Recommendations for the Use of Antiretroviral Drugs in Pregnant Women with HIV Infection and Interventions to Reduce Perinatal HIV Transmission in the United States
The information in the brief version is excerpted directly from the full-text guidelines. The brief version is a compilation of the tables and boxed recommendations.
General Principles Regarding Use of Antiretroviral Drugs during Pregnancy
Last Updated: November 14, 2017; Last Reviewed: November 14, 2017
|Rating of Recommendations: A = Strong; B = Moderate; C = Optional
Rating of Evidence: I = One or more randomized trials with clinical outcomes and/or validated laboratory endpoints; II = One or more well-designed, nonrandomized trials or observational cohort studies with long-term clinical outcomes; III = Expert opinion
In addition to the standard antenatal assessments for all pregnant women, the initial evaluation of women living with HIV should include assessment of HIV disease status, and recommendations for HIV-related medical care. This initial assessment should include the following:
- Review of prior HIV-related illnesses and past CD4 T lymphocyte (CD4) cell counts and plasma HIV RNA levels;
- Current CD4 cell count;
- Current plasma HIV RNA level;
- Assessment of the need for prophylaxis against opportunistic infections such as Pneumocystis jirovecii pneumonia and Mycobacterium avium complex (see Adult and Adolescent Opportunistic Infections Guidelines);
- Screening for hepatitis A virus (HAV), hepatitis C virus, and tuberculosis in addition to standard screening for hepatitis B virus (HBV) infection;
- Screening for and treatment of sexually transmitted infections such as syphilis, Chlamydia trachomatis and Neisseria gonorrhea and trichomonas;1,2
- Assessment of the need for immunizations per guidelines from the American College of Obstetricians and Gynecologists, the Centers for Disease Control and Prevention (CDC), and the Infectious Diseases Society of America with particular attention to HAV, HBV, influenza, pneumococcus, and Tdap immunizations;3,4
- Complete blood cell count and renal and liver function testing;
- HLA-B*5701 testing if abacavir use is anticipated (see Table 9);
- History of prior and current antiretroviral (ARV) drug use, including prior ARV use for prevention of perinatal transmission or treatment of HIV and history of adherence problems;
- Results of prior and current ARV drug-resistance studies;
- History of adverse effects or toxicities from prior ARV regimens;
- Assessment of supportive care needs (e.g., mental health services, substance abuse treatment, smoking cessation), as well as support to help ensure lifelong antiretroviral therapy (ART);
- Intimate partner violence-related screening and supportive care needs;
- Referral of sexual partner(s) for HIV testing and ARV treatment or prophylaxis; and
- Referral of children for HIV testing
The National Perinatal HIV Hotline
The National Perinatal HIV Hotline (888-448-8765) is a federally funded service providing free clinical consultation to providers caring for women living with HIV and their infants.
How Antiretrovirals Prevent Perinatal Transmission
ARV drugs reduce the risk of perinatal transmission of HIV in all pregnant women, regardless of CD4 cell counts and HIV RNA levels. ARV drugs can reduce perinatal transmission through a number of mechanisms. Antenatal drug administration decreases maternal viral load in blood and genital secretions. Although the risk of perinatal transmission in women with undetectable plasma HIV RNA levels appears to be extremely low, it has been reported even among women on antiretroviral therapy (ART).5-7 Low-level cervicovaginal HIV RNA and DNA shedding has been detected even in women treated with ART who have undetectable plasma viral load.8-10 Penetration of ARV drugs into the female genital tract varies by drug.11-13,14 Because maternal viremia is not the only risk factor for HIV transmission, another important mechanism of protection is infant pre-exposure prophylaxis achieved by maternal administration of ARV drugs that cross the placenta and produce adequate systemic drug levels in the fetus. In addition, infant post-exposure prophylaxis is achieved by administering drugs to the infant after birth, providing protection from cell-free or cell-associated virus that may have entered the fetal/infant systemic circulation during labor and delivery. The importance of the pre- and post-exposure components of prophylaxis in reducing perinatal transmission is demonstrated by the reduced efficacy of interventions that involve administration of ARVs only during labor and/or to the newborns.15-21 Therefore, combined preconception ART, confirmation of antepartum plasma viral load suppression, scheduled surgical delivery (if indicated, based on most recent maternal plasma viral load), intrapartum continuation of current regimen with addition of intravenous zidovudine (if indicated, based on the most recent maternal plasma viral load), and infant ARV prophylaxis are all recommended to prevent perinatal transmission of HIV.
