Fran Lowry

TORONTO — A large, randomized comparison of three standard regimens for the initial treatment of HIV has demonstrated that all three are safe and effective, but a regimen of efavirenz plus two nucleosides was significantly better at reducing HIV viral load, investigators reported at the 16th International AIDS Conference.

The regimens for first-line therapy of HIV that are currently recommended by the Department of Health and Human Services are the protease inhibitor lopinavir and the nonnucleoside reverse transcriptase inhibitor efavirenz, each given with two nucleoside reverse transcriptase inhibitors.

However, these regimens have not been compared in adequately powered, randomized clinical trials. Nor has the nucleoside-sparing regimen of efavirenz plus lopinavir, said Dr. Sharon A. Riddler, of the University of Pittsburgh, in a late-breaking clinical trial session.

Dr. Riddler and her coinvestigators of the open-label, prospective AIDS Clinical Trials Group (ACTG) 5142 study compared these three regimens in 753 naive subjects with HIV RNA greater than 2,000 copies/mL and any CD4 cell count. Participants were randomized equally to one of three arms: lopinavir soft gel capsules plus two nucleosides, efavirenz plus two nucleosides, and lopinavir soft gel capsules plus efavirenz.

With a median follow-up of 112 weeks, the time to virologic failure was significantly shorter in the lopinavir plus two nucleosides arm, compared with the efavirenz plus two nucleosides arm. At week 96, the proportion of subjects without virologic failure was 76% for those in the efavirenz plus two nucleosides arm, 74% for lopinavir plus efavirenz, and 67% for lopinavir plus two nucleosides, Dr. Riddler reported.

“Our findings suggest that the efavirenz plus two nucleosides was the best of the three approaches as initial therapy, even in patients with relatively advanced HIV disease,” she said.

However, she cautioned that the study is undergoing further analysis and that the results are still preliminary.

“The main message from this study is that it is an incremental step toward understanding the most useful regimens to be used for initial therapy in HIV-infected individuals,” Dr. Riddler said in an interview.

“All of the three regimens were effective, with significant increases in CD4 cell counts and the vast majority of individuals having undetectable viral loads, regardless of which regimen was initiated,” he continued.

“ACTG 5142 is a very important study,” said Dr. Scott M. Hammer, professor of medicine at Columbia University, New York, and an ACTG investigator. “It's the first study to look at these three standard-of-care regimens in naive individuals randomized upfront, and the data are important for how we actually tease out a lopinavir-based regimen compared to an efavirenz-based regimen.

“The results may change or reinforce our standards of care, but they are definitely going to influence them,” Dr. Hammer concluded.

ELSEVIER GLOBAL MEDICAL NEWS

TORONTO — A large, randomized comparison of three standard regimens for the initial treatment of HIV has demonstrated that all three are safe and effective, but a regimen of efavirenz plus two nucleosides was significantly better at reducing HIV viral load, investigators reported at the 16th International AIDS Conference.

The regimens for first-line therapy of HIV that are currently recommended by the Department of Health and Human Services are the protease inhibitor lopinavir and the nonnucleoside reverse transcriptase inhibitor efavirenz, each given with two nucleoside reverse transcriptase inhibitors.

However, these regimens have not been compared in adequately powered, randomized clinical trials. Nor has the nucleoside-sparing regimen of efavirenz plus lopinavir, said Dr. Sharon A. Riddler, of the University of Pittsburgh, in a late-breaking clinical trial session.

Dr. Riddler and her coinvestigators of the open-label, prospective AIDS Clinical Trials Group (ACTG) 5142 study compared these three regimens in 753 naive subjects with HIV RNA greater than 2,000 copies/mL and any CD4 cell count. Participants were randomized equally to one of three arms: lopinavir soft gel capsules plus two nucleosides, efavirenz plus two nucleosides, and lopinavir soft gel capsules plus efavirenz.

With a median follow-up of 112 weeks, the time to virologic failure was significantly shorter in the lopinavir plus two nucleosides arm, compared with the efavirenz plus two nucleosides arm. At week 96, the proportion of subjects without virologic failure was 76% for those in the efavirenz plus two nucleosides arm, 74% for lopinavir plus efavirenz, and 67% for lopinavir plus two nucleosides, Dr. Riddler reported.

“Our findings suggest that the efavirenz plus two nucleosides was the best of the three approaches as initial therapy, even in patients with relatively advanced HIV disease,” she said.

However, she cautioned that the study is undergoing further analysis and that the results are still preliminary.

“The main message from this study is that it is an incremental step toward understanding the most useful regimens to be used for initial therapy in HIV-infected individuals,” Dr. Riddler said in an interview.

“All of the three regimens were effective, with significant increases in CD4 cell counts and the vast majority of individuals having undetectable viral loads, regardless of which regimen was initiated,” he continued.

“ACTG 5142 is a very important study,” said Dr. Scott M. Hammer, professor of medicine at Columbia University, New York, and an ACTG investigator. “It's the first study to look at these three standard-of-care regimens in naive individuals randomized upfront, and the data are important for how we actually tease out a lopinavir-based regimen compared to an efavirenz-based regimen.

“The results may change or reinforce our standards of care, but they are definitely going to influence them,” Dr. Hammer concluded.

ELSEVIER GLOBAL MEDICAL NEWS

TORONTO — A large, randomized comparison of three standard regimens for the initial treatment of HIV has demonstrated that all three are safe and effective, but a regimen of efavirenz plus two nucleosides was significantly better at reducing HIV viral load, investigators reported at the 16th International AIDS Conference.

The regimens for first-line therapy of HIV that are currently recommended by the Department of Health and Human Services are the protease inhibitor lopinavir and the nonnucleoside reverse transcriptase inhibitor efavirenz, each given with two nucleoside reverse transcriptase inhibitors.

However, these regimens have not been compared in adequately powered, randomized clinical trials. Nor has the nucleoside-sparing regimen of efavirenz plus lopinavir, said Dr. Sharon A. Riddler, of the University of Pittsburgh, in a late-breaking clinical trial session.

Dr. Riddler and her coinvestigators of the open-label, prospective AIDS Clinical Trials Group (ACTG) 5142 study compared these three regimens in 753 naive subjects with HIV RNA greater than 2,000 copies/mL and any CD4 cell count. Participants were randomized equally to one of three arms: lopinavir soft gel capsules plus two nucleosides, efavirenz plus two nucleosides, and lopinavir soft gel capsules plus efavirenz.

With a median follow-up of 112 weeks, the time to virologic failure was significantly shorter in the lopinavir plus two nucleosides arm, compared with the efavirenz plus two nucleosides arm. At week 96, the proportion of subjects without virologic failure was 76% for those in the efavirenz plus two nucleosides arm, 74% for lopinavir plus efavirenz, and 67% for lopinavir plus two nucleosides, Dr. Riddler reported.

“Our findings suggest that the efavirenz plus two nucleosides was the best of the three approaches as initial therapy, even in patients with relatively advanced HIV disease,” she said.

However, she cautioned that the study is undergoing further analysis and that the results are still preliminary.

“The main message from this study is that it is an incremental step toward understanding the most useful regimens to be used for initial therapy in HIV-infected individuals,” Dr. Riddler said in an interview.

“All of the three regimens were effective, with significant increases in CD4 cell counts and the vast majority of individuals having undetectable viral loads, regardless of which regimen was initiated,” he continued.

“ACTG 5142 is a very important study,” said Dr. Scott M. Hammer, professor of medicine at Columbia University, New York, and an ACTG investigator. “It's the first study to look at these three standard-of-care regimens in naive individuals randomized upfront, and the data are important for how we actually tease out a lopinavir-based regimen compared to an efavirenz-based regimen.

“The results may change or reinforce our standards of care, but they are definitely going to influence them,” Dr. Hammer concluded.

ELSEVIER GLOBAL MEDICAL NEWS

TORONTO — With age comes enhanced adherence to HIV therapy, according to a study presented at the 16th International AIDS Conference.

Michael J. Silverberg, Ph.D., of Kaiser Permanente's Division of Research, Oakland, Calif., and his associates took a prospective look at about 5,000 patients in their registry from 1995 to 2004. Of those, 1,000 were aged at least 50 years. All were in the Kaiser Permanente Northern California health plan for the 6 months prior to antiretroviral therapy.

They found that subjects over age 50 were more adherent to highly active antiretroviral therapy (HAART)—a cocktail of a protease inhibitor plus two reverse transcriptase inhibitors—than were younger patients.

As a result, they were 15% more likely to reach undetectable levels of HIV infection and had higher CD4 counts after 3 years of HAART than did their younger counterparts, Dr. Silverberg said. These good results were entirely due to their excellent adherence, he added.

Patients older than 50 years were more likely to achieve HIV RNA levels of less than 500 copies/mL, and, like patients aged 40–49 years, they had a blunted immune response in the first year of therapy. That response was compensated for, however, by faster subsequent increases in CD4 cell counts compared with those of 18 to 39-year-old patients, Dr. Silverberg reported.

Older patients were more likely to have more comorbidities such as metabolic syndrome, abnormal blood lipids, and heart disease, which was linked to a higher first-year incidence of laboratory abnormalities. In addition, HAART was associated with reduced tolerability of the drugs.

