Background:  Transmitted or acquired resistance prior to combination ART (cART) may compromise the effectivness of nevirapine (NVP) -based HAART regimens, particularly where zidovudine (AZT) or NVP is provided for the prevention of mother-to-child transmission (pMTCT).

Methods:  In July 2003 in Chitungwiza, Zimbabwe, 87 adults with AIDS (33 men and 54 women) started NVP-based ART. Of the 54 women, 28 had received short-course AZT between 1999 and 2001, 21 single-dose NVP between 2000 and 2003, and 4 short-course AZT and then single-dose NVP between 1999 and 2003. Men were the partners of exposed women, but reported no prior ART exposure. Average reported adherence to ART was > 98%. Baseline (week 0) plasma samples were assessed from 25 of 87 (29%) with HIV RNA >400 copies/mL at 16, 24, and 48 weeks on treatment. Drug resistance mutations in consensus plasma HIV RNA were assessed by population sequencing and minority variant populations of K103N were examined by allele specific polymerase chain reaction (AS-PCR).

Results:  Of 25 subjects, 5 with virologic failure (20%) had detectable mutations in population sequence at codons associated with antiretroviral drug resistance:  K103N in 2 women and K238N in 1, with all 3 reporting single-dose NVP exposure 17 to 39 months prior to ART initiation; 1 man had G190A and 1 had a T215/INST mixture, a T215F/Y revertant associated with AZT resistance. A polymorphism associated with NVP resistance, V179D, was identified in 1 woman. The AS-PCR for K103N minority variants detected high levels of AAC/T (>20% AAC) in the 2 women with K103N in consensus sequence; and 3 additional women had 0.35 to 3% AAC by AS-PCR, above the lower limit of detection (0.2%), but wild type sequence. Of these, 2 had been exposed to single-dose NVP 10 and 19 months before ART, and 1 reported only AZT exposure.

Conclusions:  Combining population sequencing and AS-PCR for K103N, transmitted or acquired drug-resistance mutations prior to ART initiation were identified in baseline samples from 8 of 25 (32%) subjects with viremia >16 weeks on ART:  by population sequencing in 5 and by K103N AS-PCR in an additional 3. Surveillance for drug-resistance mutations in AIDS patients with subtype C HIV may be warranted in settings where single-dose NVP and short-course AZT are used for pMTCT. Screening for K103N by AS-PCR may identify risk for virologic failure.