Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States
Postpartum Follow-Up of HIV-Infected Women
(Last updated:3/28/2014; last reviewed:3/28/2014)
- Decisions regarding continuing combination antiretroviral therapy (cART) after delivery should be made in consultation with the 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 varies by pre-treatment CD4 T lymphocyte (CD4) count. Decisions should take into account current recommendations for initiation of cART in adults, pre-treatment CD4 cell counts and trajectory, HIV RNA levels, adherence issues, whether a woman has an HIV-uninfected sexual partner, and patient preference.
- For women continuing cART postpartum, arrangements for new or continued supportive services should be made before hospital discharge because the immediate postpartum period poses unique challenges to adherence (AII).
- Contraceptive counseling should be a critical aspect of postpartum care (AIII).
- Women with a positive rapid HIV antibody test during labor require immediate linkage to HIV care and comprehensive follow-up, including confirmation of HIV infection. If infection is confirmed, a full health assessment is warranted, including evaluation for associated medical conditions, counseling related to newly diagnosed HIV infection, and assessment of need for cART and opportunistic infection prophylaxis (AII).
- Breastfeeding is not recommended for HIV-infected women in the United States, including those receiving cART (AII).
|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
The postpartum period provides an opportunity to review and optimize women’s health care. Comprehensive medical care and supportive services are particularly important for HIV-infected women and their families, who often face multiple medical and social challenges. Components of comprehensive care include the following services as needed:
- Primary, gynecologic/obstetric, and HIV specialty care for the HIV-infected woman;
- Pediatric care for her infant;
- Family planning services;
- Mental health services;
- Substance abuse treatment;
- Support services; and
- Coordination of care through case management for a woman, her child(ren), and other family members.
Support services should be tailored to the individual woman’s needs and can include case management; child care; respite care; assistance with basic life needs, such as housing, food, and transportation; peer counseling; and legal and advocacy services. Ideally, this care should begin before pregnancy and continue throughout pregnancy and the postpartum period.
During the postpartum period, maternal medical services must be coordinated between obstetric care providers and HIV specialists. Decisions about continuing combination antiretroviral therapy (cART) after delivery should be made in consultation with the woman and her HIV provider, ideally prior to delivery. It is especially critical to ensure continuity of cART between the antepartum and postpartum periods.
cART is currently recommended for all HIV-infected individuals to reduce the risk of disease progression and to prevent HIV sexual transmission; the strength and evidence for this recommendation varies by pretreatment CD4 T lymphocyte (CD4) cell count.1 Randomized clinical trials have demonstrated clear evidence of individual clinical benefit for starting cART in persons with CD4 <350 cells/mm3. Data from observational studies support initiation of cART in individuals with CD4 cell counts of 350 to 500 cells/mm3. Data from observational studies are conflicting regarding individual clinical benefit for starting cART in individuals with CD4 cell counts >500 cells/mm3. The HPTN 052 clinical trial, which evaluated immediate versus delayed initiation of cART to HIV-infected individuals with CD4 cell counts between 350 and 550 cells/mm3, showed that earlier initiation of antiretroviral (ARV) drugs led to a significant reduction in sexual transmission of HIV to uninfected partners in serodiscordant couples (see Preconception Counseling). The Adult and Adolescent Guidelines note that when discussing initiation of cART at high CD4 cell counts, clinicians should inform patients that the data on clinical benefit of starting treatment at study levels are not conclusive, but that viral suppression can reduce the risk of sexual transmission to others.1 It is important to counsel the woman that no single method (including treatment of the infected partner) is fully protective against HIV transmission and safer sexual practices must be continued.
