Researchers Present HIV, Hepatitis C Clinical Trial Results at Annual ICAAC Conference

Scientists this week during the 43rd annual Interscience Conference on Antimicrobial Agents and Chemotherapy conference are presenting results of several clinical studies examining HIV and hepatitis C, including treatments for the two diseases. The conference is organized by the American Society for Microbiology and is being held in Chicago from Sept. 14 through Sept. 17. Study findings include those listed below:

• Hepatitis C in Saliva: Researchers from the University of Washington Harborview Medical Center Hepatitis Research Clinic and colleagues collected saliva samples from 12 volunteers for 21 consecutive days. Out of the 248 samples collected from participants, researchers found that 52 samples, or 21%, tested positive for hepatitis C. Researchers determined that participants with higher viral loads, who reported "less frequent tooth brushing" or who reported gum bleeding when brushing their teeth were more likely to have hepatitis C present in their saliva. However, the data do not provide information on whether the virus present in saliva was infectious, leading researchers to conclude that further study is necessary (ICAAC release, 9/15).
  

• Nelfinavir for Hepatitis C Virus/HIV Coinfection: Researchers from New York City's Mt. Sinai Medical Center and colleagues conducted a retrospective chart study of safety data, viral load, CD4+ T cell count and treatment history for 1,094 HCV/HIV coinfected patients who were receiving a protease inhibitor as part of their highly active antiretroviral therapy. Researchers found that patients taking nelfinavir, compared with other protease inhibitors -- including indinavir, saquinavir, ritonavir and amprenavir -- had fewer grade three and grade four levels of aspartate aminotransferase and alanine aminotransferase, which can be indicators of liver damage. Researchers concluded that the study indicates nelfinavir is safe for treating HIV in patients coinfected with hepatitis C, adding that further study is warranted by the findings. The study was funded by Agouron Pharmaceuticals, a Pfizer company (ICAAC release, 9/15).
  

• HAART Interruption: Researchers from the Division of Infectious Diseases of Italy's Ospedali Riuniti of Bergamo Hospital examined 114 HIV-positive patients who had HIV viral loads levels of less than 50 copies/mL and CD4 cell counts above 800 cells/mm3. Researchers assigned patients on a two-to-one basis to either stop their current treatment or continue it, with the goal of maintaining a CD4 cell count of above 400 cells/mm3 for patients in the interruption group. Treatment was resumed for 21% of patients in the interruption group because their CD4 cell counts fell below 400 cells/mm3. Researchers found that participants with lower CD4 cell counts prior to interruption of treatment experienced more CD4 cell loss once the treatment stopped. Researchers noted that all patients who resumed treatment experienced a rapid increase in CD4 cell counts. Researchers concluded that the findings could help HIV-positive patients who have not begun treatment to determine when to initiate treatment (Carter, aidsmap, 9/14).
  

• HAART Combination Efficacy: A combination of abacavir, lamivudine and efavirenz may be equally as effective as a combination of zidovudine, lamivudine and efavirenz; however, patients taking the abacavir combination may experience a greater increase in CD4 cell count from their baseline cell count. Researchers randomly assigned 649 HIV-positive patients who had not yet begun HAART to receive either ABC/3TC/EFV or ZDV/3TC/EFV. After 48 weeks, researchers found that 70% of patients in the abacavir group had a viral load below 50 copies/mL, compared with 69% of people in the zidovudine group. In addition, researchers found an average CD4 cell increase of 209 cells/mm3 among patients in the abacavir group, compared with a gain of 155 cells/mm3 in the zidovudine group, indicating a "significantly better immunological response by the end of the study" among the abacavir group, the researchers concluded (Carter, aidsmap, 9/14).
  

