Maternal plasma viral load, zidovudine and mother-to-child transmission of HIV-1 in Africa: DITRAME ANRS 049a trial.

OBJECTIVE: To study the relationship between maternal plasma RNA levels and mother-to-child transmission (MTCT) of HIV-1 in African breastfed children. DESIGN: Nested case-control study within a randomized trial assessing the efficacy of a short maternal zidovudine (ZDV) regimen to reduce MTCT. METHODS: Eligible women received either 300 mg of ZDV twice a day until labour, 600 mg at the beginning of labour and 300 mg twice a day for 7 days post-partum or a placebo. The diagnosis of paediatric HIV-1 infection was based on PCR tests at days 1--8, 45, 90 and 180 then on serology performed at 3 monthl intervals. Plasma HIV-1 RNA was measured at inclusion and on day 8 after delivery for all women who did transmit HIV to their children (cases) using a Chiron branched DNA assay (sensitivity 50 copies/ml) and compared with women who did not transmit (two per case) matched for phase trial, treatment allocation and site. RESULTS: At inclusion, mean log10 viral load was 4.6 among 55 transmitting mothers and 3.7 among 117 non transmitters (P = 0.0001). Among transmitters, the mean difference in log10 viral load between day 8 post-partum and inclusion was -0.13 in the ZDV group (n = 23) versus 0.27 in the placebo group (n = 32; P = 0.01); among non transmitters it was -0.35 for the ZDV group (n = 47) versus 0.27 in the placebo group (n = 70; P < 10(-4)). In multivariate logistic regression analysis, odds ratios for MTCT were 8.7 (95% confidence interval, 3.7-20.6) for 1 log(10) increase of maternal RNA at inclusion and 4.2 (95% confidence interval, 1.7--10.3) for 1 log(10) increase difference from inclusion to day 8 post-partum. CONCLUSION: High maternal viral load at inclusion strongly predicts MTCT of HIV in Africa. A short ZDV treatment regimen decreases significantly maternal viral load from its pretreatment level