Association between Detection of HIV-1 DNA Resistance Mutations by a Sensitive Assay at Initiation of Antiretroviral Therapy and Virologic Failure

Background. Antiretroviral therapy (ART) has become more available throughout the developing world during the past 5 years. The World Health Organization recommends nonnucleoside reverse-transcriptase inhibitor–based regimens as initial ART. However, their efficacy may be compromised by resistance mutations selected by single-dose nevirapine (sdNVP) used to prevent mother-to-child transmission of human immunodeficiency virus (HIV)–1. There is no simple and efficient method to detect such mutations at the initiation of ART. Methods. One hundred eighty-one women who were participating in a clinical trial to prevent mother-to-child transmission and who started NVP-ART after they had received sdNVP or a placebo were included in the study. One hundred copies of each patient's HIV-1 DNA were tested for NVP-resistance point-mutations (K103N, Y181C, and G190A) with a sensitive oligonucleotide ligation assay that was able to detect mutants even at low concentrations (⩾5% of the viral population). Virologic failure was defined as confirmed plasma HIV-1 RNA >50 copies/mL after 6 to 18 months of NVP-ART. Results. At initiation of NVP-ART, resistance mutations were identified in 38 (26%) of 148 participants given sdNVP (K103N in 19 [13%], Y181C in 8 [5%], G190A in 28 [19%], and ⩾2 mutations in 15 [10%]), at a median 9.3 months after receipt of sdNVP. The risk of virologic failure was 0.62 (95% confidence interval [CI], 0.46–0.77) in women with ⩾1 resistance mutation, compared with a risk of 0.25 (95% CI, 0.17–0.35) in those without detectable resistance mutations (P < .001). Failure was independently associated with resistance, an interval of