Laboratory abnormalities frequently seen after initiation of HAART in older individuals included hyperglycemia, abnormal bilirubin, neutrophil, ALT and AST levels, and elevated creatinine, Dr. Silverberg said.

“Because of these abnormalities, we feel that older patients need particularly close monitoring, especially at the beginning of their therapy,” Dr. Silverberg said. “However, they do quite well. I guess with age, people become more disciplined with their treatment,” he added.

Older patients were 15% more likely to reach undetectable levels of HIV infection and had higher CD4 counts. DR. SILVERBERG

TORONTO — With age comes enhanced adherence to HIV therapy, according to a study presented at the 16th International AIDS Conference.

Michael J. Silverberg, Ph.D., of Kaiser Permanente's Division of Research, Oakland, Calif., and his associates took a prospective look at about 5,000 patients in their registry from 1995 to 2004. Of those, 1,000 were aged at least 50 years. All were in the Kaiser Permanente Northern California health plan for the 6 months prior to antiretroviral therapy.

They found that subjects over age 50 were more adherent to highly active antiretroviral therapy (HAART)—a cocktail of a protease inhibitor plus two reverse transcriptase inhibitors—than were younger patients.

As a result, they were 15% more likely to reach undetectable levels of HIV infection and had higher CD4 counts after 3 years of HAART than did their younger counterparts, Dr. Silverberg said. These good results were entirely due to their excellent adherence, he added.

Patients older than 50 years were more likely to achieve HIV RNA levels of less than 500 copies/mL, and, like patients aged 40–49 years, they had a blunted immune response in the first year of therapy. That response was compensated for, however, by faster subsequent increases in CD4 cell counts compared with those of 18 to 39-year-old patients, Dr. Silverberg reported.

Older patients were more likely to have more comorbidities such as metabolic syndrome, abnormal blood lipids, and heart disease, which was linked to a higher first-year incidence of laboratory abnormalities. In addition, HAART was associated with reduced tolerability of the drugs.

Laboratory abnormalities frequently seen after initiation of HAART in older individuals included hyperglycemia, abnormal bilirubin, neutrophil, ALT and AST levels, and elevated creatinine, Dr. Silverberg said.

“Because of these abnormalities, we feel that older patients need particularly close monitoring, especially at the beginning of their therapy,” Dr. Silverberg said. “However, they do quite well. I guess with age, people become more disciplined with their treatment,” he added.

Older patients were 15% more likely to reach undetectable levels of HIV infection and had higher CD4 counts. DR. SILVERBERG

TORONTO — With age comes enhanced adherence to HIV therapy, according to a study presented at the 16th International AIDS Conference.

Michael J. Silverberg, Ph.D., of Kaiser Permanente's Division of Research, Oakland, Calif., and his associates took a prospective look at about 5,000 patients in their registry from 1995 to 2004. Of those, 1,000 were aged at least 50 years. All were in the Kaiser Permanente Northern California health plan for the 6 months prior to antiretroviral therapy.

They found that subjects over age 50 were more adherent to highly active antiretroviral therapy (HAART)—a cocktail of a protease inhibitor plus two reverse transcriptase inhibitors—than were younger patients.

As a result, they were 15% more likely to reach undetectable levels of HIV infection and had higher CD4 counts after 3 years of HAART than did their younger counterparts, Dr. Silverberg said. These good results were entirely due to their excellent adherence, he added.

Patients older than 50 years were more likely to achieve HIV RNA levels of less than 500 copies/mL, and, like patients aged 40–49 years, they had a blunted immune response in the first year of therapy. That response was compensated for, however, by faster subsequent increases in CD4 cell counts compared with those of 18 to 39-year-old patients, Dr. Silverberg reported.

Older patients were more likely to have more comorbidities such as metabolic syndrome, abnormal blood lipids, and heart disease, which was linked to a higher first-year incidence of laboratory abnormalities. In addition, HAART was associated with reduced tolerability of the drugs.

Laboratory abnormalities frequently seen after initiation of HAART in older individuals included hyperglycemia, abnormal bilirubin, neutrophil, ALT and AST levels, and elevated creatinine, Dr. Silverberg said.

“Because of these abnormalities, we feel that older patients need particularly close monitoring, especially at the beginning of their therapy,” Dr. Silverberg said. “However, they do quite well. I guess with age, people become more disciplined with their treatment,” he added.

Older patients were 15% more likely to reach undetectable levels of HIV infection and had higher CD4 counts. DR. SILVERBERG

TORONTO — A large, randomized comparison of three standard regimens for initial treatment of HIV has shown that all are safe and effective, but a regimen of efavirenz plus two nucleosides was significantly better at reducing HIV viral load, investigators said at the 16th International AIDS Conference.

The regimens for first-line therapy of HIV that are currently recommended by the Department of Health and Human Services are the protease inhibitor lopinavir and the nonnucleoside reverse transcriptase inhibitor efavirenz, each given with two nucleoside reverse transcriptase inhibitors.

However, these regimens have not been compared in adequately powered, randomized clinical trials. Nor has the nucleoside-sparing regimen of efavirenz plus lopinavir, said Dr. Sharon A. Riddler, of the University of Pittsburgh.

Dr. Riddler and her coinvestigators of the open-label, prospective AIDS Clinical Trials Group (ACTG) 5142 study compared these three regimens in 753 naive subjects with HIV RNA greater than 2,000 copies/mL and any CD4 cell count. Participants were randomized equally to one of three arms: lopinavir soft gel capsules plus two nucleosides, efavirenz plus two nucleosides, and lopinavir soft gel capsules plus efavirenz.

With a median follow-up of 112 weeks, the time to virologic failure was significantly shorter in the lopinavir plus two nucleosides arm, compared with the efavirenz plus two nucleosides arm. At week 96, the proportion of subjects without virologic failure was 76% for those in the efavirenz plus two nucleosides arm, 74% for lopinavir plus efavirenz, and 67% for lopinavir plus two nucleosides, Dr. Riddler reported.

“Our findings suggest that the efavirenz plus two nucleosides was the best of the three approaches as initial therapy, even in patients with relatively advanced HIV disease,” she said.

“The main message from this study is that it is an incremental step toward understanding the most useful regimens to be used for initial therapy in HIV-infected individuals,” Dr. Riddler said in an interview. “All of the three regimens were effective, with significant increases in CD4 cell counts and the vast majority of individuals having undetectable viral loads, regardless of which regimen was initiated.”

ACTG 5142 “is the first study to look at these three standard-of-care regimens in naive individuals randomized upfront, and the data are important for how we actually tease out a lopinavir-based regimen compared to an efavirenz-based regimen,” said Dr. Scott M. Hammer, professor of medicine at Columbia University, New York, and an ACTG investigator.

TORONTO — A large, randomized comparison of three standard regimens for initial treatment of HIV has shown that all are safe and effective, but a regimen of efavirenz plus two nucleosides was significantly better at reducing HIV viral load, investigators said at the 16th International AIDS Conference.

The regimens for first-line therapy of HIV that are currently recommended by the Department of Health and Human Services are the protease inhibitor lopinavir and the nonnucleoside reverse transcriptase inhibitor efavirenz, each given with two nucleoside reverse transcriptase inhibitors.

However, these regimens have not been compared in adequately powered, randomized clinical trials. Nor has the nucleoside-sparing regimen of efavirenz plus lopinavir, said Dr. Sharon A. Riddler, of the University of Pittsburgh.

Dr. Riddler and her coinvestigators of the open-label, prospective AIDS Clinical Trials Group (ACTG) 5142 study compared these three regimens in 753 naive subjects with HIV RNA greater than 2,000 copies/mL and any CD4 cell count. Participants were randomized equally to one of three arms: lopinavir soft gel capsules plus two nucleosides, efavirenz plus two nucleosides, and lopinavir soft gel capsules plus efavirenz.

With a median follow-up of 112 weeks, the time to virologic failure was significantly shorter in the lopinavir plus two nucleosides arm, compared with the efavirenz plus two nucleosides arm. At week 96, the proportion of subjects without virologic failure was 76% for those in the efavirenz plus two nucleosides arm, 74% for lopinavir plus efavirenz, and 67% for lopinavir plus two nucleosides, Dr. Riddler reported.

“Our findings suggest that the efavirenz plus two nucleosides was the best of the three approaches as initial therapy, even in patients with relatively advanced HIV disease,” she said.

“The main message from this study is that it is an incremental step toward understanding the most useful regimens to be used for initial therapy in HIV-infected individuals,” Dr. Riddler said in an interview. “All of the three regimens were effective, with significant increases in CD4 cell counts and the vast majority of individuals having undetectable viral loads, regardless of which regimen was initiated.”

ACTG 5142 “is the first study to look at these three standard-of-care regimens in naive individuals randomized upfront, and the data are important for how we actually tease out a lopinavir-based regimen compared to an efavirenz-based regimen,” said Dr. Scott M. Hammer, professor of medicine at Columbia University, New York, and an ACTG investigator.

TORONTO — A large, randomized comparison of three standard regimens for initial treatment of HIV has shown that all are safe and effective, but a regimen of efavirenz plus two nucleosides was significantly better at reducing HIV viral load, investigators said at the 16th International AIDS Conference.

