing investigations – most of them in Phase I – of HIV vaccines with therapeutic and eradication targets.

Susan B. Zolla-Pazner, Ph.D., of New York University, discussed the prime-boost vaccination strategies in development that "can focus the antibody response on selected epitopes." Early in vivo work has shown a long-lasting response to this type of strategy in animals, "with neutralizing antibodies detectable more than a year after the last boost," she said.

While a vaccine offering durable, complete protection remains an obvious goal, Robin Shattock, Ph.D., of Imperial College London questioned whether it was time to consider the value of vaccines offering incomplete or shorter-term protection as part of a combination strategy that includes microbicides, male circumcision, condoms, and, where available, antiretroviral prophylaxis.

"A partially efficacious vaccine is a truly viable option if combined" with other approaches, Dr. Shattock said, adding that it was time not only to consider combining proven partially effective interventions, but to initiate randomized controlled trials comparing combinations.

Dr. Shattock said he envisioned a large, four-arm trial comparing two or three combined interventions in each arm. "The effect size of each intervention adds up," he said. "You don’t have to be a mathematician to see that combining the values is likely to give significant improvement."

VRCO2 and VRCO1 were identified by Dr. Nabel’s department, the Vaccine Research Center at the National Institutes of Health. Dr. Zolla-Pazner, Dr. Shattock and Dr. Cohen did not disclose whether or not they had conflicts of interest.

ROME – In a conference abuzz about new strategies for preventing HIV infection with antiretroviral medications, excitement about the potential for a vaccine was comparably subdued.

With so much success at preventing the transmission of the virus by using antiretroviral therapy prophylactically, one might ask, "Do we still need a vaccine?" The answer is an unequivocal ‘yes,’ according to Dr. Gary J. Nabel of the Vaccine Research Center at the National Institutes of Health.

Dr. Myron S. Cohen of the University of North Carolina Chapel Hill, agreed. Though Dr. Cohen presented the conference’s most celebrated finding – that early initiation of antiretroviral therapy was associated with a 96% reduction in transmission to an uninfected partner in heterosexual serodiscordant couples – he cautioned that transmission can occur at "any CD4 count. ... The bottom line: Make a vaccine and that will solve the problem."

Concerns about the costs and logistics of scaling up antiretroviral therapy for use in prevention, particularly in settings where eligible HIV-infected people have limited access to such agents in the first place, further underscored the urgency to produce a durable, effective vaccine.

"We need to maintain our devotion to an HIV vaccine. ... We mustn’t forget how cost effective an HIV vaccine is," Dr. Nabel said at the International AIDS Society Conference on HIV Pathogenesis and Treatment.

While many were disappointed by 2009 results from a Phase III trial in Thailand (n = 16,402) of a prime-boost vaccine that lowered the risk of HIV infection by less than a third compared to placebo (N. Engl. J. Med. 2009;361:2209-20), Dr. Nabel asserted that opportunities for vaccine development have never been more promising. The past year has seen a surge of optimism about vaccines thanks to the discovery of VRCO2 and VRCO1, two potent antigens that neutralize more than 90% of all known HIV strains, he noted.

The pre-VRCO1 era, Dr. Nabel said, should now be regarded as "the dark ages" for HIV vaccine development.

Further, a better understanding of HIV-1 entry "has provided an opportunity for AIDS vaccine development through the definition of highly conserved invariant viral structures" that can be targeted by broadly neutralizing antibodies, he said.

Several scientists presented an overview and update of the more than 40 ongoing investigations – most of them in Phase I – of HIV vaccines with therapeutic and eradication targets.

Susan B. Zolla-Pazner, Ph.D., of New York University, discussed the prime-boost vaccination strategies in development that "can focus the antibody response on selected epitopes." Early in vivo work has shown a long-lasting response to this type of strategy in animals, "with neutralizing antibodies detectable more than a year after the last boost," she said.

While a vaccine offering durable, complete protection remains an obvious goal, Robin Shattock, Ph.D., of Imperial College London questioned whether it was time to consider the value of vaccines offering incomplete or shorter-term protection as part of a combination strategy that includes microbicides, male circumcision, condoms, and, where available, antiretroviral prophylaxis.

"A partially efficacious vaccine is a truly viable option if combined" with other approaches, Dr. Shattock said, adding that it was time not only to consider combining proven partially effective interventions, but to initiate randomized controlled trials comparing combinations.

Dr. Shattock said he envisioned a large, four-arm trial comparing two or three combined interventions in each arm. "The effect size of each intervention adds up," he said. "You don’t have to be a mathematician to see that combining the values is likely to give significant improvement."

VRCO2 and VRCO1 were identified by Dr. Nabel’s department, the Vaccine Research Center at the National Institutes of Health. Dr. Zolla-Pazner, Dr. Shattock and Dr. Cohen did not disclose whether or not they had conflicts of interest.

ROME – In a conference abuzz about new strategies for preventing HIV infection with antiretroviral medications, excitement about the potential for a vaccine was comparably subdued.

With so much success at preventing the transmission of the virus by using antiretroviral therapy prophylactically, one might ask, "Do we still need a vaccine?" The answer is an unequivocal ‘yes,’ according to Dr. Gary J. Nabel of the Vaccine Research Center at the National Institutes of Health.

Dr. Myron S. Cohen of the University of North Carolina Chapel Hill, agreed. Though Dr. Cohen presented the conference’s most celebrated finding – that early initiation of antiretroviral therapy was associated with a 96% reduction in transmission to an uninfected partner in heterosexual serodiscordant couples – he cautioned that transmission can occur at "any CD4 count. ... The bottom line: Make a vaccine and that will solve the problem."

Concerns about the costs and logistics of scaling up antiretroviral therapy for use in prevention, particularly in settings where eligible HIV-infected people have limited access to such agents in the first place, further underscored the urgency to produce a durable, effective vaccine.

"We need to maintain our devotion to an HIV vaccine. ... We mustn’t forget how cost effective an HIV vaccine is," Dr. Nabel said at the International AIDS Society Conference on HIV Pathogenesis and Treatment.

While many were disappointed by 2009 results from a Phase III trial in Thailand (n = 16,402) of a prime-boost vaccine that lowered the risk of HIV infection by less than a third compared to placebo (N. Engl. J. Med. 2009;361:2209-20), Dr. Nabel asserted that opportunities for vaccine development have never been more promising. The past year has seen a surge of optimism about vaccines thanks to the discovery of VRCO2 and VRCO1, two potent antigens that neutralize more than 90% of all known HIV strains, he noted.

The pre-VRCO1 era, Dr. Nabel said, should now be regarded as "the dark ages" for HIV vaccine development.

Further, a better understanding of HIV-1 entry "has provided an opportunity for AIDS vaccine development through the definition of highly conserved invariant viral structures" that can be targeted by broadly neutralizing antibodies, he said.

Several scientists presented an overview and update of the more than 40 ongoing investigations – most of them in Phase I – of HIV vaccines with therapeutic and eradication targets.

Susan B. Zolla-Pazner, Ph.D., of New York University, discussed the prime-boost vaccination strategies in development that "can focus the antibody response on selected epitopes." Early in vivo work has shown a long-lasting response to this type of strategy in animals, "with neutralizing antibodies detectable more than a year after the last boost," she said.

While a vaccine offering durable, complete protection remains an obvious goal, Robin Shattock, Ph.D., of Imperial College London questioned whether it was time to consider the value of vaccines offering incomplete or shorter-term protection as part of a combination strategy that includes microbicides, male circumcision, condoms, and, where available, antiretroviral prophylaxis.

"A partially efficacious vaccine is a truly viable option if combined" with other approaches, Dr. Shattock said, adding that it was time not only to consider combining proven partially effective interventions, but to initiate randomized controlled trials comparing combinations.

Dr. Shattock said he envisioned a large, four-arm trial comparing two or three combined interventions in each arm. "The effect size of each intervention adds up," he said. "You don’t have to be a mathematician to see that combining the values is likely to give significant improvement."

VRCO2 and VRCO1 were identified by Dr. Nabel’s department, the Vaccine Research Center at the National Institutes of Health. Dr. Zolla-Pazner, Dr. Shattock and Dr. Cohen did not disclose whether or not they had conflicts of interest.

ROME – The risk of sexually transmitted HIV was reduced by 96% when the infected partner received a combination of three or more antiretroviral drugs immediately following detection of HIV infection, according to the findings of a randomized controlled trial known as HPTN 052.

These striking results offer "definitive proof of a concept," lead trial investigator Dr. Myron S. Cohen of the University of North Carolina at Chapel Hill said July 18 at the International AIDS Society Conference on HIV Pathogenesis and Treatment.

The study researchers received a prolonged standing ovation at the meeting, where the results were presented in their entirety for the first time. The findings were simultaneously published online July 18 in the New England Journal of Medicine (2011 [10.1056/NEJMoa1105243]).

The concept behind early initiation of antiretroviral therapy (ART) in HIV-positive members of serodiscordant couples, a strategy dubbed "treatment as prevention," had been hypothesized based on known virology and pharmacology, Dr. Cohen said, but the evidence that early initiation of antiretroviral therapy prevents infection "is obviously thrilling."

