General Principles Regarding Use of Antiretroviral Drugs during Pregnancy
Rating of Recommendations: A = Strong; B = Moderate; C = Optional
In addition to the standard antenatal assessments for all pregnant women, the initial evaluation of women with HIV should include an 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 count;
- Current plasma HIV RNA level;
- Assessment of the need for prophylaxis against opportunistic infections, such as Pneumocystis jirovecii pneumonia (see the 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), see Hepatitis B Virus/HIV Coinfection and Hepatitis C Virus/HIV Coinfection;
- Screening for and treatment of sexually transmitted infections (STIs), such as syphilis, Chlamydia trachomatis, Trichomonas vaginalis, and Neisseria gonorrhea;1-3
- Assessment of the need for HAV, HBV, influenza, pneumococcus, and Tdap immunizations;4,5
- Complete blood cell count and renal and liver function testing;
- HLA-B*5701 testing, if the use of abacavir is anticipated (see Table 10);
- History of prior and current antiretroviral (ARV) drug use, including prior ARV drug use for the prevention of perinatal transmission or treatment of HIV;
- Assessment of the patient’s self-affirmed gender identify, preferred pronouns, use of gender-affirming hormonal therapy, and potential interactions with ARV (see Transgender People with HIV);
- History of adherence problems;
- Results of prior and current ARV drug-resistance tests;
- History of adverse effects or toxicities caused by previous ARV regimens;
- Screening for depression and anxiety (see Screening for Perinatal Depression);6
- Assessment of the need for supportive care (e.g., social services, mental health services, substance use disorder treatment services, smoking cessation services), as well as support to help ensure lifelong adherence to antiretroviral therapy (ART);
- Screening for intimate partner violence and assessment of the need for interventions or referrals for supportive care;
- Assessing the HIV status of sexual partner(s) and referral of partner(s) for HIV testing and ARV treatment or prophylaxis as needed (see Pre-Exposure Prophylaxis [PrEP] to Reduce the Risk of Acquiring HIV During Periconception, Antepartum, and Postpartum Periods); and
- Referral of children for HIV testing.
The National Perinatal HIV Hotline
The National Perinatal HIV Hotline (1-888-448-8765) is a federally funded service that provides free clinical consultation to providers who are caring for women with HIV and their infants.
How Antiretroviral Drugs Prevent Perinatal Transmission and Improve Maternal Health
All pregnant women with HIV should receive ART early in pregnancy, regardless of their viral load or CD4 count, to maximize their health and to prevent perinatal HIV transmission and secondary sexual transmission. ARV drugs are important for maintaining maternal health, because they decrease the rate of HIV disease progression, reduce the risk of opportunistic disease, and reduce the risk of maternal death.
ARV drugs reduce the risk of perinatal transmission of HIV in all pregnant women, regardless of their CD4 counts and HIV RNA levels. ARV drugs can reduce the risk of perinatal transmission through several mechanisms. Antenatal drug administration decreases maternal viral load in blood and genital secretions.7-9 Strict adherence to an ARV regimen is needed to achieve rapid and sustained viral suppression and minimize the risk of perinatal transmission. Although the risk of perinatal transmission in women with undetectable plasma HIV RNA levels appears to be extremely low, perinatal transmission has been reported among women on ART (see Recommendations for Use of Antiretroviral Drugs During Pregnancy).10-13 Studies have reported low-level cervicovaginal HIV RNA and DNA shedding in women who were on ART and who had undetectable plasma viral loads.14-16 Penetration of ARV drugs into the female genital tract varies by drug.17-20
Infant pre-exposure prophylaxis should also be used to prevent perinatal transmission, because maternal viremia is not the only risk factor for perinatal HIV transmission. Pre-exposure prophylaxis is achieved by administering ARV drugs to the mother that cross the placenta and produce adequate systemic drug levels in the fetus. In addition, infant post-exposure prophylaxis is achieved by administering ARV 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 the risk of perinatal transmission is demonstrated by the reduced efficacy of interventions that involve administration of ARV drugs only during labor and/or to the newborns.21-28 Therefore, using a combination of 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 the current regimen with the addition of intravenous zidovudine (if indicated, based on the most recent maternal plasma viral load), and infant ARV prophylaxis or presumptive HIV therapy is recommended to prevent perinatal transmission of HIV.
General Principles of Drug Selection
In general, the recommendations for the use of ART in pregnant women are the same as those for women who are not pregnant. However, the Perinatal Guidelines may differ from the Adult and Adolescent Antiretroviral Guidelines in some instances where regimen selection has been modified based on concerns about specific drugs or limited experience with newer drugs during pregnancy (see Table 4 and Recommendations for Use of Antiretroviral Drugs During Pregnancy).
Clinicians and patients should discuss the substantial benefits of ARV drugs for maternal health and for reducing the risk of transmission of HIV to infants; this helps put the potential risks of using these drugs into perspective (see Table 10 and Appendix B: Supplement: Safety and Toxicity of Individual Antiretroviral Agents in Pregnancy). Counseling of pregnant women about ARV drug use should be directive and noncoercive, and providers should help women make informed decisions regarding the use of ARV drugs.
