Background:  After single-dose nevirapine (SDNVP) for prevention of mother-to-child HIV transmission, viral resistance can emerge; women who initiate non-nucleoside reverse transcriptase inhibitor (NNRTI)-based ART within 6 to 12 months of SDNVP exposure may have poorer virologic responses. We assessed whether low level viremia (40 to 399 copies/mL) at 24 weeks was associated with NNRTI mutations or SDNVP exposure.

Methods:  The NNRTI Response Study enrolled 217 SDNVP-exposed (n = 87) and unexposed (n = 130) women in Thailand to determine virologic response to NNRTI-based ART. Viral load (VL) was performed with COBAS TaqMan or Roche Amplicor assays. Bulk sequencing evaluated reverse transcriptase codons 1 to 251; sensitive real-time PCR screened baseline specimens from SDNVP-exposed women. Backwards step-wise regression analysis determined factors associated with low-level viremia 24 weeks after ART initiation.

Results:  Two hundred one (92.6%) women were infected with CRF01_AE, 14 (6.5%) with subtype B, and 2 (0.9%) were unclassified. By real-time PCR, 13 (6.2%) women had baseline NNRTI-associated mutations (K103N = 5, V106I = 4, Y181C = 4, G190A = 1, K103T = 1,); 4 of these women had a mutation detected by bulk sequencing. At 24 weeks, 152 had VL <40 copies/mL, 34 had 40 to 399 copies/mL, 9 had VL >400 copies/mL, and 22 had died/discontinued the study or NNRTI. Of the 186 women with VL <400 copies/mL, 111 (59.7%) had no SDNVP exposure, 13 (7.0%) were exposed <6 months prior to ART initiation, 4 (2.2%) 7 to 12 months prior, and 58 (31.2%) >12 months prior. Most (33/34) women with VL 40 to 399 copies/mL at 24 weeks continued NNRTI-based ART until week 48 (1 discontinued ART); at 48 weeks, 25 (73.5%) of 33 women had VL <40 copies/mL, 5 (14.7%) had VL 40-399 copies/mL, and 3 (8.8%) had VL >400 copies/mL. In multivariate analysis, baseline VL >100,000 copies/mL (OR 2.5, 95%CI 1.1 to 5.7), age >30 years (OR 3.3, 95%CI 1.2 to 9.2), and subtype B (OR 6.3, 95%CI 1.4 to 29.7) were associated with low-level viremia at 24 weeks. Prior SDNVP exposure and baseline mutations were not associated with low-level viremia.

Conclusions:  Most women with low-level viremia at 24 weeks had undetectable VL at 48 weeks on an NNRTI regimen, suggesting that high baseline VL, and not early ART failure, was responsible for the low-level viremia. Neither prior SDNVP exposure nor baseline mutations predicted low level viremia. SDNVP-exposed women with low-level viremia at 24 weeks may be continued on NNRTI-based ART, but should be monitored closely for treatment failure.