Key changes to the Recommendations for the Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women and Interventions to Reduce Perinatal HIV Transmission in the United States are summarized below. Some content has been reorganized and revised to enhance usability. Text, appendices, and references have been updated to include new data and publications where relevant. The terms "mother-to-child transmission (MTCT)" and "prevention of mother-to-child transmission (PMTCT)" have been replaced with "perinatal transmission" and "prevention of perinatal transmission," respectively. All changes are highlighted throughout the PDF version of the guidelines.
Preconception Counseling and Care for HIV-Infected Women of Childbearing Age
- The Panel recommends that all HIV-infected women contemplating pregnancy be on a maximally suppressive antiretroviral (ARV) regimen (AII).
- HIV-infected women who do not desire pregnancy should be offered effective and appropriate contraceptive methods. They can use all available contraceptive methods, including hormonal contraception and emergency contraception, as appropriate.
- Further discussion about drug interactions between ARV agents and hormonal contraceptives has been added, including revised and updated Table 3: Drug Interactions between Antiretroviral Agents and Hormonal Contraceptives.
Reproductive Options for HIV-Concordant and Serodiscordant Couples
- The Panel recommends that HIV-infected partner(s) in HIV-seroconcordant and HIV-serodiscordant couples planning pregnancy attain maximum viral suppression before attempting conception (AIII).
- The Panel notes that periconception administration of ARV pre-exposure prophylaxis (PrEP) for HIV-uninfected partners may offer an additional tool to reduce the risk of sexual transmission (CIII). A new table has been added reviewing clinical trials of PrEP (see Table 4: Clinical Trials of Pre-Exposure Prophylaxis).
- The Panel also notes that no studies exist about the utility of PrEP in an uninfected individual whose infected partner is receiving combination antiretroviral therapy (cART) and has a suppressed viral load.
- Pregnancy is not a contraindication to PrEP.
General Principles Regarding Use of Antiretroviral Drugs during Pregnancy
- This section incorporates content previously included in separate, earlier sections (Mechanisms of Action of Antiretroviral Prophylaxis in Reducing Perinatal Transmission of HIV and Perinatal Transmission of HIV and Maternal HIV RNA Copy Number).
Nevirapine and Hepatic/Rash Toxicity
- Language has been strengthened to indicate that in patients with pre-existing liver disease, use of ARV medications other than nevirapine should be considered.
Recommendations for Use of Antiretroviral Drugs during Pregnancy
- A new table has been added indicating cART regimen choices for ARV-naive HIV-infected pregnant women and including the rationale for the choices (see Table 6: What to Start: Initial Combination Regimens for Antiretroviral Naive-Pregnant Women).
- Table 7: Antiretrovirals in Pregnancy: Pharmacokinetics, Toxicity and Dosing Recommendations has been redesigned, streamlined, and updated to summarize information about formulation, dosing, and recommendations for use of individual ARV drugs in pregnancy. More detailed information on individual drugs is found in Appendix B: Safety and Toxicity of Individual Antiretroviral Agents in Pregnancy.
- The Preferred dual nucleoside analogue reverse transcriptase inhibitors (NRTI) for ARV-naive pregnant women have been expanded to include abacavir plus lamivudine and tenofovir plus emtricitabine or lamivudine in addition to zidovudine plus lamivudine.
- The Preferred protease inhibitors (PIs) for ARV-naive pregnant women remain ritonavir-boosted atazanavir and ritonavir-boosted lopinavir. Alternative PIs include ritonavir-boosted darunavir and ritonavir-boosted saquinavir.
- The Preferred non-nucleoside reverse transcriptase inhibitor (NNRTI) for ARV-naive pregnant women is now efavirenz, initiated after the first 8 weeks of pregnancy. Nevirapine is the alternative NNRTI for ARV-naive pregnant women.
- Raltegravir has been moved to the Alternative category for ARV-naive pregnant women, for consideration particularly when drug interactions with PI -based regimens are a concern.
- Drugs for which data are currently insufficient in pregnancy to recommend routine use in ARV-naive women include dolutegravir, elvitegravir/cobicistat/tenofovir/emtricitabine fixed drug combination, ritonavir-boosted fosamprenavir, maraviroc, and rilpivirine.
