Background:  In Africa, single-dose nevirapine (sdNVP) and short-course of zidovudine (ZDV)+ lamivudine (3TC) frequently induce viral resistance when used to prevent mother-to-child HIV-1 transmission. The ANRS DITRAME Plus study is an open-label cohort evaluating the combination of a short-course of ZDV+3TC and sdNVP, ending with 3 days of ZDV+3TC post-partum. We describe the frequency of genotypic resistance mutations with this regimen to prevent mother-to-child transmission.

Methods:  In Abidjan in 2002 to 2003, 329 consenting pregnant women started oral ZDV+3TC at ≥ 32 weeks of gestation, received an extra dose of ZDV+3TC and sdNVP at beginning of labor, then ZDV+3TC for 3 days post-partum. Neonates received ZDV for 7 days + sdNVP on day 2. Mothers’ plasma HIV-1 RNA levels (viral load) were quantified at baseline and at day 2 post-partum. Genotypic resistance analysis was performed by sequencing reverse transcriptase gene at week 4 post-partum among transmitting mothers (n = 16), in a random sample of 80 non-transmitting mothers stratified on baseline viral load and CD4 cell count distributions and in infected children (n = 16). In case of mutations detected at week 4 post-partum, baseline samples were also tested. Mothers’ NVP plasma concentrations were determined by a validated HPLC assay at day 2 post-partum.

Results:  The 6-week HIV-1 transmission rate was 4.7% (95%CI 2.4 to 7.0%). Median baseline CD4⁺ cell count was 293/mm³ for transmitting mothers and 416/mm³ for non-transmitters; median viral load was 5.16 and 4.45 log₁₀ copies/mL, respectively. Most of the HIV-1 isolates were subtype CRF02. At day 2 post-partum, viral load was < 2.3 log₁₀ copies/mL for 52% of the women. Only 1 non-transmitting woman had detectable NVP resistance mutations (103N, 181C) and 3TC resistance mutations (184V); 7 other women had 184V resistance mutations. The overall frequency of resistance mutations was 1.14% (CI 0.03 to 6.17%) for NVP and 8.33% (CI 3.66 to 15.76%) for 3TC. No resistant virus was detectable at baseline for these 8 women. The median plasma NVP concentration was 713 ng/mL (31 to 2111) at day 2 post-partum. In multivariate analysis, duration of ZDV+3TC pre-partum prophylaxis was significantly associated with detection of 184V variant (p = 0.009). Of 16 infected children, 1 developed NVP and 3TC mutations and 3 had 3TC mutations.

Conclusions:  A short-course regimen of ZDV+3TC with sdNVP, together with 3 days of ZDV+3TC post-partum prevents most peri-partum HIV-1 transmission in Africa and minimizes viral resistance to NVP.

Keywords: nevirapine resistance; Prevention of HIV mother-to-child transmission; Africa