The regimens for first-line therapy of HIV that are currently recommended by the Department of Health and Human Services are the protease inhibitor lopinavir and the nonnucleoside reverse transcriptase inhibitor efavirenz, each given with two nucleoside reverse transcriptase inhibitors.

However, these regimens have not been compared in adequately powered, randomized clinical trials. Nor has the nucleoside-sparing regimen of efavirenz plus lopinavir, said Dr. Sharon A. Riddler, of the University of Pittsburgh.

Dr. Riddler and her coinvestigators of the open-label, prospective AIDS Clinical Trials Group (ACTG) 5142 study compared these three regimens in 753 naive subjects with HIV RNA greater than 2,000 copies/mL and any CD4 cell count. Participants were randomized equally to one of three arms: lopinavir soft gel capsules plus two nucleosides, efavirenz plus two nucleosides, and lopinavir soft gel capsules plus efavirenz.

With a median follow-up of 112 weeks, the time to virologic failure was significantly shorter in the lopinavir plus two nucleosides arm, compared with the efavirenz plus two nucleosides arm. At week 96, the proportion of subjects without virologic failure was 76% for those in the efavirenz plus two nucleosides arm, 74% for lopinavir plus efavirenz, and 67% for lopinavir plus two nucleosides, Dr. Riddler reported.

“Our findings suggest that the efavirenz plus two nucleosides was the best of the three approaches as initial therapy, even in patients with relatively advanced HIV disease,” she said.

“The main message from this study is that it is an incremental step toward understanding the most useful regimens to be used for initial therapy in HIV-infected individuals,” Dr. Riddler said in an interview. “All of the three regimens were effective, with significant increases in CD4 cell counts and the vast majority of individuals having undetectable viral loads, regardless of which regimen was initiated.”

ACTG 5142 “is the first study to look at these three standard-of-care regimens in naive individuals randomized upfront, and the data are important for how we actually tease out a lopinavir-based regimen compared to an efavirenz-based regimen,” said Dr. Scott M. Hammer, professor of medicine at Columbia University, New York, and an ACTG investigator.

TORONTO — Adding a fourth drug to a standard three-drug regimen in the initial treatment of HIV-infected subjects has no advantage, according to research presented at the 16th International AIDS Conference.

“The high rates of virologic suppression achieved in this study support current guidelines that recommend two nucleosides plus efavirenz among preferred regimens for the initial treatment of HIV-1 infection. Adding abacavir as a fourth drug to the standard initial three-drug regimen did not change toxicity or adherence but provided no additional benefit,” said Dr. Roy M. Gulick of Weill Cornell Medical College, New York.

The standard three-drug regimen is effective for most individuals with HIV, but some researchers have hypothesized that if three is good, four must be better, Dr. Gulick said at a press briefing.

To test this theory, the AIDS Clinical Trials Group (ACTG) A5095 study looked at 765 treatment-naive subjects in a double-blind, placebo-controlled study conducted between March 2001 and March 2005. The patients were randomized to a three-drug regimen consisting of zidovudine/lamivudine plus efavirenz (382 patients) or to a four-drug regimen consisting of zidovudine/lamivudine/abacavir plus efavirenz (383).

The primary objectives of the study were to determine the safety and tolerability of the two regimens, to show a noninferior rate of virologic failure with the four-drug regimen, and to compare the time to virologic failure between the two treatments. Virologic failure was defined as two consecutive HIV RNA measurements that were at least 200 copies/mL at week 16 or later.

Overall, the results of the two regimens were virtually identical, Dr. Gulick said. With a median of 3 years of follow-up, virologic failure occurred in 99 (26%) of subjects on the three-drug regimen and 94 (25%) of subjects on the four-drug regimen. Similarly, time to first virologic failure did not differ significantly between the two groups. Virologic load was also similar with the two regimens at 3 years, as were the CD4 cell counts and incidence of adverse events.

The study participants did well, with more than 80% reducing their HIV RNA levels to less than 50 copies/mL at 3 years, he noted.

“Our study affirms that the three-drug regimen we use to treat HIV infection today is very effective for most people, and adding a fourth drug is of no benefit in terms of decreasing viral load levels or increasing T cells,” Dr. Gulick added in an interview.

'Adding a fourth drug is of no benefit in termsof decreasing viral load levelsor increasingT cells.' DR. GULICK

TORONTO — Adding a fourth drug to a standard three-drug regimen in the initial treatment of HIV-infected subjects has no advantage, according to research presented at the 16th International AIDS Conference.

“The high rates of virologic suppression achieved in this study support current guidelines that recommend two nucleosides plus efavirenz among preferred regimens for the initial treatment of HIV-1 infection. Adding abacavir as a fourth drug to the standard initial three-drug regimen did not change toxicity or adherence but provided no additional benefit,” said Dr. Roy M. Gulick of Weill Cornell Medical College, New York.

The standard three-drug regimen is effective for most individuals with HIV, but some researchers have hypothesized that if three is good, four must be better, Dr. Gulick said at a press briefing.

To test this theory, the AIDS Clinical Trials Group (ACTG) A5095 study looked at 765 treatment-naive subjects in a double-blind, placebo-controlled study conducted between March 2001 and March 2005. The patients were randomized to a three-drug regimen consisting of zidovudine/lamivudine plus efavirenz (382 patients) or to a four-drug regimen consisting of zidovudine/lamivudine/abacavir plus efavirenz (383).

The primary objectives of the study were to determine the safety and tolerability of the two regimens, to show a noninferior rate of virologic failure with the four-drug regimen, and to compare the time to virologic failure between the two treatments. Virologic failure was defined as two consecutive HIV RNA measurements that were at least 200 copies/mL at week 16 or later.

Overall, the results of the two regimens were virtually identical, Dr. Gulick said. With a median of 3 years of follow-up, virologic failure occurred in 99 (26%) of subjects on the three-drug regimen and 94 (25%) of subjects on the four-drug regimen. Similarly, time to first virologic failure did not differ significantly between the two groups. Virologic load was also similar with the two regimens at 3 years, as were the CD4 cell counts and incidence of adverse events.

The study participants did well, with more than 80% reducing their HIV RNA levels to less than 50 copies/mL at 3 years, he noted.

“Our study affirms that the three-drug regimen we use to treat HIV infection today is very effective for most people, and adding a fourth drug is of no benefit in terms of decreasing viral load levels or increasing T cells,” Dr. Gulick added in an interview.

'Adding a fourth drug is of no benefit in termsof decreasing viral load levelsor increasingT cells.' DR. GULICK

TORONTO — Adding a fourth drug to a standard three-drug regimen in the initial treatment of HIV-infected subjects has no advantage, according to research presented at the 16th International AIDS Conference.

“The high rates of virologic suppression achieved in this study support current guidelines that recommend two nucleosides plus efavirenz among preferred regimens for the initial treatment of HIV-1 infection. Adding abacavir as a fourth drug to the standard initial three-drug regimen did not change toxicity or adherence but provided no additional benefit,” said Dr. Roy M. Gulick of Weill Cornell Medical College, New York.

The standard three-drug regimen is effective for most individuals with HIV, but some researchers have hypothesized that if three is good, four must be better, Dr. Gulick said at a press briefing.

To test this theory, the AIDS Clinical Trials Group (ACTG) A5095 study looked at 765 treatment-naive subjects in a double-blind, placebo-controlled study conducted between March 2001 and March 2005. The patients were randomized to a three-drug regimen consisting of zidovudine/lamivudine plus efavirenz (382 patients) or to a four-drug regimen consisting of zidovudine/lamivudine/abacavir plus efavirenz (383).

The primary objectives of the study were to determine the safety and tolerability of the two regimens, to show a noninferior rate of virologic failure with the four-drug regimen, and to compare the time to virologic failure between the two treatments. Virologic failure was defined as two consecutive HIV RNA measurements that were at least 200 copies/mL at week 16 or later.

Overall, the results of the two regimens were virtually identical, Dr. Gulick said. With a median of 3 years of follow-up, virologic failure occurred in 99 (26%) of subjects on the three-drug regimen and 94 (25%) of subjects on the four-drug regimen. Similarly, time to first virologic failure did not differ significantly between the two groups. Virologic load was also similar with the two regimens at 3 years, as were the CD4 cell counts and incidence of adverse events.

The study participants did well, with more than 80% reducing their HIV RNA levels to less than 50 copies/mL at 3 years, he noted.

“Our study affirms that the three-drug regimen we use to treat HIV infection today is very effective for most people, and adding a fourth drug is of no benefit in terms of decreasing viral load levels or increasing T cells,” Dr. Gulick added in an interview.

'Adding a fourth drug is of no benefit in termsof decreasing viral load levelsor increasingT cells.' DR. GULICK

ATLANTA — Postmenopausal women with early-stage hormone-receptive breast cancer who have done well on 2–3 years of tamoxifen therapy have significantly improved disease-free and overall survival if they are switched to exemestane midway through their hormonal treatment, researchers reported at the annual meeting of the American Society of Clinical Oncology.

The beneficial effects of tamoxifen tend to wane the longer women are treated, said Dr. Judith Bliss, director of the Clinical Trials and Statistics Unit at the Institute for Cancer Research in London. “Five years of tamoxifen has been the gold standard of treatment for hormone-sensitive postmenopausal breast cancer patients. But we know that the amount of benefit for tamoxifen is greater in the early years, compared with the later years of its use. We wanted to determine what we could add to this treatment to improve on the good results we already have,” she said.

