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

Antepartum HIV Care

Overview

In addition to the standard antepartum assessments during pregnancy, intitial evaluations in the context of HIV should include an assessment of HIV disease status and recommendations for HIV-related medical care (see Recommendations for the Use of Antiretroviral Drugs During Pregnancy: Overview). See Initial Evaluation and Continued Monitoring of HIV-Related Assessments During Pregnancy and Laboratory Testing for Initial Assessment and Monitoring of People with HIV Receiving Antiretroviral Therapy for the recommended schedule of HIV-related laboratory tests during pregnancy. Initial assessment and ongoing care during pregnancy with HIV should include the following items (see Table 4. HIV-Related Antepartum Screenings and Assessments During Pregnancy):

• 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 B virus (HBV), hepatitis C virus (HCV), and tuberculosis (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^1-4; Repeat STI testing in the third trimester may be indicated based on individual risk factors or as required by state laws;
• Assessment of the need for HAV, HBV, influenza, pneumococcus, Tdap (tetanus, diphtheria, acellular pertussis), or SARS-CoV-2 immunizations (including boosters). Counseling on the importance of vaccinations during all pregnancies, and specifically during pregnancies with HIV, should be addressed and vaccinations provided when indicated^5-8; consideration of other vaccinations, such as for meningococcus, may be warranted based on individual patient considerations. Human papillomavirus vaccination may be indicated postpartum if not previously vaccinated;
• Complete blood cell count and renal and liver function testing;
• HLA-B*5701 testing, if the use of abacavir is anticipated (see Table 14. Antiretroviral Drug Use in Pregnancy: Pharmacokinetic and Toxicity Data in Human Pregnancy and Recommendations for Use in Pregnancy);
• History of prior or current antiretroviral (ARV) drug use or experience with adverse events or toxicities. Counseling should also address prior or anticipated challenges with adherence;
• Screening for depression and anxiety (see Screening and Diagnosis of Mental Health Conditions During Pregnancy and Postpartum), as well as for substance use disorders, and referral for mental health care services if indicated⁹;
• Assessment of the need for supportive care (e.g., social services, mental health services, substance use disorder treatment services, smoking cessation services, other community-based resources) for pregnancy-specific needs, as well as to help ensure lifelong adherence to antiretroviral therapy (ART);
• Screening for intimate partner violence (IPV) and assessment of the need for referrals for supportive care;
• Assessment of testosterone or other hormonal medications^10,11;
• Assessment of the HIV status of sexual partner(s) and referral of partner(s) for HIV testing and ART or prophylaxis as needed (see Pre-Exposure Prophylaxis [PrEP] to Prevent HIV During Periconception, Antepartum, and Postpartum Periods);
• Referral of children for HIV testing if HIV status is unknown; and
• Counseling about key intrapartum and postpartum considerations, including mode of delivery, lifelong HIV therapy, family planning and contraceptive options, infant feeding choices, infant ARV prophylaxis, and timing of infant diagnostic testing.

Prenatal Screening, Diagnosis, and Therapy

According to the American College of Obstetricians and Gynecologists (ACOG), prenatal genetic screening and diagnostic testing options should be discussed and offered for all pregnancies, regardless of age or risk of chromosomal abnormality. After review and discussion, every patient has the right to pursue or decline prenatal genetic screening and diagnostic testing.¹² Prenatal screening for aneuploidy should be offered using noninvasive methods with high sensitivity and low false-positive rates, as recommended by ACOG. Counseling on noninvasive genetic screening options is no different for people with HIV than for those without HIV. Noninvasive screening can be accomplished using either of the following: 

• Cell-free DNA screening with or without nuchal translucency; or
• Serum analyte screening alone or combined with nuchal translucency (sequential or integrated).