Photo credit: Steve Forrest/Worker's Photos

In their study, Dr. Cohen and his colleagues enrolled 1,763 mostly heterosexual serodiscordant couples in several African countries, Brazil, India, Thailand, and the United States. The HIV-infected partners were randomly assigned to either immediately start triple or quadruple antiretroviral therapy, regardless of CD4 count, or to a deferred-treatment group that started therapy only after their counts dropped below 250 cells/mcL, or they developed pneumocystis pneumonia, or another AIDS-related event. All couples received information and counseling about safe sex and were treated for any HIV-related complications.

At the end of the 20-month study period, 39 previously uninfected partners became infected with HIV. Of these, 28 infections were shown by genetic analysis to be linked, meaning they were transferred from the known infected member of the couple and not a different partner. The vast majority of linked transmissions (27) occurred in the delayed-treatment arm of the study. Only one linked transmission occurred in the immediate-treatment arm.

This highly significant difference corresponded to a 96% risk reduction attributed to immediate therapy, and spurred the independent data and safety monitoring board’s recommendation in April that the deferred-treatment arm be stopped early. The study results initially were reported earlier this year by the National Institute of Allergy and Infectious Diseases, which sponsored the study.

Dr. Cohen encouraged physicians to talk to their patients about the results, which are expected to soon influence treatment guidelines for serodiscordant couples.

He also said that physicians should counsel patients that the infected partner must be on suppression therapy for at least several weeks before unprotected intercourse is attempted, though partners should be encouraged to continue using condoms. ART adds a benefit that is "superimposed" onto the benefits of condoms, he said.

In a related presentation, Dr. Mina C. Hosseinipour of the University of North Carolina Chapel Hill, and a site investigator for the study in Malawi, discussed her analysis of trial outcomes by region.

Some 82% of the transmissions, linked and unlinked, occurred at African study sites, despite the fact that African sites accounted for only 54% of trial participants. This, Dr. Hosseinipour said, related to a combination of factors, including baseline HIV RNA and CD4 counts, HIV subtype, adherence and response to ART, self-reported sexual behavior, and differential timing of ART initiation in the delayed arm.

Self-reported sexual behavior was different in the African sites, Dr. Hosseinipour said, where 29% of the HIV-infected partners reported three or more sex acts in the previous week, compared with 18% at the Asian and American sites. A greater proportion of HIV-infected partners at the African sites – 9% – were more likely to report unprotected sex in the previous week, compared with 4% elsewhere.

Adherence to ART regimens was uniformly high at 99% across regions, Dr. Hosseinipour reported.

The important question of how to use the trial results and when to initiate ART was addressed in a separate presentation by Dr. Beatriz Grinsztejn of the Instituto de Pesquisa Clinica Evandro Chagas-Fiocruz in Brazil.

While Dr. Grinsztejn acknowledged that there remains some controversy about when to initiate ART, the new trial evidence demonstrated a 41% reduction in the number of HIV-related adverse events, including tuberculosis, bacterial pneumonias, severe bacterial infections, and death, among HIV-infected individuals in the immediate-treatment arm. For example, there were 17 cases of tuberculosis in the immediate-ART arm versus 33 in the delayed-treatment arm.

This means that early ART represents a "true benefit to the person taking it and not just [to] the partner," she said.

HPTN 052 was conducted by the HIV Prevention Trials Network, largely funded by NIAID, and also received funding from the National Institute on Drug Abuse and the National Institute of Mental Health; the AIDS Clinical Trials Group, funded by NIAID, also provided support for the study. The 11 antiretroviral drugs used in various combinations in the in the study were provided by the manufacturers, Abbott Laboratories; Boehringer Ingelheim Pharmaceuticals; Bristol-Myers Squibb; Gilead Sciences; GlaxoSmithKline/ViiV Healthcare; and Merck.

ROME – The risk of sexually transmitted HIV was reduced by 96% when the infected partner received a combination of three or more antiretroviral drugs immediately following detection of HIV infection, according to the findings of a randomized controlled trial known as HPTN 052.

These striking results offer "definitive proof of a concept," lead trial investigator Dr. Myron S. Cohen of the University of North Carolina at Chapel Hill said July 18 at the International AIDS Society Conference on HIV Pathogenesis and Treatment.

The study researchers received a prolonged standing ovation at the meeting, where the results were presented in their entirety for the first time. The findings were simultaneously published online July 18 in the New England Journal of Medicine (2011 [10.1056/NEJMoa1105243]).

The concept behind early initiation of antiretroviral therapy (ART) in HIV-positive members of serodiscordant couples, a strategy dubbed "treatment as prevention," had been hypothesized based on known virology and pharmacology, Dr. Cohen said, but the evidence that early initiation of antiretroviral therapy prevents infection "is obviously thrilling."

Photo credit: Steve Forrest/Worker's Photos

In their study, Dr. Cohen and his colleagues enrolled 1,763 mostly heterosexual serodiscordant couples in several African countries, Brazil, India, Thailand, and the United States. The HIV-infected partners were randomly assigned to either immediately start triple or quadruple antiretroviral therapy, regardless of CD4 count, or to a deferred-treatment group that started therapy only after their counts dropped below 250 cells/mcL, or they developed pneumocystis pneumonia, or another AIDS-related event. All couples received information and counseling about safe sex and were treated for any HIV-related complications.

At the end of the 20-month study period, 39 previously uninfected partners became infected with HIV. Of these, 28 infections were shown by genetic analysis to be linked, meaning they were transferred from the known infected member of the couple and not a different partner. The vast majority of linked transmissions (27) occurred in the delayed-treatment arm of the study. Only one linked transmission occurred in the immediate-treatment arm.

This highly significant difference corresponded to a 96% risk reduction attributed to immediate therapy, and spurred the independent data and safety monitoring board’s recommendation in April that the deferred-treatment arm be stopped early. The study results initially were reported earlier this year by the National Institute of Allergy and Infectious Diseases, which sponsored the study.

Dr. Cohen encouraged physicians to talk to their patients about the results, which are expected to soon influence treatment guidelines for serodiscordant couples.

He also said that physicians should counsel patients that the infected partner must be on suppression therapy for at least several weeks before unprotected intercourse is attempted, though partners should be encouraged to continue using condoms. ART adds a benefit that is "superimposed" onto the benefits of condoms, he said.

In a related presentation, Dr. Mina C. Hosseinipour of the University of North Carolina Chapel Hill, and a site investigator for the study in Malawi, discussed her analysis of trial outcomes by region.

Some 82% of the transmissions, linked and unlinked, occurred at African study sites, despite the fact that African sites accounted for only 54% of trial participants. This, Dr. Hosseinipour said, related to a combination of factors, including baseline HIV RNA and CD4 counts, HIV subtype, adherence and response to ART, self-reported sexual behavior, and differential timing of ART initiation in the delayed arm.

Self-reported sexual behavior was different in the African sites, Dr. Hosseinipour said, where 29% of the HIV-infected partners reported three or more sex acts in the previous week, compared with 18% at the Asian and American sites. A greater proportion of HIV-infected partners at the African sites – 9% – were more likely to report unprotected sex in the previous week, compared with 4% elsewhere.

Adherence to ART regimens was uniformly high at 99% across regions, Dr. Hosseinipour reported.

The important question of how to use the trial results and when to initiate ART was addressed in a separate presentation by Dr. Beatriz Grinsztejn of the Instituto de Pesquisa Clinica Evandro Chagas-Fiocruz in Brazil.

While Dr. Grinsztejn acknowledged that there remains some controversy about when to initiate ART, the new trial evidence demonstrated a 41% reduction in the number of HIV-related adverse events, including tuberculosis, bacterial pneumonias, severe bacterial infections, and death, among HIV-infected individuals in the immediate-treatment arm. For example, there were 17 cases of tuberculosis in the immediate-ART arm versus 33 in the delayed-treatment arm.

This means that early ART represents a "true benefit to the person taking it and not just [to] the partner," she said.

HPTN 052 was conducted by the HIV Prevention Trials Network, largely funded by NIAID, and also received funding from the National Institute on Drug Abuse and the National Institute of Mental Health; the AIDS Clinical Trials Group, funded by NIAID, also provided support for the study. The 11 antiretroviral drugs used in various combinations in the in the study were provided by the manufacturers, Abbott Laboratories; Boehringer Ingelheim Pharmaceuticals; Bristol-Myers Squibb; Gilead Sciences; GlaxoSmithKline/ViiV Healthcare; and Merck.

ROME – The risk of sexually transmitted HIV was reduced by 96% when the infected partner received a combination of three or more antiretroviral drugs immediately following detection of HIV infection, according to the findings of a randomized controlled trial known as HPTN 052.

These striking results offer "definitive proof of a concept," lead trial investigator Dr. Myron S. Cohen of the University of North Carolina at Chapel Hill said July 18 at the International AIDS Society Conference on HIV Pathogenesis and Treatment.

The study researchers received a prolonged standing ovation at the meeting, where the results were presented in their entirety for the first time. The findings were simultaneously published online July 18 in the New England Journal of Medicine (2011 [10.1056/NEJMoa1105243]).

The concept behind early initiation of antiretroviral therapy (ART) in HIV-positive members of serodiscordant couples, a strategy dubbed "treatment as prevention," had been hypothesized based on known virology and pharmacology, Dr. Cohen said, but the evidence that early initiation of antiretroviral therapy prevents infection "is obviously thrilling."

