Charlene Laino

RIO DE JANEIRO — An investigational protease inhibitor, TMC114, has potent antiviral activity in heavily pretreated HIV-infected patients with primary protease inhibitor mutations, according to results from the POWER-1 study.

The agent plus low-dose ritonavir was effective even in patients harboring three or more primary protease inhibitor (PI) mutations in the 24-week, randomized study (Performance of TMC114/r When Evaluated in Triple-Class-Experienced Patients With PI Resistance), reported Christine Katlama, M.D., of the AIDS clinical research unit at the Hôpital Pitié-Salpêtrière in Paris.

In a poster session at the International AIDS Society Conference on HIV Pathogenesis and Treatment, Dr. Katlama said that overall, the primary end point of 1 log₁₀ or greater viral load reduction from baseline was achieved by 77% of 65 patients taking 600 mg of TMC114 plus 100 mg of ritonavir twice daily, compared with 25% of 63 control patients taking investigator-selected PIs.

A viral load of less than 50 copies/mL was achieved by 53% of the patients on 600 mg of TMC114 plus ritonavir vs. 18% of the control patients

Of the 29 patients with three or more primary PI mutations, 59% of those treated with 600 mg of TMC114 plus ritonavir achieved HIV-1 viral loads below 50 copies/mL vs. 9% of control patients.

There was no excess toxicity in the TMC114 group, Dr. Katlama said. Grade 3 and grade 4 events were observed in 29% of control patients vs. 23% of those treated with 600 mg of TMC114.

For the phase IIb study, 300 patients were randomized to receive one of four doses of TMC114 plus ritonavir, or to receive investigator-selected protease inhibitors. Dr. Katlama presented detailed data only on the most effective regimen of 600 mg of TMC114 plus 100 mg of ritonavir twice daily, which has been chosen for future study.

The patients in this study received an optimal background regimen of nucleoside reverse transcriptase inhibitors, with or without enfuvirtide. They had triple-class experience, had more than one primary PI mutation, were on stable antiretroviral therapy, and had HIV-1 RNA levels greater than 1,000 copies/mL at baseline. TMC114 binds to HIV protease, providing a wide range of durable activity, Dr. Katlama said.

Mark A. Wainberg, Ph.D., director of the McGill University AIDS Centre in Montreal and moderator of the session, said that more than half of the patients on TMC114 achieved viral loads of less than 50 copies/mL. TMC114 “looks to be the next generation PI. It has excellent potency and can make an important difference in experienced patients and probably naive patients as well,” he said.

RIO DE JANEIRO — An investigational protease inhibitor, TMC114, has potent antiviral activity in heavily pretreated HIV-infected patients with primary protease inhibitor mutations, according to results from the POWER-1 study.

The agent plus low-dose ritonavir was effective even in patients harboring three or more primary protease inhibitor (PI) mutations in the 24-week, randomized study (Performance of TMC114/r When Evaluated in Triple-Class-Experienced Patients With PI Resistance), reported Christine Katlama, M.D., of the AIDS clinical research unit at the Hôpital Pitié-Salpêtrière in Paris.

In a poster session at the International AIDS Society Conference on HIV Pathogenesis and Treatment, Dr. Katlama said that overall, the primary end point of 1 log₁₀ or greater viral load reduction from baseline was achieved by 77% of 65 patients taking 600 mg of TMC114 plus 100 mg of ritonavir twice daily, compared with 25% of 63 control patients taking investigator-selected PIs.

A viral load of less than 50 copies/mL was achieved by 53% of the patients on 600 mg of TMC114 plus ritonavir vs. 18% of the control patients

Of the 29 patients with three or more primary PI mutations, 59% of those treated with 600 mg of TMC114 plus ritonavir achieved HIV-1 viral loads below 50 copies/mL vs. 9% of control patients.

There was no excess toxicity in the TMC114 group, Dr. Katlama said. Grade 3 and grade 4 events were observed in 29% of control patients vs. 23% of those treated with 600 mg of TMC114.