Accordingly, Dr. Bliss and her colleagues initiated the Intergroup Exemestane Study of more than 4,700 patients from 37 countries and 366 centers worldwide. In the study, patients who remained disease free after 2–3 years of tamoxifen therapy were randomized to continue on tamoxifen, or to start treatment with exemestane, an aromatase inhibitor approved for this purpose by the Food and Drug Administration and marketed as Aromasin by Pfizer. Disease-free survival, the trial's primary end point, was increased by approximately 25% in the women who were switched to exemestane, compared with women who remained on tamoxifen, Dr. Bliss reported.

At the time Dr. Bliss and her colleagues started the trial, routine testing of estrogen-receptor status was not being done in several countries. When they went back to determine estrogen-receptor status in their population, they were able to identify 122 women as hormone-receptor negative. After omitting them and reanalyzing the data, the results remained virtually the same, Dr. Bliss said in an interview.

Serious side effects overall were very low. Cardiovascular side effects were equal for both treatments. There was a slight increase in musculoskeletal side effects in women switched to exemestane. However, it is difficult to determine whether this increase was due to cessation of tamoxifen, which is known to be protective of bone, or due to exemestane, Dr. Bliss noted. “I think what we are seeing here is very exciting. By incorporating this switch, we add to the early benefit from treatment with tamoxifen,” she said.

ATLANTA — Postmenopausal women with early-stage hormone-receptive breast cancer who have done well on 2–3 years of tamoxifen therapy have significantly improved disease-free and overall survival if they are switched to exemestane midway through their hormonal treatment, researchers reported at the annual meeting of the American Society of Clinical Oncology.

The beneficial effects of tamoxifen tend to wane the longer women are treated, said Dr. Judith Bliss, director of the Clinical Trials and Statistics Unit at the Institute for Cancer Research in London. “Five years of tamoxifen has been the gold standard of treatment for hormone-sensitive postmenopausal breast cancer patients. But we know that the amount of benefit for tamoxifen is greater in the early years, compared with the later years of its use. We wanted to determine what we could add to this treatment to improve on the good results we already have,” she said.

Accordingly, Dr. Bliss and her colleagues initiated the Intergroup Exemestane Study of more than 4,700 patients from 37 countries and 366 centers worldwide. In the study, patients who remained disease free after 2–3 years of tamoxifen therapy were randomized to continue on tamoxifen, or to start treatment with exemestane, an aromatase inhibitor approved for this purpose by the Food and Drug Administration and marketed as Aromasin by Pfizer. Disease-free survival, the trial's primary end point, was increased by approximately 25% in the women who were switched to exemestane, compared with women who remained on tamoxifen, Dr. Bliss reported.

At the time Dr. Bliss and her colleagues started the trial, routine testing of estrogen-receptor status was not being done in several countries. When they went back to determine estrogen-receptor status in their population, they were able to identify 122 women as hormone-receptor negative. After omitting them and reanalyzing the data, the results remained virtually the same, Dr. Bliss said in an interview.

Serious side effects overall were very low. Cardiovascular side effects were equal for both treatments. There was a slight increase in musculoskeletal side effects in women switched to exemestane. However, it is difficult to determine whether this increase was due to cessation of tamoxifen, which is known to be protective of bone, or due to exemestane, Dr. Bliss noted. “I think what we are seeing here is very exciting. By incorporating this switch, we add to the early benefit from treatment with tamoxifen,” she said.

ATLANTA — Postmenopausal women with early-stage hormone-receptive breast cancer who have done well on 2–3 years of tamoxifen therapy have significantly improved disease-free and overall survival if they are switched to exemestane midway through their hormonal treatment, researchers reported at the annual meeting of the American Society of Clinical Oncology.

The beneficial effects of tamoxifen tend to wane the longer women are treated, said Dr. Judith Bliss, director of the Clinical Trials and Statistics Unit at the Institute for Cancer Research in London. “Five years of tamoxifen has been the gold standard of treatment for hormone-sensitive postmenopausal breast cancer patients. But we know that the amount of benefit for tamoxifen is greater in the early years, compared with the later years of its use. We wanted to determine what we could add to this treatment to improve on the good results we already have,” she said.

Accordingly, Dr. Bliss and her colleagues initiated the Intergroup Exemestane Study of more than 4,700 patients from 37 countries and 366 centers worldwide. In the study, patients who remained disease free after 2–3 years of tamoxifen therapy were randomized to continue on tamoxifen, or to start treatment with exemestane, an aromatase inhibitor approved for this purpose by the Food and Drug Administration and marketed as Aromasin by Pfizer. Disease-free survival, the trial's primary end point, was increased by approximately 25% in the women who were switched to exemestane, compared with women who remained on tamoxifen, Dr. Bliss reported.

At the time Dr. Bliss and her colleagues started the trial, routine testing of estrogen-receptor status was not being done in several countries. When they went back to determine estrogen-receptor status in their population, they were able to identify 122 women as hormone-receptor negative. After omitting them and reanalyzing the data, the results remained virtually the same, Dr. Bliss said in an interview.

Serious side effects overall were very low. Cardiovascular side effects were equal for both treatments. There was a slight increase in musculoskeletal side effects in women switched to exemestane. However, it is difficult to determine whether this increase was due to cessation of tamoxifen, which is known to be protective of bone, or due to exemestane, Dr. Bliss noted. “I think what we are seeing here is very exciting. By incorporating this switch, we add to the early benefit from treatment with tamoxifen,” she said.

ATLANTA — Postmenopausal women with breast cancer who undergo adjuvant chemotherapy with anthracycline have a significantly increased long-term risk of developing heart failure, researchers reported at the annual meeting of the American Society of Clinical Oncology.

Women aged 66–70 who received anthracycline-based chemotherapy had a 38% higher risk of developing heart failure, compared with women of similar age treated with nonanthracycline chemotherapy regimens, said Dr. Sharon H. Giordano, professor of medicine at the University of Texas M.D. Anderson Cancer Center, Houston.

Data are scant on the long-term cardiac safety of anthracycline chemotherapy in women over age 65, Dr. Giordano said in an interview.

Long-term rates and predictors of heart failure were evaluated in a population-based cohort of older women in Medicare's Surveillance, Epidemiology and End Results (SEER) registry, which collects data on U.S. incident cancer rates. Women aged 66–90 years old with invasive breast cancer diagnosed in 1992–1999 were included.

The 31,326 women were placed in one of three groups: 27,324 received no adjuvant chemotherapy, 1,682 received adjuvant anthracyclines, and 2,320 were treated with adjuvant nonanthracycline chemotherapy. A total of 7,414 patients had subsequent claims for heart failure.

Patient characteristics differed in each group. Those “who did not receive chemotherapy were older and had higher comorbidities than did the patients in the other two groups. The anthracycline-treated group was slightly younger and healthier than the nonanthracycline chemotherapy group,” Dr. Giordano said.

Despite being younger and healthier at baseline, a substantially higher proportion of the anthracycline-treated patients had developed heart failure after 10 years.

“At 5 years of follow-up, 85% of anthracycline-treated patients remained free of heart failure, as compared to 88% of other patients,” Dr. Giordano said. At 10 years, the differences were more pronounced, with 61% of anthracycline-treated patients being free of heart failure, compared with 74% of those treated with nonanthracycline regimens and 73% of women who received no chemotherapy.

But in women aged at least 71 years, there were no differences among the three groups. This might be the result of older women being given lower doses of adjuvant therapy or to selection bias in which only the healthiest patients would be eligible for anthracycline, she said.

Despite being healthier at baseline, more anthracycline-treated patients developed heart failure. DR. GIORDANO

ATLANTA — Postmenopausal women with breast cancer who undergo adjuvant chemotherapy with anthracycline have a significantly increased long-term risk of developing heart failure, researchers reported at the annual meeting of the American Society of Clinical Oncology.

Women aged 66–70 who received anthracycline-based chemotherapy had a 38% higher risk of developing heart failure, compared with women of similar age treated with nonanthracycline chemotherapy regimens, said Dr. Sharon H. Giordano, professor of medicine at the University of Texas M.D. Anderson Cancer Center, Houston.

Data are scant on the long-term cardiac safety of anthracycline chemotherapy in women over age 65, Dr. Giordano said in an interview.

Long-term rates and predictors of heart failure were evaluated in a population-based cohort of older women in Medicare's Surveillance, Epidemiology and End Results (SEER) registry, which collects data on U.S. incident cancer rates. Women aged 66–90 years old with invasive breast cancer diagnosed in 1992–1999 were included.

The 31,326 women were placed in one of three groups: 27,324 received no adjuvant chemotherapy, 1,682 received adjuvant anthracyclines, and 2,320 were treated with adjuvant nonanthracycline chemotherapy. A total of 7,414 patients had subsequent claims for heart failure.

Patient characteristics differed in each group. Those “who did not receive chemotherapy were older and had higher comorbidities than did the patients in the other two groups. The anthracycline-treated group was slightly younger and healthier than the nonanthracycline chemotherapy group,” Dr. Giordano said.

