Actualizado
Dic. 30, 2021
Reviewed
Dic. 30, 2021

General Principles Regarding Use of Antiretroviral Drugs during Pregnancy

Overview

Panel's Recommendations: General Principles Regarding Use of Antiretroviral Drugs during Pregnancy

Panel's Recommendations
  • Initial evaluation of pregnant people with HIV should include an assessment of HIV disease status and plans to initiate, continue, or modify antiretroviral therapy (ART) (AI). The National Perinatal HIV Hotline (1-888-448-8765) provides free clinical consultation on all aspects of perinatal HIV care.
  • All pregnant people with HIV should initiate ART as early in pregnancy as possible, regardless of their HIV RNA level or CD4 T lymphocyte count, to maximize their health and prevent perinatal HIV transmission and secondary sexual transmission (AI). Persons with HIV should maintain an HIV viral load that is below the limit of detection during pregnancy, postpartum, and throughout their lives (AII).
  • Antiretroviral (ARV) drug-resistance genotype evaluations or assays should be performed before starting ARV drug regimens in people who are ARV-naive (AII) or ARV-experienced (AIII) and before modifying ARV drug regimens (AII) in people whose HIV RNA levels are above the threshold for resistance testing (i.e., >500 copies/mL to 1,000 copies/mL).
  • In pregnant people who are not already receiving ART, ART should be initiated before results of drug-resistance testing are available because earlier viral suppression has been associated with lower risk of transmission. When ART is initiated before results are available, the regimen should be modified, if necessary, based on resistance assay results (AII).
  • To minimize the risk of perinatal transmission, people with HIV should receive ART throughout pregnancy (including the intrapartum period), and neonates should receive appropriate ARV drugs (AI). See Recommendations for Use of Antiretroviral Drugs During Pregnancy and Antiretroviral Management of Newborns with Perinatal HIV Exposure or HIV Infection.
  • People with HIV should be counseled on the known benefits and potential risks of all medications, including ARV drugs used during pregnancy and postpartum, as well as the importance of ART adherence (AIII).
  • If an ARV drug regimen must be stopped during pregnancy (e.g., for severe toxicity), all ARV drugs should be stopped simultaneously, and a complete, effective ARV regimen should be reinitiated as soon as possible (AII).
  • Coordination of services among prenatal care providers, primary care and HIV specialty care providers, and, when appropriate, mental health and substance use disorder treatment services, intimate partner violence support services, and public assistance programs is essential to support and enable adherence to medication (AII).
  • Providers should initiate counseling about key intrapartum and postpartum considerations during pregnancy, including mode of delivery, lifelong HIV therapy, family planning and contraceptive options, infant feeding, infant ARV prophylaxis, and timing of infant diagnostic testing (AIII).
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 people, the initial evaluation of persons 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, Tdap, or SARS-CoV-2 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 11);
  • 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 identity, the pronouns they use, use of testosterone or other gender-affirming hormonal therapy, and potential interactions with ARV drugs6,7 (see Perinatal HIV Prevention for Transgender and Gender Diverse People Assigned Female Sex at Birth and Transgender People with HIV);
  • History of adherence challenges and facilitators;
  • 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);8
  • 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 Prevent 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 people 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 diseases, and reduce the risk of maternal death.

ARV drugs reduce the risk of perinatal transmission of HIV in all pregnant people, 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.9-11 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 people 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).12-15 Studies have reported low-level cervicovaginal HIV RNA and DNA shedding in women who were on ART and who had undetectable plasma viral loads.16-18 Penetration of ARV drugs into the female genital tract varies by drug.19-22

Infant pre-exposure prophylaxis also should 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 HIV transmission is demonstrated by the reduced efficacy of interventions that involve administration of ARV drugs only during labor and/or to the newborns.23-30 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 people who are pregnant are the same as those for people who are not pregnant. 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 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 HIV transmission to infants; this helps put the potential risks of using these drugs into perspective (see Table 11 and Appendix B: Supplement: Safety and Toxicity of Individual Antiretroviral Agents in Pregnancy). Counseling of pregnant patients about ARV drug use should be directive and noncoercive, and providers should help patients make informed decisions regarding the use of ARV drugs.

Discussions with patients 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;31
  • The benefits of ART for preventing perinatal transmission of HIV;13
  • The benefits of using ART to achieve and maintain viral suppression, which reduce the risk of sexual transmission of HIV to partners who do not have HIV;32
  • 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 potential adverse effects of ARV drugs for pregnant people, fetuses, and infants, including potential interactions with other medications the patient may already be receiving (see Recommendations for Use of Antiretroviral Drugs During Pregnancy);33-36and
  • The limited long-term outcome data for infants who were exposed to ARV drugs in utero, especially for newer ARV drugs.

In pregnant patients with HIV who are not receiving treatment currently, plasma HIV RNA levels should be measured and ART should be initiated. In patients 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.37,38 The ARV regimen can be modified, if necessary, based on resistance assay results39 (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. Patients with poor adherence during pregnancy are more likely to have detectable viral loads at delivery.40

Transplacental passage of ARV drugs is thought to be an important mechanism of infant pre-exposure prophylaxis. Thus, when selecting an ARV regimen for use during pregnancy, ARV drugs with high placental transfer should be included as a component of the ARV regimen (see Table 11).41-45

Discontinuation of ARVs

The Panel on Treatment of HIV During Pregnancy and Prevention of Perinatal Transmission (the Panel) strongly recommends against discontinuing ART. However, if an ARV drug regimen must be stopped for any reason, all ARV drugs should be stopped simultaneously. ART should be reinitiated as soon as possible, whether the patient restarts the same regimen or initiates a new regimen. If an ARV drug that is known to have a long serum half-life (e.g., non-nucleoside reverse transcriptase inhibitors) must be stopped for more than a few days, clinicians should consider assessing the patient for rebound viremia after a new regimen is started, and viral suppression would be expected; if optimal viral suppression has not been achieved, potential drug resistance should be assessed.46

