Recommendations for the Use of Antiretroviral Drugs During Pregnancy and Interventions to Reduce Perinatal HIV Transmission in the United States

Recommendations for the Use of Antiretroviral Drugs During Pregnancy

Use of Antiretroviral Drugs to Prevent Perinatal HIV Transmission and Improve Health for Pregnant People

All pregnant people with HIV should receive antiretroviral therapy (ART) early in pregnancy, preferably prior to conception, regardless of their viral load or CD4 T lymphocyte (CD4) count, to maximize their health and to prevent perinatal HIV transmission and secondary sexual transmission (see Recommendations for Use of Antiretroviral Drugs During Pregnancy: Overview). Antiretroviral (ARV) drugs are important for maintaining health before, during, and after pregnancy because they decrease the rate of HIV disease progression, reduce the risk of opportunistic diseases, and reduce the risk of death.¹ Use of an ARV regimen that successfully reduces plasma HIV RNA to undetectable levels substantially lowers the risk of vertical transmission of HIV to <1%, improves pregnancy outcomes, minimizes the need to consider elective cesarean delivery as an intervention to reduce the risk of transmission, and reduces the risk of ARV drug resistance.

ARV drugs reduce the risk of perinatal transmission of HIV in all pregnant people, regardless of their CD4 counts and HIV RNA levels, through several mechanisms. Antenatal drug administration decreases viral load in blood and genital secretions.^2-4 Early and sustained control of HIV viral replication with a suppressed viral load at the time of delivery markedly reduces the risk of perinatal HIV transmission. In the prospective multicenter French Perinatal Cohort, both maternal viral load at delivery and the timing of ART initiation were independently associated with perinatal HIV transmission rate.⁵ Among women treated at conception who had detectable viral load near delivery, transmission risk was 1.08% (95% confidence interval [CI], 0.049–2.04), but among women treated at conception with undetectable viral load near delivery, there were no infections in 5,482 infants (95% CI, 0.00–0.07).⁶ Other studies have similarly found lack of early and sustained viremic control to be strongly associated with increased risk of perinatal HIV transmission.^7,8 

In addition, several studies have found that higher viral load during pregnancy is associated with adverse pregnancy outcomes, including preterm birth and pregnancy loss through miscarriage or stillbirth.^9,10 These data suggest that ideally, ART should be initiated and viral suppression should be achieved prior to conception. When not started prior to conception, ART should be initiated as early as possible in pregnant people. Prompt initiation of ART is particularly important in pregnant people with acute HIV infection or who have high baseline viral loads.^11-14

Antenatal drug administration also provides infant pre-exposure prophylaxis (PrEP); this is important because viremia during pregnancy is not the only risk factor for perinatal HIV transmission and ART use during pregnancy reduces vertical transmission.^7,15-17 Infant PrEP is achieved by administering ARV drugs during pregnancy that cross the placenta and produce adequate drug levels that prevent HIV acquisition by inhibiting viral replication in the fetus. This is particularly important during the birth process, when there can be extensive viral exposure during passage through the birth canal. All Preferred nucleoside reverse transcriptase inhibitors—as well as integrase strand transfer inhibitors, such as dolutegravir and raltegravir—are known to have high transplacental passage (see Table 14. Antiretroviral Drug Use in Pregnant People With HIV: Pharmacokinetic and Toxicity Data in Human Pregnancy and Recommendations for Use in Pregnancy).^18-22

ARV drugs administered to the infant after birth provide post-exposure prophylaxis by providing protection from cell-free or cell-associated virus that may have entered the fetal/infant systemic circulation during labor and delivery (see Antiretroviral Management of Newborns with Perinatal HIV Exposure or HIV Infection).²³ The importance of the pre- and post-exposure components of prophylaxis in reducing the risk of perinatal HIV transmission is demonstrated by the lower efficacy of interventions that involve administration of ARV drugs only during labor and/or as a single dose to the newborn compared to regimens that include postnatal infant antiretroviral medications.^24-31

In conclusion, the most effective way to prevent perinatal transmission of HIV is (1) to begin ART as early as possible in pregnancy (ideally before conception) to achieve antepartum plasma viral load suppression as quickly as possible and to provide infant PrEP, (2) to maintain viral suppression throughout pregnancy, and (3) to provide infant ARV post-exposure prophylaxis or presumptive HIV therapy appropriate to their risk of HIV acquisition to reduce the risk of peri-partum transmission. Information about the historical context of perinatal HIV prevention is available in the Archived Guidelines (see Appendix A: Review of Clinical Trials of Antiretroviral Interventions to Prevent Perinatal HIV Transmission in the guidelines archived on January 31, 2024).