General Principles of Drug Selection
In general, guidelines for the use of ART for the benefit of maternal health during pregnancy are the same as for women who are not pregnant, with some modifications in regimen selection based on concerns about specific drugs or limited experience with newer drugs during pregnancy, where the perinatal guidelines may differ from the adult guidelines.
The known benefits and known and unknown risks of ARV drug use during pregnancy should be considered and discussed with women (see Table 9 and Supplement: Safety and Toxicity of Individual Antiretroviral Agents in Pregnancy). Potential risks of these drugs should be placed into perspective by reviewing the substantial benefits of ARV drugs for maternal health and for reducing the risk of transmission of HIV to infants. Counseling of pregnant women about ARV use should be directive and non-coercive, and providers should help women make informed decisions regarding use of ARV drugs.
Discussions with women about initiation of ART regimens should include information about:
- Maternal risk of disease progression and benefits and risks of initiation of therapy for maternal health;
- Benefit of ART for preventing perinatal transmission of HIV;6
- Benefits of therapy for reducing sexual transmission to partners who do not have HIV when viral suppression is maintained;22
- The need for strict adherence to the prescribed drug regimen to avoid resistance;
- Potential adverse effects of ARV drugs for mothers, fetuses, and infants, including potential interactions with other medications the women may already be receiving (see Recommendations for use of ARVs during Pregnancy); and
- The limited long-term outcome data after in utero drug exposure, especially for new antiretrovirals.
Transplacental passage of ARV drugs is thought to be an important mechanism of infant pre-exposure prophylaxis. Thus, when selecting an ARV regimen for a pregnant woman, at least one nucleoside/nucleotide reverse transcriptase inhibitor agent with high placental transfer should be included as a component of the ART regimen (see Table 9).23-27
In women with plasma HIV RNA levels above the threshold for resistance testing (i.e., >500 to 1,000 copies/mL), ARV drug-resistance studies should be performed before starting ART. However, in pregnant women not already receiving ART, ART should be initiated while awaiting results of genotype resistance testing because earlier viral suppression is associated with lower risk of perinatal transmission.28 The ART regimen can be modified, if necessary, based on resistance assay results29 (see Antiretroviral Drug Resistance and Resistance Testing in Pregnancy). Counseling should emphasize the importance of adherence to the ARV drug regimen to minimize the development of resistance.
All pregnant women living with HIV should initiate or continue ART during pregnancy to minimize the risk of transmission of HIV to their infants and partners. Providers should begin to counsel women living with HIV about what they can expect during labor and delivery and the postnatal period. This includes discussions about the mode of delivery, possible intrapartum zidovudine, as well as family planning and contraceptive options in the postpartum period. Providers should also discuss possible changes to the pregnant woman’s ART regimen post-delivery, because lifelong ART is recommended for all individuals living with HIV. In addition, discussions regarding prevention of postnatal transmission to the neonate should include recommendations about infant feeding, neonatal ARV prophylaxis, infant diagnostic HIV testing, and the avoidance of premastication of food.