When there is desire for diagnostic testing or indications for diagnostic testing during pregnancy (e.g., abnormal ultrasound or aneuploidy screening), counseling should be provided about the potential risk of perinatal HIV transmission, along with other risks of the procedure, so that informed decisions can be made about invasive testing. Although the data on women who are receiving ART are limited, the risk of perinatal HIV transmission does not appear to increase with the use of amniocentesis or other invasive diagnostic procedures in women who have virologic suppression on ART.^13,14 This is in contrast to the era before effective ART, during which invasive procedures, such as amniocentesis and chorionic villus sampling, were associated with a twofold to fourfold increase in the risk of perinatal transmission of HIV.^15-18 Although no transmissions occurred among 159 reported cases of amniocentesis or other invasive diagnostic procedures performed in women who were on effective ART, a small increase in the risk of transmission cannot be ruled out.^19-22

At a minimum, effective ART should be recommended during pregnancy before undergoing any invasive prenatal testing. Patients ideally should have undetectable HIV RNA levels at the time of the procedure, and every effort should be made to avoid inserting the needle through, or very close to, the placenta. Families often make complex personal decisions about continuing a pregnancy after a prenatal diagnosis, and those decisions are made even more complex by evolving state laws regarding access to abortion. A patient-centered discussion regarding delaying diagnostic procedures to allow for viral suppression should also consider the impact of that delay on the options available to a patient for terminating a pregnancy, if that is something they are considering. If a patient with detectable HIV RNA levels requires invasive prenatal testing, consultation with an expert in the management of HIV during pregnancy should be considered (see Intrapartum HIV Care).

Fetal therapy is an area of maternal-fetal medicine in which insufficient data exist about the risk of HIV transmission through such procedures as selective fetoscopic laser photocoagulation, vesicoamniotic or thoracoamniotic shunts, intrauterine transfusions, in utero repair of neural tube defects, and other invasive procedures. In the absence of evidence to guide these decisions, it is recommended that patients with HIV who may require advanced care for fetal abnormalities receive consultation at specialized centers where they can receive coordinated, multidisciplinary counseling. As with the above discussion regarding prenatal diagnosis, it is recommended that individuals have achieved viral suppression prior to procedures.

The National Perinatal HIV Hotline

The National Clinical Consultation Center Perinatal HIV hotline (1-888-448-8765) is a federally funded service that provides free clinical consultation to providers managing HIV care during pregnancy and infancy.

ART Adherence Support During Pregnancy

In general, the recommendations for the use of ART during pregnancy are the same as for nonpregnant adults. However, the Perinatal Guidelines do 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 6. What to Start: Initial Antiretroviral Regimens During Pregnancy When Antiretroviral Therapy Has Never Been Received and Table 7. Situation-Specific Recommendations for Use of Antiretroviral Drugs During Pregnancy and When Trying to Conceive and Recommendations for Use of Antiretroviral Drugs During Pregnancy: Overview).

Clinicians should discuss the substantial benefits of ARV drugs for optimal health during pregnancy and for reducing the risk of perinatal HIV transmission; this helps put the potential risks of using these drugs into perspective (see Table 14. Antiretroviral Drug Use in Pregnancy: Pharmacokinetic and Toxicity Data in Human Pregnancy and Recommendations for Use in Pregnancy and Appendix B: Supplement: Safety and Toxicity of Individual Antiretroviral Agents in Pregnancy). Counseling about ARV drug use during pregnancy should be directive and noncoercive, and providers should help patients make informed decisions regarding the use of ARV drugs.

Counseling about regimens should include information about the following:

• The risk of HIV disease progression and the benefits and risks of therapy on maternal health during pregnancy²³;
• The benefits of ART for preventing perinatal transmission of HIV²⁴;
• The benefits of using ART to achieve and maintain viral suppression, which reduces the risk of sexual transmission of HIV to partners who do not have HIV²⁵;
• The need for strict adherence to the prescribed ARV drug regimen to avoid drug resistance, optimize health outcomes, and minimize the risk of perinatal HIV transmission;
• The risks and adverse effects of ARV drugs during pregnancy, their impact on fetuses and infants, and possible interactions with existing medications (see Recommendations for Use of Antiretroviral Drugs During Pregnancy: Overview)^26-29;
• The limited long-term outcome data for infants who were exposed to ARV drugs in utero, especially for newer ARV drugs; and
• The importance of considering pregnancy-specific challenges to adherence, such as nausea and vomiting or adverse social determinants of health. Patients should be advised to remain in close communication with their providers about these challenges.

