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Session 13 Oral Abstract Session Antiretroviral Chemotherapy: Combination Therapy, Drug Resistance, and Treatment Interruption Session Time: Tuesday, 10 am - 12:30 pm Room 4B

12:15   50. Viral Populations Emerging in Plasma during Sequential Structured Treatment Interruptions in Chronically HIV-Infected Individuals Are Genetically Distinct between Time-Points and Tissues J. Martinez-Picado*1, S. D. W. Frost2, S. Marfil1, T. Puig1, B. Clotet1, and L. Ruiz1 1irsiCaixa Fndn., Badalona, Spain and 2Univ. of California, San Diego Background: The sources of re-emerging HIV-1 in plasma during sequential structured treatment interruptions (SSTI) in asymptomatic infected patients have not been completely elucidated yet. Our goal was to determine whether viral populations from plasma RNA and PBMC DNA following STI are genetically distinct between time-points and/or tissues. Methods: The study included 12 adults with chronic HIV-1 infection that underwent 4 SSTIs. Genetic analysis of length polymorphism fragments from regions V1-V2 and V4-V5 in gp120 were studied in both PBMCs DNA and plasma RNA. Exhaustive clonal sequencing was done in the C2-V5 region of 3 patients. Phylogenetic and nonparametric analysis of clustering were performed. Results: The env genetic structure of the re-emerging viral population in plasma, as far as fragments length variation is concerned, was quite stable in some patients (3, 8, 12), slightly shifted (2, 5, 7, 10), or significatively changed in others (1, 4, 11). The genotypic pattern of V1-V2 and V4-V5 fragments in DNA recovered from latently infected PBMCs was stable or slightly changed in 3 patients (2, 7, 8), but drastically shifted in the rest. These patterns were mostly different from those found in the plasma. Phylogenetic trees for patients 4, 6, and 11 showed that, despite several clusters of sequences within patients, sequences did not cluster perfectly by either tissue or time, with variable levels of intermingling between subpopulations in different individuals. Nonparametric analysis showed that patient 4 had significant levels of clustering by time (p<0.001), but relatively little clustering by tissue. In contrast, patient 11 showed significant levels of clustering by tissue (p<0.001), but not over time. There was very little clustering by either time or tissue in patient 6, although the level of diversity in this patient was low. Conclusions: These results indicate that env genetic characteristics of the population that rebound in plasma during SSTIs may significantly vary from the pre-therapy plasma viral population; it may change along with STIs, and may also reseed the PBMCs reservoir after the first STI. Therefore, the source of virus re-emerging during STIs is unpredictable and may change in SSTIs. In this scenario, the strengthening of HIV-specific cell-mediated immune responses might be limited in asymptomatic infected patients because the exposed viral antigens keep changing over sequential STIs.

©2002 9th Conference on Retroviruses and Opportunistic Infections