Despite being younger and healthier at baseline, a substantially higher proportion of the anthracycline-treated patients had developed heart failure after 10 years.

“At 5 years of follow-up, 85% of anthracycline-treated patients remained free of heart failure, as compared to 88% of other patients,” Dr. Giordano said. At 10 years, the differences were more pronounced, with 61% of anthracycline-treated patients being free of heart failure, compared with 74% of those treated with nonanthracycline regimens and 73% of women who received no chemotherapy.

But in women aged at least 71 years, there were no differences among the three groups. This might be the result of older women being given lower doses of adjuvant therapy or to selection bias in which only the healthiest patients would be eligible for anthracycline, she said.

Despite being healthier at baseline, more anthracycline-treated patients developed heart failure. DR. GIORDANO

ATLANTA — Postmenopausal women with breast cancer who undergo adjuvant chemotherapy with anthracycline have a significantly increased long-term risk of developing heart failure, researchers reported at the annual meeting of the American Society of Clinical Oncology.

Women aged 66–70 who received anthracycline-based chemotherapy had a 38% higher risk of developing heart failure, compared with women of similar age treated with nonanthracycline chemotherapy regimens, said Dr. Sharon H. Giordano, professor of medicine at the University of Texas M.D. Anderson Cancer Center, Houston.

Data are scant on the long-term cardiac safety of anthracycline chemotherapy in women over age 65, Dr. Giordano said in an interview.

Long-term rates and predictors of heart failure were evaluated in a population-based cohort of older women in Medicare's Surveillance, Epidemiology and End Results (SEER) registry, which collects data on U.S. incident cancer rates. Women aged 66–90 years old with invasive breast cancer diagnosed in 1992–1999 were included.

The 31,326 women were placed in one of three groups: 27,324 received no adjuvant chemotherapy, 1,682 received adjuvant anthracyclines, and 2,320 were treated with adjuvant nonanthracycline chemotherapy. A total of 7,414 patients had subsequent claims for heart failure.

Patient characteristics differed in each group. Those “who did not receive chemotherapy were older and had higher comorbidities than did the patients in the other two groups. The anthracycline-treated group was slightly younger and healthier than the nonanthracycline chemotherapy group,” Dr. Giordano said.

Despite being younger and healthier at baseline, a substantially higher proportion of the anthracycline-treated patients had developed heart failure after 10 years.

“At 5 years of follow-up, 85% of anthracycline-treated patients remained free of heart failure, as compared to 88% of other patients,” Dr. Giordano said. At 10 years, the differences were more pronounced, with 61% of anthracycline-treated patients being free of heart failure, compared with 74% of those treated with nonanthracycline regimens and 73% of women who received no chemotherapy.

But in women aged at least 71 years, there were no differences among the three groups. This might be the result of older women being given lower doses of adjuvant therapy or to selection bias in which only the healthiest patients would be eligible for anthracycline, she said.

Despite being healthier at baseline, more anthracycline-treated patients developed heart failure. DR. GIORDANO

FORT LAUDERDALE, FLA. — The Colpexin sphere, an intravaginal device for women with advanced genital prolapse that supports the prolapse above the levator musculature and helps patients strengthen their pelvic floor muscles, can also serve as a test to objectively assess the contractility and strength of pelvic floor muscles, Dr. G. Willy Davila said at a symposium on pelvic floor disorders sponsored by the Cleveland Clinic Florida.

An objective test of the pelvic floor musculature has long been needed, said Dr. Davila, chairman of the department of gynecology at the Cleveland Clinic in Weston, Fla. Until now, clinicians have had to rely on subjective methods, such as manual testing using the Brink classification system, which was first published in 1989. “You can see from the date it was published that we really haven't done very much to improve our assessment of pelvic floor contractions,” Dr. Davila said.

In using the Colpexin sphere pull test to objectively assess pelvic floor musculature strength and tone, a tensiometer is attached to the sphere and then the patient is asked to contract her pelvic floor muscles.

The force required to extract the device while the woman is resisting its removal is then measured, explained Dr. Davila, who has received research funding from and is a consultant for Adamed Inc., the maker of the Colpexin sphere.

Early results obtained with the Colpexin pull test show a significant improvement in contractile strength over a 16-week period in women with prolapse who performed Kegel exercises regularly with the sphere in place. “This is the first time that we have had the ability to objectively evaluate pelvic floor strength and to measure improvement over time in our patients,” he said.

The Colpexin device, which was developed in Poland, has just gained Food and Drug Administration approval and will be marketed within a few months, Dr. Davila said.

'This is the first time that we have had the ability to objectively evaluate pelvic floor strength.' DR. DAVILA

EMILY BRANNAN, ILLUSTRATION

FORT LAUDERDALE, FLA. — The Colpexin sphere, an intravaginal device for women with advanced genital prolapse that supports the prolapse above the levator musculature and helps patients strengthen their pelvic floor muscles, can also serve as a test to objectively assess the contractility and strength of pelvic floor muscles, Dr. G. Willy Davila said at a symposium on pelvic floor disorders sponsored by the Cleveland Clinic Florida.

An objective test of the pelvic floor musculature has long been needed, said Dr. Davila, chairman of the department of gynecology at the Cleveland Clinic in Weston, Fla. Until now, clinicians have had to rely on subjective methods, such as manual testing using the Brink classification system, which was first published in 1989. “You can see from the date it was published that we really haven't done very much to improve our assessment of pelvic floor contractions,” Dr. Davila said.

In using the Colpexin sphere pull test to objectively assess pelvic floor musculature strength and tone, a tensiometer is attached to the sphere and then the patient is asked to contract her pelvic floor muscles.

The force required to extract the device while the woman is resisting its removal is then measured, explained Dr. Davila, who has received research funding from and is a consultant for Adamed Inc., the maker of the Colpexin sphere.

Early results obtained with the Colpexin pull test show a significant improvement in contractile strength over a 16-week period in women with prolapse who performed Kegel exercises regularly with the sphere in place. “This is the first time that we have had the ability to objectively evaluate pelvic floor strength and to measure improvement over time in our patients,” he said.

The Colpexin device, which was developed in Poland, has just gained Food and Drug Administration approval and will be marketed within a few months, Dr. Davila said.

'This is the first time that we have had the ability to objectively evaluate pelvic floor strength.' DR. DAVILA

EMILY BRANNAN, ILLUSTRATION

FORT LAUDERDALE, FLA. — The Colpexin sphere, an intravaginal device for women with advanced genital prolapse that supports the prolapse above the levator musculature and helps patients strengthen their pelvic floor muscles, can also serve as a test to objectively assess the contractility and strength of pelvic floor muscles, Dr. G. Willy Davila said at a symposium on pelvic floor disorders sponsored by the Cleveland Clinic Florida.

An objective test of the pelvic floor musculature has long been needed, said Dr. Davila, chairman of the department of gynecology at the Cleveland Clinic in Weston, Fla. Until now, clinicians have had to rely on subjective methods, such as manual testing using the Brink classification system, which was first published in 1989. “You can see from the date it was published that we really haven't done very much to improve our assessment of pelvic floor contractions,” Dr. Davila said.

In using the Colpexin sphere pull test to objectively assess pelvic floor musculature strength and tone, a tensiometer is attached to the sphere and then the patient is asked to contract her pelvic floor muscles.

The force required to extract the device while the woman is resisting its removal is then measured, explained Dr. Davila, who has received research funding from and is a consultant for Adamed Inc., the maker of the Colpexin sphere.

Early results obtained with the Colpexin pull test show a significant improvement in contractile strength over a 16-week period in women with prolapse who performed Kegel exercises regularly with the sphere in place. “This is the first time that we have had the ability to objectively evaluate pelvic floor strength and to measure improvement over time in our patients,” he said.

The Colpexin device, which was developed in Poland, has just gained Food and Drug Administration approval and will be marketed within a few months, Dr. Davila said.

'This is the first time that we have had the ability to objectively evaluate pelvic floor strength.' DR. DAVILA

EMILY BRANNAN, ILLUSTRATION

WASHINGTON — The combination of drospirenone (a progestin with antialdosterone effects) and 17-β-estradiol as hormone therapy for hypertensive postmenopausal women not only reduces hot flashes, but lowers blood pressure as well, according to a poster presented at the annual meeting of the American College of Obstetricians and Gynecologists.

Treatment with the combination of drospirenone and 17-β-estradiol for an 8-week period produced significant reductions in systolic and diastolic 24-hour ambulatory and clinic blood pressure at 2- and 3-mg doses of drospirenone, reported Dr. William B. White, professor of medicine at the University of Connecticut, Farmington.

Drospirenone plus estradiol has been used for the treatment of menopausal symptoms and is Food and Drug Administration-approved for this indication at a dose of 0.5 mg drospirenone/1 mg estradiol (marketed in the United States as Angeliq by Berlex Laboratories Inc.). During its development, it was noted that at a higher drospirenone dose, the combination also had antihypertensive properties. It is currently being used in Europe, Asia, and the rest of the world at a dose of 2 mg drospirenone/1 mg estradiol, Dr. White told this news organization. In a multicenter (42 U.S. centers and 22 European centers) trial, Dr. White and his colleagues evaluated the blood pressure-lowering efficacy of various doses of drospirenone (1, 2, or 3 mg) combined with 1 mg of estradiol in 750 postmenopausal women aged 45–75 years, with an untreated systolic blood pressure of 140–179 mm Hg and untreated diastolic blood pressure of 90–109 mm Hg. They also evaluated estradiol alone to elicit data on the effects of estrogen on ambulatory blood pressure, about which little is known, Dr. White wrote.