Medical care of pregnant women living with HIV requires coordination and communication between HIV specialists and obstetric providers. General counseling should include current knowledge about risk factors for perinatal transmission. Risk of perinatal transmission of HIV has been associated with potentially modifiable factors, including cigarette smoking, illicit drug use, and genital tract infections. Besides improving maternal health, cessation of cigarette smoking and drug use, treatment of sexually transmitted and other genital tract infections may reduce risk of perinatal transmission. Women should be assessed for mental health concerns and the risk of intimate partner violence and referred to appropriate services (i.e., depending on a woman’s individual circumstances). Coordination of services among prenatal care providers, primary care and HIV specialty care providers, mental health and drug abuse treatment services, and public assistance programs is essential to ensure that women living with HIV adhere to their ARV drug regimens.
- Adachi K, Klausner JD, Bristow CC, et al. Chlamydia and gonorrhea in HIV-infected pregnant women and infant HIV transmission. Sex Transm Dis. 2015;42(10):554-565. Available at http://www.ncbi.nlm.nih.gov/pubmed/26372927.
- American College of Obstetricinas and Gynecologists' Committee on Practice Bulletins—Obstetrics. Practice Bulletin No. 170: Critical care in pregnancy. Obstet Gynecol. 2016;128(4):e147-154. Available at https://www.ncbi.nlm.nih.gov/pubmed/27661653.
- Rubin LG, Levin MJ, Ljungman P, et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis. 2014;58(3):e44-100. Available at http://www.ncbi.nlm.nih.gov/pubmed/24311479.
- Centers for Disease Control and Prevention. Guidelines for vaccinating pregnant women, hepatitis A. 2014. Available at http://www.cdc.gov/vaccines/pubs/preg-guide.htm#hepa. Accessed October 20, 2017.
- Warszawski J, Tubiana R, Le Chenadec J, et al. Mother-to-child HIV transmission despite antiretroviral therapy in the ANRS French Perinatal Cohort. AIDS. 2008;22(2):289-299. Available at http://www.ncbi.nlm.nih.gov/pubmed/18097232.
- Tubiana R, Le Chenadec J, Rouzioux C, et al. Factors associated with mother-to-child transmission of HIV-1 despite a maternal viral load <500 copies/ml at delivery: a case-control study nested in the French perinatal cohort (EPF-ANRS CO1). Clin Infect Dis. 2010;50(4):585-596. Available at http://www.ncbi.nlm.nih.gov/pubmed/20070234.
- European Collaborative Study. Mother-to-child transmission of HIV infection in the era of highly active antiretroviral therapy. Clin Infect Dis. 2005;40(3):458-465. Available at http://www.ncbi.nlm.nih.gov/pubmed/15668871.
- Launay O, Tod M, Tschope I, et al. Residual HIV-1 RNA and HIV-1 DNA production in the genital tract reservoir of women treated with HAART: the prospective ANRS EP24 GYNODYN study. Antivir Ther. 2011;16(6):843-852. Available at http://www.ncbi.nlm.nih.gov/pubmed/21900716.
- Cu-Uvin S, DeLong AK, Venkatesh KK, et al. Genital tract HIV-1 RNA shedding among women with below detectable plasma viral load. AIDS. 2010;24(16):2489-2497. Available at http://www.ncbi.nlm.nih.gov/pubmed/20736815.
- Henning TR, Kissinger P, Lacour N, Meyaski-Schluter M, Clark R, Amedee AM. Elevated cervical white blood cell infiltrate is associated with genital HIV detection in a longitudinal cohort of antiretroviral therapy-adherent women. J Infect Dis. 2010;202(10):1543-1552. Available at http://www.ncbi.nlm.nih.gov/pubmed/20925530.
- Yeh RF, Rezk NL, Kashuba AD, et al. Genital tract, cord blood, and amniotic fluid exposures of seven antiretroviral drugs during and after pregnancy in human immunodeficiency virus type 1-infected women. Antimicrob Agents Chemother. 2009;53(6):2367-2374. Available at http://www.ncbi.nlm.nih.gov/pubmed/19307360.
- Dumond JB, Yeh RF, Patterson KB, et al. Antiretroviral drug exposure in the female genital tract: implications for oral pre- and post-exposure prophylaxis. AIDS. 2007;21(14):1899-1907. Available at http://www.ncbi.nlm.nih.gov/pubmed/17721097.
