Background:  A single dose of tenofovir (TDF) (300 mg) and emtricitabine (FTC) (200 mg) following intrapartum nevirapine (NVP) ingestion reduces evidence of NNRTI resistance by 73% at 2 weeks post partum and by 53% at 6 weeks post partum when measured via population genotyping. However, efficacy of this intervention is unknown for HIV sub-populations present at <25%.

Methods:  In a recently reported randomized trial, we allocated 397 women to receive adjunctive TDF/FTC or no study drug in the setting of short-course zidovudine (ZDV) and intrapartum NVP for perinatal HIV prevention. For this secondary analysis, we evaluated 122 random maternal specimens using an oligonucleotide ligation assay (OLA). OLA can detect resistance mutations in minority sub-populations as low as 5% of circulating virus. Mutations at codons 103, 106, 181, and 190 were considered NNRTI resistant.

Results:  Of 122 specimens tested, 38 specimens were drawn at 2 weeks post partum (15 intervention arm, 23 control arm) and 84 were drawn at 6 weeks post partum (43 intervention arm, 41 control arm). Median log₁₀ HIV-1 was not different between study arms at 2 weeks post partum (3.53 vs 3.67; p = 0.27) or at 6 weeks postpartum (4.61 vs 4.54; p = 0.44). When resistance was assessed by OLA, a 69% reduction in NNRTI resistance was observed at 2 weeks post partum (2 of 15 [13%] vs 10 of 23 [44%]; RR 0.31, 95%CI 0.08 to 1.21), while a 58% reduction in NNRTI resistance was observed at 6 weeks post partum (8 of 43 [19%] vs 18 of 41 [44%]; RR 0.42, 95%CI 0.21 to 0.87).

Conclusions:  The efficacy of single-dose TDF/FTC in reducing NNRTI drug resistance by population genotyping was confirmed with the more sensitive OLA. These findings further emphasize the role of this simple intervention in settings that rely heavily on intrapartum NVP, alone or in combination with other drugs, for perinatal HIV prevention.