References

1. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in adults and adolescents with HIV. 2023. Available at: https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/whats-new.
2. 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://pubmed.ncbi.nlm.nih.gov/19916796.
3. 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://pubmed.ncbi.nlm.nih.gov/20421749.
4. 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://pubmed.ncbi.nlm.nih.gov/21555817.
5. 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://pubmed.ncbi.nlm.nih.gov/26197844.
6. Sibiude J, Le Chenadec J, Mandelbrot L, et al. Update of perinatal HIV-1 transmission in France: zero transmission for 5,482 mothers on continuous ART from conception and with undetectable viral load at delivery. Clin Infect Dis. 2022. Available at: https://pubmed.ncbi.nlm.nih.gov/36037040.
7. 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://pubmed.ncbi.nlm.nih.gov/20070234.
8. Forbes JC, Alimenti AM, Singer J, et al. A national review of vertical HIV transmission. AIDS. 2012;26(6):757-763. Available at: https://pubmed.ncbi.nlm.nih.gov/22210635.
9. Cates JE, Westreich D, Edmonds A, et al. The effects of viral load burden on pregnancy loss among HIV-infected women in the United States. Infect Dis Obstet Gynecol. 2015;2015:362357. Available at: https://pubmed.ncbi.nlm.nih.gov/26582966.
10. Albert AYK, Elwood C, Wagner EC, et al. Investigation of factors associated with spontaneous preterm birth in pregnant women living with HIV. AIDS. 2020;34(5):719-727. Available at: https://pubmed.ncbi.nlm.nih.gov/31895145.
11. Read PJ, Mandalia S, Khan P, et al. When should HAART be initiated in pregnancy to achieve an undetectable HIV viral load by delivery? AIDS. 2012;26(9):1095-1103. Available at: https://pubmed.ncbi.nlm.nih.gov/22441248.
12. Katz IT, Shapiro R, Li D, et al. Risk factors for detectable HIV-1 RNA at delivery among women receiving highly active antiretroviral therapy in the women and infants transmission study. J Acquir Immune Defic Syndr. 2010;54(1):27-34. Available at: https://pubmed.ncbi.nlm.nih.gov/20065861.
13. Aziz N, Sokoloff A, Kornak J, et al. Time to viral load suppression in antiretroviral-naive and -experienced HIV-infected pregnant women on highly active antiretroviral therapy: implications for pregnant women presenting late in gestation. BJOG. 2013;120(12):1534-1547. Available at: https://pubmed.ncbi.nlm.nih.gov/23924192.
14. Myer L, Phillips TK, McIntyre JA, et al. HIV viraemia and mother-to-child transmission risk after antiretroviral therapy initiation in pregnancy in Cape Town, South Africa. HIV Med. 2017;18(2):80-88. Available at: https://pubmed.ncbi.nlm.nih.gov/27353189.
15. 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://pubmed.ncbi.nlm.nih.gov/18097232.
16. 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://pubmed.ncbi.nlm.nih.gov/15668871.
17. 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://pubmed.ncbi.nlm.nih.gov/28110176.
18. 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://pubmed.ncbi.nlm.nih.gov/19104016.
19. 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://pubmed.ncbi.nlm.nih.gov/18987623.
20. 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://pubmed.ncbi.nlm.nih.gov/11452705.
21. 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://pubmed.ncbi.nlm.nih.gov/15551216.
22. 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://pubmed.ncbi.nlm.nih.gov/25223699.
23. Liu XI, Momper JD, Rakhmanina NY, et al. Physiologically based pharmacokinetic modeling framework to predict neonatal pharmacokinetics of transplacentally acquired emtricitabine, dolutegravir, and raltegravir. Clin Pharmacokinet. 2021;60(6):795-809. Available at: https://pubmed.ncbi.nlm.nih.gov/33527213.
24. 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://pubmed.ncbi.nlm.nih.gov/13678973.
25. 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://pubmed.ncbi.nlm.nih.gov/11955535.
26. 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://pubmed.ncbi.nlm.nih.gov/12599045.
27. 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://pubmed.ncbi.nlm.nih.gov/14568737.
28. 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://pubmed.ncbi.nlm.nih.gov/14722452.
29. 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://pubmed.ncbi.nlm.nih.gov/16052084.
30. 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.
31. Scott GB, Brogly SB, Muenz D, Stek AM, Read JS, International Maternal Pediatric Adolescent Aids Clinical Trials Group (IMPAACT) P1025 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://pubmed.ncbi.nlm.nih.gov/28277349.