Addition of extended zidovudine to extended nevirapine prophylaxis reduces nevirapine resistance in infants who were HIV-infected in utero

Abstract

Background: In the Post-Exposure Prophylaxis of Infants (PEPI)-Malawi trial, most women received single-dose nevirapine (NVP) at delivery, and infants in the extended study arms received single-dose NVP along with 1 week of daily zidovudine (ZDV), followed by either extended daily NVP or extended daily NVP and ZDV up to 14 weeks of age. Although extended NVP prophylaxis reduces the risk of postnatal HIV transmission, it may increase the risk of NVP resistance among infants who are HIV-infected despite prophylaxis.

Methods: We analyzed 88 infants in the PEPI-Malawi trial who were HIV-infected in utero and who received prophylaxis for a median of 6 weeks prior to HIV diagnosis. HIV genotyping was performed using the ViroSeq HIV Genotyping System.

Results: At 14 weeks of age, the proportion of infants with NVP resistance was lower in the extended NVP and ZDV arm than in the extended NVP arm (28/45, 62.2% vs. 37/43, 86.0%; P = 0.015). None of the infants had ZDV resistance. Addition of extended ZDV to extended NVP was associated with reduced risk of NVP resistance at 14 weeks if prophylaxis was stopped by 6 weeks (54.5 vs. 85.7%, P = 0.007) but not if prophylaxis was continued beyond 6 weeks (83.3 vs. 87.5%, P = 1.00).

Conclusion: Addition of extended ZDV to extended NVP prophylaxis significantly reduced the risk of NVP resistance at 14 weeks in infants who were HIV-infected in utero, provided that HIV infection was diagnosed and the prophylaxis was stopped by 6 weeks of age.

Figure 1. NVP resistance at 14 weeks in infants with in utero HIV

The figure shows the proportion of infants in the extended NVP arm (triangles) and the extended NVP+ZDV arm (squares) with one or more NVP resistance mutation detected at 14 weeks of age. Prophylaxis was stopped when diagnosis of infant HIV infection was confirmed. Data are presented separately for infants whose prophylaxis was stopped at ≤3 weeks, 6 weeks, 9 weeks, and 14 weeks (full study regimen). Prophylaxis was stopped by 6 weeks in a total of 33 infants in the extended NVP+ZDV arm and 35 infants in the extended NVP arm; prophylaxis was continued beyond 6 weeks in a total of 12 infants in the extended NVP+ZDV arm and 8 infants in the extended NVP arm.