For the phase IIb study, 300 patients were randomized to receive one of four doses of TMC114 plus ritonavir, or to receive investigator-selected protease inhibitors. Dr. Katlama presented detailed data only on the most effective regimen of 600 mg of TMC114 plus 100 mg of ritonavir twice daily, which has been chosen for future study.

The patients in this study received an optimal background regimen of nucleoside reverse transcriptase inhibitors, with or without enfuvirtide. They had triple-class experience, had more than one primary PI mutation, were on stable antiretroviral therapy, and had HIV-1 RNA levels greater than 1,000 copies/mL at baseline. TMC114 binds to HIV protease, providing a wide range of durable activity, Dr. Katlama said.

Mark A. Wainberg, Ph.D., director of the McGill University AIDS Centre in Montreal and moderator of the session, said that more than half of the patients on TMC114 achieved viral loads of less than 50 copies/mL. TMC114 “looks to be the next generation PI. It has excellent potency and can make an important difference in experienced patients and probably naive patients as well,” he said.

RIO DE JANEIRO — An investigational protease inhibitor, TMC114, has potent antiviral activity in heavily pretreated HIV-infected patients with primary protease inhibitor mutations, according to results from the POWER-1 study.

The agent plus low-dose ritonavir was effective even in patients harboring three or more primary protease inhibitor (PI) mutations in the 24-week, randomized study (Performance of TMC114/r When Evaluated in Triple-Class-Experienced Patients With PI Resistance), reported Christine Katlama, M.D., of the AIDS clinical research unit at the Hôpital Pitié-Salpêtrière in Paris.

In a poster session at the International AIDS Society Conference on HIV Pathogenesis and Treatment, Dr. Katlama said that overall, the primary end point of 1 log₁₀ or greater viral load reduction from baseline was achieved by 77% of 65 patients taking 600 mg of TMC114 plus 100 mg of ritonavir twice daily, compared with 25% of 63 control patients taking investigator-selected PIs.

A viral load of less than 50 copies/mL was achieved by 53% of the patients on 600 mg of TMC114 plus ritonavir vs. 18% of the control patients

Of the 29 patients with three or more primary PI mutations, 59% of those treated with 600 mg of TMC114 plus ritonavir achieved HIV-1 viral loads below 50 copies/mL vs. 9% of control patients.

There was no excess toxicity in the TMC114 group, Dr. Katlama said. Grade 3 and grade 4 events were observed in 29% of control patients vs. 23% of those treated with 600 mg of TMC114.

For the phase IIb study, 300 patients were randomized to receive one of four doses of TMC114 plus ritonavir, or to receive investigator-selected protease inhibitors. Dr. Katlama presented detailed data only on the most effective regimen of 600 mg of TMC114 plus 100 mg of ritonavir twice daily, which has been chosen for future study.

The patients in this study received an optimal background regimen of nucleoside reverse transcriptase inhibitors, with or without enfuvirtide. They had triple-class experience, had more than one primary PI mutation, were on stable antiretroviral therapy, and had HIV-1 RNA levels greater than 1,000 copies/mL at baseline. TMC114 binds to HIV protease, providing a wide range of durable activity, Dr. Katlama said.

Mark A. Wainberg, Ph.D., director of the McGill University AIDS Centre in Montreal and moderator of the session, said that more than half of the patients on TMC114 achieved viral loads of less than 50 copies/mL. TMC114 “looks to be the next generation PI. It has excellent potency and can make an important difference in experienced patients and probably naive patients as well,” he said.

RIO DE JANEIRO — Fears that a new, multidrug-resistant, rapidly progressing strain of HIV-1 had surfaced in New York City have been alleviated, with medical researchers reporting that they have tracked down the most likely source of the infection.

Concerns have existed since February, when officials from the New York City Department of Health and Mental Hygiene announced that a middle-aged man had purportedly been infected with a unique, highly virulent strain of HIV.