Temporary discontinuation of ARV drug regimens during pregnancy may be indicated in some situations, including cases of serious drug-related toxicity, pregnancy-induced hyperemesis that is unresponsive to antiemetics, or acute illnesses or planned surgeries that prevent a patient from taking oral medications. Possible toxicity or intolerance to a single ARV agent should prompt discussion about options for modifying rather than stopping an entire ARV regimen (see Pregnant People With HIV Who Are Currently Receiving Antiretroviral Therapy).46

Discontinuation of therapy could lead to an increase in viral load, with possible disease progression and decline in immune status for the mother and increased risk of in utero transmission of HIV. An analysis from a prospective cohort of 937 mother–child pairs from the Italian Registry for HIV infection in children found that interruption of ART during pregnancy, including interruption in the first and third trimesters, was independently associated with an increased rate of perinatal HIV transmission.47 During the first trimester, the median gestational age at interruption was 6 weeks, and length of time without therapy was 8 weeks (interquartile range [IQR] 7–11 weeks); in the third trimester, the median gestational age at interruption was 32 weeks, and length of time without therapy was 6 weeks (IQR 2–9 weeks). Although the perinatal transmission rate for the entire cohort was only 1.3%, transmission occurred in 4.9% of mother–child pairs with first-trimester interruption (95% confidence interval [CI], 1.9% to 13.2%; adjusted odds ratio [aOR] 10.33; P = 0.005) and 18.2% of mother–child pairs with third-trimester interruption (95% CI, 4.5% to 72.7%; aOR 46.96; = 0.002).47

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 patients with HIV are well supported during all stages of their pregnancies and during the postpartum period. Medical care of pregnant people 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, alcohol consumption, 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. Patients 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.48 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 patients who are planning to disclose their status,49,50 and patients who have not disclosed their status require support to maintain privacy during telemedicine visits. Transgender and gender-diverse individuals may have specific concerns—such as the effects of stopping gender-affirming hormones during pregnancy or restarting them after they give birth—that should be assessed and addressed6 (see Perinatal HIV Prevention for Transgender and Gender Diverse People Assigned Female Sex at Birth). Because testosterone is a classified as teratogen, patients should be instructed not to take this gender-affirming hormone when trying to conceive and during pregnancy.7

In addition, providers should counsel patients 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 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 Counseling and Managing Individuals with HIV in the United States Who Desire to Breastfeed).

References

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  23. 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.
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  25. 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.
  26. 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.
  27. 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.
  28. 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.
  29. 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.
  30. 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://www.ncbi.nlm.nih.gov/pubmed/28277349.
  31. 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.
  32. 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.
  33. 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.
  34. 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.
  35. 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.
  36. 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.
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  38. 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.
  39. 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.
  40. 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.
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General Principles Regarding Use of Antiretroviral Drugs during Pregnancy

Overview

Panel's Recommendations: General Principles Regarding Use of Antiretroviral Drugs during Pregnancy

Panel's Recommendations
  • Initial evaluation of pregnant people with HIV should include an assessment of HIV disease status and plans to initiate, continue, or modify antiretroviral therapy (ART) (AI). The National Perinatal HIV Hotline (1-888-448-8765) provides free clinical consultation on all aspects of perinatal HIV care.
  • All pregnant people with HIV should initiate ART as early in pregnancy as possible, regardless of their HIV RNA level or CD4 T lymphocyte count, to maximize their health and prevent perinatal HIV transmission and secondary sexual transmission (AI). Persons with HIV should maintain an HIV viral load that is below the limit of detection during pregnancy, postpartum, and throughout their lives (AII).
  • Antiretroviral (ARV) drug-resistance genotype evaluations or assays should be performed before starting ARV drug regimens in people who are ARV-naive (AII) or ARV-experienced (AIII) and before modifying ARV drug regimens (AII) in people whose HIV RNA levels are above the threshold for resistance testing (i.e., >500 copies/mL to 1,000 copies/mL).
  • In pregnant people who are not already receiving ART, ART should be initiated before results of drug-resistance testing are available because earlier viral suppression has been associated with lower risk of transmission. When ART is initiated before results are available, the regimen should be modified, if necessary, based on resistance assay results (AII).
  • To minimize the risk of perinatal transmission, people with HIV should receive ART throughout pregnancy (including the intrapartum period), and neonates should receive appropriate ARV drugs (AI). See Recommendations for Use of Antiretroviral Drugs During Pregnancy and Antiretroviral Management of Newborns with Perinatal HIV Exposure or HIV Infection.
  • People with HIV should be counseled on the known benefits and potential risks of all medications, including ARV drugs used during pregnancy and postpartum, as well as the importance of ART adherence (AIII).
  • If an ARV drug regimen must be stopped during pregnancy (e.g., for severe toxicity), all ARV drugs should be stopped simultaneously, and a complete, effective ARV regimen should be reinitiated as soon as possible (AII).
  • Coordination of services among prenatal care providers, primary care and HIV specialty care providers, and, when appropriate, mental health and substance use disorder treatment services, intimate partner violence support services, and public assistance programs is essential to support and enable adherence to medication (AII).
  • Providers should initiate counseling about key intrapartum and postpartum considerations during pregnancy, including mode of delivery, lifelong HIV therapy, family planning and contraceptive options, infant feeding, infant ARV prophylaxis, and timing of infant diagnostic testing (AIII).
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

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