Counseling at the onset of antepartum care and at each subsequent visit 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. Patients with poor adherence during pregnancy are more likely to have detectable viral loads at delivery.³⁰ In addition, multiple adverse social determinants of health, including housing instability,³¹ nondisclosure of HIV status,^32,33 lack of social support,³⁴ and other factors—are known to affect adherence. As a result, adherence counseling should include careful attention to the patient’s social needs, social support, and mental health.

Patient Counseling and Coordination of Care

Coordination of services among antepartum 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 comprehensive support for HIV care during all stages of pregnancy and the postpartum period. Medical care during pregnancy with HIV requires coordination and communication between HIV specialists and obstetric providers.

Anticipatory guidance provided during pregnancy in the context of HIV is generally similar to counseling that is recommended without HIV.³⁵ However, HIV-specific antepartum 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 tobacco use, substance use disorders, alcohol consumption, and genital tract infections. In addition to improving maternal and fetal health, cessation of tobacco and drug use and treatment of STIs and other genital tract infections may reduce the risk of perinatal transmission. Other risk factors for ART nonadherence, such as housing instability, food insecurity, mental health disorders,³⁶ and IPV,³⁷ also require particular attention for patients with HIV. Patients should be screened for mental health conditions, assessed for the risk of IPV, and counseled about disclosure of their HIV status when needed.³⁸

Fears of stigma and violence that could result from undesired HIV status disclosure require comprehensive, culturally informed services to support planned disclosure of HIV status during pregnancy and postpartum,^39,40 and to ensure privacy during health care encounters (including telemedicine visits and in-person care) when HIV status has not yet been disclosed.⁴¹ The use of medications such as testosterone or less common forms of self-expression may present specific concerns and needs for added support when receiving services in settings designed for pregnancy care.

In addition, providers should counsel patients with HIV about what to expect during labor, delivery, and the postpartum period. This counseling should include discussing the mode of delivery and the possible use of intrapartum zidovudine, as well as unique disclosure circumstances that may occur in the context of intrapartum care. Guidance must also address reproductive choice and postpartum contraceptive options. Providers also should discuss the possibility of simplifying a patient’s ARV regimen after delivery, which can help promote long-term adherence to ART. Discussions regarding the prevention of postnatal transmission to the neonate also should include recommendations about infant feeding, neonatal ARV prophylaxis, infant diagnostic HIV testing, and the avoidance of premastication of food (see Preventing HIV Transmission During Infant Feeding). Anticipatory guidance about postpartum care also must include plans for transitioning health care from the obstetric team to the long-term health care team.