Photo credit: Steve Forrest/Worker's Photos

In their study, Dr. Cohen and his colleagues enrolled 1,763 mostly heterosexual serodiscordant couples in several African countries, Brazil, India, Thailand, and the United States. The HIV-infected partners were randomly assigned to either immediately start triple or quadruple antiretroviral therapy, regardless of CD4 count, or to a deferred-treatment group that started therapy only after their counts dropped below 250 cells/mcL, or they developed pneumocystis pneumonia, or another AIDS-related event. All couples received information and counseling about safe sex and were treated for any HIV-related complications.

At the end of the 20-month study period, 39 previously uninfected partners became infected with HIV. Of these, 28 infections were shown by genetic analysis to be linked, meaning they were transferred from the known infected member of the couple and not a different partner. The vast majority of linked transmissions (27) occurred in the delayed-treatment arm of the study. Only one linked transmission occurred in the immediate-treatment arm.

This highly significant difference corresponded to a 96% risk reduction attributed to immediate therapy, and spurred the independent data and safety monitoring board’s recommendation in April that the deferred-treatment arm be stopped early. The study results initially were reported earlier this year by the National Institute of Allergy and Infectious Diseases, which sponsored the study.

Dr. Cohen encouraged physicians to talk to their patients about the results, which are expected to soon influence treatment guidelines for serodiscordant couples.

He also said that physicians should counsel patients that the infected partner must be on suppression therapy for at least several weeks before unprotected intercourse is attempted, though partners should be encouraged to continue using condoms. ART adds a benefit that is "superimposed" onto the benefits of condoms, he said.

In a related presentation, Dr. Mina C. Hosseinipour of the University of North Carolina Chapel Hill, and a site investigator for the study in Malawi, discussed her analysis of trial outcomes by region.

Some 82% of the transmissions, linked and unlinked, occurred at African study sites, despite the fact that African sites accounted for only 54% of trial participants. This, Dr. Hosseinipour said, related to a combination of factors, including baseline HIV RNA and CD4 counts, HIV subtype, adherence and response to ART, self-reported sexual behavior, and differential timing of ART initiation in the delayed arm.

Self-reported sexual behavior was different in the African sites, Dr. Hosseinipour said, where 29% of the HIV-infected partners reported three or more sex acts in the previous week, compared with 18% at the Asian and American sites. A greater proportion of HIV-infected partners at the African sites – 9% – were more likely to report unprotected sex in the previous week, compared with 4% elsewhere.

Adherence to ART regimens was uniformly high at 99% across regions, Dr. Hosseinipour reported.

The important question of how to use the trial results and when to initiate ART was addressed in a separate presentation by Dr. Beatriz Grinsztejn of the Instituto de Pesquisa Clinica Evandro Chagas-Fiocruz in Brazil.

While Dr. Grinsztejn acknowledged that there remains some controversy about when to initiate ART, the new trial evidence demonstrated a 41% reduction in the number of HIV-related adverse events, including tuberculosis, bacterial pneumonias, severe bacterial infections, and death, among HIV-infected individuals in the immediate-treatment arm. For example, there were 17 cases of tuberculosis in the immediate-ART arm versus 33 in the delayed-treatment arm.

This means that early ART represents a "true benefit to the person taking it and not just [to] the partner," she said.

HPTN 052 was conducted by the HIV Prevention Trials Network, largely funded by NIAID, and also received funding from the National Institute on Drug Abuse and the National Institute of Mental Health; the AIDS Clinical Trials Group, funded by NIAID, also provided support for the study. The 11 antiretroviral drugs used in various combinations in the in the study were provided by the manufacturers, Abbott Laboratories; Boehringer Ingelheim Pharmaceuticals; Bristol-Myers Squibb; Gilead Sciences; GlaxoSmithKline/ViiV Healthcare; and Merck.

ROME – Exposure to tenofovir and other antiretroviral agents over time is not independently associated with an increased risk of bone fracture in aging men living with HIV, investigators reported.

Complications of HIV and antiretroviral treatment are particularly important to identify – and separate from traditional risk factors – in aging HIV-positive populations. Several presenters at the International AIDS Society Conference on HIV Pathogenesis and Treatment focused on complications of long-term infection and exposure to treatment agents. The antiretroviral drug tenofovir, for example, is known to be associated with decreased bone mineral density.

Dr. Roger Bedimo of the VA North Texas Health Care System and the University of Texas Southwestern Medical Center in Dallas told the conference that his group’s retrospective cohort study looked at 56,660 people with HIV (mean age, 45), 98% of whom were male. Patients received different antiretroviral regimens between 1988 and 2009.

Antiretroviral therapy (ART) with tenofovir and ART with boosted protease inhibitors were regimens found to be associated with a modest increased risk of osteoporotic fracture after a median 4.5 years of follow-up – but this risk was no longer significant when the investigators controlled for the traditional risk factors of race, body mass index, age, tobacco use, and diabetes.

Though an increased risk of fracture was seen in the cohort as a whole after the introduction of highly active antiretroviral therapy in 1996, this was believed to be attributable to aging and longer survival of subjects. Bone mineral density was not measured in the study.

Separately, Italian researchers, led by Dr. Giovanni Guaraldi of the University of Modena, presented findings from a smaller study designed to test interactions between bone density and elevated coronary artery calcium – a known risk factor for cardiovascular disease – in a group of 681 HIV-infected patients. They found elevated coronary artery calcium to be significantly associated with low femoral bone mineral density (OR, 2.24) but not low lumbar bone mineral density.

Dr. Guaraldi said that further studies were needed to determine "how heart and bone disease talk to each other" in aging HIV-positive populations, and that he felt that nondrug interventions might be able to simultaneously mediate bone-density and cardiovascular risks in this patient group. "Lifestyle is a key component of the risk of both cardiovascular risk and fracture," Dr. Guaraldi said. "Properly designed studies to improve lifestyle may help these patients to reduce cardiovascular and bone disease."

The investigators did not report whether they had any relevant financial disclosures.

ROME – Exposure to tenofovir and other antiretroviral agents over time is not independently associated with an increased risk of bone fracture in aging men living with HIV, investigators reported.

Complications of HIV and antiretroviral treatment are particularly important to identify – and separate from traditional risk factors – in aging HIV-positive populations. Several presenters at the International AIDS Society Conference on HIV Pathogenesis and Treatment focused on complications of long-term infection and exposure to treatment agents. The antiretroviral drug tenofovir, for example, is known to be associated with decreased bone mineral density.

Dr. Roger Bedimo of the VA North Texas Health Care System and the University of Texas Southwestern Medical Center in Dallas told the conference that his group’s retrospective cohort study looked at 56,660 people with HIV (mean age, 45), 98% of whom were male. Patients received different antiretroviral regimens between 1988 and 2009.

Antiretroviral therapy (ART) with tenofovir and ART with boosted protease inhibitors were regimens found to be associated with a modest increased risk of osteoporotic fracture after a median 4.5 years of follow-up – but this risk was no longer significant when the investigators controlled for the traditional risk factors of race, body mass index, age, tobacco use, and diabetes.

Though an increased risk of fracture was seen in the cohort as a whole after the introduction of highly active antiretroviral therapy in 1996, this was believed to be attributable to aging and longer survival of subjects. Bone mineral density was not measured in the study.

Separately, Italian researchers, led by Dr. Giovanni Guaraldi of the University of Modena, presented findings from a smaller study designed to test interactions between bone density and elevated coronary artery calcium – a known risk factor for cardiovascular disease – in a group of 681 HIV-infected patients. They found elevated coronary artery calcium to be significantly associated with low femoral bone mineral density (OR, 2.24) but not low lumbar bone mineral density.

Dr. Guaraldi said that further studies were needed to determine "how heart and bone disease talk to each other" in aging HIV-positive populations, and that he felt that nondrug interventions might be able to simultaneously mediate bone-density and cardiovascular risks in this patient group. "Lifestyle is a key component of the risk of both cardiovascular risk and fracture," Dr. Guaraldi said. "Properly designed studies to improve lifestyle may help these patients to reduce cardiovascular and bone disease."

The investigators did not report whether they had any relevant financial disclosures.

ROME – Exposure to tenofovir and other antiretroviral agents over time is not independently associated with an increased risk of bone fracture in aging men living with HIV, investigators reported.

Complications of HIV and antiretroviral treatment are particularly important to identify – and separate from traditional risk factors – in aging HIV-positive populations. Several presenters at the International AIDS Society Conference on HIV Pathogenesis and Treatment focused on complications of long-term infection and exposure to treatment agents. The antiretroviral drug tenofovir, for example, is known to be associated with decreased bone mineral density.

Dr. Roger Bedimo of the VA North Texas Health Care System and the University of Texas Southwestern Medical Center in Dallas told the conference that his group’s retrospective cohort study looked at 56,660 people with HIV (mean age, 45), 98% of whom were male. Patients received different antiretroviral regimens between 1988 and 2009.

Antiretroviral therapy (ART) with tenofovir and ART with boosted protease inhibitors were regimens found to be associated with a modest increased risk of osteoporotic fracture after a median 4.5 years of follow-up – but this risk was no longer significant when the investigators controlled for the traditional risk factors of race, body mass index, age, tobacco use, and diabetes.

