AEGiS-15IAC: Therapeutic response of HIV-1 subtype C in African patients co-infected with mycobacterium tuberculosis or HHV-8.

15th International AIDS Conference

Bangkok, Thailand - July 11-16, 2004

Therapeutic response of HIV-1 subtype C in African patients co-infected with mycobacterium tuberculosis or HHV-8.

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. ThOrA1402)

Cassol E, Page T, Mosam A, Cassol S, Jack C, Lalloo U, Friedland G, Coovadia HM
HIV Molecular Virology and Bioinformatics Unit, Africa Centre, Doris Duke Research Institute, University of KwaZulu-Natal, Durban, South Africa

BACKGROUND: A potential confounder of antiretroviral therapy in Africa is the high prevalence of tuberculosis (TB) and opportunistic infections (OIs). OI-induced activation has the potential to alter the kinetics of HIV-1 clearance by increasing viral replication and target cell availability.

METHODS: Plasma viral load (VL) decay was monitored during the first 12 weeks of antiretroviral therapy. HIV-1 patients co-infected with TB (n = 21) received received ddI, 3TC and EFV, and standard TB treatment; patients co-infected with HHV-8, the causative agent of Kaposi's Sarcoma (KS), received d4T, 3TC and NVP plus chemotherapy, beginning on day 28.

RESULTS: No significant difference was observed in the mean baseline CD4+ counts between the TB vs KS groups (202 vs 223 cells/mul). Both cohorts exhibited a rapid phase I decline, followed by a more prolonged and variable phase II decline in viral load. The mean decrease in phase I virus, measured at day 7, was similar for TB vs KS patients (99.0% and 96.4%, respectively), despite a higher mean baseline VL in the TB cohort (5.41 vs. 4.81 RNA copies/mL). TB patients and late-stage KS patients with CD4+ counts<200 cells/mul had the steepest, most rapid phase I clearance kinetics. These same patients showed the greatest initial rise in CD4+ counts, and were the first to reach undetectable plasma HIV-1 RNA. The proportion of patients reaching undetectable VL (<40 copies) at days 7, 14, 28, 60 and 90 were 15.8%, 30.0%, 52.6%, 78.9% and 93.8% (Pearson chi[2] = 50.5, p<0.001) for TB, and 0.0%, 5.0%, 22.2%, 64.7% and 80.0% (Pearson chi[2] = 63.6, p<0.001) for KS patients. Conclusion These initial responses are equivalent to those observed during the treatment of subtype B infections. Although unproven, the slower more protracted phase II clearance, suggests that KS patients have a larger reservoir of long-lived, chronically-infected cells.

Keywords: AEGIS, HIV-1, Herpesvirus 8, Human, CD4 Lymphocyte Count, Viral Load, Didanosine, Stavudine, Mycobacterium tuberculosis, Sarcoma, Kaposi, Lamivudine, African Continental Ancestry Group, AIDS-Related Opportunistic Infections, Viremia, Infection, Africa, Humans

040711
ThOrA1402