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

Prepregnancy Counseling and Care

Overview

Overview

The Centers for Disease Control and Prevention (CDC), the American College of Obstetricians and Gynecologists (ACOG), and other national organizations recommend offering comprehensive family planning and the opportunity to receive prepregnancy counseling and care as a component of routine primary medical care when there is the potential for pregnancy. The purpose of prepregnancy care is to improve health before conception by identifying risk factors for maternal and fetal adverse outcomes, tailoring education and counseling to individual needs, and treating or stabilizing medical conditions to optimize outcomes for the pregnancy and the fetus/newborn.^1,2 Prepregnancy care is not something that occurs in a single clinical visit; rather, it requires integrating ongoing care and interventions into primary care to address needs during the different stages of reproductive life. Integrating comprehensive family planning and prepregnancy care into routine HIV health care visits can help patients reach their desired reproductive outcomes by supporting them to make informed decisions about their fertility and contraceptive use that are aligned with their preferences and reproductive goals.^3-6 Providers should initiate and document a nonjudgmental conversation with all people of reproductive age about their reproductive desires because they may be reluctant to bring up the subject themselves.^7-12

A meta-analysis of 50 studies found a 42% prevalence of fertility desire among people with HIV. In a pooled analysis, fertility desire was associated with being on antiretroviral therapy (ART), male sex, being younger than 30, being married or cohabitating, having a secondary education or higher, and being childless.¹³ In a retrospective study among 255 women with HIV, 69 (27.1%) reported an intended pregnancy. Those with intended pregnancies were more likely to be older, White, married, privately insured, and college educated. They were less likely than those with unintended pregnancies to use tobacco, alcohol, opiates, or cocaine during pregnancy; more likely to disclose their HIV status to the father of the baby by delivery; and more likely to receive less effective contraception (e.g., condoms) postpartum. In a multivariate analysis, pregnancy intendedness was an important predictor of nondetectable viral load at pregnancy entry but not at delivery.¹⁴ Pregnancy intentions may not be binary and may change over time, thus underscoring the need for health care providers to engage in ongoing discussions to support dynamic pregnancy intentions.¹¹

Health care providers who routinely care for people of reproductive age with HIV play an important role in promoting prepregnancy health and informed reproductive decisions. However, even among providers who offer primary HIV care, the delivery of comprehensive reproductive counseling often falls short of the current guidelines.^15-17

The fundamental principles of prepregnancy counseling and care are outlined in the CDC Preconception Care Work Group’s Recommendations to Improve Preconception Health and Health Care and in ACOG’s Prepregnancy Counseling guidance. In addition to the general components of prepregnancy counseling and care that are appropriate for all people of reproductive age, people with HIV have specific needs that should be addressed.^18-21