Though an increased risk of fracture was seen in the cohort as a whole after the introduction of highly active antiretroviral therapy in 1996, this was believed to be attributable to aging and longer survival of subjects. Bone mineral density was not measured in the study.

Separately, Italian researchers, led by Dr. Giovanni Guaraldi of the University of Modena, presented findings from a smaller study designed to test interactions between bone density and elevated coronary artery calcium – a known risk factor for cardiovascular disease – in a group of 681 HIV-infected patients. They found elevated coronary artery calcium to be significantly associated with low femoral bone mineral density (OR, 2.24) but not low lumbar bone mineral density.

Dr. Guaraldi said that further studies were needed to determine "how heart and bone disease talk to each other" in aging HIV-positive populations, and that he felt that nondrug interventions might be able to simultaneously mediate bone-density and cardiovascular risks in this patient group. "Lifestyle is a key component of the risk of both cardiovascular risk and fracture," Dr. Guaraldi said. "Properly designed studies to improve lifestyle may help these patients to reduce cardiovascular and bone disease."

The investigators did not report whether they had any relevant financial disclosures.

The European Commission has approved ipilimumab, a novel immunotherapy, for the second-line treatment of adult patients with previously treated, advanced melanoma, the medicine’s manufacturer said July 14.

Ipilimumab (Bristol-Myers Squibb’s Yervoy) was recommended in May by the European Medicines Agency for the indication, and was approved in March by the U.S. Food and Drug Administration. Ipilimumab, a monoclonal antibody, causes tumor cell death by blocking the inhibitory signal of CTLA-4, resulting in T-cell activation, proliferation, and lymphocyte infiltration into tumors.

The medication was shown in one manufacturer-funded, randomized, controlled trial to prolong overall survival for an unprecedented amount of time for people with metastasized unresectable melanoma (N. Engl. J. Med. 2010; 363:711-23).

Patients in the trial (n = 676) received ipilimumab plus glycoprotein 100 (gp100), gp100 alone, or ipilimumab alone, in four intravenous infusions at 3 mg/kg of body weight over 12 weeks. Patients who received the combination therapy or ipilimumab alone saw a median overall survival of about 10 months, compared with 6.4 months for those receiving only gp100. Gp100 was not found to improve the efficacy of ipilimumab.

Responding patients could receive additional courses of ipilimumab, and more than a fifth of patients in the ipilimumab arms survived 2 years or longer.

Adverse reactions to ipilimumab were mostly immune related, and included enterocolitis, hepatitis, dermatitis (including toxic epidermal necrolysis), neuropathy, and endocrinopathy.

European Commission approval means that ipilimumab will be available to patients throughout the European Union. However, pricing may differ, depending on procurement and patient-access schemes in each country. In the United States, ipilimumab is estimated to cost $120,000 per course of treatment.

The European Commission has approved ipilimumab, a novel immunotherapy, for the second-line treatment of adult patients with previously treated, advanced melanoma, the medicine’s manufacturer said July 14.

Ipilimumab (Bristol-Myers Squibb’s Yervoy) was recommended in May by the European Medicines Agency for the indication, and was approved in March by the U.S. Food and Drug Administration. Ipilimumab, a monoclonal antibody, causes tumor cell death by blocking the inhibitory signal of CTLA-4, resulting in T-cell activation, proliferation, and lymphocyte infiltration into tumors.

The medication was shown in one manufacturer-funded, randomized, controlled trial to prolong overall survival for an unprecedented amount of time for people with metastasized unresectable melanoma (N. Engl. J. Med. 2010; 363:711-23).

Patients in the trial (n = 676) received ipilimumab plus glycoprotein 100 (gp100), gp100 alone, or ipilimumab alone, in four intravenous infusions at 3 mg/kg of body weight over 12 weeks. Patients who received the combination therapy or ipilimumab alone saw a median overall survival of about 10 months, compared with 6.4 months for those receiving only gp100. Gp100 was not found to improve the efficacy of ipilimumab.

Responding patients could receive additional courses of ipilimumab, and more than a fifth of patients in the ipilimumab arms survived 2 years or longer.

Adverse reactions to ipilimumab were mostly immune related, and included enterocolitis, hepatitis, dermatitis (including toxic epidermal necrolysis), neuropathy, and endocrinopathy.

European Commission approval means that ipilimumab will be available to patients throughout the European Union. However, pricing may differ, depending on procurement and patient-access schemes in each country. In the United States, ipilimumab is estimated to cost $120,000 per course of treatment.

The European Commission has approved ipilimumab, a novel immunotherapy, for the second-line treatment of adult patients with previously treated, advanced melanoma, the medicine’s manufacturer said July 14.

Ipilimumab (Bristol-Myers Squibb’s Yervoy) was recommended in May by the European Medicines Agency for the indication, and was approved in March by the U.S. Food and Drug Administration. Ipilimumab, a monoclonal antibody, causes tumor cell death by blocking the inhibitory signal of CTLA-4, resulting in T-cell activation, proliferation, and lymphocyte infiltration into tumors.

The medication was shown in one manufacturer-funded, randomized, controlled trial to prolong overall survival for an unprecedented amount of time for people with metastasized unresectable melanoma (N. Engl. J. Med. 2010; 363:711-23).

Patients in the trial (n = 676) received ipilimumab plus glycoprotein 100 (gp100), gp100 alone, or ipilimumab alone, in four intravenous infusions at 3 mg/kg of body weight over 12 weeks. Patients who received the combination therapy or ipilimumab alone saw a median overall survival of about 10 months, compared with 6.4 months for those receiving only gp100. Gp100 was not found to improve the efficacy of ipilimumab.

Responding patients could receive additional courses of ipilimumab, and more than a fifth of patients in the ipilimumab arms survived 2 years or longer.

Adverse reactions to ipilimumab were mostly immune related, and included enterocolitis, hepatitis, dermatitis (including toxic epidermal necrolysis), neuropathy, and endocrinopathy.

European Commission approval means that ipilimumab will be available to patients throughout the European Union. However, pricing may differ, depending on procurement and patient-access schemes in each country. In the United States, ipilimumab is estimated to cost $120,000 per course of treatment.

Patients with a history of contact allergies may be less likely to develop nonmelanoma skin cancer, brain cancer, and breast cancer, a study has shown.

In research published online July 11 in BMJ Open (doi:10.1136/bmjopen-2011-000084), investigators conversely found diagnoses of bladder cancer more likely in people with a history of contact allergies.

Any protective effects could possibly be explained by the stimulation of natural killer T (NKT) cells through contact allergic reactions, the observational study’s lead author, Kaare Engkilde, Ph.D., of the national allergy research center at Copenhagen University Hospital, said in an interview. "You would probably think that [contact allergy] could lead to skin cancer, but that is not what we found," Dr. Engkilde said.

Contact allergic reactions are delayed reactions caused by chemicals small enough to penetrate the skin – triggers can include perfumes, hair dyes, cobalt, nickel, and formaldehyde. Animal studies have shown that contact allergens have the ability to increase the number of NKT cells, at least temporarily, Dr. Engkilde said.

For their research, Dr. Engkilde and his colleagues used a database of 16,922 Danish patients patch tested for type IV allergies between 1984 and 2008. Of these, 6,065 (35.8%) had at least one positive reaction (26.1% of men, 41.4% of women). Linkage with the Danish Cancer Registry showed 3,200, or 18.9%, of dermatitis patients had a benign tumor, a malignant cancer diagnosis, or both, and 1,207 (37.7%) of these patients had had a positive patch test reaction.

Dr. Engkilde and his colleagues looked specifically at 15 types of cancers, all of which affected at least 40 people in the study population.

The investigators found an inverse association between diagnosed contact allergy and nonmelanoma skin cancer (OR, 0.82) along with breast cancer (OR, 0.80) among both men and women. Dr. Engkilde and his colleagues also noted an inverse trend for brain cancer among women with contact allergies, though the P value was above.05 (OR, 0.36).

The findings related to nonmelanoma skin cancers were on some level expected, Dr. Engkilde said; however, the researchers said they were surprised not to see any protective effect against melanomas.

Dr. Engkilde said his group had no hypothesis for the inverse breast cancer finding, but noted that an earlier study had found that self-reported perfume allergy, a type IV allergy, was related inversely to brain cancer incidence (Am. J. Epidemiol. 2007;166:941-50).

The positive association between contact allergy and bladder cancer (OR, 1.44) was more likely related to accumulations of chemical metabolites of type IV allergens in the bladder than to an effect on NKT cells or another immune response, the investigators said.

They cautioned that the relationships between type IV reactions and cancers were "uncertain and not necessarily the result of causality," and that future analyses would have to adjust for social class and smoking, as the latter can increase the risk of developing nickel contact allergies and several types of cancer.

Also, they wrote, "studies focusing on specific chemical exposures are required to further our understanding of the role of contact allergies in the development of cancer." However, if the relationships are in fact etiologic, the findings have "implications for understanding how contact allergy can affect cancer development and vice versa," they said.

Dr. Engkilde and his coauthors received research support from Aage Bang’s Foundation and the Capital Region’s Research Foundation, and disclosed no competing interests.

Patients with a history of contact allergies may be less likely to develop nonmelanoma skin cancer, brain cancer, and breast cancer, a study has shown.