The New York City patient had rapidly progressed to late-stage HIV infection, with a CD4 cell count of 60 cells/mcL within 20 months of infection.

But viral testing suggested that the New York City patient was infected by a Connecticut man whose disease has followed a more typical clinical course, said Gary Blick, M.D., medical and research director of Circle Medical LLC in Norwalk, Conn.

“The Connecticut man's virus is a 99.5% pol[ymerase] gene match to that of the New York City man. They're essentially identical,” Dr. Blick reported at the International AIDS Society Conference on HIV Pathogenesis and Treatment.

The man from Connecticut, referred to as “Patient Zero,” and the New York City man have acknowledged having had unprotected sex together after using crystal methamphetamine in October 2004.

Since Patient Zero has become compliant with highly active antiretroviral treatment, he has had a stable CD4 count and viral load.

“He is not a rapidly progressive patient,” Dr. Blick said.

So why did the New York City man's disease progress so quickly?

Most likely, his behavior is the culprit, Dr. Blick commented. The New York City patient admitted not only to being promiscuous, but also to being a heavy user of crystal methamphetamine, a street drug that lowers inhibitions and increases risky sexual behavior. Genetic susceptibility also may have played a role.

Mark A. Wainberg, Ph.D., director of the McGill University AIDS Centre, Montreal, pointed out that having multiple sex partners and repeatedly using crystal “meth” may pummel the immune system, facilitating infection with multidrug-resistant HIV.

Dr. Wainberg said that these findings should end talk of a new HIV strain.

“It's a well-done analysis that shows the strains are virtually identical,” he explained.

RIO DE JANEIRO — Fears that a new, multidrug-resistant, rapidly progressing strain of HIV-1 had surfaced in New York City have been alleviated, with medical researchers reporting that they have tracked down the most likely source of the infection.

Concerns have existed since February, when officials from the New York City Department of Health and Mental Hygiene announced that a middle-aged man had purportedly been infected with a unique, highly virulent strain of HIV.

The New York City patient had rapidly progressed to late-stage HIV infection, with a CD4 cell count of 60 cells/mcL within 20 months of infection.

But viral testing suggested that the New York City patient was infected by a Connecticut man whose disease has followed a more typical clinical course, said Gary Blick, M.D., medical and research director of Circle Medical LLC in Norwalk, Conn.

“The Connecticut man's virus is a 99.5% pol[ymerase] gene match to that of the New York City man. They're essentially identical,” Dr. Blick reported at the International AIDS Society Conference on HIV Pathogenesis and Treatment.

The man from Connecticut, referred to as “Patient Zero,” and the New York City man have acknowledged having had unprotected sex together after using crystal methamphetamine in October 2004.

Since Patient Zero has become compliant with highly active antiretroviral treatment, he has had a stable CD4 count and viral load.

“He is not a rapidly progressive patient,” Dr. Blick said.

So why did the New York City man's disease progress so quickly?

Most likely, his behavior is the culprit, Dr. Blick commented. The New York City patient admitted not only to being promiscuous, but also to being a heavy user of crystal methamphetamine, a street drug that lowers inhibitions and increases risky sexual behavior. Genetic susceptibility also may have played a role.

Mark A. Wainberg, Ph.D., director of the McGill University AIDS Centre, Montreal, pointed out that having multiple sex partners and repeatedly using crystal “meth” may pummel the immune system, facilitating infection with multidrug-resistant HIV.

Dr. Wainberg said that these findings should end talk of a new HIV strain.

“It's a well-done analysis that shows the strains are virtually identical,” he explained.

RIO DE JANEIRO — Fears that a new, multidrug-resistant, rapidly progressing strain of HIV-1 had surfaced in New York City have been alleviated, with medical researchers reporting that they have tracked down the most likely source of the infection.

