AEGiS-13IAC: NZT4002: 64 week analysis of Combivir (COM)-based triple and quadruple therapy in antiretroviral-narve, HIV-1 infected subjects.

13th International AIDS Conference

Durban, South Africa - July 9-July 14, 2000

NZT4002: 64 week analysis of Combivir (COM)-based triple and quadruple therapy in antiretroviral-narve, HIV-1 infected subjects.

Int Conf AIDS 2000 Jul 9-14; 13:(abstract no. WeOrB608)

Eron J, Junod P, Becker S, Ruane P, Thompson M, Arduino R, Walmsley S, Pierce A, Platek G, Snidow J
J. Eron, University of North Carolina-Chapel Hill, Division of Infectious Diseases, 547 Burnett-Womack Building / UNC CB#7030, Chapel Hill, NC 27599, United States, Tel.: +1 919 966 2536, Fax: +1 919 966 6714, E-mail: jws3144@glaxowellcome.com

BACKGROUND: This study examined durability of viral suppression in adults receiving either 3 drugs (COM bid/nelfinavir tid) or 4 drugs (COM/abacavir/amprenavir bid).

METHODS: Subjects (HIV-1 RNA > = 5000 c/mL, CD4 counts > = 50 cells/mm³) were randomized to open-label therapy. Substitution of protease inhibitors and d4T for AZT was allowed for intolerance. Virologic failure was defined as failure to achieve plasma viral load (pVL) > = 120 c/mL by week 24 or confirmed viral rebound >120 c/mL.

RESULTS: Median baseline (BL) values for pVL (log₁₀/mL) and CD4 (cells/mm³) were 4.56 and 330, respectively, in the 3-drug arm (n = 152), and 4.64 and 356 in the 4-drug arm (n = 150). The primary analysis found that time to failure using combined virologic & toxicity endpoints occurred earlier in the 4-drug arm (p = 0.017) due to a greater number of adverse events (AEs) and withdrawals. In subjects achieving pVL > = 120 c/mL, there was no difference in duration of viral suppression (p = 0.533) or time to virologic failure (p = 1.0). The as treated analysis showed 70% (65/93) of subjects on the 3-drug arm had pVL > = 120 c/mL compared with 87% (53/61) on the 4-drug arm (p = 0.016). The proportion of subjects with pVL >40 c/mL was 66% (61/93) and 77% (47/61) on the 3- and 4-drug arms, respectively (p = 0.132). Median CD4 increase from BL was 188 and 185 cells/mm³ on the 3-and 4-drug arms, respectively, and median change in cholesterol AUCs was 28.3 and 14.4 mg/dL (p>0.001). Treatment-related AEs reported commonly on the 4-drug arm were nausea & vomiting, malaise & fatigue, and rash whereas diarrhea, nausea, malaise & fatigue were frequently reported on the 3-drug arm.

CONCLUSIONS: For those remaining on therapy, COM-based quadruple therapy achieved a greater proportion of subjects with viral suppression, but therapy was complicated by more AEs and withdrawals. Increase in cholesterol was significantly less with quadruple therapy.

Keywords: AEGIS, Zidovudine, Lamivudine, HIV-1, Drug Combinations, CD4 Lymphocyte Count, Dideoxynucleosides, Viral Load, Nelfinavir, Antiretroviral Therapy, Highly Active, Drug Therapy, Combination, Stavudine, Combivir, abacavir, Adult, therapy, virology, drug therapy
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WeOrB608