IAS 2011

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 – 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.