HIV-Infected Pregnant Women Who Have Never Received Antiretroviral Treatment
- The Panel discusses the use of raltegravir in late pregnancy in women with high viral load, but because the efficacy and safety of this approach have only been described in anecdotal reports, the Panel does not routinely recommend this approach.
HIV-Infected Pregnant Women Who Have Previously Received Antiretroviral Treatment
- The Panel discusses updated data related to virologic response to cART in women who previously received cART but subsequently stopped therapy and were on no ARV drugs prior to re-starting cART in the current pregnancy.
HIV/Hepatitis C Coinfection
- The Panel discusses availability of new anti-hepatitis C drugs and the lack of data on these new agents in pregnancy. Interferon alfa and pegylated interferon are not recommended in pregnancy and ribavirin should not be used in pregnancy (AII). Because management of HIV/hepatitis C coinfection in pregnancy is complex, consultation with an expert in management of these conditions is recommended.
HIV-2 Infection and Pregnancy
- The Panel discusses difficulties in diagnosis of HIV-2 and difficulties with the currently available tests in the United States; confirmatory testing for HIV-2 can be obtained from the Centers for Disease Control and Prevention.
- No validated HIV-2 genotype or phenotype resistance assays are available in the United States; European experts have developed a rule set and an automated tool for HIV-2 drug resistance analyses that is freely available on the Internet (see http://www.hiv-grade.de).
Monitoring of the Woman and Fetus during Pregnancy
- While monitoring of CD4 T lymphocyte (CD4) cell count during pregnancy is generally recommended every 3 months, this can be reduced to 6-month intervals in patients on cART with consistently suppressed viral load who have immune reconstitution (CD4 cell count increase well above the threshold for risk of opportunistic infection) (CIII).
Intrapartum Antiretroviral Therapy/Prophylaxis
- The HIV RNA threshold for requiring administration of intravenous (IV) zidovudine during labor (in addition to continuing antepartum cART) has been modified to be consistent with the threshold for scheduled cesarean delivery and based on additional data summarized in the section.
- IV zidovudine should be administered to HIV-infected women with HIV RNA >1,000 copies/mL (or unknown HIV RNA) near delivery (AI), but it is not required for HIV-infected women receiving combination ARV regimens who have HIV RNA ≤1,000 copies/mL consistently during late pregnancy and near delivery and no concerns regarding adherence to the regimen.
Postpartum Follow-Up of HIV-Infected Women
- The Panel’s discussion about continuing cART postpartum has been revised to highlight collaborative decision-making between provider and patient, the importance of ensuring continuity of treatment from the antepartum to the postpartum period, and to reflect the current adult ARV treatment guidelines.
- Decisions about continuing cART after delivery should be made in consultation with a woman and her HIV provider, ideally before delivery (AIII). cART is currently recommended for all HIV-infected individuals to reduce the risk of disease progression and to prevent HIV sexual transmission, although the strength and evidence for this recommendation vary by pretreatment CD4 cell count.
Infant Antiretroviral Prophylaxis
- A 4-week neonatal zidovudine chemoprophylaxis regimen can be considered when the mother has received standard cART during pregnancy with consistent viral suppression and there are no concerns related to maternal adherence (BII).
- The Panel provides information on the case of a functional cure in an infant. The Panel notes that further investigation is ongoing and clinical trials are planned to address whether administration of a three-drug regimen in therapeutic doses to HIV-exposed high-risk infants could alter the establishment and long-term persistence of HIV infection. Investigation also is ongoing and clinical trials are planned to assess the safety of such an approach in infants, particularly in the setting of preterm delivery for which pharmacokinetic data on most drugs are lacking.
- The NICHD/HPTN 040/P1043 two-drug infant prophylaxis regimen of 6 weeks of zidovudine plus 3 doses of nevirapine in the first week of life continues to be the general recommendation for infant prophylaxis for infants born to mothers who did not receive antepartum ARV drugs or received only intrapartum drugs (AI); the regimen should be initiated as soon after delivery as possible. Decisions about use of alternative combination ARV prophylaxis regimens in infants should be made in consultation with a pediatric HIV specialist before delivery, if possible, and should be accompanied by a discussion with the mothers about potential risks and benefits of this approach.
Appendix A. Lessons from Clinical Trials of Antiretroviral Interventions to Reduce Perinatal Transmission of HIV