Concerns have existed since February, when officials from the New York City Department of Health and Mental Hygiene announced that a middle-aged man had purportedly been infected with a unique, highly virulent strain of HIV.

The New York City patient had rapidly progressed to late-stage HIV infection, with a CD4 cell count of 60 cells/mcL within 20 months of infection.

But viral testing suggested that the New York City patient was infected by a Connecticut man whose disease has followed a more typical clinical course, said Gary Blick, M.D., medical and research director of Circle Medical LLC in Norwalk, Conn.

“The Connecticut man's virus is a 99.5% pol[ymerase] gene match to that of the New York City man. They're essentially identical,” Dr. Blick reported at the International AIDS Society Conference on HIV Pathogenesis and Treatment.

The man from Connecticut, referred to as “Patient Zero,” and the New York City man have acknowledged having had unprotected sex together after using crystal methamphetamine in October 2004.

Since Patient Zero has become compliant with highly active antiretroviral treatment, he has had a stable CD4 count and viral load.

“He is not a rapidly progressive patient,” Dr. Blick said.

So why did the New York City man's disease progress so quickly?

Most likely, his behavior is the culprit, Dr. Blick commented. The New York City patient admitted not only to being promiscuous, but also to being a heavy user of crystal methamphetamine, a street drug that lowers inhibitions and increases risky sexual behavior. Genetic susceptibility also may have played a role.

Mark A. Wainberg, Ph.D., director of the McGill University AIDS Centre, Montreal, pointed out that having multiple sex partners and repeatedly using crystal “meth” may pummel the immune system, facilitating infection with multidrug-resistant HIV.

Dr. Wainberg said that these findings should end talk of a new HIV strain.

“It's a well-done analysis that shows the strains are virtually identical,” he explained.

RIO DE JANEIRO — Adult circumcision may protect against infection with HIV in heterosexual men, according to the first randomized controlled trial to test the procedure.

After 21 months of follow-up observation, “Circumcision prevented 6 to 7 out of 10 potential HIV infections” in young heterosexual South African men who were circumcised as adults, compared with those who were not, said Bertran Auvert, M.D., at the International AIDS Society Conference on HIV Pathogenesis and Treatment.

Circumcision was found to be so effective at preventing infection with HIV that the trial was stopped early so that all the young men in the study could be offered the procedure, said Dr. Auvert, professor of public health at the University of Versailles Saint Quentin, France.

A feasibility study that was conducted prior to the trial demonstrated that approximately 70% of uncircumcised young men will opt to undergo the procedure if it has been shown to reduce the risk of HIV infection.

Observational studies dating back to the 1980s, and a more recent metaanalysis suggesting that circumcision may be protective against HIV, led to the randomized trial of 3,128 men, aged 18–24 years, Dr. Auvert said.

The participants lived in a neighborhood outside of Johannesburg, South Africa, that has historically high rates of HIV transmission.

The men, 90% of whom were sexually active, were randomly assigned either to undergo the procedure or to remain uncircumcised.

In the intervention group, circumcision was performed by trained physicians using sterile surgical procedures to remove the penile foreskin under local anesthesia.

After 21 months, 51 men who had not been circumcised had been infected with HIV, compared with only 18 of the men who had undergone the procedure. This translates into a statistically significant 65% protective effect—an outcome that remained unchanged even after controlling for sexual behavior variables, Dr. Auvert said.

Upon hearing the findings, other researchers expressed cautious optimism.

Helene Gayle, M.D., president of the International AIDS Society and director for HIV, TB, and reproductive health at the Bill and Melinda Gates Foundation, said, “If [the] results are confirmed by other ongoing studies, this could be an important tool for HIV prevention.”

“But it would be premature to recommend widespread circumcision for HIV prevention at this time,” she said. The findings come at a time when only one in five at-risk persons have access to prevention, she noted.

Dr. Gayle advised clinicians to caution young patients that circumcision should not be used as an excuse for unsafe sex or other risky behaviors. “We want to make sure people do not develop a false sense of security and increase their high-risk behaviors,” she said.