In research published online July 11 in BMJ Open (doi:10.1136/bmjopen-2011-000084), investigators conversely found diagnoses of bladder cancer more likely in people with a history of contact allergies.

Any protective effects could possibly be explained by the stimulation of natural killer T (NKT) cells through contact allergic reactions, the observational study’s lead author, Kaare Engkilde, Ph.D., of the national allergy research center at Copenhagen University Hospital, said in an interview. "You would probably think that [contact allergy] could lead to skin cancer, but that is not what we found," Dr. Engkilde said.

Contact allergic reactions are delayed reactions caused by chemicals small enough to penetrate the skin – triggers can include perfumes, hair dyes, cobalt, nickel, and formaldehyde. Animal studies have shown that contact allergens have the ability to increase the number of NKT cells, at least temporarily, Dr. Engkilde said.

For their research, Dr. Engkilde and his colleagues used a database of 16,922 Danish patients patch tested for type IV allergies between 1984 and 2008. Of these, 6,065 (35.8%) had at least one positive reaction (26.1% of men, 41.4% of women). Linkage with the Danish Cancer Registry showed 3,200, or 18.9%, of dermatitis patients had a benign tumor, a malignant cancer diagnosis, or both, and 1,207 (37.7%) of these patients had had a positive patch test reaction.

Dr. Engkilde and his colleagues looked specifically at 15 types of cancers, all of which affected at least 40 people in the study population.

The investigators found an inverse association between diagnosed contact allergy and nonmelanoma skin cancer (OR, 0.82) along with breast cancer (OR, 0.80) among both men and women. Dr. Engkilde and his colleagues also noted an inverse trend for brain cancer among women with contact allergies, though the P value was above.05 (OR, 0.36).

The findings related to nonmelanoma skin cancers were on some level expected, Dr. Engkilde said; however, the researchers said they were surprised not to see any protective effect against melanomas.

Dr. Engkilde said his group had no hypothesis for the inverse breast cancer finding, but noted that an earlier study had found that self-reported perfume allergy, a type IV allergy, was related inversely to brain cancer incidence (Am. J. Epidemiol. 2007;166:941-50).

The positive association between contact allergy and bladder cancer (OR, 1.44) was more likely related to accumulations of chemical metabolites of type IV allergens in the bladder than to an effect on NKT cells or another immune response, the investigators said.

They cautioned that the relationships between type IV reactions and cancers were "uncertain and not necessarily the result of causality," and that future analyses would have to adjust for social class and smoking, as the latter can increase the risk of developing nickel contact allergies and several types of cancer.

Also, they wrote, "studies focusing on specific chemical exposures are required to further our understanding of the role of contact allergies in the development of cancer." However, if the relationships are in fact etiologic, the findings have "implications for understanding how contact allergy can affect cancer development and vice versa," they said.

Dr. Engkilde and his coauthors received research support from Aage Bang’s Foundation and the Capital Region’s Research Foundation, and disclosed no competing interests.

Patients with a history of contact allergies may be less likely to develop nonmelanoma skin cancer, brain cancer, and breast cancer, a study has shown.

In research published online July 11 in BMJ Open (doi:10.1136/bmjopen-2011-000084), investigators conversely found diagnoses of bladder cancer more likely in people with a history of contact allergies.

Any protective effects could possibly be explained by the stimulation of natural killer T (NKT) cells through contact allergic reactions, the observational study’s lead author, Kaare Engkilde, Ph.D., of the national allergy research center at Copenhagen University Hospital, said in an interview. "You would probably think that [contact allergy] could lead to skin cancer, but that is not what we found," Dr. Engkilde said.

Contact allergic reactions are delayed reactions caused by chemicals small enough to penetrate the skin – triggers can include perfumes, hair dyes, cobalt, nickel, and formaldehyde. Animal studies have shown that contact allergens have the ability to increase the number of NKT cells, at least temporarily, Dr. Engkilde said.

For their research, Dr. Engkilde and his colleagues used a database of 16,922 Danish patients patch tested for type IV allergies between 1984 and 2008. Of these, 6,065 (35.8%) had at least one positive reaction (26.1% of men, 41.4% of women). Linkage with the Danish Cancer Registry showed 3,200, or 18.9%, of dermatitis patients had a benign tumor, a malignant cancer diagnosis, or both, and 1,207 (37.7%) of these patients had had a positive patch test reaction.

Dr. Engkilde and his colleagues looked specifically at 15 types of cancers, all of which affected at least 40 people in the study population.

The investigators found an inverse association between diagnosed contact allergy and nonmelanoma skin cancer (OR, 0.82) along with breast cancer (OR, 0.80) among both men and women. Dr. Engkilde and his colleagues also noted an inverse trend for brain cancer among women with contact allergies, though the P value was above.05 (OR, 0.36).

The findings related to nonmelanoma skin cancers were on some level expected, Dr. Engkilde said; however, the researchers said they were surprised not to see any protective effect against melanomas.

Dr. Engkilde said his group had no hypothesis for the inverse breast cancer finding, but noted that an earlier study had found that self-reported perfume allergy, a type IV allergy, was related inversely to brain cancer incidence (Am. J. Epidemiol. 2007;166:941-50).

The positive association between contact allergy and bladder cancer (OR, 1.44) was more likely related to accumulations of chemical metabolites of type IV allergens in the bladder than to an effect on NKT cells or another immune response, the investigators said.

They cautioned that the relationships between type IV reactions and cancers were "uncertain and not necessarily the result of causality," and that future analyses would have to adjust for social class and smoking, as the latter can increase the risk of developing nickel contact allergies and several types of cancer.

Also, they wrote, "studies focusing on specific chemical exposures are required to further our understanding of the role of contact allergies in the development of cancer." However, if the relationships are in fact etiologic, the findings have "implications for understanding how contact allergy can affect cancer development and vice versa," they said.

Dr. Engkilde and his coauthors received research support from Aage Bang’s Foundation and the Capital Region’s Research Foundation, and disclosed no competing interests.

Patients with a history of contact allergies may be less likely to develop nonmelanoma skin cancer, brain cancer, and breast cancer, a study has shown.

In research published online July 11 in BMJ Open (doi:10.1136/bmjopen-2011-000084), investigators conversely found diagnoses of bladder cancer more likely in people with a history of contact allergies.

Any protective effects could possibly be explained by the stimulation of natural killer T (NKT) cells through contact allergic reactions, the observational study’s lead author, Kaare Engkilde, Ph.D., of the national allergy research center at Copenhagen University Hospital, said in an interview. "You would probably think that [contact allergy] could lead to skin cancer, but that is not what we found," Dr. Engkilde said.

Contact allergic reactions are delayed reactions caused by chemicals small enough to penetrate the skin – triggers can include perfumes, hair dyes, cobalt, nickel, and formaldehyde. Animal studies have shown that contact allergens have the ability to increase the number of NKT cells, at least temporarily, Dr. Engkilde said.

For their research, Dr. Engkilde and his colleagues used a database of 16,922 Danish patients patch tested for type IV allergies between 1984 and 2008. Of these, 6,065 (35.8%) had at least one positive reaction (26.1% of men, 41.4% of women). Linkage with the Danish Cancer Registry showed 3,200, or 18.9%, of dermatitis patients had a benign tumor, a malignant cancer diagnosis, or both, and 1,207 (37.7%) of these patients had had a positive patch test reaction.

Dr. Engkilde and his colleagues looked specifically at 15 types of cancers, all of which affected at least 40 people in the study population.

The investigators found an inverse association between diagnosed contact allergy and nonmelanoma skin cancer (OR, 0.82) along with breast cancer (OR, 0.80) among both men and women. Dr. Engkilde and his colleagues also noted an inverse trend for brain cancer among women with contact allergies, though the P value was above.05 (OR, 0.36).

The findings related to nonmelanoma skin cancers were on some level expected, Dr. Engkilde said; however, the researchers said they were surprised not to see any protective effect against melanomas.

Dr. Engkilde said his group had no hypothesis for the inverse breast cancer finding, but noted that an earlier study had found that self-reported perfume allergy, a type IV allergy, was related inversely to brain cancer incidence (Am. J. Epidemiol. 2007;166:941-50).

The positive association between contact allergy and bladder cancer (OR, 1.44) was more likely related to accumulations of chemical metabolites of type IV allergens in the bladder than to an effect on NKT cells or another immune response, the investigators said.

They cautioned that the relationships between type IV reactions and cancers were "uncertain and not necessarily the result of causality," and that future analyses would have to adjust for social class and smoking, as the latter can increase the risk of developing nickel contact allergies and several types of cancer.

Also, they wrote, "studies focusing on specific chemical exposures are required to further our understanding of the role of contact allergies in the development of cancer." However, if the relationships are in fact etiologic, the findings have "implications for understanding how contact allergy can affect cancer development and vice versa," they said.

Dr. Engkilde and his coauthors received research support from Aage Bang’s Foundation and the Capital Region’s Research Foundation, and disclosed no competing interests.

Patients with a history of contact allergies may be less likely to develop nonmelanoma skin cancer, brain cancer, and breast cancer, a study has shown.

In research published online July 11 in BMJ Open (doi:10.1136/bmjopen-2011-000084), investigators conversely found diagnoses of bladder cancer more likely in people with a history of contact allergies.

