Reduced antiretroviral drug susceptibility among patients with primary HIVinfection

Context The transmission of drug-resistant hu man immunodeficiency virus (H IV) has been documented, but the prevalence of such transmission is unknown . Objective To assess the spectrum and frequency of antiretroviral susceptibi lity among subjects with primary HIV infection. Design, Setting, and Patients Retrospective analysis of 141 subjects identi fied from clinical research centers in 5 major metropolitan areas, enrolled from 1989 to 1998, with HIV seroconversion within the preceding 12 months and no more than 7 days' prior antiretroviral (ARV) therapy. Main Outcome Measures Phenotypic and genotypic ARV susceptibility of HIV fr om plasma samples. Results The transmission of drug-resistant HIV as assessed by a greater tha n 10-fold reduction in ARV susceptibility to 1 or more drugs was observed i n 3 (2%) of 141 subjects, including to a nonnucleoside reverse transcriptas e inhibitor in 1 patient and to a nucleoside reverse transcriptase inhibito r and a protease inhibitor in 2 patients. Population-based sequence analysi s of these 3 samples identified multidrug-resistance mutations in reverse t ranscriptase (M184V, T215Y, K219K/R) and protease (L10I/V, K20R, M36I, M46I , G48V, L63P, A71T, V77I, V82T, I84V, L90M) in the 2 latter patient samples , along with numerous polymorphisms. A reduction in susceptibility of great er than 2.5- to 10-fold to 1 or more drugs was observed in viral isolates f rom 36 patients (26%). Sequence analysis of these 36 samples identified wel l-characterized drug resistance mutation in reverse transcriptase and prote ase in only 1 of these patients. Conclusions Reductions in drug susceptibility of more than 10-fold were rar e among this cohort of recently HIV-infected subjects and were distributed among each of the 3 major classes of ARV drugs tested. Reductions in suscep tibility of more than 2.5- to 10-fold to certain ARV drugs of unknown clini cal significance were highly prevalent among newly infected patients. Resis tance testing may be warranted to monitor the frequency of drug resistance over time and to assess the potential for geographic variability.