Dr. Auvert agreed, adding that since all the men were heterosexual, the results apply only to transmission from women to men; no conclusions can be drawn regarding male-to-male transmission or male-to-female transmission. Also still unknown is whether the findings will hold up over the long term. Last year, there were 5 million new HIV infections worldwide—more than in any other year.

RIO DE JANEIRO — Adult circumcision may protect against infection with HIV in heterosexual men, according to the first randomized controlled trial to test the procedure.

After 21 months of follow-up observation, “Circumcision prevented 6 to 7 out of 10 potential HIV infections” in young heterosexual South African men who were circumcised as adults, compared with those who were not, said Bertran Auvert, M.D., at the International AIDS Society Conference on HIV Pathogenesis and Treatment.

Circumcision was found to be so effective at preventing infection with HIV that the trial was stopped early so that all the young men in the study could be offered the procedure, said Dr. Auvert, professor of public health at the University of Versailles Saint Quentin, France.

A feasibility study that was conducted prior to the trial demonstrated that approximately 70% of uncircumcised young men will opt to undergo the procedure if it has been shown to reduce the risk of HIV infection.

Observational studies dating back to the 1980s, and a more recent metaanalysis suggesting that circumcision may be protective against HIV, led to the randomized trial of 3,128 men, aged 18–24 years, Dr. Auvert said.

The participants lived in a neighborhood outside of Johannesburg, South Africa, that has historically high rates of HIV transmission.

The men, 90% of whom were sexually active, were randomly assigned either to undergo the procedure or to remain uncircumcised.

In the intervention group, circumcision was performed by trained physicians using sterile surgical procedures to remove the penile foreskin under local anesthesia.

After 21 months, 51 men who had not been circumcised had been infected with HIV, compared with only 18 of the men who had undergone the procedure. This translates into a statistically significant 65% protective effect—an outcome that remained unchanged even after controlling for sexual behavior variables, Dr. Auvert said.

Upon hearing the findings, other researchers expressed cautious optimism.

Helene Gayle, M.D., president of the International AIDS Society and director for HIV, TB, and reproductive health at the Bill and Melinda Gates Foundation, said, “If [the] results are confirmed by other ongoing studies, this could be an important tool for HIV prevention.”

“But it would be premature to recommend widespread circumcision for HIV prevention at this time,” she said. The findings come at a time when only one in five at-risk persons have access to prevention, she noted.

Dr. Gayle advised clinicians to caution young patients that circumcision should not be used as an excuse for unsafe sex or other risky behaviors. “We want to make sure people do not develop a false sense of security and increase their high-risk behaviors,” she said.

Dr. Auvert agreed, adding that since all the men were heterosexual, the results apply only to transmission from women to men; no conclusions can be drawn regarding male-to-male transmission or male-to-female transmission. Also still unknown is whether the findings will hold up over the long term. Last year, there were 5 million new HIV infections worldwide—more than in any other year.

RIO DE JANEIRO — Adult circumcision may protect against infection with HIV in heterosexual men, according to the first randomized controlled trial to test the procedure.

After 21 months of follow-up observation, “Circumcision prevented 6 to 7 out of 10 potential HIV infections” in young heterosexual South African men who were circumcised as adults, compared with those who were not, said Bertran Auvert, M.D., at the International AIDS Society Conference on HIV Pathogenesis and Treatment.

Circumcision was found to be so effective at preventing infection with HIV that the trial was stopped early so that all the young men in the study could be offered the procedure, said Dr. Auvert, professor of public health at the University of Versailles Saint Quentin, France.

A feasibility study that was conducted prior to the trial demonstrated that approximately 70% of uncircumcised young men will opt to undergo the procedure if it has been shown to reduce the risk of HIV infection.

Observational studies dating back to the 1980s, and a more recent metaanalysis suggesting that circumcision may be protective against HIV, led to the randomized trial of 3,128 men, aged 18–24 years, Dr. Auvert said.