In a study of postpartum women in Haiti, women who stopped ARVs after delivery with antepartum CD4 cell counts between 350 and 499 cells/mm3 near delivery progressed to CD4 cell counts <350 cells/mm3 by 19 months post-delivery, whereas women with CD4 cell counts ≥500 cells/mm3 took significantly longer (5 to 7 years) to progress to CD4 cell counts <350 cells/mm3; mortality was confined to women with CD4 cell counts <350 cells/mm3.2 Similar data were reported in the HPTN 046 study in Africa, in which 37% of women with CD4 cell counts 400 to 549 cells /mm3 near delivery had CD4 cell counts decline to <350 cells/mm3 by 12 months post-delivery, whereas only 7% of women with CD4 cell counts ≥550 cells/mm3 had a similar decline.3 Factors to be taken into consideration regarding continuation of postpartum cART should include current recommendations for initiation of cART in adults, pretreatment CD4 cell counts and trajectory, HIV RNA levels, adherence issues, partner HIV status, and patient preference. The risks versus benefits of stopping cART postpartum in women with high CD4 cell counts are being evaluated in the ongoing PROMISE study (clinical trial number NCT00955968). Unplanned changes in ARV regimens and discontinuations of cART in the postpartum period have led to viral load rebound, although no change in viral setpoint has been observed.4,5 In contrast to results from treatment interruption studies in adults, in a study of biomarkers in postpartum HIV-infected women with pre-cART CD4 cell counts >350 cells/mm3 who received cART during pregnancy, significant decreases in the levels of D-dimer, highly sensitive C-reactive protein, and interleukin-6 in the postpartum period were seen in both women who stopped as well as those who continued cART postpartum.6
Systematic monitoring of retention in HIV care is recommended for all HIV-infected individuals but special attention is warranted during the postpartum period. Retention in care is associated with improved indivual health outcomes, including HIV biomarker and clinical variables, and may reduce community-level viral burden.7 Because the postpartum period is a particularly vulnerable period for a new mother with HIV, interventions to improve adherence to medical care—to ensure follow-up medical appointments and cART adherence—can include medication management services, community outreach, one-on-one adherence support, group education and support, peer support, reminder devices, and home visits by medical HIV case managers.7 A number of studies have suggested that postpartum depression may be common among HIV-infected women.8-11 Health care providers should be vigilant for signs of depression and illicit drug or alcohol use that may require intervention assessment to avoid problems with adherence. Poor adherence has been shown to be associated with virologic failure, development of resistance, and decreased long-term effectiveness of cART.12-14 Simplification of a cART regimen (e.g., to once-daily medications) can be considered. For women who are unable to adhere to their regimens postpartum, it may be preferable to temporarily interrupt cART while they work with their health care provider on strategies to improve adherence. Efforts to maintain adequate adherence during the postpartum period may prolong the effectiveness of therapy (see the section on Adherence in the Adult and Adolescent Antiretroviral Guidelines).
The postpartum period also is a critical time for addressing the issue of safer sex practices, secondary transmission prevention, and contraception. It is important that comprehensive family planning and preconception care be integrated into routine health visits. Women who receive family planning counseling during prenatal care are more likely to use effective contraception postpartum.15 Lack of breastfeeding is associated with earlier return of fertility; ovulation returns as early as 6 weeks postpartum, and earlier in some women—even before resumption of menses—putting them at risk of pregnancy shortly after delivery.16 Interpregnancy intervals of less than 18 months have been associated with increased risk of poor perinatal and maternal outcomes in HIV-uninfected women.17 Because of the stresses and demands of a new baby, women may be more receptive to use of effective contraception, yet simultaneously at higher risk of nonadherence to contraceptive use and, thus, unintended pregnancy.4 This is an important concern in women who are on an efavirenz-containing regimen because of the potential risk of teratogencity in the first 5 to 6 weeks of pregnancy (the neural tube closes at 36–39 days after the last menstrual period). A dual-protection strategy (e.g., use of condoms plus a second highly effective contraceptive) is ideal for HIV-infected women because it provides simultaneous protection against unintended pregnancy, transmission of HIV, and acquisition or transmission of sexually transmitted disease.18 Longer-term reversible contraceptive methods, such as injectables, implants, and intrauterine devices (IUDs) should be included as options.
Drug interactions have been documented between oral contraceptives and many ARV drugs; however, data primarily come from pharmacokinetic studies and the clinical implications have not been well studied. The magnitude of changes in contraceptive drug levels that may reduce contraceptive efficacy or increase contraceptive-associated adverse effects is unknown. Hormonal contraceptives can be used with cART in women who have no other contraindications. Additional or alternative methods of contraception can be recommended where drug interactions are known. ARV-contraceptive interactions are discussed in Preconception Counseling and Care for HIV-Infected Women of Childbearing Age and Table 3. A systematic review conducted for the World Health Organization has summarized the research on hormonal contraception, IUD use, and risk of HIV infection.19,20 Permanent sterilization is appropriate only for women who are certain they do not desire future childbearing.