Any protective effects could possibly be explained by the stimulation of natural killer T (NKT) cells through contact allergic reactions, the observational study’s lead author, Kaare Engkilde, Ph.D., of the national allergy research center at Copenhagen University Hospital, said in an interview. "You would probably think that [contact allergy] could lead to skin cancer, but that is not what we found," Dr. Engkilde said.

Contact allergic reactions are delayed reactions caused by chemicals small enough to penetrate the skin – triggers can include perfumes, hair dyes, cobalt, nickel, and formaldehyde. Animal studies have shown that contact allergens have the ability to increase the number of NKT cells, at least temporarily, Dr. Engkilde said.

For their research, Dr. Engkilde and his colleagues used a database of 16,922 Danish patients patch tested for type IV allergies between 1984 and 2008. Of these, 6,065 (35.8%) had at least one positive reaction (26.1% of men, 41.4% of women). Linkage with the Danish Cancer Registry showed 3,200, or 18.9%, of dermatitis patients had a benign tumor, a malignant cancer diagnosis, or both, and 1,207 (37.7%) of these patients had had a positive patch test reaction.

Dr. Engkilde and his colleagues looked specifically at 15 types of cancers, all of which affected at least 40 people in the study population.

The investigators found an inverse association between diagnosed contact allergy and nonmelanoma skin cancer (OR, 0.82) along with breast cancer (OR, 0.80) among both men and women. Dr. Engkilde and his colleagues also noted an inverse trend for brain cancer among women with contact allergies, though the P value was above.05 (OR, 0.36).

The findings related to nonmelanoma skin cancers were on some level expected, Dr. Engkilde said; however, the researchers said they were surprised not to see any protective effect against melanomas.

Dr. Engkilde said his group had no hypothesis for the inverse breast cancer finding, but noted that an earlier study had found that self-reported perfume allergy, a type IV allergy, was related inversely to brain cancer incidence (Am. J. Epidemiol. 2007;166:941-50).

The positive association between contact allergy and bladder cancer (OR, 1.44) was more likely related to accumulations of chemical metabolites of type IV allergens in the bladder than to an effect on NKT cells or another immune response, the investigators said.

They cautioned that the relationships between type IV reactions and cancers were "uncertain and not necessarily the result of causality," and that future analyses would have to adjust for social class and smoking, as the latter can increase the risk of developing nickel contact allergies and several types of cancer.

Also, they wrote, "studies focusing on specific chemical exposures are required to further our understanding of the role of contact allergies in the development of cancer." However, if the relationships are in fact etiologic, the findings have "implications for understanding how contact allergy can affect cancer development and vice versa," they said.

Dr. Engkilde and his coauthors received research support from Aage Bang’s Foundation and the Capital Region’s Research Foundation, and disclosed no competing interests.

Patients with a history of contact allergies may be less likely to develop nonmelanoma skin cancer, brain cancer, and breast cancer, a study has shown.

In research published online July 11 in BMJ Open (doi:10.1136/bmjopen-2011-000084), investigators conversely found diagnoses of bladder cancer more likely in people with a history of contact allergies.

Any protective effects could possibly be explained by the stimulation of natural killer T (NKT) cells through contact allergic reactions, the observational study’s lead author, Kaare Engkilde, Ph.D., of the national allergy research center at Copenhagen University Hospital, said in an interview. "You would probably think that [contact allergy] could lead to skin cancer, but that is not what we found," Dr. Engkilde said.

Contact allergic reactions are delayed reactions caused by chemicals small enough to penetrate the skin – triggers can include perfumes, hair dyes, cobalt, nickel, and formaldehyde. Animal studies have shown that contact allergens have the ability to increase the number of NKT cells, at least temporarily, Dr. Engkilde said.

For their research, Dr. Engkilde and his colleagues used a database of 16,922 Danish patients patch tested for type IV allergies between 1984 and 2008. Of these, 6,065 (35.8%) had at least one positive reaction (26.1% of men, 41.4% of women). Linkage with the Danish Cancer Registry showed 3,200, or 18.9%, of dermatitis patients had a benign tumor, a malignant cancer diagnosis, or both, and 1,207 (37.7%) of these patients had had a positive patch test reaction.

Dr. Engkilde and his colleagues looked specifically at 15 types of cancers, all of which affected at least 40 people in the study population.

The investigators found an inverse association between diagnosed contact allergy and nonmelanoma skin cancer (OR, 0.82) along with breast cancer (OR, 0.80) among both men and women. Dr. Engkilde and his colleagues also noted an inverse trend for brain cancer among women with contact allergies, though the P value was above.05 (OR, 0.36).

The findings related to nonmelanoma skin cancers were on some level expected, Dr. Engkilde said; however, the researchers said they were surprised not to see any protective effect against melanomas.

Dr. Engkilde said his group had no hypothesis for the inverse breast cancer finding, but noted that an earlier study had found that self-reported perfume allergy, a type IV allergy, was related inversely to brain cancer incidence (Am. J. Epidemiol. 2007;166:941-50).

The positive association between contact allergy and bladder cancer (OR, 1.44) was more likely related to accumulations of chemical metabolites of type IV allergens in the bladder than to an effect on NKT cells or another immune response, the investigators said.

They cautioned that the relationships between type IV reactions and cancers were "uncertain and not necessarily the result of causality," and that future analyses would have to adjust for social class and smoking, as the latter can increase the risk of developing nickel contact allergies and several types of cancer.

Also, they wrote, "studies focusing on specific chemical exposures are required to further our understanding of the role of contact allergies in the development of cancer." However, if the relationships are in fact etiologic, the findings have "implications for understanding how contact allergy can affect cancer development and vice versa," they said.

Dr. Engkilde and his coauthors received research support from Aage Bang’s Foundation and the Capital Region’s Research Foundation, and disclosed no competing interests.

For years, hospitalists at University of Utah Healthcare have yearned for a fast, elegant way to share information with referring physicians.

When patients are referred from nonaffiliated practices, "they arrive with medical records burned onto a CD," said Dr. Mike Strong, a hospitalist and the chief medical information officer for the university’s hospitals and clinics, which are based in Salt Lake City.

Photo credit: University of Utah Healthcare

"One of the big frustrations is the referring physicians say ‘we love the care that you give us, but it feels like our patients are going into a black hole,’ " Dr. Strong said. "We take care of them, and the patients come back, but the physicians feel that they don’t see the whole story."

For Utah Healthcare and others grappling with similar problems, the solution may lie in the "cloud," medical IT experts say. With cloud technology, electronic medical records (EMRs) and images, and the programs used to access them, can be stored and processed on the Web.

The cloud can be likened to a public utility. Under the cloud model, computing power, like electricity, draws from the equivalent of a grid. Giant server "farms" – such as those now supported by Amazon.com and other cloud vendors – can provide not only storage but also processing power, making applications and information accessible at high speed to anyone with a computer or even a smartphone.

"A CD takes 2 or 3 days to arrive," Dr. Strong said. If a referring hospital were able to upload images into a cloud, and we would have the records up and running before a patient even gets here, it would be great, he said.

Cloud-based services are already widespread in business and personal use – think Gmail, Facebook, Google Docs, or online banking. Proponents of cloud in health care suggest that its flexibility (hospitals can use as little or as much storage and computing capacity as they need), its processing power and speed, which can help smaller hospitals perform sophisticated modeling programs the way large ones do and allowing them to run the kind of algorithms that would tie up or crash their own servers.

Those less keen on the cloud cite its vulnerability to crashes and privacy violations.

Freedom and Flexibility

Cloud applications promise greater physical freedom to hospitalists, who need to gather information on patients from a wide variety of sources and to retrieve or deliver information from wherever they happen to be in the hospital. And hospitalists, members of one of the younger-demographic medical specialties, are hardly technology-averse.

"As a practicing hospitalist working in a system that has computer-order entry and electronic records, I live in the IT world," said Dr. Robert Pendleton, Dr. Strong’s colleague at University of Utah and codirector of its hospitalist program. EMRs and portable devices "have changed my work flow. When we were paper chart–based, I had to go to the patient’s unit." Now, Dr. Pendleton said, "we pull up data as we’re rounding, and I come back to my office and put in my notes electronically."

A shift to the cloud and mobile technologies could eliminate the trip back to the office or, better still, offer hospitalists more intuitive approaches to information sharing.

"Health care is about teamwork," says Dr. Jonathan Bloor, the cofounder, along with fellow surgeon Jonathon Shaw of DocCom, a U.K.-based company that sells cloud applications modeled after such social networks as Facebook, as an alternative to traditional e-mail in hospitals. Dr. Bloor and Dr. Shaw developed the platform while working together at University Hospitals Bristol, part of the U.K.’s National Health Service, where they noticed gaps in team communication that they felt threatened patient care.

Yet while hospitalists’ work flow could greatly benefit from Web-based applications designed for physicians, cloud dependence has a flip side: The April crash of Internet behemoth Amazon’s cloud server was a stark and devastating reminder that the cloud is hardly invulnerable. Some high-profile websites that rely on Amazon’s server were left with minimal or no processing power for a week.

Safety or Speed?

With the cloud, security and encryption are also handled offsite, and information is only as secure as an individual user’s password.