• Fuzeon: Patients taking Roche's antiretroviral Fuzeon, or enfuviritide, who had undetectable viral load levels at 24 weeks continued to show similar results at week 48, according to a Roche/Trimeris release (Roche/Trimeris release, 9/15). Fuzeon, approved by the FDA in March, is in a new class of drugs called fusion inhibitors, which prevent HIV from entering cells by preventing the virus from attaching to cell membranes. The drug is designed for HIV/AIDS patients who have failed to respond to other medications (Kaiser Daily HIV/AIDS Report, 8/25). For the TORO 1 and TORO 2 studies, researchers enrolled 1,000 HIV patients with documented treatment resistance at 112 international health centers and randomly assigned patients on a two-to-one basis to either add Fuzeon to an existing antiretroviral treatment regimen or receive the treatment regimen without Fuzeon, respectively. Researchers found that participants in the Fuzeon group experienced an increase of twice as many CD4 cells as increases among patients in the group that did not receive Fuzeon (Roche/Trimeris release, 9/15).
  

• T-1249: A 10-day trial of T-1249, another fusion inhibitor, showed "promis[ing]" results, according to drug makers Roche and Trimeris, Reuters reports (Reuters, 9/15). T-1249 is part of the next generation of this type of drug and is intended to be used when the virus becomes resistant to Fuzeon (Kaiser Daily HIV/AIDS Report, 2/12). Researchers in the Phase I/II study enrolled 58 HIV-positive patients with viral load levels of between 5,000 copies/mL and 500,000 copies/mL at two consecutive clinic visits while taking Fuzeon. Participants stopped Fuzeon as part of their combination therapy and replaced it with T-1249. Researchers found that 73% of the patients receiving the T-1249 treatment demonstrated a 90% reduction from their baseline viral load after 11 days (Roche/Trimeris release, 9/15). Roche and Trimeris have not yet established a schedule for further clinical trials of T-1249, Reuters reports (Reuters, 9/15).
  

• Didanosine in HAART Regimens: Adding didanosine to HAART regimens for patients with detectable viral load and nucleoside reverse transcriptase inhibitor resistance can lead to significant reductions in viral load, according to researchers. Researchers randomly assigned 110 HIV-positive patients with viral loads of between 1,000 copies/mL and 100,000 copies/mL despite therapy and NRTI resistance to receive once-daily doses of enteric coated didanosine in addition to their HAART. The researchres also assigned 53 patients to receive a placebo. Researchers found that after four weeks, 33 participants in the didanosine group had a viral load below 400 copies/mL, compared with three participants in the placebo group (Carter, aidsmap, 9/14).
  

• Risk Factors for Drug-Resistant HIV Patients: About 15% of HIV-positive patients who have not experienced a reduction in viral load after treatment with protease inhibitors, NRTIs or nonnucleoside reverse transcriptase inhibitors will die within three years, according to a study presented at the conference. The PLATO, or "Pursuing Later Treatment Options," study included 2,488 HIV-positive participants with viral resistance to the three main classes of antiretroviral drugs from 13 cohort studies. Researchers determined the death rate and mortality risk factors. Researchers found that the death rate was 5.5 per 100 person years of follow up and the three-year predicted mortality rate was 15%. Researchers found that the "strongest predictor" for death was a CD4 cell count below 50 cells/mm3, but they did not identify a connection between the last viral load recorded before death and the risk of mortality. Researchers also found that a lack of antiretroviral treatment, a previous AIDS-defining illness, age and injection drug use also significantly influenced the risk of death (Carter, aidsmap, 9/14).
  

• Viral Decay Rate With NNRTI Therapy: Patients taking HIV treatment regimens containing nevirapine or efavirenz experience comparable viral decay rates -- the rate of decline in viral load after the start of therapy -- over the first two weeks of treatment, according to the results of a sub-study of the 2NN trial. In addition, the study showed that treatment failure after 48 weeks in patients treated with the drugs, both NNRTIs, was unrelated to a higher viral decay rate, leading researchers to state that patient non-compliance or viral resistance are the most likely factors for virologic failure in such patients (Boehringer Ingelheim release, 9/15).
  

• Kaletra Over Five Years: A study of 100 HIV-positive patients showed that 67 of the patients who used Abbott Laboratories' Kaletra as part of their initial HIV treatment regimen for 252 weeks had undetectable HIV viral loads at the end of the period, the Chicago Sun-Times reports. In addition, none of those patients developed resistance to Kaletra, which is a combination protease inhibitor containing lopinavir and ritonavir. The patients took Kaletra with lamivudine and stavudine, both NRTIs (Knowles, Chicago Sun-Times, 9/16).