In addition, because drugs which induce aldosterone blockade have been shown to increase serum potassium, the researchers evaluated the metabolic effects of the combination therapy.

Following a single-blind, placebo phase for 3–4 weeks to establish baseline blood pressure and laboratory values, the women were randomized to one of the three combination treatment arms, to estradiol alone, or to placebo. Twenty-four-hour ambulatory blood pressure monitoring was done at baseline and at 8 weeks.

Drospirenone at the 2-mg dose reduced clinical systolic and diastolic blood pressures by a mean of 12.1 and 9.2 mm Hg, respectively; and by a mean of 13.8 and 8.5 mm Hg, respectively, at the 3-mg dose. Drospirenone at the 1-mg dose was less effective, reducing systolic BP by a mean of 9.8 mm Hg and diastolic BP by a mean of 7.0 mm Hg. The blood pressure-lowering effect of estradiol (−7.6 mm Hg systolic and −5.9 mm Hg diastolic) was similar to that seen with placebo, Dr. White wrote.

Reductions in ambulatory blood pressure showed findings similar to clinic readings, although the combination with 1 mg of drospirenone also had marginal benefits compared with placebo and estradiol alone, he added.

Changes in potassium levels were similar in all groups: Five patients in each of the drospirenone groups and five in the placebo group developed a serum potassium less than or equal to 5.5 mEq/L. The mean maximal change from baseline in drospirenone-treated patients was not significantly different among the five treatment groups and ranged from 0.29 mEq/L to 0.37 mEq/L.

Regarding the combination's effect on lipid levels, total and LDL cholesterol levels also were lowered significantly in women taking drospirenone and estradiol, with a 13.6-mg/dL drop in LDL cholesterol at the 3-mg dose, a 10.4-mg/dL drop at the 2-mg dose, and a 12.2 drop at the 1-mg dose. Triglyceride levels were not affected, Dr. White wrote.

Side effects varied according to drospirenone dose; those seen with a frequency greater than 2% included breast discomfort, vaginal bleeding or spotting, and upper respiratory infection, according to the researchers.

“This is a novel progestin which actually impacts upon aldosterone and therefore has a dose-related reduction in blood pressure—especially systolic blood pressure—which is associated with cardiovascular risk.

“We actually studied a full spectrum of doses, along with estradiol alone and placebo, so the strength of the study is that we actually had these two control groups showing that, in fact, it was the drospirenone that was the important component that lowered the blood pressure. And it did that without any significant metabolic consequences,” Dr. White said in an interview.

Dr. White disclosed that he serves as a consultant for Berlex Laboratories Inc., which markets Angeliq, as well as other pharmaceutical companies.

WASHINGTON — The combination of drospirenone (a progestin with antialdosterone effects) and 17-β-estradiol as hormone therapy for hypertensive postmenopausal women not only reduces hot flashes, but lowers blood pressure as well, according to a poster presented at the annual meeting of the American College of Obstetricians and Gynecologists.

Treatment with the combination of drospirenone and 17-β-estradiol for an 8-week period produced significant reductions in systolic and diastolic 24-hour ambulatory and clinic blood pressure at 2- and 3-mg doses of drospirenone, reported Dr. William B. White, professor of medicine at the University of Connecticut, Farmington.

Drospirenone plus estradiol has been used for the treatment of menopausal symptoms and is Food and Drug Administration-approved for this indication at a dose of 0.5 mg drospirenone/1 mg estradiol (marketed in the United States as Angeliq by Berlex Laboratories Inc.). During its development, it was noted that at a higher drospirenone dose, the combination also had antihypertensive properties. It is currently being used in Europe, Asia, and the rest of the world at a dose of 2 mg drospirenone/1 mg estradiol, Dr. White told this news organization. In a multicenter (42 U.S. centers and 22 European centers) trial, Dr. White and his colleagues evaluated the blood pressure-lowering efficacy of various doses of drospirenone (1, 2, or 3 mg) combined with 1 mg of estradiol in 750 postmenopausal women aged 45–75 years, with an untreated systolic blood pressure of 140–179 mm Hg and untreated diastolic blood pressure of 90–109 mm Hg. They also evaluated estradiol alone to elicit data on the effects of estrogen on ambulatory blood pressure, about which little is known, Dr. White wrote.

In addition, because drugs which induce aldosterone blockade have been shown to increase serum potassium, the researchers evaluated the metabolic effects of the combination therapy.

Following a single-blind, placebo phase for 3–4 weeks to establish baseline blood pressure and laboratory values, the women were randomized to one of the three combination treatment arms, to estradiol alone, or to placebo. Twenty-four-hour ambulatory blood pressure monitoring was done at baseline and at 8 weeks.

Drospirenone at the 2-mg dose reduced clinical systolic and diastolic blood pressures by a mean of 12.1 and 9.2 mm Hg, respectively; and by a mean of 13.8 and 8.5 mm Hg, respectively, at the 3-mg dose. Drospirenone at the 1-mg dose was less effective, reducing systolic BP by a mean of 9.8 mm Hg and diastolic BP by a mean of 7.0 mm Hg. The blood pressure-lowering effect of estradiol (−7.6 mm Hg systolic and −5.9 mm Hg diastolic) was similar to that seen with placebo, Dr. White wrote.

Reductions in ambulatory blood pressure showed findings similar to clinic readings, although the combination with 1 mg of drospirenone also had marginal benefits compared with placebo and estradiol alone, he added.

Changes in potassium levels were similar in all groups: Five patients in each of the drospirenone groups and five in the placebo group developed a serum potassium less than or equal to 5.5 mEq/L. The mean maximal change from baseline in drospirenone-treated patients was not significantly different among the five treatment groups and ranged from 0.29 mEq/L to 0.37 mEq/L.

Regarding the combination's effect on lipid levels, total and LDL cholesterol levels also were lowered significantly in women taking drospirenone and estradiol, with a 13.6-mg/dL drop in LDL cholesterol at the 3-mg dose, a 10.4-mg/dL drop at the 2-mg dose, and a 12.2 drop at the 1-mg dose. Triglyceride levels were not affected, Dr. White wrote.

Side effects varied according to drospirenone dose; those seen with a frequency greater than 2% included breast discomfort, vaginal bleeding or spotting, and upper respiratory infection, according to the researchers.

“This is a novel progestin which actually impacts upon aldosterone and therefore has a dose-related reduction in blood pressure—especially systolic blood pressure—which is associated with cardiovascular risk.

“We actually studied a full spectrum of doses, along with estradiol alone and placebo, so the strength of the study is that we actually had these two control groups showing that, in fact, it was the drospirenone that was the important component that lowered the blood pressure. And it did that without any significant metabolic consequences,” Dr. White said in an interview.

Dr. White disclosed that he serves as a consultant for Berlex Laboratories Inc., which markets Angeliq, as well as other pharmaceutical companies.

WASHINGTON — The combination of drospirenone (a progestin with antialdosterone effects) and 17-β-estradiol as hormone therapy for hypertensive postmenopausal women not only reduces hot flashes, but lowers blood pressure as well, according to a poster presented at the annual meeting of the American College of Obstetricians and Gynecologists.

Treatment with the combination of drospirenone and 17-β-estradiol for an 8-week period produced significant reductions in systolic and diastolic 24-hour ambulatory and clinic blood pressure at 2- and 3-mg doses of drospirenone, reported Dr. William B. White, professor of medicine at the University of Connecticut, Farmington.

Drospirenone plus estradiol has been used for the treatment of menopausal symptoms and is Food and Drug Administration-approved for this indication at a dose of 0.5 mg drospirenone/1 mg estradiol (marketed in the United States as Angeliq by Berlex Laboratories Inc.). During its development, it was noted that at a higher drospirenone dose, the combination also had antihypertensive properties. It is currently being used in Europe, Asia, and the rest of the world at a dose of 2 mg drospirenone/1 mg estradiol, Dr. White told this news organization. In a multicenter (42 U.S. centers and 22 European centers) trial, Dr. White and his colleagues evaluated the blood pressure-lowering efficacy of various doses of drospirenone (1, 2, or 3 mg) combined with 1 mg of estradiol in 750 postmenopausal women aged 45–75 years, with an untreated systolic blood pressure of 140–179 mm Hg and untreated diastolic blood pressure of 90–109 mm Hg. They also evaluated estradiol alone to elicit data on the effects of estrogen on ambulatory blood pressure, about which little is known, Dr. White wrote.

In addition, because drugs which induce aldosterone blockade have been shown to increase serum potassium, the researchers evaluated the metabolic effects of the combination therapy.

Following a single-blind, placebo phase for 3–4 weeks to establish baseline blood pressure and laboratory values, the women were randomized to one of the three combination treatment arms, to estradiol alone, or to placebo. Twenty-four-hour ambulatory blood pressure monitoring was done at baseline and at 8 weeks.

