287     High Frequency of Apparent HIV-1 Superinfection in a Seroconverter Cohort Robert Grant*1,2, J McConnell1, J Marcus1, G Spotts2, T Liegler1, R Brennan2, and F Hecht2 1Gladstone Inst of Virology and Immunology, Univ of California, San Francisco, USA and 2Univ of California, San Francisco, USA

Background:  HIV-1 superinfection, defined as sequential appearance of highly divergent viruses, has been reported in recently infected persons. In contrast, superinfection appears to be rare in chronically infected persons. The frequency, risk factors, and consequences of superinfection have not been determined.

Methods:  Acute and recent HIV-1 infection was diagnosed in the San Francisco Options Project using evolving serology. Population sequencing of the pol gene was performed. Phylogenetic analysis of baseline and follow-up time-points was conducted using bootstrapped neighbor-joining trees.

Results:  We analyzed 103 recently infected persons at 2 or more time-points, representing 194 person-years of observation. All viral sequences were subtype B. Highly divergent viral sequences appeared in 7 cases over time, representing an incidence density of 3.6 of 100 person-years (95% CI:  1.5 to 7.3%). In 4 cases, the baseline and divergent sequence clusters were confirmed by independent analysis of specimens from additional time-points; confirmatory analysis of the remaining 3 cases is in progress. Divergent viruses appeared within 4 weeks after baseline in 2 cases, likely representing dual infection. A divergent virus appeared between 120 and 168 weeks after baseline in another case. A 3-class drug-resistant HIV-1 variant was overgrown by a drug-susceptible viral variant in 1 case. Genotypic markers of non-nucleoside reverse transcriptase inhibitor resistance (NNRTI) (RT K103N or RT V108I) appeared in 2 cases. Viral load increased in 6 of the 7 cases.

Conclusions: Acquisition of NNRTI-resistant HIV-1 by apparent superinfection may reflect its high prevalence in the community and preserved replication capacity. The high rate of apparent superinfection in seroconverter cohorts contrasts with the lack of superinfection detected in chronically infected cohorts analyzed using the same virological methods. Less common superinfection in chronic infection may reflect development of protective immune responses against partner viruses, antiretroviral use, or virological interference.

Keywords: superinfection; transmission; drug resistance