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Session 100 Poster Session Molecular Epidemiology Session Time: 4:30-6:30 pm Room 4E-F

757-W. HIV Super-Infection: Rapid Replacement of AE Subtype by B Subtype S. Jost1, M. C. Bernard1, L. Kaiser1, S. Yerly1, B. Hirschel1 , L. Goh2, and L. Perrin*1 1Univ. of Geneva, Switzerland and 2GlaxoSmithKline, London, UK Background: HIV-1 circulating recombinant forms suggest that co-infection and/or super-infection occur in vivo. A 34-year-old male with multiple male partners and with an acute retroviral syndrome (ARS) was enrolled in the Quest trial (AZT, 3TC, Abacavir, Amprenavir for 26 months, with from 20 to 26 months, vaccination by either placebo or Alvac vCP 1452, or Alvac + Remune, followed by stop of all treatment at month 26). Viremia declined from >106 HIV-1 RNA copies/mL to <50 copies/mL at 28 weeks and remained <200 copies/mL while on HAART. 2 weeks after treatment interruption viremia rebounded to a first plateau of approximately 30,000 copies/mL for 6 weeks followed by a second steady plateau at 150,000-400,000 copies/mL for 3 months before re-initiation of HAART. Methods: Protease, reverse transcriptase (RT) gag, and C2V3 population sequencing were performed in both plasma and pro-viral DNA. In order to detect with high sensitivity and specificity minority strains we set up a subtype specific PCR (end Pr-proximal third of RT) using specific primers for AE and B subtypes corresponding to patient's sequences: positive strand primers (2289-2312 HXB2, and negative strand primers 2786-2806 AE, 2687-2712 B, there was 11 nucleotide differences between AE and B primers for + strand and 4 for - strand). Results: The sequences revealed in both plasma and pro-viral DNA, HIV-1 AE subtype during the ARS and the first viremia plateau after treatment stopped (15 samples analyzed) whereas B subtype was detected during the second steady plateau (8 samples). Using this subtype specific PCR, no PCR product was detected on ethidium bromide stained gel when starting with 100,000 HIV RNA copies amplified with the heterologous primers. In contrast PCR products of the correct size were detected using the homologous primers when as few as 100 ccopies of the homologous subtype were mixed with 100,000 copies of the heterologous subtype. The specific PCR confirmed the absence of B subtype in both plasma and proviral DNA before the treatment was stopped, persistence of AE subtype throughout the first 26 months on HAART and at the time of first viremia plateau, and the emergence, during the second steady plateau, of B subtype as the majority subtype in DNA and as the only detectable subtype in plasma. Based on sequential serologies and HCV RNA testing, a concomitant HCV primary infection was also detected at the time of treatment stop. Conclusions: Super-infection, although rare (no evidence in successive RT and PR sequences of 300 patients in our database) has implications for ever increasing HIV-1 genetic diversity, public health, and vaccines development.

©2002 9th Conference on Retroviruses and Opportunistic Infections