Twice-daily amprenavir I 200 mg versus amprenavir 600 mg/ritonavir 100 mg, in combination with at least 2 other antiretroviral drugs, in HIV-I-infected patients

Jeffrey P. Nadler, Joseph C. Gathe, Richard B Pollard, Gary J. Richmond, Qiming Liao, Sandy Griffith, Charles Tracey Lancaster, Jaime E. Hernandez, Keith A. Pappa, Marianna McDonald, Terri Becom, Ashwin Hirani, Brian Wine, Claressa Jolly, Carol Humpries

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Abstract

Background: Low-dose ritonavir (RTV) boosts plasma amprenavir (APV) exposure. Little has been published on the efficacy, tolerability, and safety of APV 600 mg/RTV 100 mg (APV600/RTV) twice daily (BID) compared to APV 1200 mg BID (APV1200). Methods: ESS40011 was a 24-week, multicenter, open-label, clinical trial in which antiretroviral therapy-naïve and -experienced HIV-1-infected adults were randomized 3:1 to receive either APV600/RTV BID or APV1200 BID, in combination with ≥ 2 non-protease inhibitor antiretroviral drugs. Non-inferiority of the APV600/RTV regimen to the APV1200 regimen was established if the 95% lower confidence limit for the difference in proportion of patients achieving HIV-1 RNA <200 copies/mL at week 24 with APV 600/RTV minus APV1200 was ≥-0.12. Late in the conduct of the trial, patients not yet completing 24 weeks of therapy were given the option of continuing treatment for an additional 24-week period. Results: 211 patients were randomized, 158 to APV600/RTV and 53 to APV1200. At week 24, APV600/RTV was similar to or better than APV1200 (HIV-1 RNA <200 copies/mL in 62% [73/118] vs 53% [20/38] of patients; intent-to-treat: observed analysis). In the APV600/RTV arm, significantly more patients achieved HIV-1 RNA <50 copies/mL (48% [57/118] vs 29% [11/38] with APV1200, P = 0.04), and greater mean reduction from baseline in HIV-1 RNA was observed (-2.21 vs -1.59 log10 copies/mL, P = 0.028). The two treatment arms were similar with respect to mean overall change from baseline in CD4+ count, frequency of drug-related grade 1-4 adverse events, and frequency of discontinuing treatment due to adverse events (most commonly nausea, diarrhea, vomiting or fatigue; 7% vs 8%), although a lower proportion of patients in the APV600/RTV arm experienced drug-related oral/perioral paresthesia (2% vs 8%). Eleven (73%) of 15 patients who had HIV-1 RNA <200 copies/mL at week 24 and chose to continue study treatment maintained this level of virologic suppression at follow-up 24 weeks later. Conclusions: APV600 RTV BID was similar to or better than APV1200 BID in virologic response. Virologic results in a small number of patients who continued treatment for 24 weeks post-study suggest that virologic suppression with APV600 RTV BID is durable.

Original languageEnglish (US)
Article number10
JournalBMC Infectious Diseases
Volume3
DOIs
StatePublished - Jun 10 2003
Externally publishedYes

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ASJC Scopus subject areas

  • Infectious Diseases

Cite this

Nadler, J. P., Gathe, J. C., Pollard, R. B., Richmond, G. J., Liao, Q., Griffith, S., Lancaster, C. T., Hernandez, J. E., Pappa, K. A., McDonald, M., Becom, T., Hirani, A., Wine, B., Jolly, C., & Humpries, C. (2003). Twice-daily amprenavir I 200 mg versus amprenavir 600 mg/ritonavir 100 mg, in combination with at least 2 other antiretroviral drugs, in HIV-I-infected patients. BMC Infectious Diseases, 3, [10]. https://doi.org/10.1186/1471-2334-3-10