References

1. 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://pubmed.ncbi.nlm.nih.gov/26372927.
2. Sivarajah V, Venus K, Yudin, et al. 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://pubmed.ncbi.nlm.nih.gov/28600331.
3. 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://pubmed.ncbi.nlm.nih.gov/26042815.
4. Young MR, Broadwell C, Kacanek D, et al. Sexually transmitted Infections in pregnant people with human immunodeficiency virus: temporal trends, demographic correlates, and association with preterm birth. Clin Infect Dis. 2022;75(12):2211-2218. Available at: https://pubmed.ncbi.nlm.nih.gov/35486952.
5. 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://pubmed.ncbi.nlm.nih.gov/24311479.
6. Thompson MA, Horberg MA, Agwu AL, et al. Primary care guidance for persons with human immunodeficiency virus: 2020 update by the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis. 2021;73(11):e3572-e3605. Available at: https://pubmed.ncbi.nlm.nih.gov/33225349.
7. American College of Obstetricians and Gynecologists. ACOG committee opinion no. 741: maternal immunization. Obstet Gynecol. 2022;131(6):e214-e217. Available at: https://www.acog.org/clinical/clinical-guidance/practice-advisory/articles/2022/10/maternal-immunization.
8. Murthy N, Wodi AP, Bernstein H, et al. Advisory Committee on Immunization Practices recommended immunization schedule for adults aged 19 years or older - United States, 2022. MMWR Morb Mortal Wkly Rep. 2022;71(7):229-233. Available at: https://pubmed.ncbi.nlm.nih.gov/35176010.
9. 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://pubmed.ncbi.nlm.nih.gov/30629567.
10. Brandt JS, Patel AJ, Marshall I, Bachmann GA. Transgender men, pregnancy, and the "new" advanced paternal age: a review of the literature. Maturitas. 2019;128:17-21. Available at: https://pubmed.ncbi.nlm.nih.gov/31561817.
11. Hahn M, Sheran N, Weber S, et al. Providing patient-centered perinatal care for transgender men and gender-diverse individuals: a collaborative multidisciplinary team approach. Obstet Gynecol. 2019;134(5):959-963. Available at: https://pubmed.ncbi.nlm.nih.gov/31599839.
12. American College of Obstetricians Gynecologists’ Committee on Practice Bulletins-Obstetrics. Screening for fetal chromosomal abnormalities: ACOG practice bulletin summary, number 226. Obstet Gynecol. 2020;136(4):859-867. Available at: https://pubmed.ncbi.nlm.nih.gov/32976375.
13. Peters H, Francis K, Harding K, et al. Operative vaginal delivery and invasive procedures in pregnancy among women living with HIV. Eur J Obstet Gynecol Reprod Biol. 2017;210:295-299. Available at: https://pubmed.ncbi.nlm.nih.gov/28092853.
14. Floridia M, Masuelli G, Meloni A, et al. Amniocentesis and chorionic villus sampling in HIV-infected pregnant women: a multicentre case series. BJOG. 2017;124(8):1218-1223. Available at: https://pubmed.ncbi.nlm.nih.gov/27319948.
15. Mandelbrot L, Mayaux MJ, Bongain A, et al. Obstetric factors and mother-to-child transmission of human immunodeficiency virus type 1: the French perinatal cohorts. SEROGEST French Pediatric HIV Infection Study Group. Am J Obstet Gynecol. 1996;175(3 Pt 1):661-667. Available at: http://pubmed.ncbi.nlm.nih.gov/8828431.
16. Tess BH, Rodrigues LC, Newell ML, et al. Breastfeeding, genetic, obstetric and other risk factors associated with mother-to-child transmission of HIV-1 in Sao Paulo State, Brazil. Sao Paulo Collaborative Study for Vertical Transmission of HIV-1. AIDS. 1998;12(5):513-520. Available at: http://pubmed.ncbi.nlm.nih.gov/9543450.
17. Shapiro DE, Sperling RS, Mandelbrot L, et al. Risk factors for perinatal human immunodeficiency virus transmission in patients receiving zidovudine prophylaxis. Pediatric AIDS Clinical Trials Group protocol 076 Study Group. Obstet Gynecol. 1999;94(6):897-908. Available at: http://pubmed.ncbi.nlm.nih.gov/10576173.
18. Maiques V, Garcia-Tejedor A, Perales A, et al. HIV detection in amniotic fluid samples. Amniocentesis can be performed in HIV pregnant women? Eur J Obstet Gynecol Reprod Biol. 2003;108(2):137-141. Available at: http://pubmed.ncbi.nlm.nih.gov/12781400.
19. Somigliana E, Bucceri AM, Tibaldi C, et al. Early invasive diagnostic techniques in pregnant women who are infected with the HIV: a multicenter case series. Am J Obstet Gynecol. 2005;193(2):437-442. Available at: http://pubmed.ncbi.nlm.nih.gov/16098867.
