Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States
Lessons From Clinical Trials of Antiretroviral Interventions to Reduce Perinatal Transmission of HIV
Mechanisms of Action of Antiretroviral Prophylaxis in Reducing Perinatal Transmission of HIV
(Last updated:9/14/2011)
Panel’s Recommendation:
• Antiretroviral (ARV) drugs reduce perinatal transmission by several mechanisms, including lowering maternal antepartum viral load and providing infant pre- and post-exposure prophylaxis. Therefore, combined antepartum, intrapartum, and infant ARV prophylaxis is recommended to prevent perinatal transmission of HIV (AI). |
Zidovudine and other ARV drugs can reduce perinatal transmission through a number of mechanisms. Antenatal drug administration decreases maternal viral load in blood and genital secretions, which is a particularly important mechanism of action in women with high viral loads. Even among women with HIV RNA levels <1,000 copies/mL, however, ARV drugs have been shown to reduce the risk of transmission [1]. In addition, the level of HIV RNA at delivery and receipt of antenatal ARV drugs are independently associated with risk of transmission, suggesting that reduction in viral load is not solely responsible for the efficacy of ARV prophylaxis [2-3].
Another mechanism of protection is infant pre-exposure prophylaxis achieved by administering ARV drugs that cross the placenta from mothers to infants and produce adequate systemic drug levels in the infants. This mechanism of protection likely is particularly important during passage through the birth canal, a time when infants receive intensive exposure to maternal genital-tract virus. Infant post-exposure prophylaxis is achieved by administering drugs to infants after birth. This intervention provides protection from cell-free or cell-associated virus that may have entered the fetal/infant systemic circulation through maternal-fetal transfusion associated with uterine contractions during labor or systemic dissemination of virus swallowed during infant passage through the birth canal.
The efficacy of ARV drugs in reducing perinatal transmission likely is multifactorial, and each of the mechanisms previously described may make a contribution. The importance of the pre- and post-exposure components of prophylaxis in reducing perinatal transmission is demonstrated by the efficacy of interventions that involve administration of ARVs only during labor and/or to the newborns, discussed in the next section [4-10].
References
1. Ioannidis JP, Abrams EJ, Ammann A, et al. Perinatal transmission of human immunodeficiency virus type 1 by pregnant women with RNA virus loads <1000 copies/ml. J Infect Dis. 2001 Feb 15;183(4):539-545.
2. Cooper ER, Charurat M, Mofenson L, et al. Combination antiretroviral strategies for the treatment of pregnant HIV-1-infected women and prevention of perinatal HIV-1 transmission. J Acquir Immune Defic Syndr. 2002 Apr 15;29(5):484-494.
3. Sperling RS, Shapiro DE, Coombs RW, et al. Maternal viral load, zidovudine treatment, and the risk of transmission of human immunodeficiency virus type 1 from mother to infant. Pediatric AIDS Clinical Trials Group Protocol 076 Study Group. N Engl J Med. 1996 Nov 28;335(22):1621-1629.
4. Jackson JB, Musoke P, Fleming T, et al. Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda: 18-month follow-up of the HIVNET 012 randomised trial. Lancet. 2003 Sep 13;362(9387):859-868.
5. Petra Study Team. Efficacy of three short-course regimens of zidovudine and lamivudine in preventing early and late transmission of HIV-1 from mother to child in Tanzania, South Africa, and Uganda (Petra study): a randomised, double-blind, placebo-controlled trial. Lancet. 2002 Apr 6;359(9313):1178-1186.
6. Wade NA, Birkhead GS, Warren BL, et al. Abbreviated regimens of zidovudine prophylaxis and perinatal transmission of the human immunodeficiency virus. N Engl J Med. 1998 Nov 12;339(20):1409-1414.
7. Moodley D, Moodley J, Coovadia H, et al. A multicenter randomized controlled trial of nevirapine versus a combination of zidovudine and lamivudine to reduce intrapartum and early postpartum mother-to-child transmission of human immunodeficiency virus type 1. J Infect Dis. 2003 Mar 1;187(5):725-735.
8. Taha TE, Kumwenda NI, Gibbons A, et al. Short postexposure prophylaxis in newborn babies to reduce mother-to-child transmission of HIV-1: NVAZ randomised clinical trial. Lancet. 2003 Oct 11;362(9391):1171-1177.
9. Gaillard P, Fowler MG, Dabis F, et al. Use of antiretroviral drugs to prevent HIV-1 transmission through breast-feeding: from animal studies to randomized clinical trials. J Acquir Immune Defic Syndr. 2004 Feb 1;35(2):178-187.
10. Gray GE, Urban M, Chersich MF, et al. A randomized trial of two postexposure prophylaxis regimens to reduce mother-to-child HIV-1 transmission in infants of untreated mothers. AIDS. 2005 Aug 12;19(12):1289-1297.