This in part is why hospitals like University of Utah have been hesitant to embrace it. Migrating to a cloud model – in which many businesses and institutions, not just hospitals, store information – could collaterally expose hospitals to hackers aiming at banks or other businesses. "If you’re a hacker, are you going to target a hospital system?" Utah Healthcare’s Dr. Strong said. "If we combine storage onto a cloud [used by other types of business], we could get hacked for other reasons."

Last year, when Utah Healthcare needed to create a way to move information between its two electronic medical records systems (a legacy of the hospital’s decade-old acquisition of another health care company), its IT department chose to design a Web-based bridge – a cloud-style technology. But the server hosting the bridge is the hospital’s own. In May, Utah introduced a portal allowing referring physicians to have read-only access to records on its dedicated servers, in effect approximating some of what a cloud can do, except keeping it all in house. Cloud "is still an in-vogue term," Dr. Pendleton said. "But though the majority of health care systems have Web-based elements, they still don’t capitalize on the concept in terms of the sharing and dissemination of patient information."

A few are taking the plunge anyway. This spring, the University of California San Diego Medical Center’s trauma department began using a cloud system to move radiology files, making it one of the first major hospitals in the country to switch from CDs.

The reason, said trauma surgeon Jeanne Lee, is that UC-San Diego receives referrals from trauma centers at two smaller hospitals that can take from 45 minutes to 2 hours to complete. "It’s a lot of wasted time," Dr. Lee said, which could be better used if the hospital had the radiology information before the patient arrives.

Dr. Lee said that while there had been a debate at San Diego about whether to move to a cloud model, "any system you use is liable to some sort of breach," and so far, "security hasn’t been an issue."

One Password Away

DocCom’s Dr. Bloor said that an increasing number of U.K. hospitals are using cloud-based applications, though not yet for patient records. DocCom’s own products aren’t designed to exchange patient-identifiable information but rather to coordinate teamwork within networks of National Health Service hospitals.

Still, the company aims to produce a platform capable of allowing teams to consolidate and communicate about patients, including the sharing of records – but this is probably years or even a decade before it is likely to be adopted wide scale, Dr. Bloor and Dr. Shaw concede. In the United Kingdom as in the United States, the cloud is a long way from being accepted in a hospital setting as quickly as it has been in business, they said.

One NHS hospital in London has recently begun experimenting with a cloud model for patient records that would allow both clinicians and patients to access them from Internet-connected devices. But the "records" being used are simulations, and the project has attracted some controversy – mostly over privacy and security – even before its official rollout in August.

David Sansom and Brent Hicks, codirectors of clinical IT solutions at the Cleveland Clinic, say that despite concerns about patient information on the cloud, there’s already more of it there – at least in the United States – than people realize. They point to Surescripts, one of the country’s largest e-prescription networks, which uses a Web-based system for its 220 million member records on the cloud.

The Cleveland Clinic’s innovations department is currently working on a number of inventive cloud-based technologies, Mr. Hicks and Mr. Sansom say, including some that both supply data to clinicians to aid patient care and feed clinical data back into models. Recently, Cleveland Clinic’s innovations department spun off a company called Explorys, whose cloud-based product aggregates data on 10 million patients for use in population-based studies – information that, Explorys insists, is HIPAA secure.

While Mr. Hicks and Mr. Sansom are strong advocates for using the cloud in hospital settings, neither dismisses the privacy and security concerns the technology raises.

Hospitals must have the capacity to cache months worth of data in house as a safeguard against Internet connection failures, they say, and the cloud itself can become another point of failure, as the Amazon crash showed. Meanwhile, "HIPAA requirements were never designed for cloud-based computing," Mr. Sansom said. HIPAA requires two methods of identification, which is still not secure enough. When an EMR system is run in house, Mr. Sansom said, someone has to physically come into the hospital, find an unguarded PC, and enter a password to access sensitive patient information. With the cloud, of course, it’s only a password, he points out: "And that’s the problem."

For years, hospitalists at University of Utah Healthcare have yearned for a fast, elegant way to share information with referring physicians.

When patients are referred from nonaffiliated practices, "they arrive with medical records burned onto a CD," said Dr. Mike Strong, a hospitalist and the chief medical information officer for the university’s hospitals and clinics, which are based in Salt Lake City.

Photo credit: University of Utah Healthcare

"One of the big frustrations is the referring physicians say ‘we love the care that you give us, but it feels like our patients are going into a black hole,’ " Dr. Strong said. "We take care of them, and the patients come back, but the physicians feel that they don’t see the whole story."

For Utah Healthcare and others grappling with similar problems, the solution may lie in the "cloud," medical IT experts say. With cloud technology, electronic medical records (EMRs) and images, and the programs used to access them, can be stored and processed on the Web.

The cloud can be likened to a public utility. Under the cloud model, computing power, like electricity, draws from the equivalent of a grid. Giant server "farms" – such as those now supported by Amazon.com and other cloud vendors – can provide not only storage but also processing power, making applications and information accessible at high speed to anyone with a computer or even a smartphone.

"A CD takes 2 or 3 days to arrive," Dr. Strong said. If a referring hospital were able to upload images into a cloud, and we would have the records up and running before a patient even gets here, it would be great, he said.

Cloud-based services are already widespread in business and personal use – think Gmail, Facebook, Google Docs, or online banking. Proponents of cloud in health care suggest that its flexibility (hospitals can use as little or as much storage and computing capacity as they need), its processing power and speed, which can help smaller hospitals perform sophisticated modeling programs the way large ones do and allowing them to run the kind of algorithms that would tie up or crash their own servers.

Those less keen on the cloud cite its vulnerability to crashes and privacy violations.

Freedom and Flexibility

Cloud applications promise greater physical freedom to hospitalists, who need to gather information on patients from a wide variety of sources and to retrieve or deliver information from wherever they happen to be in the hospital. And hospitalists, members of one of the younger-demographic medical specialties, are hardly technology-averse.

"As a practicing hospitalist working in a system that has computer-order entry and electronic records, I live in the IT world," said Dr. Robert Pendleton, Dr. Strong’s colleague at University of Utah and codirector of its hospitalist program. EMRs and portable devices "have changed my work flow. When we were paper chart–based, I had to go to the patient’s unit." Now, Dr. Pendleton said, "we pull up data as we’re rounding, and I come back to my office and put in my notes electronically."

A shift to the cloud and mobile technologies could eliminate the trip back to the office or, better still, offer hospitalists more intuitive approaches to information sharing.

"Health care is about teamwork," says Dr. Jonathan Bloor, the cofounder, along with fellow surgeon Jonathon Shaw of DocCom, a U.K.-based company that sells cloud applications modeled after such social networks as Facebook, as an alternative to traditional e-mail in hospitals. Dr. Bloor and Dr. Shaw developed the platform while working together at University Hospitals Bristol, part of the U.K.’s National Health Service, where they noticed gaps in team communication that they felt threatened patient care.

Yet while hospitalists’ work flow could greatly benefit from Web-based applications designed for physicians, cloud dependence has a flip side: The April crash of Internet behemoth Amazon’s cloud server was a stark and devastating reminder that the cloud is hardly invulnerable. Some high-profile websites that rely on Amazon’s server were left with minimal or no processing power for a week.

Safety or Speed?

With the cloud, security and encryption are also handled offsite, and information is only as secure as an individual user’s password.

This in part is why hospitals like University of Utah have been hesitant to embrace it. Migrating to a cloud model – in which many businesses and institutions, not just hospitals, store information – could collaterally expose hospitals to hackers aiming at banks or other businesses. "If you’re a hacker, are you going to target a hospital system?" Utah Healthcare’s Dr. Strong said. "If we combine storage onto a cloud [used by other types of business], we could get hacked for other reasons."

Last year, when Utah Healthcare needed to create a way to move information between its two electronic medical records systems (a legacy of the hospital’s decade-old acquisition of another health care company), its IT department chose to design a Web-based bridge – a cloud-style technology. But the server hosting the bridge is the hospital’s own. In May, Utah introduced a portal allowing referring physicians to have read-only access to records on its dedicated servers, in effect approximating some of what a cloud can do, except keeping it all in house. Cloud "is still an in-vogue term," Dr. Pendleton said. "But though the majority of health care systems have Web-based elements, they still don’t capitalize on the concept in terms of the sharing and dissemination of patient information."

A few are taking the plunge anyway. This spring, the University of California San Diego Medical Center’s trauma department began using a cloud system to move radiology files, making it one of the first major hospitals in the country to switch from CDs.

The reason, said trauma surgeon Jeanne Lee, is that UC-San Diego receives referrals from trauma centers at two smaller hospitals that can take from 45 minutes to 2 hours to complete. "It’s a lot of wasted time," Dr. Lee said, which could be better used if the hospital had the radiology information before the patient arrives.

Dr. Lee said that while there had been a debate at San Diego about whether to move to a cloud model, "any system you use is liable to some sort of breach," and so far, "security hasn’t been an issue."

One Password Away

DocCom’s Dr. Bloor said that an increasing number of U.K. hospitals are using cloud-based applications, though not yet for patient records. DocCom’s own products aren’t designed to exchange patient-identifiable information but rather to coordinate teamwork within networks of National Health Service hospitals.