• Discuss reproductive options; routinely assess pregnancy intentions throughout the course of care; and, when appropriate, make referrals to HIV and reproductive health specialists, including experts in reproductive endocrinology and infertility when necessary. The HIV status of one or both parents should not be a reason to withhold standard of care infertility treatment and assist individuals and couples in reaching their desired reproductive outcomes.
• When pregnancy is not currently desired, offer a full range of contraceptive methods to help achieve fertility goals. In the context of HIV, all available contraceptive methods, including hormonal contraception (e.g., pill, patch, ring, injection, implant) and intrauterine devices (IUDs) can be used; see Medical Eligibility Criteria for Contraceptive Use.²² Providers should be aware of the presence of other medical co-morbidities and potential interactions between antiretroviral (ARV) drugs, hormonal contraceptives, and other medications that could lower contraceptive efficacy or increase the risk of such adverse effects as blood clots (see Table 3 below).
• Offer emergency contraception as appropriate, including emergency contraceptive pills and IUDs (see the ACOG Practice Bulletin on Emergency Contraception). Emergency contraceptive pills that contain estrogen and progestin and those that only contain levonorgestrel (LNG) may have interactions with ARV drugs that are similar to the ones observed with combined oral contraceptives.²³ AIDS Clinical Trials Group (ACTG) 5375 showed that doubling the dose of LNG from 1.5 mg to 3 mg in women receiving efavirenz (EFV)-based ART helped overcome the drug–drug interaction with this ARV.^24,25 No data are available on potential interactions between ARV drugs and ulipristal acetate, a progesterone receptor modulator; however, ulipristal acetate is metabolized predominantly by cytochrome P450 (CYP) 3A4, so interactions may occur (see the HIV Drug Interaction Checker).
• When pregnancy is being contemplated, use the prepregnancy period to modify the ARV regimen to optimize virologic suppression and minimize potential adverse effects (see Recommendations for the Use of Antiretroviral Drugs During Pregnancy and Table 7). In the context of perinatally acquired HIV, there may be more difficulty maintaining viral suppression, a greater likelihood of multidrug-resistant virus, and there may be a benefit to providing additional psychosocial and/or adherence support²⁶ (see Prenatal Care, Antiretroviral Therapy, and HIV Management When HIV Was Perinatally Acquired).
• Recognize that patients whose self-expression is less common may have special needs.²⁷ For example, the use of testosterone may induce hypothalamic–pituitary–gonadal axis suppression, leading to decreased ovulation.²⁸
• Recognize that the primary HIV treatment goal when pregnancy is being planned should include sustained suppression of plasma HIV viral load below the limit of detection before conception for personal health, to minimize the risk of perinatal HIV transmission, and to prevent sexual HIV transmission to a partner without HIV (see Reproductive Options When One or Both Partners Have HIV). When pregnancy is being considered or planned, counseling should include that with ART started before pregnancy and an undetectable viral load maintained throughout pregnancy and delivery, the risk of HIV transmission to the infant is extremely low (<1%).^29,30
• Explain that people with HIV who take ART as prescribed and who achieve and maintain an undetectable viral load will not transmit HIV through sex, commonly known as Undetectable = Untransmittable or U=U. For more information, see Let’s Stop HIV Together.
• Encourage disclosure of HIV status to partners or co-parents before pregnancy if doing so is safe. However, this disclosure should not be a requirement of assisting couples in achieving pregnancy.
• Encourage sexual partners to receive HIV counseling and testing so that they can seek HIV care if they have HIV or seek advice about HIV prevention, including pre-exposure prophylaxis (PrEP), if they do not have HIV (see Pre-exposure Prophylaxis [PrEP] to Prevent HIV During Periconception, Antepartum, and Postpartum Periods).
• Ask about the use of alcohol, tobacco, and other substances. Provide or refer to evidence-based interventions for substance use disorder, including medication-assisted treatment for opioid use disorder (e.g., methadone, buprenorphine), and counsel on how to manage health risks (e.g., access to a syringe services program). A 2019 analysis³¹ reported that overall, 39% of women with HIV of reproductive age reported current drinking and 10% reported binge drinking. Compared to non-drinkers, binge drinkers were less likely to adhere to ART or be virally suppressed and more likely to smoke and use drugs. Between 2007 and 2019, marijuana use during pregnancy among women with HIV increased from 7.1% to 11.7%, whereas alcohol and opioid use were unchanged. Postpartum alcohol (44.4%), marijuana (13.6%), and concomitant alcohol and marijuana (10%) use were common; marijuana use increased from 10.2% in 2006 to 23.7% in 2019, whereas postpartum alcohol use was unchanged.³²
• Counsel on maintaining a healthy diet and healthy weight before and during pregnancy.
• When pregnancy is being contemplated, counsel to take a daily multivitamin that contains 400 mcg of folic acid to help prevent neural tube defects (NTDs). When there is a history of having a child with NTDs, there is a family history of NTDs, or when certain anti-epileptic medications, especially when using valproic acid, a higher dose (1,000–‍4,000 mcg) of folic acid can be prescribed. Higher doses of folate may also be considered for people receiving trimethoprim/sulfamethoxazole who are trying to conceive (see Special Considerations in Pregnancy in Pneumocystis Pneumonia in the Adult and Adolescent Opportunistic Guidelines.
• Optimize the health of people with HIV prior to pregnancy (e.g., ensure appropriate folate intake; test for all sexually transmitted infections and treat as indicated; consider the teratogenic potential of all prescribed medications; consider switching to safer medications; encourage cessation of tobacco, alcohol, and other substances; optimize management of chronic health conditions).
• Educate and counsel about the risk factors for perinatal HIV transmission, the strategies to reduce those risks, and the potential effects HIV or taking ARV drugs during pregnancy may have on the course of pregnancy and maternal and fetal health outcomes.
• Support shared decision-making about ART. Educate and counsel on the factors that affect the selection of ARVs when trying to conceive, during pregnancy, or during postpartum. For more information, see Recommendations for Use of Antiretroviral Drugs During Pregnancy: Overview.
• Consider the following factors when prescribing ART and there is the possibility of pregnancy: the regimen’s effectiveness, changes in ARV pharmacokinetics (PK) in the second and third trimesters of pregnancy, hepatitis B virus (HBV) status, possible adverse maternal and fetal health outcomes,, and the likelihood of developing drug resistance.^33-35
• Provide patient-centered, evidence-based counseling to support shared decision-making about infant feeding (see Preventing HIV Transmission During Infant Feeding). Information about and plans for infant feeding should be reviewed throughout pregnancy and again after delivery.
• Evaluate and manage ART-associated adverse effects (e.g., hyperglycemia, anemia, hepatotoxicity) that may affect maternal and fetal health outcomes.
• Administer all vaccines as indicated (see CDC’s Recommended Immunization Schedule and ACOG’s Maternal Immunization Practice Advisory, 2022), which includes vaccination for influenza, pneumococcus, HBV, tetanus, and SARS-CoV-2.³⁶ Tdap (tetanus, diphtheria, and pertussis) vaccination should be performed during each pregnancy, including pregnancies impacted by HIV, typically between 27 and 36 weeks of gestation but preferably as early in this time window as possible.
• Ask about safety at home and offer assistance or referrals to those experiencing intimate partner violence or requesting assistance.