The participants lived in a neighborhood outside of Johannesburg, South Africa, that has historically high rates of HIV transmission.

The men, 90% of whom were sexually active, were randomly assigned either to undergo the procedure or to remain uncircumcised.

In the intervention group, circumcision was performed by trained physicians using sterile surgical procedures to remove the penile foreskin under local anesthesia.

After 21 months, 51 men who had not been circumcised had been infected with HIV, compared with only 18 of the men who had undergone the procedure. This translates into a statistically significant 65% protective effect—an outcome that remained unchanged even after controlling for sexual behavior variables, Dr. Auvert said.

Upon hearing the findings, other researchers expressed cautious optimism.

Helene Gayle, M.D., president of the International AIDS Society and director for HIV, TB, and reproductive health at the Bill and Melinda Gates Foundation, said, “If [the] results are confirmed by other ongoing studies, this could be an important tool for HIV prevention.”

“But it would be premature to recommend widespread circumcision for HIV prevention at this time,” she said. The findings come at a time when only one in five at-risk persons have access to prevention, she noted.

Dr. Gayle advised clinicians to caution young patients that circumcision should not be used as an excuse for unsafe sex or other risky behaviors. “We want to make sure people do not develop a false sense of security and increase their high-risk behaviors,” she said.

Dr. Auvert agreed, adding that since all the men were heterosexual, the results apply only to transmission from women to men; no conclusions can be drawn regarding male-to-male transmission or male-to-female transmission. Also still unknown is whether the findings will hold up over the long term. Last year, there were 5 million new HIV infections worldwide—more than in any other year.

RIO DE JANEIRO - The novel nucleoside reverse transcriptase inhibitor Reverset is poised to become the newest member of the oldest class of antiretroviral agents, with researchers reporting its promise for HIV-infected patients for whom current antiretroviral regimens have failed and who have NRTI resistance.

In a 16-week randomized trial of nearly 200 treatment-experienced patients, 54% of those treated with 200 mg of Reverset daily experienced more than a 1.0- log drop in viral load (the trial's definition of response to therapy), compared with 40% of patients who received a placebo, Calvin Cohen, M.D., said at the International AIDS Society Conference on HIV Pathogenesis and Treatment.

Reverset was effective in patients with HIV resistant to other commonly used nucleoside analog reverse transcriptase inhibitors, including the two-thirds of patients with the M41L multiple thymidine analog mutation, Dr. Cohen, research director for both Harvard Vanguard Medical Associates and Community Research Initiative of New England in Boston, reported at a late-breaking session.

Formerly known as D-d4FC and yet to be assigned a generic name, Reverset is well tolerated and can be given once daily, he said. Reverset is under development by Incyte Inc., which helped fund the research. “Reverset appears to be an active, potent drug in treatment-experienced patients,” Dr. Cohen told this newspaper. “Very few of our nucleosides have maintained the kind of activity we're seeing in patients with resistant virus.”

Mark A. Wainberg, Ph.D., director of the McGill University AIDS Centre, Montreal, and moderator of the late-breaking session, agreed.

“Reverset appears to be an excellent addition to our armamentarium of nucleoside reverse transcriptase inhibitors. It is well tolerated and active against virus with various mutations,” he said.

Dr. Cohen said the new trial follows earlier studies suggesting that Reverset does not appear to cause mitochondrial toxicity or elevated lactate levels—side effects associated with other NRTIs.

For the Phase IIb trial, the researchers randomized 199 treatment-experienced patients who were failing their current regimen to one of three doses of Reverset (50 mg, 100 mg, or 200 mg) or placebo. The patients had a mean baseline viral load of 31,600 copies/mL and most had NRTI-associated mutations: 60% had the M184V mutation, 66% had M41L, 50% had four to six thymidine analogue mutations, and 6% had K65R. After 2 weeks, patients who received the 200-mg dose of Reverset as add-on therapy achieved a drop in viral load of 0.7 log₁₀ copies/mL, compared with a drop of 0.03 log₁₀ copies/mL in the placebo arm. By 16 weeks, patients who received 200 mg of Reverset as add-on therapy had a drop in viral load of 1.2 log₁₀ copies/mL, compared with a drop of 0.8 log₁₀ copies/mL in placebo patients.