Concerns have been raised about adherence to ARV regimens during the postpartum period, because a number of studies have found significant decreases in adherence postpartum.21-24 Women should be counseled that postpartum physical and psychological changes and the stresses and demands of caring for a new baby may make adherence more difficult and that additional support may be needed during this period.25-27
For women whose antepartum regimen included a non-nucleoside reverse transcriptase inhibitor (NNRTI) and who plan to stop ART after delivery, consideration should be given to stopping the NNRTI and continuing the other ARV drugs for a period of time before stopping electively. The optimal interval between stopping an NNRTI and the other ARV drugs is unknown; a minimum of 7 days is recommended. Because efavirenz-based therapy has potential to result in prolonged, detectable NNRTI concentrations for more than 3 weeks, some experts recommend that patients receiving efavirenz continue their other ARV drugs or substitute a protease inhibitor (PI) for the NNRTI drug in combination with their other ARV drugs for up to 30 days after stopping efavirenz (see Stopping Antiretroviral Drugs during Pregnancy and Antiretroviral Drug Resistance and Resistance Testing in Pregnancy). Women whose antepartum regimen did not include an NNRTI and who plan to stop cART after delivery should stop all ARV drugs at the same time. Doses of some PIs may be increased during pregnancy. For women continuing cART, available data suggest that standard doses can be used again, beginning immediately after delivery.
Immediate linking to care, comprehensive medical assessment, counseling, and follow-up are required for women who test positive on rapid HIV antibody assay during labor or at delivery. To minimize the delay in definitive diagnosis, confirmatory HIV antibody testing should be performed as soon as possible after an initial positive rapid test.28 Women who test positive on rapid HIV antibody assay should not breastfeed unless a confirmatory HIV test is negative. Women with a new HIV diagnosis postpartum should receive the same thorough evaluation as other newly identified infected patients, including consideration of cART and prophylaxis for opportunistic infections, as indicated. Other children and partner(s) should be referred for HIV testing.
- Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Available at http://aidsinfo.nih.gov/contentfiles/AdultandAdolescentGL.pdf. Last accessed March 19, 2014.
- Coria A, Noel F, Bonhomme J, et al. Consideration of postpartum management in HIV-positive Haitian women: an analysis of CD4 decline, mortality, and follow-up after delivery. J Acquir Immune Defic Syndr. 2012;61(5):636-643. Available at http://www.ncbi.nlm.nih.gov/pubmed/22842846.
- Watts DH, Brown ER, Maldonado Y, et al. HIV Disease Progression in the First Year after Delivery among African Women followed in the HPTN 046 Clinical Trial. J Acquir Immune Defic Syndr. 2013. Available at http://www.ncbi.nlm.nih.gov/pubmed/23846568.
- Sha BE, Tierney C, Cohn SE, et al. Postpartum viral load rebound in HIV-1-infected women treated with highly active antiretroviral therapy: AIDS clinical trials group protocol A5150. HIV Clin Trials. 2011;12(1):9-23. Available at http://www.ncbi.nlm.nih.gov/pubmed/21388937.
- Tungsiripat M, Drechsler H, Aberg JA. Discontinuation of antiretroviral therapy postpartum: no evidence for altered viral set point. J Acquir Immune Defic Syndr. 2007;44(1):116-117. Available at http://www.ncbi.nlm.nih.gov/pubmed/17195738.
- Hoffman RM, Leister E, Kacanek D, et al. Biomarkers from late pregnancy to six weeks postpartum in HIV-infected women who continue versus discontinue antiretroviral therapy after delivery. J Acquir Immune Defic Syndr. 2013. Available at http://www.ncbi.nlm.nih.gov/pubmed/23714738.
- Thompson MA, Mugavero MJ, Amico KR, et al. Guidelines for improving entry into and retention in care and antiretroviral adherence for persons with HIV: evidence-based recommendations from an International Association of Physicians in AIDS Care panel. Ann Intern Med. 2012;156(11):817-833, W-284–W-294. Available at http://www.ncbi.nlm.nih.gov/pubmed/22393036.
- Ross R, Sawatphanit W, Mizuno M, Takeo K. Depressive symptoms among HIV-positive postpartum women in Thailand. Arch Psychiatr Nurs. 2011;25(1):36-42. Available at http://www.ncbi.nlm.nih.gov/pubmed/21251600.
- Chibanda D, Mangezi W, Tshimanga M, et al. Postnatal depression by HIV status among women in Zimbabwe. J Womens Health (Larchmt). 2010;19(11):2071-2077. Available at http://www.ncbi.nlm.nih.gov/pubmed/20849286.
- Rubin LH, Cook JA, Grey DD, et al. Perinatal depressive symptoms in HIV-infected versus HIV-uninfected women: a prospective study from preconception to postpartum. J Womens Health (Larchmt). 2011;20(9):1287-1295. Available at http://www.ncbi.nlm.nih.gov/pubmed/21732738.
- Kapetanovic S, Christensen S, Karim R, et al. Correlates of perinatal depression in HIV-infected women. AIDS Patient Care STDS. 2009;23(2):101-108. Available at http://www.ncbi.nlm.nih.gov/pubmed/19196032.