Drug–Drug Interactions Between Hormonal Contraceptives and Antiretroviral Therapy 

Data on drug interactions between ARVs and hormonal contraceptives primarily come from drug labels and several studies on the PK and pharmacodynamics among the different forms of contraception and ARVs.^37-39 The contraceptive effectiveness of the LNG IUD is largely through local (i.e., intrauterine) release of LNG, not through systemic absorption. CDC’s U.S. Medical Eligibility Criteria for Contraceptive Use lists the LNG IUD as category 1 (no restrictions) in drug interactions with all ARVs in women who already have an IUD and category 1/2 (benefits outweigh risk) for those initiating the use of an IUD.

Hormonal contraceptives can be used with ARVs in the context of HIV without other contraindications. The contraception effect is usually attributable to the progestin component of contraceptives. Drug interactions that decrease concentrations of the progestin component may affect contraceptive efficacy. An alternative or additional contraceptive method may be recommended when drug interactions are known. When using darunavir/ritonavir-based ART, an alternative or additional contraception may be considered because the area under the curve (AUC) for oral contraceptive hormones may be decreased.⁴⁰ Cobicistat-boosted protease inhibitors are contraindicated with drosperinone-containing hormonal contraceptives due to the potential for hyperkalemia.⁴¹ Depot medroxyprogesterone acetate (DMPA) can be used without restriction because of its relatively higher dose than other progesterone-based contraception, and limited studies have shown no significant interaction between DMPA and ARVs.^42-45

Several studies have shown that the use of EFV decreases the effectiveness of hormonal implants and hormonal vaginal rings. Although contraceptive implants (e.g., etonogestrel [ENG], LNG) generally can be used when using ARVs, both PK and clinical data suggest that these implants have decreased efficacy when used with EFV-based regimens.^46-49 LNG implants are not available in the United States. A PK evaluation reported that the geometric mean ratios of LNG concentrations (patients taking EFV-based ART vs. ART-naive patients) were 0.53 at 24 weeks and 0.43 at 48 weeks. Three pregnancies occurred in the EFV group (15%) between Week 36 and Week 48, whereas no pregnancies occurred in the ART-naive or nevirapine (NVP) groups.⁵⁰

Tuberculosis Treatment, Antiretrovirals, and Contraception 

Other medications, such as concomitant tuberculosis (TB) treatment with EFV, may also have drug–drug interactions with contraceptives. PK studies of HIV/TB coinfection when using EFV-based HIV treatment and rifampicin-based TB treatment show increased metabolism of DMPA and levonorgestrel emergency contraception, suggesting that redosing DMPA more frequently or doubling the dose of emergency contraception may be required for effective contraception.^25,51-54

Vaginal Ring

For the ENG/EE contraceptive vaginal ring (NuvaRing), PK evaluation showed that ENG levels were 79% lower and EE levels were 59% lower in participants on EFV-based ART regimens compared with the control group.⁵⁶ A newer contraceptive vaginal ring containing segesterone/EE (Annovera) also is approved by the U.S. Food and Drug Administration, but no drug–drug interaction studies with this contraceptive ring and ARVs have been reported to date. The segesterone and EE in the Annovera vaginal ring may be metabolized in the same way as ENG and EE in the NuvaRing (see Table 3 below).⁵⁶

Table 3. Drug Interactions Between Antiretroviral Agents and Hormonal Contraceptives

Table 3 provides a summary of drug interactions between antiretroviral (ARV) agents and hormonal contraceptives, with recommendations for contraceptive dosing and additional contraceptive protection. Because data are limited on pregnancy rates when using different hormonal contraceptives and ARVs, some of the dosing recommendations in Table 3 are based on consensus expert opinion. Whenever possible, the recommendations are based on available data regarding pharmacokinetic interactions between ARVs and combined hormonal methods, depot medroxyprogesterone acetate, and levonorgestrel and etonogestrel implants.

Additional information can be found in the Centers for Disease Control and Prevention Update to U.S. Medical Eligibility Criteria for Contraceptive Use, 2016: Updated Recommendations for the Use of Contraception Among Women at High Risk for HIV Infection.⁵⁷

References

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