20. Coll O, Suy A, Hernandez S, et al. Prenatal diagnosis in human immunodeficiency virus-infected women: a new screening program for chromosomal anomalies. Am J Obstet Gynecol. 2006;194(1):192-198. Available at: http://pubmed.ncbi.nlm.nih.gov/16389031.
21. Ekoukou D, Khuong-Josses MA, Ghibaudo N, et al. Amniocentesis in pregnant HIV-infected patients. Absence of mother-to-child viral transmission in a series of selected patients. Eur J Obstet Gynecol Reprod Biol. 2008;140(2):212-217. Available at: http://pubmed.ncbi.nlm.nih.gov/18584937.
22. Mandelbrot L, Jasseron C, Ekoukou D, et al. Amniocentesis and mother-to-child human immunodeficiency virus transmission in the Agence Nationale de Recherches sur le SIDA et les Hepatites Virales French Perinatal Cohort. Am J Obstet Gynecol. 2009;200(2):160 e161-169. Available at: http://pubmed.ncbi.nlm.nih.gov/18986640.
23. 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://pubmed.ncbi.nlm.nih.gov/26192873.
24. 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://pubmed.ncbi.nlm.nih.gov/20070234.
25. 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://pubmed.ncbi.nlm.nih.gov/21767103.
26. 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://pubmed.ncbi.nlm.nih.gov/28325171.
27. 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.
28. 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://pubmed.ncbi.nlm.nih.gov/30020964.
29. 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://pubmed.ncbi.nlm.nih.gov/32564058.
30. 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://pubmed.ncbi.nlm.nih.gov/25599347.
31. Cassimatis IR, Ayala LD, Miller ES, et al. Third-trimester repeat HIV testing: it is time we make it universal. Am J Obstet Gynecol. 2021;225(5):494-499. Available at: https://pubmed.ncbi.nlm.nih.gov/33932342.
32. Yee LM, McGregor DV, Sutton SH, et al. Association between maternal HIV disclosure and risk factors for perinatal transmission. J Perinatol. 2018;38(6):639-644. Available at: https://pubmed.ncbi.nlm.nih.gov/29434253.
33. Chohan BH, Ronen K, Khasimwa B, et al. Food insecurity, drug resistance and non-disclosure are associated with virologic non-suppression among HIV pregnant women on antiretroviral treatment. PLoS One. 2021;16(8):e0256249. Available at: https://pubmed.ncbi.nlm.nih.gov/34407133.
34. Premkumar A, Yee LM, Benes L, Miller ES. Social vulnerability among foreign-born pregnant women and maternal virologic control of HIV. Am J Perinatol. 2021;38(8):753-758. Available at: https://pubmed.ncbi.nlm.nih.gov/33368072.
35. American Academy of Pediatrics on Fetus and Newborn, ACOG Committee on Obstetric Practice. Guidelines for perinatal care. 2017 8. Available at: https://publications.aap.org/aapbooks/book/522/Guidelines-for-Perinatal-Care.
36. Momplaisir F, Hussein M, Kacanek D, et al. Perinatal depressive symptoms, human immunodeficiency virus (HIV) suppression, and the underlying role of antiretroviral therapy adherence: a longitudinal mediation analysis in the IMPAACT P1025 Cohort. Clin Infect Dis. 2021;73(8):1379-1387. Available at: https://pubmed.ncbi.nlm.nih.gov/33982083.
37. Lin D, Zhang C, Shi H. Adverse impact of intimate partner violence against HIV-positive women during pregnancy and post-partum: results from a meta-analysis of observational studies. Trauma Violence Abuse. 2022:15248380211073845. Available at: https://pubmed.ncbi.nlm.nih.gov/35258353.
38. Zhu QY, Huang DS, Lv JD, et al. Prevalence of perinatal depression among HIV-positive women: a systematic review and meta-analysis. BMC Psychiatry. 2019;19(1):330. Available at: https://pubmed.ncbi.nlm.nih.gov/31666033.
39. Knettel BA, Minja L, Chumba LN, et al. Serostatus disclosure among a cohort of HIV-infected pregnant women enrolled in HIV care in Moshi, Tanzania: a mixed-methods study. SSM Popul Health. 2019;7:007-007. Available at: https://pubmed.ncbi.nlm.nih.gov/30560196.
40. Ngonzi J, Mugyenyi G, Kivunike M, et al. Frequency of HIV status disclosure, associated factors and outcomes among HIV positive pregnant women at Mbarara Regional Referral Hospital, southwestern Uganda. Pan Afr Med J. 2019;32:200. Available at: https://pubmed.ncbi.nlm.nih.gov/31312312.
41. Waldron EM, Miller ES, Wee V, et al. Stress, coping and the acceptability of mindfulness skills among pregnant and parenting women living with HIV in the United States: a focus group study. Health Soc Care Community. 2022;30(6):e6255-e6266. Available at: https://www.ncbi.nlm.nih.gov/pubmed/36214377.