Drospirenone at the 2-mg dose reduced clinical systolic and diastolic blood pressures by a mean of 12.1 and 9.2 mm Hg, respectively; and by a mean of 13.8 and 8.5 mm Hg, respectively, at the 3-mg dose. Drospirenone at the 1-mg dose was less effective, reducing systolic BP by a mean of 9.8 mm Hg and diastolic BP by a mean of 7.0 mm Hg. The blood pressure-lowering effect of estradiol (−7.6 mm Hg systolic and −5.9 mm Hg diastolic) was similar to that seen with placebo, Dr. White wrote.

Reductions in ambulatory blood pressure showed findings similar to clinic readings, although the combination with 1 mg of drospirenone also had marginal benefits compared with placebo and estradiol alone, he added.

Changes in potassium levels were similar in all groups: Five patients in each of the drospirenone groups and five in the placebo group developed a serum potassium less than or equal to 5.5 mEq/L. The mean maximal change from baseline in drospirenone-treated patients was not significantly different among the five treatment groups and ranged from 0.29 mEq/L to 0.37 mEq/L.

Regarding the combination's effect on lipid levels, total and LDL cholesterol levels also were lowered significantly in women taking drospirenone and estradiol, with a 13.6-mg/dL drop in LDL cholesterol at the 3-mg dose, a 10.4-mg/dL drop at the 2-mg dose, and a 12.2 drop at the 1-mg dose. Triglyceride levels were not affected, Dr. White wrote.

Side effects varied according to drospirenone dose; those seen with a frequency greater than 2% included breast discomfort, vaginal bleeding or spotting, and upper respiratory infection, according to the researchers.

“This is a novel progestin which actually impacts upon aldosterone and therefore has a dose-related reduction in blood pressure—especially systolic blood pressure—which is associated with cardiovascular risk.

“We actually studied a full spectrum of doses, along with estradiol alone and placebo, so the strength of the study is that we actually had these two control groups showing that, in fact, it was the drospirenone that was the important component that lowered the blood pressure. And it did that without any significant metabolic consequences,” Dr. White said in an interview.

Dr. White disclosed that he serves as a consultant for Berlex Laboratories Inc., which markets Angeliq, as well as other pharmaceutical companies.

ATLANTA — It's not only the bicycle seat that causes erectile dysfunction in some men who cycle—it may also be the way in which they sit on the seat, according to a poster presentation at the annual meeting of the American Urological Association.

Erectile dysfunction (ED) resulting from penile hypoxia can sometimes occur after prolonged bicycling, particularly when men who ride road or touring bikes lean far forward, as when using dropped handlebars. ED may occur even when riders use grooved seats to reduce pelvic compression. One new solution may be to sit up straight, or at least somewhat straighter, thereby reducing compression on the internal pudendal artery and nerve, said Dr. John M. Gemery, professor of radiology, Dartmouth-Hitchcock Medical Center, Lebanon, N.H.

Erectile dysfunction is theoretically less likely to occur in racing cyclists, who spend much of their riding time standing up. But men who ride for a few hours on flat surfaces and stay bent forward over the handlebars may be more likely to end up with ED, Dr. Gemery said in an interview.

Much effort has gone into designing bicycle seats that have a central groove or cutout to reduce perineal pressure. Study results have shown that it helps when a male rider uses a grooved seat. However, penile artery compression can still occur with a grooved seat when the rider leans far forward. No matter what seat a rider chooses, leaning forward causes higher compression (and hence greater potential for ED), compared with sitting upright while riding, Dr. Gemery said.

He became interested in cycling-induced erectile dysfunction when he was an interventional radiology fellow at Boston Medical Center, working with Dr. Irwin Goldstein, who raised the first concerns about bike seats and ED. “I was doing angiograms for him, so I also became interested in the problem. We were trying to figure out where, in fact, the blood vessels to the penis get compressed.”

Dr. Gemery continued this research at Dartmouth-Hitchcock, where he developed three-dimensional digital models created from CT scans of the pelvis of an adult male volunteer, as well as three bicycle seat designs.

He worked closely with Dr. Ajay Nangia, who is a professor of surgery (urology) at Dartmouth-Hitchcock Medical Center and an expert in male infertility and microsurgery.

The seats were chosen to represent the full spectrum of designs, including a narrow racing seat (Selle Italia Flite), a tensioned leather seat (Brooks Professional), and a seat with a central groove (Specialized Body Geometry Comp). Dr. Gemery and his associates then took lateral radiographs of the volunteer sitting on a bicycle in various positions to determine the position of the bony pelvis relative to the bicycle seat. They found that the most likely site for compression of the internal pudendal arteries was between the bicycle seat and the pubic symphysis.

“As the rider leaned further forward, the pubic symphysis got progressively closer to the seat, so that the space between the undersurface of the pubic symphysis and the top of the seat got smaller. These arteries have to run underneath the pubic symphysis to get out to the base of the penis, so as that space between the seat and symphysis closes, there is less space for those arteries, and in fact, for the pudendal nerves as well,” Dr. Gemery explained.

Although a seat with a central groove should reduce the risk of compression and thus erectile dysfunction, rider positioning seems to have a potentially equal or even greater role in preventing the problem, he concluded. Because the study was based on just one subject, follow-up research needs to be done to confirm if it will be true in riders with varying anatomy, he said.

ATLANTA — It's not only the bicycle seat that causes erectile dysfunction in some men who cycle—it may also be the way in which they sit on the seat, according to a poster presentation at the annual meeting of the American Urological Association.

Erectile dysfunction (ED) resulting from penile hypoxia can sometimes occur after prolonged bicycling, particularly when men who ride road or touring bikes lean far forward, as when using dropped handlebars. ED may occur even when riders use grooved seats to reduce pelvic compression. One new solution may be to sit up straight, or at least somewhat straighter, thereby reducing compression on the internal pudendal artery and nerve, said Dr. John M. Gemery, professor of radiology, Dartmouth-Hitchcock Medical Center, Lebanon, N.H.

Erectile dysfunction is theoretically less likely to occur in racing cyclists, who spend much of their riding time standing up. But men who ride for a few hours on flat surfaces and stay bent forward over the handlebars may be more likely to end up with ED, Dr. Gemery said in an interview.

Much effort has gone into designing bicycle seats that have a central groove or cutout to reduce perineal pressure. Study results have shown that it helps when a male rider uses a grooved seat. However, penile artery compression can still occur with a grooved seat when the rider leans far forward. No matter what seat a rider chooses, leaning forward causes higher compression (and hence greater potential for ED), compared with sitting upright while riding, Dr. Gemery said.

He became interested in cycling-induced erectile dysfunction when he was an interventional radiology fellow at Boston Medical Center, working with Dr. Irwin Goldstein, who raised the first concerns about bike seats and ED. “I was doing angiograms for him, so I also became interested in the problem. We were trying to figure out where, in fact, the blood vessels to the penis get compressed.”

Dr. Gemery continued this research at Dartmouth-Hitchcock, where he developed three-dimensional digital models created from CT scans of the pelvis of an adult male volunteer, as well as three bicycle seat designs.

He worked closely with Dr. Ajay Nangia, who is a professor of surgery (urology) at Dartmouth-Hitchcock Medical Center and an expert in male infertility and microsurgery.

The seats were chosen to represent the full spectrum of designs, including a narrow racing seat (Selle Italia Flite), a tensioned leather seat (Brooks Professional), and a seat with a central groove (Specialized Body Geometry Comp). Dr. Gemery and his associates then took lateral radiographs of the volunteer sitting on a bicycle in various positions to determine the position of the bony pelvis relative to the bicycle seat. They found that the most likely site for compression of the internal pudendal arteries was between the bicycle seat and the pubic symphysis.

“As the rider leaned further forward, the pubic symphysis got progressively closer to the seat, so that the space between the undersurface of the pubic symphysis and the top of the seat got smaller. These arteries have to run underneath the pubic symphysis to get out to the base of the penis, so as that space between the seat and symphysis closes, there is less space for those arteries, and in fact, for the pudendal nerves as well,” Dr. Gemery explained.

Although a seat with a central groove should reduce the risk of compression and thus erectile dysfunction, rider positioning seems to have a potentially equal or even greater role in preventing the problem, he concluded. Because the study was based on just one subject, follow-up research needs to be done to confirm if it will be true in riders with varying anatomy, he said.

ATLANTA — It's not only the bicycle seat that causes erectile dysfunction in some men who cycle—it may also be the way in which they sit on the seat, according to a poster presentation at the annual meeting of the American Urological Association.

Erectile dysfunction (ED) resulting from penile hypoxia can sometimes occur after prolonged bicycling, particularly when men who ride road or touring bikes lean far forward, as when using dropped handlebars. ED may occur even when riders use grooved seats to reduce pelvic compression. One new solution may be to sit up straight, or at least somewhat straighter, thereby reducing compression on the internal pudendal artery and nerve, said Dr. John M. Gemery, professor of radiology, Dartmouth-Hitchcock Medical Center, Lebanon, N.H.

Erectile dysfunction is theoretically less likely to occur in racing cyclists, who spend much of their riding time standing up. But men who ride for a few hours on flat surfaces and stay bent forward over the handlebars may be more likely to end up with ED, Dr. Gemery said in an interview.

