Kaiser Daily HIV/AIDS Report Rounds Up HIV/AIDS Research Presented at 1st IAS Conference on HIV Pathogenesis and Treatment

The 1st International AIDS Society Conference on HIV Pathogenesis and Treatment took place in Buenos Aires, Argentina, this week, with about 3,000 attendees and 748 scientific presentations. The conference, with a slogan of "Science will drive the future," focused on defining strategies for improved care management for "patients in the North" and "the role that science can play in the battle to expand access to treatment and care in the South," according to Dr. Stefano Vella, president of IAS (Vella, Medscape.com Conference Coverage, 7/8). The following are brief summaries of some of the research presented at the conference. For more complete coverage of the conference, including Web cast sessions, visit IAS' Web site at www.ias.se.

Drug Resistance Testing

• Virco's VirtualPhenotype and Antivirogram HIV drug resistance tests "can predict clinical response to HIV treatment for up to two years." Results from a retrospective analysis of 681 HIV-positive patients showed that patients who received three or more "active drugs, as measured by the resistance tests," had "significantly greater reductions in viral load and increases in CD4 cell counts over the 96-week study" (Tibotec-Virco release, 7/10).
• ViroLogic, Inc. presented research that showed that its PhenoSense HIV drug resistance test is "nearly 10 times more sensitive than other commercially available drug resistance assays." The test's results were "consisten[t]" on blood samples with viral load measurements as low as 125 copies/mL. The research also showed that the test could "accurately" measure drug resistance in "non-B subtypes" of HIV, which are common in Africa, South America, Eastern Europe, India and Southeast Asia (ViroLogic release, 7/10).

Treatment-Naive Patients

• The clinical trials plenary session of the conference was opened by Dr. Bonaventura Clotet of Barcelona, Spain, who addressed the debate over whether it is better to begin initial treatment for HIV with protease inhibitor-based or non-nucleoside reverse transcriptase inhibitor (NNRTI)-based highly active antiretroviral therapy. Clotet concluded that for patients with "very low" CD4 cell counts (100,000 copies/mL), protease inhibitor-based HAART is preferable as a "first line" treatment (Boyle, HIVandHepatitis.com, 7/11). However, U.S. federal guidelines for the treatment of HIV infection in adults and adolescents lists efavirenz, a NNRTI, as one of the drugs "strongly recommended" for first line use ("Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents," 4/23). Changing treatment regimens after the virus is suppressed can reduce the risk of lipodystrophy associated with long term use of protease inhibitor-based therapy, Clotet added ( HIVandHepatitis.com, 7/11).
• Dr. Franco Lori and colleagues presented results of a randomized controlled trial that compared the suppression of HIV in chronic patients receiving continuous antiretroviral therapy to those receiving structured treatment interruptions (STI) and concluded that while studies have indicated that STI can lower viral load "set-point" for patients in the "very early stages" of acute infection, the same technique is not successful in chronic patients. Sixty patients were put on combination antiretroviral therapy for 12 weeks before being randomly assigned to either continuous therapy or a 24-week "fixed-schedule" STI. Viral load "rebounded" to near base-level numbers in the STI group after each interruption. However, when therapy resumed, the viral load decreased to levels "similar" to the levels of the group on continuous therapy (Boyle, HIVandHepatitis.com, 7/11). Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, also presented evidence from another study that found after a year of STI, patients did not exhibit evidence of a "rebound" of viral load nor the "emergence" of drug resistant HIV strains (Susman, UPI Science News, 7/10).
• Shire Pharmaceuticals Group presented findings of a 48-week study that showed that a two-tablet twice daily regimen of Ziagen (abacavir) and Combivir (zidovudine/lamivudine), both of which are made by GlaxoSmithKline, was "better tolera[ted]" than a "more complex" regimen of indinavir and Combivir. Seventy-two percent of patients taking the Ziagen combination reported 95% adherence, compared to 45% of patients on the protease inhibitor regimen (Shire release, 7/10).
• DuPont Pharmaceuticals reported that patients taking a combination therapy that included its drug Sustiva (efavirenz), a non-nucleoside reverse transcriptase inhibitor, had lower rates of treatment failure than those taking regimens that included nevirapine or a protease inhibitor. After six months of treatment, 92% of patients taking the regimen with Sustiva were still responding "successfully" to the treatment, compared to 83% in the nevirapine group and 79% in the protease inhibitor group (DuPont release, 7/9).
• Boehringer Ingelheim Pharmaceuticals Inc. announced results from a year-long study comparing the efficacy of a combination of Viramune (nevirapine) and Combivir with that of Combivir plus nelfinavir, a protease inhibitor. The two regimens showed "comparable" results, but the Viramune combination required only four tablets a day versus 12 tablets for the nelfinavir combination (Boehringer Ingelheim release, 7/9).
• Sixty weeks into an international multi-site study of the efficacy of combination therapy with either Kaletra (lopinavir/ritonavir) or Viracept (nelfinavir) plus Zerit (stavudine) and Epivir (lamivudine), researchers found that those patients receiving Kaletra as part of their treatment regimen did "significantly better" in terms of viral suppression. Seventy-four percent of patients on Kaletra achieved a viral load of less than 400 copies/mL versus 61% of patients on the protease inhibitor regimen (Boyle, HIVandHepatitis.com, 7/11).
• Agouron Pharmaceuticals, a Pfizer company, reported that a retrospective chart review of 1,309 HIV patients who received Viracept as part of their initial HAART showed that the drug "provided durable and potent HIV viral load suppression" and increased CD4 cell counts. The patients showed a mean increase in CD4 cell count of 230 cells/mm3 (Agouron release, 7/11).

