87   Transmission of Specific Antiviral Resistance Mutations within Partner Pairs.

F. M. Hecht*¹, J. O. Kahn¹, M. Warmerdam², M. Webb¹, L. Digilio², K. H. Lee², and R. M. Grant.
¹Univ. of California, San Francisco and²Gladstone Inst. of Immunology and Virology, San Francisco, CA.

Background:Preferential transmission of wild-type viral variants from persons with ZDV resistance mutations has been suggested from prior studies, implying that there may be selective pressure against transmission of some drug resistant HIV variants. We studied partner pairs to determine whether specific drug resistance mutations were transmitted to spread partners when they were present in the source partner.

Methods:Participants in the on-going Options Project study of primary HIV were interviewed to determine potential source partners; these partners were recruited for study. Plasma from both partners was used for genotyping using dye primer cycle sequencing of protease (PR) and reverse transcriptase (RT) gene segments (Visible Genetics). Primary or secondary mutations were identified using IAS-USA classification (JAMA, 2000). Preliminary phylogenetic analysis was performed using RT and PR sequences at sites not associated with resistance; env sequence analysis is being performed to confirm linkages.

RESULTS:We evaluated 14 partner pairs, consisting of 27 individual subjects (1 subject was the suspected source to 2 spread cases; 1 pair has been previously reported, NEJM, 1998). Phylogenetic analysis indicated high genetic similarity between suspected linked couples except in 3 couples with divergent viral sequences, who were excluded. In the remaining 11 pairs, the median time between evaluation of the spread and source partners was 10 days (range 3—321). The median HIV-1 RNA level in the source partner was 26,891 copies/ml. Two source partners had primary NRTI mutations: T69D (n = 1) and M184 (n = 1). Both were transmitted. One source partner had a primary NNRTI mutation, K103N, which was transmitted. No primary PI mutations were present in source partners. Two source partners had a total of 3 secondary NRTI mutations (M41L in both, L210W in 1); all were transmitted. Three source partners had 4 secondary PI mutations (M36I in 1, A71V in 1, A71T in 1, and V77I in 2); all were transmitted.

Conclusions:We did not find evidence for selective pressure against transmission of RT or PR mutations. All 10 mutations in RT or PR that we identified in source partners were transmitted.