Much effort has gone into designing bicycle seats that have a central groove or cutout to reduce perineal pressure. Study results have shown that it helps when a male rider uses a grooved seat. However, penile artery compression can still occur with a grooved seat when the rider leans far forward. No matter what seat a rider chooses, leaning forward causes higher compression (and hence greater potential for ED), compared with sitting upright while riding, Dr. Gemery said.

He became interested in cycling-induced erectile dysfunction when he was an interventional radiology fellow at Boston Medical Center, working with Dr. Irwin Goldstein, who raised the first concerns about bike seats and ED. “I was doing angiograms for him, so I also became interested in the problem. We were trying to figure out where, in fact, the blood vessels to the penis get compressed.”

Dr. Gemery continued this research at Dartmouth-Hitchcock, where he developed three-dimensional digital models created from CT scans of the pelvis of an adult male volunteer, as well as three bicycle seat designs.

He worked closely with Dr. Ajay Nangia, who is a professor of surgery (urology) at Dartmouth-Hitchcock Medical Center and an expert in male infertility and microsurgery.

The seats were chosen to represent the full spectrum of designs, including a narrow racing seat (Selle Italia Flite), a tensioned leather seat (Brooks Professional), and a seat with a central groove (Specialized Body Geometry Comp). Dr. Gemery and his associates then took lateral radiographs of the volunteer sitting on a bicycle in various positions to determine the position of the bony pelvis relative to the bicycle seat. They found that the most likely site for compression of the internal pudendal arteries was between the bicycle seat and the pubic symphysis.

“As the rider leaned further forward, the pubic symphysis got progressively closer to the seat, so that the space between the undersurface of the pubic symphysis and the top of the seat got smaller. These arteries have to run underneath the pubic symphysis to get out to the base of the penis, so as that space between the seat and symphysis closes, there is less space for those arteries, and in fact, for the pudendal nerves as well,” Dr. Gemery explained.

Although a seat with a central groove should reduce the risk of compression and thus erectile dysfunction, rider positioning seems to have a potentially equal or even greater role in preventing the problem, he concluded. Because the study was based on just one subject, follow-up research needs to be done to confirm if it will be true in riders with varying anatomy, he said.

WASHINGTON — Oral medroxyprogesterone acetate and oral contraceptives are equally effective in stopping nongestational acute uterine bleeding, according to a small randomized controlled trial presented at the annual meeting of the American College of Obstetricians and Gynecologists.

Cessation of bleeding occurred in 88% of the women randomized to oral contraceptives and in 76% of the women randomized to medroxyprogesterone. The mean time to cessation in the oral contraceptive group was 3.2 days vs. 3.8 days in the medroxyprogesterone group, reported Dr. Malcolm G. Munro, professor of obstetrics and gynecology at the University of California, Los Angeles, and chairman of the abnormal uterine bleeding working group for Kaiser Permanente, Southern California.

Women with nongestational acute uterine bleeding are seen frequently, and yet there has been a paucity of research on how best to treat them. Oral contraceptives are the most commonly used treatment in North America, but their efficacy for this indication has not been scientifically tested, Dr. Munro said.

Only two studies of acute uterine bleeding have been reported in the literature. The first, a study of unopposed estrogen given intravenously in 32 women, was published in the early 1980s, and the second, a study of medroxyprogesterone acetate in 24 women, was published in 1997.

In an open-label trial, Dr. Munro and his colleagues at Kaiser Permanente randomized 40 women with acute uterine bleeding, defined as excessively heavy or prolonged bleeding that was not related to pregnancy, to receive either medroxyprogesterone acetate, 20 mg three times a day for 7 days, followed by 20 mg a day for 3 weeks, or combination oral contraceptive treatment with norethindrone, 1 mg, and ethinyl estradiol, 35 mcg, in one tablet three times a day for 7 days, followed by one tablet a day for 3 weeks.

At the end of the study, 33 of the original 40 patients remained, and in these patients both treatments were “roughly equivalent” with respect to efficacy and time to bleeding cessation. Patient satisfaction in both groups was high. There was a trend toward more nausea in the oral contraceptive group, and this trend may have been significant if we had a larger sample size, Dr. Munro said.

One patient in the oral contraceptive group required an emergency procedure, compared with none in the medroxyprogesterone acetate group. “All of the women in the study had been bleeding for more than 10 days. They were the type of patient who is often taken to the operating room. At the very least, they needed emergent intervention, and only one required an emergent intervention in this study,” he added.

Oral contraceptives are the most commonly used treatment in North America, but their efficacy has not been tested. DR. MUNRO

WASHINGTON — Oral medroxyprogesterone acetate and oral contraceptives are equally effective in stopping nongestational acute uterine bleeding, according to a small randomized controlled trial presented at the annual meeting of the American College of Obstetricians and Gynecologists.

Cessation of bleeding occurred in 88% of the women randomized to oral contraceptives and in 76% of the women randomized to medroxyprogesterone. The mean time to cessation in the oral contraceptive group was 3.2 days vs. 3.8 days in the medroxyprogesterone group, reported Dr. Malcolm G. Munro, professor of obstetrics and gynecology at the University of California, Los Angeles, and chairman of the abnormal uterine bleeding working group for Kaiser Permanente, Southern California.

Women with nongestational acute uterine bleeding are seen frequently, and yet there has been a paucity of research on how best to treat them. Oral contraceptives are the most commonly used treatment in North America, but their efficacy for this indication has not been scientifically tested, Dr. Munro said.

Only two studies of acute uterine bleeding have been reported in the literature. The first, a study of unopposed estrogen given intravenously in 32 women, was published in the early 1980s, and the second, a study of medroxyprogesterone acetate in 24 women, was published in 1997.

In an open-label trial, Dr. Munro and his colleagues at Kaiser Permanente randomized 40 women with acute uterine bleeding, defined as excessively heavy or prolonged bleeding that was not related to pregnancy, to receive either medroxyprogesterone acetate, 20 mg three times a day for 7 days, followed by 20 mg a day for 3 weeks, or combination oral contraceptive treatment with norethindrone, 1 mg, and ethinyl estradiol, 35 mcg, in one tablet three times a day for 7 days, followed by one tablet a day for 3 weeks.

At the end of the study, 33 of the original 40 patients remained, and in these patients both treatments were “roughly equivalent” with respect to efficacy and time to bleeding cessation. Patient satisfaction in both groups was high. There was a trend toward more nausea in the oral contraceptive group, and this trend may have been significant if we had a larger sample size, Dr. Munro said.

One patient in the oral contraceptive group required an emergency procedure, compared with none in the medroxyprogesterone acetate group. “All of the women in the study had been bleeding for more than 10 days. They were the type of patient who is often taken to the operating room. At the very least, they needed emergent intervention, and only one required an emergent intervention in this study,” he added.

Oral contraceptives are the most commonly used treatment in North America, but their efficacy has not been tested. DR. MUNRO

WASHINGTON — Oral medroxyprogesterone acetate and oral contraceptives are equally effective in stopping nongestational acute uterine bleeding, according to a small randomized controlled trial presented at the annual meeting of the American College of Obstetricians and Gynecologists.

Cessation of bleeding occurred in 88% of the women randomized to oral contraceptives and in 76% of the women randomized to medroxyprogesterone. The mean time to cessation in the oral contraceptive group was 3.2 days vs. 3.8 days in the medroxyprogesterone group, reported Dr. Malcolm G. Munro, professor of obstetrics and gynecology at the University of California, Los Angeles, and chairman of the abnormal uterine bleeding working group for Kaiser Permanente, Southern California.

Women with nongestational acute uterine bleeding are seen frequently, and yet there has been a paucity of research on how best to treat them. Oral contraceptives are the most commonly used treatment in North America, but their efficacy for this indication has not been scientifically tested, Dr. Munro said.

Only two studies of acute uterine bleeding have been reported in the literature. The first, a study of unopposed estrogen given intravenously in 32 women, was published in the early 1980s, and the second, a study of medroxyprogesterone acetate in 24 women, was published in 1997.

In an open-label trial, Dr. Munro and his colleagues at Kaiser Permanente randomized 40 women with acute uterine bleeding, defined as excessively heavy or prolonged bleeding that was not related to pregnancy, to receive either medroxyprogesterone acetate, 20 mg three times a day for 7 days, followed by 20 mg a day for 3 weeks, or combination oral contraceptive treatment with norethindrone, 1 mg, and ethinyl estradiol, 35 mcg, in one tablet three times a day for 7 days, followed by one tablet a day for 3 weeks.

At the end of the study, 33 of the original 40 patients remained, and in these patients both treatments were “roughly equivalent” with respect to efficacy and time to bleeding cessation. Patient satisfaction in both groups was high. There was a trend toward more nausea in the oral contraceptive group, and this trend may have been significant if we had a larger sample size, Dr. Munro said.

One patient in the oral contraceptive group required an emergency procedure, compared with none in the medroxyprogesterone acetate group. “All of the women in the study had been bleeding for more than 10 days. They were the type of patient who is often taken to the operating room. At the very least, they needed emergent intervention, and only one required an emergent intervention in this study,” he added.

Oral contraceptives are the most commonly used treatment in North America, but their efficacy has not been tested. DR. MUNRO