Discussions with women about initiation of ARV regimens should include information about the following:
- Maternal risk of disease progression and the benefits and risks of therapy for maternal health;29
- The benefits of ART for preventing perinatal transmission of HIV;11
- The benefits of using ART to achieve and maintain viral suppression, which reduces the risk of sexual transmission to partners who do not have HIV;30
- The need for strict adherence to the prescribed drug regimen to avoid resistance, optimize health outcomes, and minimize the risk of perinatal HIV transmission;
- The potential adverse effects of ARV drugs for women, fetuses, and infants, including potential interactions with other medications the women may already be receiving (see Recommendations for Use of Antiretroviral Drugs During Pregnancy);31-34 and
- The limited long-term outcome data for infants who were exposed to ARV drugs in utero, especially for newer ARV drugs.
In pregnant women with HIV who are not currently receiving treatment, plasma HIV RNA levels should be measured, and ART should be initiated. In women with plasma HIV RNA levels above the threshold for standard genotypic resistance testing (i.e., >500 copies/mL to 1,000 copies/mL), ARV drug-resistance testing should be sent for analysis before starting ART; however, ART should be initiated before results of drug-resistance testing are available, because earlier viral suppression is associated with a lower risk of perinatal transmission.35,36 The ARV regimen can be modified, if necessary, based on resistance assay results37 (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 and support the effectiveness of ART in achieving viral suppression. Women with poor adherence during pregnancy are more likely to have detectable viral loads at delivery.38
Transplacental passage of ARV drugs is thought to be an important mechanism of infant pre-exposure prophylaxis. Thus, when selecting a regimen for a pregnant woman, ARVs with high placental transfer should be included as a component of the ARV regimen (see Table 10).39-43
Patient Counseling and Coordination of Care
Coordination of services among prenatal care providers, primary care and HIV specialty care providers, mental health and substance use disorder treatment services, social services, and public assistance programs is essential to ensure that women with HIV are well supported during all stages of their pregnancies and during the postpartum period. Medical care of pregnant women with HIV requires coordination and communication between HIV specialists and obstetric providers. General counseling should include current knowledge about risk factors for perinatal HIV transmission. Risk of perinatal transmission of HIV has been associated with potentially modifiable factors, including cigarette smoking, substance use disorders, and genital tract infections. Besides improving maternal health, cessation of cigarette smoking and drug use and treatment of STIs and other genital tract infections may reduce the risk of perinatal transmission. Women should be screened for mental health conditions, assessed for the risk of intimate partner violence, and counseled about disclosure of their HIV status when needed.44 It is important to be aware that COVID-19 may increase the risk of depression, substance use, and intimate partner violence at a time when the frequency of in-person health care services has decreased (see Interim Guidance for COVID-19 and Persons with HIV). Fears of stigma and violence that could result from disclosure require comprehensive culturally informed services to assist pregnant and postpartum women planning to disclose their status,45,46 and women who have not disclosed their status require support to maintain privacy during telemedicine visits. Transgender and non-binary individuals may have specific concerns, particularly regarding interactions of ARV drugs with gender affirming-hormones, that should be assessed and addressed.
In addition, providers should counsel women with HIV about what to expect during labor, delivery, and the postnatal period. This includes discussing the mode of delivery and the possible use of intrapartum zidovudine, as well as family planning and contraceptive options during the postpartum period. Providers should also discuss the possibility of simplifying a woman’s ARV regimen after delivery, which can help promote long-term adherence to ART. Discussions regarding the prevention of postnatal transmission to the neonate should also include recommendations about infant feeding, neonatal ARV prophylaxis, infant diagnostic HIV testing, and the avoidance of premastication of food (see Counseling and Managing Women with HIV in the United States Who Desire to Breastfeed).
- 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: https://www.ncbi.nlm.nih.gov/pubmed/26372927.
- Sivarajah V, Venus K, Yudin MH, Murphy KE, Morrison SA, Tan DH. Does maternal HSV-2 coinfection increase mother-to-child transmission of HIV? a systematic review. Sex Transm Infect. 2017;93(8):535-542. Available at: https://www.ncbi.nlm.nih.gov/pubmed/28600331.
- Workowski KA, Bolan GA, Centers for Disease Control Prevention. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015;64(RR-03):1-137. Available at: https://www.ncbi.nlm.nih.gov/pubmed/26042815.
- 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: https://www.ncbi.nlm.nih.gov/pubmed/24311479.
- Centers for Disease Control and Prevention. Guidelines for vaccinating pregnant women. 2017. Available at: https://www.cdc.gov/vaccines/pregnancy/hcp/guidelines.html.
