Abstract 395 - Viral Reservoirs after Two Years of Sustained Serum Viral Suppression in Patients in whom HAART Was Initiated Early: The Merck 060/ICC 004 Cohort.

395 Viral Reservoirs after Two Years of Sustained Serum Viral Suppression in Patients in whom HAART Was Initiated Early: The Merck 060/ICC 004 Cohort.

T.-W. Chun*, D. McMahon, J. S. Justement, B. Sha, C. Carpenter, D. Goodwin, J. Pientka, M. Seniuk, R. Leavitt, A. Meibohm, and M. Robertson.
NIAID, NIH, Bethesda, MD; Univ. of Pittsburgh, PA; Rush Med. Ctr., Chicago, IL; Miriam Hosp., Providence, RI; Glaxo Wellcome, Res. Triangle Park, NC; and Merck Res. Labs., West Point, PA.

Background:Initiation of HAART early in HIV disease may decrease latent viral reservoirs.

Methods:A prospective open-label trial of antiretroviral naïve, clinically well HIV-infected patients with CD4 cell counts always ³ 500/mm³and RNA >1000 copies/mL who were treated with IDV/ZDV/3TC. ZDV-intolerant patients were allowed to substitute stavudine. Viral reservoirs were measured following 2 years of undetectable viral load (<50 copies/ml) in a subset of these patients.

Results:For the 199 patients enrolled, the geometric mean of the baseline serum viral RNA (vRNA) level was 8227 copies/ml (mean = 3.92 log₁₀) and mean CD4 cell count was 597 cells/mm³. 138 patients completed at least 96 weeks of therapy, and, of these, 123 patients had vRNA measurements at week 96. 119/123 (97%) had serum HIV levels < 400 copies/mL and 115/123 (94%) had levels < 50 copies/mL at week 96. A subset of patients who had <50 copies/mL serum HIV RNA for at least 96 consecutive weeks were selected for a series of viral reservoir sub-studies. First, highly enriched resting CD4⁺T cells (8—96 × 10⁶) from the PBMC compartment were cultured for HIV (PBMC culture). 12/16 patients studied thus far have had negative PBMC cultures. Of those with negative PBMC cultures, 5 patients have undergone leukopheresis to obtain large numbers of resting CD4⁺T cells for analysis. Two of these 5 patients had no detectable replication-competent HIV even when up to 4.7 × 10⁸resting CD4⁺T cells were examined, and one additional patient was only detectable when this number of cells was examined. Leukopheresis of the other 7 PBMC culture-negative patients is ongoing. CSF, genital secretions, and lymph nodes will also be examined for latent HIV.

ConclusionsInstitution of HAART early in HIV disease may suppress viral reservoirs after 2 years of treatment.