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Therapeutic response of HIV-1 subtype C in African patients coinfected with either Mycobacterium tuberculosis or human herpesvirus-8.

Cassol E, Page T, Mosam A, Friedland G, Jack C, Lalloo U, Kopetka J, Patterson B, Esterhuizen T, Coovadia HM

HIV-1 Molecular Virology and Bioinformatics Unit, Africa Centre for Health and Population Studies, and Centre for HIV/AIDS Networking, Doris Duke Medical Research Institute, Durban, South Africa. ecassol@mrc.ac.za

BACKGROUND: A potential confounding factor in the treatment of human immunodeficiency virus (HIV) infection in Africa is the frequent occurrence of opportunistic infections (OIs). OI-induced immune activation can interfere with HIV-1 clearance by increasing viral replication and target cell availability. STUDY DESIGN: Treatment outcomes for patients dually infected with HIV-1 and Mycobacterium tuberculosis or HIV-1 and human herpesvirus (HHV)-8 were assessed by measuring changes in viral load and CD4(+) cell counts and by determining the time taken to reach undetectable HIV-1 RNA levels, assessed by means of Kaplan-Meier survival analysis. Patients with HIV-1 and Kaposi sarcoma (KS) received generic nevirapine, stavudine, and lamivudine (3TC); patients with HIV-1 and tuberculosis (TB) received standard commercial didanosine, 3TC, and efavirenz. RESULTS: Both cohorts exhibited a rapid, near-exponential phase I decline in viral load. Patients with TB and late-stage KS had the steepest decay kinetics. These same patients had the greatest initial increase in CD4(+) cell counts. Phase II clearance was slower and more variable. The proportions of patients reaching undetectable plasma HIV-1 levels at days 7, 14, 28, 60, and 90 were, respectively, 15.8%, 30.0%, 52.6%, 78.9%, and 93.8% (Pearson's chi 2=50.5; P<.001) for patients with TB and 0.0%, 5.0%, 22.2%, 64.7%, and 80.0% (Pearson's chi 2=63.6; P<.001) for patients with KS. CONCLUSIONS: Nucleoside reverse-transcriptase inhibitor/nonnucleoside reverse-transcriptase inhibitor-based treatment regimens are highly effective in clearing rapidly replicating (phase I) virus in African patients dually infected with HIV-1 and either TB or KS.

Published 5 January 2005 in J Infect Dis, 191(3): 324-32.
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