- American College of Obstetricians and Gynecologists. ACOG committee opinion no. 757: screening for perinatal depression. Obstet Gynecol. 2018;132(5):e208-e212. Available at: https://www.ncbi.nlm.nih.gov/pubmed/30629567.
- Pilotto JH, Velasque LS, Friedman RK, et al. Maternal outcomes after HAART for the prevention of mother-to-child transmission in HIV-infected women in Brazil. Antivir Ther. 2011;16(3):349-356. Available at: https://www.ncbi.nlm.nih.gov/pubmed/21555817.
- Becquet R, Bland R, Ekouevi DK, Dabis F, Newell ML. Universal antiretroviral therapy among pregnant and postpartum HIV-infected women would improve maternal health and decrease postnatal HIV transmission. AIDS. 2010;24(8):1239-1241. Available at: https://www.ncbi.nlm.nih.gov/pubmed/20421749.
- Becquet R, Ekouevi DK, Arrive E, et al. Universal antiretroviral therapy for pregnant and breast-feeding HIV-1-infected women: towards the elimination of mother-to-child transmission of HIV-1 in resource-limited settings. Clin Infect Dis. 2009;49(12):1936-1945. Available at: https://www.ncbi.nlm.nih.gov/pubmed/19916796.
- 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: https://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: https://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: https://www.ncbi.nlm.nih.gov/pubmed/15668871.
- Raffe SF, Savage C, Perry LA, et al. The management of HIV in pregnancy: a 10-year experience. Eur J Obstet Gynecol Reprod Biol. 2017;210:310-313. Available at: https://www.ncbi.nlm.nih.gov/pubmed/28110176.
- 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: https://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: https://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: https://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: https://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: https://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: https://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: https://www.ncbi.nlm.nih.gov/pubmed/13678973.
- 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;359(9313):1178-1186. Available at: https://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: https://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: https://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: https://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: https://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. Available at: https://www.ncbi.nlm.nih.gov/pubmed/22716975
- Scott GB, Brogly SB, Muenz D, Stek AM, Read JS, International Maternal Pediatric Adolescent AIDS Clinical Trials Group P. Study Team. Missed opportunities for prevention of mother-to-child transmission of human immunodeficiency virus. Obstet Gynecol. 2017;129(4):621-628. Available at: https://www.ncbi.nlm.nih.gov/pubmed/28277349.
- INSIGHT START Study Group, Lundgren JD, Babiker AG, et al. Initiation of antiretroviral therapy in early asymptomatic HIV infection. N Engl J Med. 2015;373(9):795-807. Available at: https://www.ncbi.nlm.nih.gov/pubmed/26192873.
- 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: https://www.ncbi.nlm.nih.gov/pubmed/21767103.
- Grignolo S, Agnello R, Gerbaldo D, et al. Pregnancy and neonatal outcomes among a cohort of HIV-infected women in a large Italian teaching hospital: a 30-year retrospective study. Epidemiol Infect. 2017;145(8):1658-1669. Available at: https://www.ncbi.nlm.nih.gov/pubmed/28325171.
- Harrington B, Phulusa J, Melhado C, et al. Incidence of hepatotoxicity among HIV-positive pregnant women initiating efavirenz-based ART through option B+ in Malawi. Presented at: International AIDS Society. 2017. Paris, France.
- Stringer EM, Kendall MA, Lockman S, et al. Pregnancy outcomes among HIV-infected women who conceived on antiretroviral therapy. PLoS One. 2018;13(7):e0199555. Available at: https://www.ncbi.nlm.nih.gov/pubmed/30020964.
- Theron G, Brummel S, Fairlie L, et al. Pregnancy outcomes of women conceiving on antiretroviral therapy (ART) compared to those commenced on ART during pregnancy. Clin Infect Dis. 2020;ciaa805. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32564058.
- 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;61(11):1715-1725. Available at: https://www.ncbi.nlm.nih.gov/pubmed/26197844.
- Favarato G, Bailey H, Burns F, Prieto L, Soriano-Arandes A, Thorne C. Migrant women living with HIV in Europe: are they facing inequalities in the prevention of mother-to-child-transmission of HIV?: the European pregnancy and paediatric HIV cohort collaboration (EPPICC) study group in EuroCoord. Eur J Public Health. 2017;28(1):55-60. Available at: https://www.ncbi.nlm.nih.gov/pubmed/28449111.
- 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: https://www.ncbi.nlm.nih.gov/pubmed/21499113.
- Katz IT, Leister E, Kacanek D, et al. Factors associated with lack of viral suppression at delivery among highly active antiretroviral therapy-naive women with HIV: a cohort study. Ann Intern Med. 2015;162(2):90-99. Available at: https://www.ncbi.nlm.nih.gov/pubmed/25599347.
- 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: https://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: https://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: https://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: https://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: https://www.ncbi.nlm.nih.gov/pubmed/25223699.
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General Principles Regarding Use of Antiretroviral Drugs during Pregnancy
Rating of Recommendations: A = Strong; B = Moderate; C = Optional