The results were best in patients who did not receive lamivudine or emtricitabine, which have a similar chemical structure to Reverset, Dr. Cohen said. In this subset, 80% of patients who had Reverset achieved a barely discernible viral load of less than 50 copies/mL, compared with 25% on placebo. Using a combination of drugs that that target different sites within the virus packs a more powerful punch, he explained.

Both the 100-mg and 50-mg doses of Reverset were less effective than the 200-mg dose, so the higher dose will be used for future study, Dr. Cohen said.

Side effects were generally mild; however, 50% of patients receiving 200 mg of Reverset with didanosine showed an elevation of pancreatic enzymes and two patients on 100 mg of Reverset developed symptomatic pancreatitis.

RIO DE JANEIRO - The novel nucleoside reverse transcriptase inhibitor Reverset is poised to become the newest member of the oldest class of antiretroviral agents, with researchers reporting its promise for HIV-infected patients for whom current antiretroviral regimens have failed and who have NRTI resistance.

In a 16-week randomized trial of nearly 200 treatment-experienced patients, 54% of those treated with 200 mg of Reverset daily experienced more than a 1.0- log drop in viral load (the trial's definition of response to therapy), compared with 40% of patients who received a placebo, Calvin Cohen, M.D., said at the International AIDS Society Conference on HIV Pathogenesis and Treatment.

Reverset was effective in patients with HIV resistant to other commonly used nucleoside analog reverse transcriptase inhibitors, including the two-thirds of patients with the M41L multiple thymidine analog mutation, Dr. Cohen, research director for both Harvard Vanguard Medical Associates and Community Research Initiative of New England in Boston, reported at a late-breaking session.

Formerly known as D-d4FC and yet to be assigned a generic name, Reverset is well tolerated and can be given once daily, he said. Reverset is under development by Incyte Inc., which helped fund the research. “Reverset appears to be an active, potent drug in treatment-experienced patients,” Dr. Cohen told this newspaper. “Very few of our nucleosides have maintained the kind of activity we're seeing in patients with resistant virus.”

Mark A. Wainberg, Ph.D., director of the McGill University AIDS Centre, Montreal, and moderator of the late-breaking session, agreed.

“Reverset appears to be an excellent addition to our armamentarium of nucleoside reverse transcriptase inhibitors. It is well tolerated and active against virus with various mutations,” he said.

Dr. Cohen said the new trial follows earlier studies suggesting that Reverset does not appear to cause mitochondrial toxicity or elevated lactate levels—side effects associated with other NRTIs.

For the Phase IIb trial, the researchers randomized 199 treatment-experienced patients who were failing their current regimen to one of three doses of Reverset (50 mg, 100 mg, or 200 mg) or placebo. The patients had a mean baseline viral load of 31,600 copies/mL and most had NRTI-associated mutations: 60% had the M184V mutation, 66% had M41L, 50% had four to six thymidine analogue mutations, and 6% had K65R. After 2 weeks, patients who received the 200-mg dose of Reverset as add-on therapy achieved a drop in viral load of 0.7 log₁₀ copies/mL, compared with a drop of 0.03 log₁₀ copies/mL in the placebo arm. By 16 weeks, patients who received 200 mg of Reverset as add-on therapy had a drop in viral load of 1.2 log₁₀ copies/mL, compared with a drop of 0.8 log₁₀ copies/mL in placebo patients.

