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Session 25 Oral Abstract Session Immunology Session Time: Wednesday, 10 am - 12:30 pm Room 6C

11:45   108. HIV-Specific Cellular Immunity and Partial Control of Drug-Resistant vs Wild-Type Viremia S. G. Deeks*1, E. Sinclair2, J. M. Harris, H. T. Maecker, B. Bredt2, E. Hagos1, J. Martin1, and J. M. McCune2 1Univ. of California, San Francisco; 2Gladstone Inst. of Virology and Immunology, San Francisco Gen. Hosp., CA; and 3BD BioSci., San Jose, CA Background: HIV-specific CD4 and CD8 T cells are key determinants of the virologic "set-point" in untreated patients. It is not known if HIV-specific cellular immunity plays a role in determining steady-state viral load in treated patients, particularly those who maintain partial virologic suppression despite the emergence of drug resistance. Methods:This is a cross-sectional analysis of chronically infected adults. Participants with either no treatment or who were on a stable combination antiretroviral regimen for at least 4 months were included. The proportion of CD4 and CD8 T cells that express intracellular gamma-interferon after exposure to gag-peptides was measured using flow cytometry. Results:170 participants were evaluated: 90 treated with VL <50; 52 treated but with detectable and drug-resistant viremia (median decrease in plasma HIV RNA levels from the off-therapy set-point was 1.4 log); and 28 untreated. The proportion of patients with gag-specific CD4 responses was higher in treated patients with detectable drug-resistant HIV (82%) than untreated patients (36%) or treated patients with undetectable viremia (14%) (p < 0.01). At lower levels of viremia (< log 3.5) there was a positive correlation between viral load and the frequency of both gag-specific CD4 and CD8 T cells (rho = 0.49, p=0.002 for CD4 and rho=0.34, p=0.04 for CD8). In contrast, at higher levels of viremia (> log 3.5) there was a negative correlation between viral load and gag-specific CD4 response (rho= -0.44, p =0.001). There was no relation between gag-specific CD8 and viral load among those with high viral loads. The highest proportion of gag-specific CD4 T cells was observed in patients with viral loads in the 1000 to 10,000 copies RNA/mL range. Conclusions:HIV-specific cellular immunity appears to be stimulated and expanded by HIV at low levels of viremia and compromised at high levels of viremia. Collectively, these correlative data support a testable hypothesis that the immune system is able to partially control drug-resistant HIV, perhaps because the fitness of the virus is reduced and less able to deplete virus-specific CD4 T-cell responses.

©2002 9th Conference on Retroviruses and Opportunistic Infections