- Else LJ, Taylor S, Back DJ, Khoo SH. Pharmacokinetics of antiretroviral drugs in anatomical sanctuary sites: the male and female genital tract. Antivir Ther. 2011;16(8):1149-1167. Available at http://www.ncbi.nlm.nih.gov/pubmed/22155899.
- Drake A, Kinuthia J, Materno D, et al. Plasma and genital HIV decline on ART among pregnant/postpartum women with recent HIV infection. Presented at: International AIDS Conference. 2016. Durban, South Africa.
- 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;362(9387):859-868. Available at http://www.ncbi.nlm.nih.gov/pubmed/13678973.
- Petra Study T. 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;359(9313):1178-1186. Available at http://www.ncbi.nlm.nih.gov/pubmed/11955535.
- 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;187(5):725-735. Available at http://www.ncbi.nlm.nih.gov/pubmed/12599045.
- 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;362(9391):1171-1177. Available at http://www.ncbi.nlm.nih.gov/pubmed/14568737.
- 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;35(2):178-187. Available at http://www.ncbi.nlm.nih.gov/pubmed/14722452.
- 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;19(12):1289-1297. Available at http://www.ncbi.nlm.nih.gov/pubmed/16052084.
- Nielsen-Saines K, Watts H, Veloso VG, et al. Phase III randomized trial of the safety and efficacy of three neonatal antiretroviral postpartum regimens for the prevention of intrapartum HIV-1 transmission: NICHD HPTN 040/PACTG 1043 study results. N Engl J Med. 2012.
- Cohen MS, Chen YQ, McCauley M, et al. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med. 2011;365(6):493-505. Available at http://www.ncbi.nlm.nih.gov/pubmed/21767103.
- Hirt D, Urien S, Rey E, et al. Population pharmacokinetics of emtricitabine in human immunodeficiency virus type 1-infected pregnant women and their neonates. Antimicrob Agents Chemother. 2009;53(3):1067-1073. Available at http://www.ncbi.nlm.nih.gov/pubmed/19104016.
- Hirt D, Urien S, Ekouevi DK, et al. Population pharmacokinetics of tenofovir in HIV-1-infected pregnant women and their neonates (ANRS 12109). Clin Pharmacol Ther. 2009;85(2):182-189. Available at http://www.ncbi.nlm.nih.gov/pubmed/18987623.
- Moodley D, Pillay K, Naidoo K, et al. Pharmacokinetics of zidovudine and lamivudine in neonates following coadministration of oral doses every 12 hours. J Clin Pharmacol. 2001;41(7):732-741. Available at http://www.ncbi.nlm.nih.gov/pubmed/11452705.
- Wade NA, Unadkat JD, Huang S, et al. Pharmacokinetics and safety of stavudine in HIV-infected pregnant women and their infants: Pediatric AIDS Clinical Trials Group protocol 332. J Infect Dis. 2004;190(12):2167-2174. Available at http://www.ncbi.nlm.nih.gov/pubmed/15551216.
- McCormack SA, Best BM. Protecting the fetus against HIV infection: a systematic review of placental transfer of antiretrovirals. Clin Pharmacokinet. 2014;53(11):989-1004. Available at http://www.ncbi.nlm.nih.gov/pubmed/25223699.
- Mandelbrot L, Tubiana R, Le Chenadec J, et al. No perinatal HIV-1 transmission from women with effective antiretroviral therapy starting before conception. Clin Infect Dis. 2015. Available at http://www.ncbi.nlm.nih.gov/pubmed/26197844.
- Tariq S, Townsend CL, Cortina-Borja M, et al. Use of zidovudine-sparing HAART in pregnant HIV-infected women in Europe: 2000-2009. J Acquir Immune Defic Syndr. 2011;57(4):326-333. Available at http://www.ncbi.nlm.nih.gov/pubmed/21499113.