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Session 72 Poster Session Treatment Interruption Session Time: 4:30-6:30 pm Room 4E-F

531-M. Long-Term Multicompartment Evolutionary Study of HIV-env in a Chronically HIV-Infected Patient before and during HAART Followed by 5 Structured Treatment Interruptions (STI) B. Joos*1, M. Fischer1, A. Trkola1, J. Böni3, H. Kuster1, A. Oxenius4, J. K. Wong5, R. Phillips4, B. Hirschel2, R. Weber1, and H. Gunthard1 Univ. Hosp., 1Zürich and 2Geneva; and 3NZR Univ., Zürich, Switzerland; 4Oxford Univ., UK; and 5Univ. of California, San Diego Background: Extensive study on HIV env sequence evolution over 5 years in a patient undergoing multiple STI cycles and induction of host immune responses. Methods: Patient history: Infected with HIV-1B without therapy for >6 years. Successful ART for 34 months. Enrollment into Swiss Spanish Intermittent Therapy Trial by week 0.4 STI cycles (2 weeks off, 8 weeks on ART). ART interrupted at week 40 and restarted at week 50. Specimen collection: Plasma and PBMC before any ART, on ART and during STI (week 0, 2, 10, 12, 20, 22, 30, 32, 40, 42, 49). Tonsil biopsies before ART. Virus culture supernatants (week 2, 41). Analyses: HIV-RNA subjected to RT-PCR, cloning (15-20 clones/sample), and sequencing of env C2V3C3 domain. 400 sequences analyzed (PHYLIP, MEGA). Results: A diverse spectrum of HIV env quasispecies with several distinct phylogenetic groups was present prior to ART. Cluster A, predominant in pre-ART tonsils and PBMC (30/47 clones), persisted during continued ART (14/16,PBMC week 0) and comprised the rebounding virus in plasma during the 1st STI (16/16,week 2). During later STI cycles, this population was cleared. Plasma virus rebounding during STI (week 12-49) belonged to a uniform cluster B which was also present in pre-ART plasma, PBMC and tonsils. Autologous virus isolated at week 2 from PBMC belonged to cluster B. The neutralizing activity of patient plasma against B and the nonsynonymous vs synonymous mutations ratio in clonal plasma env sequences continuously increased in parallel after the second STI (week 12-49). This indicates selective pressure on the env gene most likely due to induction of neutralizing antibodies. HIV-specific CTL against 5 epitopes were detectable before, declined to low levels on ART and were partially reinduced during STI. Conclusion: HIV populations emerging during successive STI may reflect both stochastic reactivation of archived subpopulations and ongoing selection due to host antibody and CTL responses. Pretreatment viral diversity and continued co-evolution of virus and host immune responses appear to be important factors in restricting replicating viral subpopulations during STI.

©2002 9th Conference on Retroviruses and Opportunistic Infections