The results were best in patients who did not receive lamivudine or emtricitabine, which have a similar chemical structure to Reverset, Dr. Cohen said. In this subset, 80% of patients who had Reverset achieved a barely discernible viral load of less than 50 copies/mL, compared with 25% on placebo. Using a combination of drugs that that target different sites within the virus packs a more powerful punch, he explained.

Both the 100-mg and 50-mg doses of Reverset were less effective than the 200-mg dose, so the higher dose will be used for future study, Dr. Cohen said.

Side effects were generally mild; however, 50% of patients receiving 200 mg of Reverset with didanosine showed an elevation of pancreatic enzymes and two patients on 100 mg of Reverset developed symptomatic pancreatitis.

RIO DE JANEIRO - The novel nucleoside reverse transcriptase inhibitor Reverset is poised to become the newest member of the oldest class of antiretroviral agents, with researchers reporting its promise for HIV-infected patients for whom current antiretroviral regimens have failed and who have NRTI resistance.

In a 16-week randomized trial of nearly 200 treatment-experienced patients, 54% of those treated with 200 mg of Reverset daily experienced more than a 1.0- log drop in viral load (the trial's definition of response to therapy), compared with 40% of patients who received a placebo, Calvin Cohen, M.D., said at the International AIDS Society Conference on HIV Pathogenesis and Treatment.

Reverset was effective in patients with HIV resistant to other commonly used nucleoside analog reverse transcriptase inhibitors, including the two-thirds of patients with the M41L multiple thymidine analog mutation, Dr. Cohen, research director for both Harvard Vanguard Medical Associates and Community Research Initiative of New England in Boston, reported at a late-breaking session.

Formerly known as D-d4FC and yet to be assigned a generic name, Reverset is well tolerated and can be given once daily, he said. Reverset is under development by Incyte Inc., which helped fund the research. “Reverset appears to be an active, potent drug in treatment-experienced patients,” Dr. Cohen told this newspaper. “Very few of our nucleosides have maintained the kind of activity we're seeing in patients with resistant virus.”

Mark A. Wainberg, Ph.D., director of the McGill University AIDS Centre, Montreal, and moderator of the late-breaking session, agreed.

“Reverset appears to be an excellent addition to our armamentarium of nucleoside reverse transcriptase inhibitors. It is well tolerated and active against virus with various mutations,” he said.

Dr. Cohen said the new trial follows earlier studies suggesting that Reverset does not appear to cause mitochondrial toxicity or elevated lactate levels—side effects associated with other NRTIs.

For the Phase IIb trial, the researchers randomized 199 treatment-experienced patients who were failing their current regimen to one of three doses of Reverset (50 mg, 100 mg, or 200 mg) or placebo. The patients had a mean baseline viral load of 31,600 copies/mL and most had NRTI-associated mutations: 60% had the M184V mutation, 66% had M41L, 50% had four to six thymidine analogue mutations, and 6% had K65R. After 2 weeks, patients who received the 200-mg dose of Reverset as add-on therapy achieved a drop in viral load of 0.7 log₁₀ copies/mL, compared with a drop of 0.03 log₁₀ copies/mL in the placebo arm. By 16 weeks, patients who received 200 mg of Reverset as add-on therapy had a drop in viral load of 1.2 log₁₀ copies/mL, compared with a drop of 0.8 log₁₀ copies/mL in placebo patients.

The results were best in patients who did not receive lamivudine or emtricitabine, which have a similar chemical structure to Reverset, Dr. Cohen said. In this subset, 80% of patients who had Reverset achieved a barely discernible viral load of less than 50 copies/mL, compared with 25% on placebo. Using a combination of drugs that that target different sites within the virus packs a more powerful punch, he explained.

Both the 100-mg and 50-mg doses of Reverset were less effective than the 200-mg dose, so the higher dose will be used for future study, Dr. Cohen said.

Side effects were generally mild; however, 50% of patients receiving 200 mg of Reverset with didanosine showed an elevation of pancreatic enzymes and two patients on 100 mg of Reverset developed symptomatic pancreatitis.