Single-Dose Tenofovir and Emtricitabine for Reduction of Viral Resistance to Non-nucleoside Reverse Transcriptase Inhibitory Drugs in Women Given Intrapartum Nevirapine for Perinatal HIV Prevention: An Open-Label Randomized Trial

Abstract

Administration of single-dose nevirapine intrapartum and neonatally is essential for preventing perinatal HIV in settings where resources are limited. But after a single dose, a substantial proportion of women become resistant to nonnucleoside reverse transcriptase inhibitors. The present randomized study was an attempt to learn whether adding a combination of the antiretroviral drugs tenofovir disoproxil fumarate and emtricitabine would lessen the emergence of resistance in the weeks following treatment. Of 400 HIV-infected pregnant women cared for at 2 primary health facilities in Zambia, one was excluded. Two hundred were randomly assigned to receive a single oral dose of 300 mg tenofovir with 200 mg emtricitabine under direct observation. The remaining 199 women received neither of these drugs. All the women were offered a brief course of zidovudine as well as intrapartum nevirapine. The major outcome was resistance to nonnucleoside reverse transcriptase inhibitors 6 weeks after delivery. Women who received the intervention were 53% less likely than control women to have a mutation conferring resistance to nonnucleoside reverse transcriptase inhibitors 6 weeks after delivery. The risk ratio was 0.47, with a 95% confidence interval of 0.29–0.76. The overall rate of perinatal HIV transmission was similar in the intervention and control groups (5.6% and 8.0%, respectively). This held true for both intrauterine transmission and intrapartum or early postpartum transmission. Four women in each group were anemic in the postpartum period. Serious adverse events were recorded for 10% of infants in the intervention group and 12% of control infants. Septicemia and pneumonia were the most common problems. None of these events was thought to have resulted from the intervention. A single dose combining tenofovir and emtricitabine, given at the time of delivery to HIV-infected women, substantially reduced the frequency of resistance to nonnucleoside reverse transcriptase inhibitors 6 weeks postpartum in this study. The investigators believe that this can be an important adjunct to intrapartum nevirapine in circumstances where several days of combination drug treatment may not be feasible.