- Paterson DL, Swindells S, Mohr J, et al. Adherence to protease inhibitor therapy and outcomes in patients with HIV infection. Ann Intern Med. 2000;133(1):21-30. Available at http://www.ncbi.nlm.nih.gov/pubmed/10877736.
- Le Moing V, Chene G, Carrieri MP, et al. Clinical, biologic, and behavioral predictors of early immunologic and virologic response in HIV-infected patients initiating protease inhibitors. J Acquir Immune Defic Syndr. 2001;27(4):372-376. Available at http://www.ncbi.nlm.nih.gov/pubmed/11468425.
- Murri R, Ammassari A, Gallicano K, et al. Patient-reported nonadherence to HAART is related to protease inhibitor levels. J Acquir Immune Defic Syndr. 2000;24(2):123-128. Available at http://www.ncbi.nlm.nih.gov/pubmed/10935687.
- Jackson E. Controversies in postpartum contraception: when is it safe to start oral contraceptives after childbirth? Thromb Res. 2011;127 Suppl 3:S35-39. Available at http://www.ncbi.nlm.nih.gov/pubmed/21262436.
- Jackson E, Glasier A. Return of ovulation and menses in postpartum nonlactating women: a systematic review. Obstet Gynecol. 2011;117(3):657-662. Available at http://www.ncbi.nlm.nih.gov/pubmed/21343770.
- Sholapurkar SL. Is there an ideal interpregnancy interval after a live birth, miscarriage or other adverse pregnancy outcomes? J Obstet Gynaecol. 2010;30(2):107-110. Available at http://www.ncbi.nlm.nih.gov/pubmed/20143964.
- Cates W, Jr., Steiner MJ. Dual protection against unintended pregnancy and sexually transmitted infections: what is the best contraceptive approach? Sex Transm Dis. 2002;29(3):168-174. Available at http://www.ncbi.nlm.nih.gov/pubmed/11875378.
- World Health Organization. Review of Priorities in Research on Hormnonal Contraception and IUDs and HIV Infection. Geneva, Switzerland; 2010.
- Polis CB, Curtis KM. Use of hormonal contraceptives and HIV acquisition in women: a systematic review of the epidemiological evidence. Lancet Infect Dis. 2013;13(9):797-808. Available at http://www.ncbi.nlm.nih.gov/pubmed/23871397.
- Kreitchmann R, Harris R, Kakehasi F, et al. Adherence during pregnancy and post-partum: Latin America. Abstract 1016. Paper presented at: 6th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention; 2011; Rome, Italy.
- Kaida A, Kanters S, Chaworth-Musters T, et al. Antiretroviral adherence during pregnancy and postpartum among HIV-positive women receiving highly active antiretroviral therapy (HAART) in British Columbia (BC), Canada (1997–2008). CDB397-CD-ROM. Paper presented at: 6th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention; 2011; Rome, Italy.
- Mellins CA, Chu C, Malee K, et al. Adherence to antiretroviral treatment among pregnant and postpartum HIV-infected women. AIDS Care. 2008;20(8):958-968. Available at http://www.ncbi.nlm.nih.gov/pubmed/18608073.
- Nachega J, Uthman C, Mills E, Muessig K, al e. Adherence to antiretroviral therapy (ART) during and after pregnancy in low, middle and high income countries: a systematic review and meta-analysis. Abstract 1006. Paper presented at: 19th Conference on Retroviruses and Opportunistic Infections; 2012; Seattle, WA.
- Cohn SE, Umbleja T, Mrus J, Bardeguez AD, Andersen JW, Chesney MA. Prior illicit drug use and missed prenatal vitamins predict nonadherence to antiretroviral therapy in pregnancy: adherence analysis A5084. AIDS Patient Care STDS. 2008;22(1):29-40. Available at http://www.ncbi.nlm.nih.gov/pubmed/18442305.
- Ickovics JR, Wilson TE, Royce RA, et al. Prenatal and postpartum zidovudine adherence among pregnant women with HIV: results of a MEMS substudy from the Perinatal Guidelines Evaluation Project. J Acquir Immune Defic Syndr. 2002;30(3):311-315. Available at http://www.ncbi.nlm.nih.gov/pubmed/12131568.
- Bardeguez AD, Lindsey JC, Shannon M, et al. Adherence to antiretrovirals among US women during and after pregnancy. J Acquir Immune Defic Syndr. 2008;48(4):408-417. Available at http://www.ncbi.nlm.nih.gov/pubmed/18614923.
- Centers for Disease Control and Prevention. Rapid HIV-1 antibody testing during labor and delivery for women of unknown HIV status: a practical guide and model protocol. 2004. Available at http://stacks.cdc.gov/view/cdc/13256/. Last accessed March 19, 2014.