Treatment-Experienced Patients

• Patients taking a suppressive protease inhibitor-containing double nucleoside reverse transcriptase inhibitor regimen who switch their protease inhibitor to DuPont's Sustiva maintain "viral load suppression for a longer period of time than patients who remained on their protease inhibitor-containing regimen," according to DuPont. Of the patients who switched drugs, 84% maintained a viral load level below 50 copies/mL, compared to 73% of the patients who did not switch. DuPont suggests that this treatment strategy "may allow for improved long term treatment success" (DuPont release, 7/10).
• Another study evaluating patients on a double NRTI and protease regimen who switch to either nevirapine or efavirenz "raised safety concerns regarding the nevirapine arm," according to HIVandHepatitis.com. Six of the 50 patients in the nevirapine arm discontinued the study due to rash or liver toxicities, compared to only two of 47 in the efavirenz arm who discontinued due to side effects. Despite the toxicities, the researchers concluded that switching a protease inhibitor to nevirapine or efavirenz is effective in controlling viral load (Boyle, HIVandHepatitis.com, 7/11).
• Three-year data was presented by DuPont on Sustiva showing that the NNRTI, in combination with NRTIs, "provide[s] greater and more durable viral suppression ... than combination therapy using a protease inhibitor" in patients who were protease inhibitor-, NNRTI- and lamivudine-naive at the time of enrollment. Seventy-eight of 154 patients on the Sustiva-containing regimen showed a viral load of less than 50 copies/mL, compared to 43 of 148 in the protease inhibitor arm (DuPont release, 7/9).

In The Pipeline

• Phase II data showed that Boehringer Ingelheim's investigational non-peptidic protease inhibitor tipranavir demonstrates "antiretroviral potency and durability" in patients who had experienced treatment failure with two or more protease inhibitor-containing regimens. The study included 41 NNRTI-naive patients who were randomized to two arms: Group A received tipranavir 500 mg twice a day plus ritonavir, efavirenz and a new NRTI, and Group B received tipranavir 1000 mg twice a day plus ritonavir, efavirenz and a new NRTI. At 48 weeks, 79% of Group A patients and 50% of Group B patients had viral load levels below 400 copies/mL (Boehringer Ingelheim release, 7/9).
• A trial evaluating the acceptance of T-20, an investigational fusion inhibitor being developed by Roche and Trimeris Inc., showed that HIV patients "have endorsed" the treatment, which is delivered through a subcutaneous injection twice daily, Reuters reports (Reuters, 7/11). The study was conducted to determine potential adherence to the medicine and how the delivery of the drug would impact the daily lives of patients. Eighty-five percent of patients said that the injection procedure was "very easy/easy" or "not bad" (Trimeris release, 7/11).
• Research on Bristol-Myers Squibb's experimental protease inhibitor atazanavir (formerly BMS-232632) showed that the drug did not increase patients' lipid levels, a side effect of many protease inhibitors that can cause dangerously high levels of cholesterol and triglycerides. Atazanavir, which is taken once a day, when compared to nelfinavir had fewer side effects and was safe and effective (Baker, HIVandHepatitis.com, 7/10).
• Results from a Phase I/II study comparing mozenavir (DMP 450), "a non-peptidomimetic, water soluable, cyclic urea," in combination with stavudine and lamivudine, to indinavir, stavudine and lamivudine in 50 treatment-naive patients show that the regimens had similar effectiveness. However, mozenavir had fewer effects on cholesterol than indinavir, with a 20 mg/dL median increase in cholesterol in the mozenavir arm versus a 60 mg/dL increase in the indinavir arm (Boyle, HIVandHepatitis.com, 7/11).