Still, the company aims to produce a platform capable of allowing teams to consolidate and communicate about patients, including the sharing of records – but this is probably years or even a decade before it is likely to be adopted wide scale, Dr. Bloor and Dr. Shaw concede. In the United Kingdom as in the United States, the cloud is a long way from being accepted in a hospital setting as quickly as it has been in business, they said.

One NHS hospital in London has recently begun experimenting with a cloud model for patient records that would allow both clinicians and patients to access them from Internet-connected devices. But the "records" being used are simulations, and the project has attracted some controversy – mostly over privacy and security – even before its official rollout in August.

David Sansom and Brent Hicks, codirectors of clinical IT solutions at the Cleveland Clinic, say that despite concerns about patient information on the cloud, there’s already more of it there – at least in the United States – than people realize. They point to Surescripts, one of the country’s largest e-prescription networks, which uses a Web-based system for its 220 million member records on the cloud.

The Cleveland Clinic’s innovations department is currently working on a number of inventive cloud-based technologies, Mr. Hicks and Mr. Sansom say, including some that both supply data to clinicians to aid patient care and feed clinical data back into models. Recently, Cleveland Clinic’s innovations department spun off a company called Explorys, whose cloud-based product aggregates data on 10 million patients for use in population-based studies – information that, Explorys insists, is HIPAA secure.

While Mr. Hicks and Mr. Sansom are strong advocates for using the cloud in hospital settings, neither dismisses the privacy and security concerns the technology raises.

Hospitals must have the capacity to cache months worth of data in house as a safeguard against Internet connection failures, they say, and the cloud itself can become another point of failure, as the Amazon crash showed. Meanwhile, "HIPAA requirements were never designed for cloud-based computing," Mr. Sansom said. HIPAA requires two methods of identification, which is still not secure enough. When an EMR system is run in house, Mr. Sansom said, someone has to physically come into the hospital, find an unguarded PC, and enter a password to access sensitive patient information. With the cloud, of course, it’s only a password, he points out: "And that’s the problem."

For years, hospitalists at University of Utah Healthcare have yearned for a fast, elegant way to share information with referring physicians.

When patients are referred from nonaffiliated practices, "they arrive with medical records burned onto a CD," said Dr. Mike Strong, a hospitalist and the chief medical information officer for the university’s hospitals and clinics, which are based in Salt Lake City.

Photo credit: University of Utah Healthcare

"One of the big frustrations is the referring physicians say ‘we love the care that you give us, but it feels like our patients are going into a black hole,’ " Dr. Strong said. "We take care of them, and the patients come back, but the physicians feel that they don’t see the whole story."

For Utah Healthcare and others grappling with similar problems, the solution may lie in the "cloud," medical IT experts say. With cloud technology, electronic medical records (EMRs) and images, and the programs used to access them, can be stored and processed on the Web.

The cloud can be likened to a public utility. Under the cloud model, computing power, like electricity, draws from the equivalent of a grid. Giant server "farms" – such as those now supported by Amazon.com and other cloud vendors – can provide not only storage but also processing power, making applications and information accessible at high speed to anyone with a computer or even a smartphone.

"A CD takes 2 or 3 days to arrive," Dr. Strong said. If a referring hospital were able to upload images into a cloud, and we would have the records up and running before a patient even gets here, it would be great, he said.

Cloud-based services are already widespread in business and personal use – think Gmail, Facebook, Google Docs, or online banking. Proponents of cloud in health care suggest that its flexibility (hospitals can use as little or as much storage and computing capacity as they need), its processing power and speed, which can help smaller hospitals perform sophisticated modeling programs the way large ones do and allowing them to run the kind of algorithms that would tie up or crash their own servers.

Those less keen on the cloud cite its vulnerability to crashes and privacy violations.

Freedom and Flexibility

Cloud applications promise greater physical freedom to hospitalists, who need to gather information on patients from a wide variety of sources and to retrieve or deliver information from wherever they happen to be in the hospital. And hospitalists, members of one of the younger-demographic medical specialties, are hardly technology-averse.

"As a practicing hospitalist working in a system that has computer-order entry and electronic records, I live in the IT world," said Dr. Robert Pendleton, Dr. Strong’s colleague at University of Utah and codirector of its hospitalist program. EMRs and portable devices "have changed my work flow. When we were paper chart–based, I had to go to the patient’s unit." Now, Dr. Pendleton said, "we pull up data as we’re rounding, and I come back to my office and put in my notes electronically."

A shift to the cloud and mobile technologies could eliminate the trip back to the office or, better still, offer hospitalists more intuitive approaches to information sharing.

"Health care is about teamwork," says Dr. Jonathan Bloor, the cofounder, along with fellow surgeon Jonathon Shaw of DocCom, a U.K.-based company that sells cloud applications modeled after such social networks as Facebook, as an alternative to traditional e-mail in hospitals. Dr. Bloor and Dr. Shaw developed the platform while working together at University Hospitals Bristol, part of the U.K.’s National Health Service, where they noticed gaps in team communication that they felt threatened patient care.

Yet while hospitalists’ work flow could greatly benefit from Web-based applications designed for physicians, cloud dependence has a flip side: The April crash of Internet behemoth Amazon’s cloud server was a stark and devastating reminder that the cloud is hardly invulnerable. Some high-profile websites that rely on Amazon’s server were left with minimal or no processing power for a week.

Safety or Speed?

With the cloud, security and encryption are also handled offsite, and information is only as secure as an individual user’s password.

This in part is why hospitals like University of Utah have been hesitant to embrace it. Migrating to a cloud model – in which many businesses and institutions, not just hospitals, store information – could collaterally expose hospitals to hackers aiming at banks or other businesses. "If you’re a hacker, are you going to target a hospital system?" Utah Healthcare’s Dr. Strong said. "If we combine storage onto a cloud [used by other types of business], we could get hacked for other reasons."

Last year, when Utah Healthcare needed to create a way to move information between its two electronic medical records systems (a legacy of the hospital’s decade-old acquisition of another health care company), its IT department chose to design a Web-based bridge – a cloud-style technology. But the server hosting the bridge is the hospital’s own. In May, Utah introduced a portal allowing referring physicians to have read-only access to records on its dedicated servers, in effect approximating some of what a cloud can do, except keeping it all in house. Cloud "is still an in-vogue term," Dr. Pendleton said. "But though the majority of health care systems have Web-based elements, they still don’t capitalize on the concept in terms of the sharing and dissemination of patient information."

A few are taking the plunge anyway. This spring, the University of California San Diego Medical Center’s trauma department began using a cloud system to move radiology files, making it one of the first major hospitals in the country to switch from CDs.

The reason, said trauma surgeon Jeanne Lee, is that UC-San Diego receives referrals from trauma centers at two smaller hospitals that can take from 45 minutes to 2 hours to complete. "It’s a lot of wasted time," Dr. Lee said, which could be better used if the hospital had the radiology information before the patient arrives.

Dr. Lee said that while there had been a debate at San Diego about whether to move to a cloud model, "any system you use is liable to some sort of breach," and so far, "security hasn’t been an issue."

One Password Away

DocCom’s Dr. Bloor said that an increasing number of U.K. hospitals are using cloud-based applications, though not yet for patient records. DocCom’s own products aren’t designed to exchange patient-identifiable information but rather to coordinate teamwork within networks of National Health Service hospitals.

Still, the company aims to produce a platform capable of allowing teams to consolidate and communicate about patients, including the sharing of records – but this is probably years or even a decade before it is likely to be adopted wide scale, Dr. Bloor and Dr. Shaw concede. In the United Kingdom as in the United States, the cloud is a long way from being accepted in a hospital setting as quickly as it has been in business, they said.

One NHS hospital in London has recently begun experimenting with a cloud model for patient records that would allow both clinicians and patients to access them from Internet-connected devices. But the "records" being used are simulations, and the project has attracted some controversy – mostly over privacy and security – even before its official rollout in August.

David Sansom and Brent Hicks, codirectors of clinical IT solutions at the Cleveland Clinic, say that despite concerns about patient information on the cloud, there’s already more of it there – at least in the United States – than people realize. They point to Surescripts, one of the country’s largest e-prescription networks, which uses a Web-based system for its 220 million member records on the cloud.

The Cleveland Clinic’s innovations department is currently working on a number of inventive cloud-based technologies, Mr. Hicks and Mr. Sansom say, including some that both supply data to clinicians to aid patient care and feed clinical data back into models. Recently, Cleveland Clinic’s innovations department spun off a company called Explorys, whose cloud-based product aggregates data on 10 million patients for use in population-based studies – information that, Explorys insists, is HIPAA secure.

While Mr. Hicks and Mr. Sansom are strong advocates for using the cloud in hospital settings, neither dismisses the privacy and security concerns the technology raises.

Hospitals must have the capacity to cache months worth of data in house as a safeguard against Internet connection failures, they say, and the cloud itself can become another point of failure, as the Amazon crash showed. Meanwhile, "HIPAA requirements were never designed for cloud-based computing," Mr. Sansom said. HIPAA requires two methods of identification, which is still not secure enough. When an EMR system is run in house, Mr. Sansom said, someone has to physically come into the hospital, find an unguarded PC, and enter a password to access sensitive patient information. With the cloud, of course, it’s only a password, he points out: "And that’s the problem."