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
Overview
(Last updated:9/14/2011)
One of the major achievements in HIV research was the demonstration by the Pediatric AIDS Clinical Trials Group 076 (PACTG 076) clinical trial that administration of zidovudine to the pregnant woman and her infant could reduce the risk of perinatal transmission by nearly 70% [1]. Following the results of PACTG 076, in the United States and in other resource-abundant countries, implementation of the zidovudine regimen coupled with increased antenatal HIV counseling and testing rapidly resulted in significant declines in transmission [2-5]. Subsequent clinical trials and observational studies demonstrated that combination antiretroviral (ARV) prophylaxis (initially dual- and then triple- combination therapy) given to the mother antenatally was associated with further declines in transmission to less than 2% [2, 6-7]. It is currently estimated that fewer than 200 HIV-infected infants are now born each year in the United States [4, 8].
Each individual birth of an infected infant is a sentinel event representing missed opportunities and barriers to prevention [9-10]. Important obstacles to eradication of perinatal transmission in the United States include the continued increase of HIV infection among women of childbearing age; absent or delayed prenatal care, particularly in women using illicit drugs; acute (primary) infection in late pregnancy and in women who are breastfeeding; poor adherence to prescribed ARV regimens among pregnant women; and lack of full implementation of routine, universal prenatal HIV counseling and testing [10].
Following the results of PACTG 076, researchers began to explore the development of shorter, less expensive prophylactic regimens more applicable to resource-constrained settings. Clinical trials initially focused on shortened zidovudine-alone prophylaxis regimens and moved to evaluating whether combination ARV regimens, such as short-course zidovudine combined with lamivudine, might have improved efficacy over zidovudine alone. Studies also evaluated whether even simpler, less expensive, single-drug regimens, such as single-dose intrapartum/neonatal nevirapine, would be effective and whether combining such regimens with other short-course regimens might result in improved efficacy. These studies have provided important insights into the mechanisms of action of ARV drugs in reducing perinatal transmission and in determining optimal regimens for use in the United States and other resource-rich countries.
References
1. Connor EM, Sperling RS, Gelber R, et al. Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. Pediatric AIDS Clinical Trials Group Protocol 076 Study Group. N Engl J Med. 1994 Nov 3;331(18):1173-1180.
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. Wortley PM, Lindegren ML, Fleming PL. Successful implementation of perinatal HIV prevention guidelines. A multistate surveillance evaluation. MMWR Recomm Rep. 2001 May 11;50(RR-6):17-28.
4. Centers for Disease Control and Prevention (CDC). Achievements in public health. Reduction in perinatal transmission of HIV infection--United States, 1985-2005. MMWR Morb Mortal Wkly Rep. 2006 Jun 2;55(21):592-597.
5. European Collaborative Study. HIV-infected pregnant women and vertical transmission in Europe since 1986. European Collaborative Study. AIDS. 2001;15(6):761-770.
6. Mandelbrot L, Landreau-Mascaro A, Rekacewicz C, et al. Lamivudine-zidovudine combination for prevention of maternal-infant transmission of HIV-1. JAMA. 2001 Apr 25;285(16):2083-2093.
7. Dorenbaum A, Cunningham CK, Gelber RD, et al. Two-dose intrapartum/newborn nevirapine and standard antiretroviral therapy to reduce perinatal HIV transmission: a randomized trial. JAMA. 2002 Jul 10;288(2):189-198.
8. McKenna MT, Hu X. Recent trends in the incidence and morbidity that are associated with perinatal human immunodeficiency virus infection in the United States. Am J Obstet Gynecol. 2007 Sep;197(3 Suppl):S10-16.
9. Peters V, Liu KL, Gill B, et al. Missed opportunities for perinatal HIV prevention among HIV-exposed infants born 1996-2000, pediatric spectrum of HIV disease cohort. Pediatrics. 2004 Sep;114(3):905-906.
10. Mofenson LM. Successes and challenges in the perinatal HIV-1 epidemic in the United States as illustrated by the HIV-1 Serosurvey of childbearing women. Arch Pediatr Adolesc Med. 2004 May;158(5):422-425.