Research Article: Antiretroviral Strategies to Prevent Mother-to-Child Transmission of HIV: Striking a Balance between Efficacy, Feasibility, and Resistance

Date Published: October 27, 2009

Publisher: Public Library of Science

Author(s): Dara A. Lehman, Grace C. John-Stewart, Julie Overbaugh

Abstract: Dara Lehman and colleagues discuss a randomized trial that found that adding up to a week of twice-daily zidovudine+lamivudine to single-dose nevirapine reduces the risk of resistance in mothers and infants.

Partial Text: Prevention of mother-to-child transmission (MTCT) of HIV has been both a great success and a continued challenge. Today, in resource-rich countries, new infant infections are a rare event. However, nearly 400,000 infant HIV-1 infections still occur each year in settings in which highly active antiretroviral therapy (HAART), elective caesarean sections, and safe alternatives to breastfeeding are not readily available. In these settings, various short-course antiretroviral therapies that include a single-dose of nevirapine (sdNVP) are used to prevent transmission to infants [1]. The sdNVP regimen effectively reduces MTCT by close to 50% and is an inexpensive and simple regimen, feasible for use in resource-limited settings [2],[3]. However, resistance to sdNVP arises commonly and quickly and can adversely affect the future treatment of NVP-exposed women [4]–[6]. Ideal alternatives to the sdNVP regimen would reduce the emergence of resistance while preserving efficacy and feasibility.

A variety of alternative regimens have efficacy in preventing MTCT in resource-poor settings. These include daily zidovudine (AZT) or zidovudine/lamivudine (AZT/3TC) combinations, short-course HAART, and infant-only prophylaxis [7]. When considering which strategy is most appropriate for use in resource-limited settings, data on transmission rates must be balanced with factors such as resistance, safety, feasibility, and adherence.

As described in a paper in this issue of PLoS Medicine, Martinson et al. conducted a randomized trial to determine whether adding up to a week of twice-daily AZT/3TC to sdNVP would reduce the risk of resistance in mothers and infants [12]. The addition of AZT and 3TC (half-lives 1–2 h and 5–7 h, respectively) decreases the amount of time that NVP (half-life 45 h) would be present alone, potentially limiting selection pressure for resistance to emerge. At 6 wk postpartum, drug resistance in both mothers and infants was reduced by over 80% in the sdNVP plus AZT/3TC arms, compared to sdNVP alone. In addition, at 2 wk postpartum, viral loads were lower in the women on combination treatment compared to those who received sdNVP alone, which may also have contributed to the observed reduction in resistance. Not only did the overall percentage of women and children with resistance decrease, but following sdNVP plus the “tail” of AZT/3TC, fewer acquired multiple mutations and resistance appeared to fade more quickly.



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