Antimicrobial Agents and Chemotherapy: Combination PI-Containing Regimen for HIV-Infected, Treatment-Experienced Patients
Combination PI-Containing Regimen for HIV-Infected, Treatment-Experienced Patients
Speaker: Robert Schooley, MD, Head of Infectious Diseases and Professor of Medicine, University of Colorado, Denver, Colorado.
Based on a preliminary 24-week analysis, amprenavir 600 mg (Agenerase, GlaxoSmithKline)/ritonavir 100 mg (Norvir drug, Abbott) twice daily might be a better treatment regimen than amprenavir 900 mg/ritonavir 100 mg twice daily because the lower amprenavir dose results in a similar efficacy, a lower incidence of adverse events and patient withdrawals, and a lower pill burden.
To reach these conclusions, a study was designed to provide data on the most efficacious and well-tolerated ampre-navir dosage regimen in combination with low-dose ritonavir plus other antiretroviral drugs, to be used as a treatment option for HIV-1-infected adults who are changing from a failing antiretroviral regimen. Two dosages of amprenavir 600 mg twice daily and 900 mg twice daily were chosen to be evaluated in combination with ritonavir 100 mg twice daily. Riton-avir was selected because it enhances the antiviral effect of amprenavir while reducing the pill burden.
A total of 115 treatment-experienced HIV-1 infected adults who had been on failing therapy for more than 12 weeks, whose HIV-1 RNA levels were more than 1,000 copies/ml, whose lymphocyte counts were more than 50 cells/mm3, and whose HIV-1 isolates were susceptible to the study drug combination, were enrolled in a 48-week, open-label pilot study. The patients were randomized to the two amprenavir/ritonavir dosage regimens plus either abacavir generic, another nucleoside reverse transcriptase inhibitor (NRTI) and efavirenz or abacavir, another NRTI, and tenofovir. Data is available for 104 patients, with median duration on the study drugs being 120 days and 113 days for the 600-and 900-mg dosages, respectively, at time of analysis. The primary endpoint used to measure effectiveness is the proportion of patients with plasma HIV-1 RNA levels of less than 200 copies/ml at week 48. Because the study is still ongoing, the proportion of patients with HIV-1 RNA levels of less than 200 copies/ml at week 24 was presented.
In the primary efficacy analysis, the majority of patients in both amprenavir treatment groups (69% and 73%) achieved plasma HIV-1 RNA levels of less than 200 copies/ml at week 24. For both treatment groups, there was a greater than 2 log10 copies/ ml reduction in the plasma HIV-1 RNA by week 24. None of the patients in either group experienced progression of HIV disease. Also, changes in the lipid profiles of the patients were minimal. The number of patients who met the definition of virologic failure was low and similar in both the amprenavir 600-mg (3 patients) and 900-mg (2 patients) groups.
Antiretrovirals Concomitantly with Methadone for Hepatitis C/HIV Co-Infections
Speaker: Lawrence S. Brown, Jr., MD, MPH, Senior Vice President, Addiction Research and Treatment Corporation, Brooklyn, New York, and Clinical Associate Professor of Public Health, Weill Medical College of Cornell University, New York, New York.
Data from a multisite study demonstrate that in opiate-dependent patients with concurrent HIV and hepatitis C, the combination of the protease inhibitor nelfinavir (Viracept generic, Agouron) as part of the antiretroviral therapy, and methadone (Roxane), as part of the maintenance treatment for opiate dependency, is safe, well-tolerated, effective, and durable.
Drug addiction is a continuing, major risk behavior associated with HIV and hepatitis C. Substance abuse is associated with a higher risk of hepatic toxicity in patients with concurrent HIV and hepatitis C infections. This is especially true because of the potential for hepatotoxicity caused by antiretroviral agents, particularly some protease inhibitors. A retrospective chart review was carried out to identify persons at risk with HIV and hepatitis C co-infection enrolled in a large multiclinical methadone maintenance treatment agency encompassing a total population of 2,800 patients who were being treated for drug addiction. Patients in the study had to be taking nelfinavir as part of their antiretroviral therapy, and must have been on a stable methadone dose for one month prior to initiating nelfinavir.
As of this report, 32 patients have been identified as meeting these criteria, and have data available. Of these patients, 29 had been on a stable dose of methadone for 30 days or longer before starting nelfinavir treatment. Only two of the 29 patients reported nelfinavir-related diarrhea; both were moderate cases. The median length of nelfinavir treatment was 22 months. The prevalence of methadone dose adjustment by patients was only 17%, although 80% of the patients had their methadone adjusted by clinicians. None of these HIV and hepatitis C co-infected patients needed to switch off of their nelfinavir-containing regimens because of virologic failure or drug-related adverse events—which demonstrates the efficacy, safety and durability of this approach. Further studies are needed to corroborate these findings.
