Primary Infection with HIV-1 with Reduced Drug Susceptibility Does Not Appear to Result from Point Source Transmission
J. K. WONG1‚2, A. J. LEIGH-BROWN3, M. QUIGG3, S. ALBANIL1, E. DAAR4, R. D’AQUILA5, P. KAISER6, E. CONNICK7, C. PETROPOULOS8, J. WHITCOMB8, N. HELLMANN8, D. D. RICHMAN1‚2, and S. LITTLE1. 1Univ. of California, San Diego; 2VA San Diego Hlth. Care Ctr.; 3Univ. of Edinburgh, Scotland; 4Univ. of California, Los Angeles/Cedars Sinai Med. Ctr.; 5Harvard Univ., Boston, MA; 6Univ. of Texas, Southwestern; 7Univ. of Colorado; and 8ViroLogic, San Francisco, CA
Recent studies of primary HIV infection have demonstrated a subset of drug naive patients infected with virus with reduced antiviral drug susceptibility. It is not known whether such individuals might be epidemiologically linked. We examined pol sequences from 35 patients recently infected with virus having reduced susceptibility and 14 patients with virus having wild-type susceptibility. Phylogenetic reconstruction based on all sites, and on synonymous sites alone, failed to detect any general clustering of patients infected with virus with reduced susceptibility. However, in at least three patient pairs, virus from within each pair were significantly associated by bootstrap analysis. In each pair, the two patients were from the same geographical region however, no epidemiological linkage was evident. In one of these pairs infection had occured 2.5 years apart. In two patient pairs, both patients’ viruses exhibited reduced susceptibility to non-nucleoside reverse transcriptase inhibitors (NNRTI) while in the third pair, only one member of the pair did so. Although these findings suggest that some members of this cohort may have been infected by common sources, there is no present evidence to suggest that a point source is responsible for most patients observed with virus having reduced drug susceptibility. These data are consistent with the interpretation that the low level of reduced susceptibility observed in this cohort represents a naturally-occcuring variation in the baseline susceptibility of "wild-type"/drug-naive virus to certain anti-retroviral drugs.
Key Words: Drug resistance, epidemiology, Primary infection
Conference on Retroviruses and Opportunistic Infections,