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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: August 6, 2015; last reviewed: August 6, 2015)
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 (AI). Decisions should take into account current recommendations for initiation of cART in adults, HIV RNA levels, adherence issues, whether a woman has an HIV-uninfected sexual partner, and patient preferences.
Because the immediate postpartum period poses unique challenges to antiretroviral adherence, arrangements for new or continued supportive services should be made before hospital discharge for women continuing cART (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 (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
Postpartum Follow-Up of HIV-Infected Women
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;
Coordination of care through case management for a woman, her child(ren), and other family members; and
Prevention of secondary transmission for serodiscordant partners, including counseling on the use of condoms, combination antiretroviral therapy (cART) to maintain virologic suppression in the infected partner (i.e., Treatment as Prevention [TasP]), and potential use of pre-exposure prophylaxis (PrEP) by the uninfected partner.
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.
Immediate linkage 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, the fourth-generation combined antibody-antigen test should be employed if available1 (or confirmatory HIV antibody testing should be performed as soon as possible after an initial positive rapid test). The updated Centers for Disease Control and Prevention algorithm for HIV testing may allow for results of the antigen/antibody combination immunoassay and then the HIV-1/HIV-2 antibody differentiation assay to be available prior to a woman’s discharge after delivery. 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 should receive the same thorough evaluation as other newly identified infected patients, including recommendation of cART and prophylaxis for opportunistic infections, as indicated. Other children and partner(s) should be referred for HIV testing. Counseling on prevention of secondary transmission to the uninfected partner should include condoms, cART for the infected partner to maintain viral suppression, and potential use of PrEP by the uninfected partner.
During the postpartum period, maternal medical services must be coordinated between obstetric care providers and HIV specialists. Decisions to continue cART after delivery should be made in consultation with a 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.2 The START and TEMPRANO trials were randomized clinical trials that demonstrated that early cART can reduce the risk of disease progression even in individuals with CD4 T lymphocyte cell count >500 cells/mm3, and the HPTN 052 randomized clinical trial demonstrated that early cART can reduce risk of sexual transmission to a discordant partner by 96%.3-5 It is important to counsel a woman that no single method (including treatment) is 100% protective against HIV transmission, so safer sexual practices should be continued.
Studies have demonstrated significant decreases in cART adherence postpartum.6-9 During the postpartum period, women may have difficulty with medical appointment follow-up, which can affect cART adherence. Systematic monitoring of retention in HIV care is recommended for all HIV-infected individuals, but special attention is warranted during the postpartum period. A number of studies have suggested that postpartum depression may be common among HIV-infected women.10-14 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.15-17
Health care providers should be vigilant in screening for signs of depression, intimate partner violence, and illicit drug or alcohol use that may require intervention to avoid problems with cART adherence. Interventions to improve adherence to medical care and cART can include medication management services, referral to psychological services, community outreach, one-on-one adherence support, group education and support, peer support, reminder devices, and home visits by HIV case managers.18 Poor adherence has been shown to be associated with virologic failure, development of resistance, and decreased long-term effectiveness of cART.19-21 Simplification of a cART regimen (e.g., a change 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 ensure effectiveness of therapy (see the section on Adherence in the Adult and Adolescent Antiretroviral Guidelines). For women continuing cART who had received increased protease inhibitor doses during pregnancy, available data suggest that standard doses can be used again, beginning immediately after delivery.
It is important that comprehensive family planning and preconception care be integrated into routine prenatal and health visits. 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.22 Interpregnancy intervals of less than 18 months have been associated with increased risk of poor perinatal and maternal outcomes in HIV-uninfected women.23 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.24 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 to a partner, and acquisition or transmission of sexually transmitted disease.25 Longer-term reversible contraceptive methods, such as injectables, implants, and intrauterine devices (IUDs) should be included as options.
The postpartum period is a critical time for addressing safer sex practices in order to reduce sexual transmission of HIV to HIV-uninfected partners and contraception to avoid unwanted pregnancies. Ideally these issues will be addressed during the prenatal period. There are drug-drug interactions between a number of antiretroviral (ARV) drugs and hormonal contraceptives as 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 and recommends the use of all contraceptive methods in women with HIV.26,27 Findings from a systematic review of hormonal contraceptive methods and risk of HIV transmission to uninfected partners concluded that oral contraceptives and medroxyprogesterone do not increase risk of HIV transmission in women who are on cART though data are limited and have methological issues.28 Permanent sterilization is appropriate only for women who are certain they do not desire future childbearing.
Avoidance of breastfeeding has been and continues to be a standard, strong recommendation for HIV-infected women in the United States, because maternal cART dramatically reduces but does not eliminate breastmilk transmission. Further, safe infant feeding alternatives are readily available in the United States. In addition there are concerns about other potential risks, including toxicity for the neonate or increased risk of development of ARV drug resistance, should transmission occur, due to variable passage of drugs into breastmilk. However, clinicians should be aware that women may face social, familial, and personal pressures to consider breastfeeding despite this recommendation.29 It is important to address possible barriers to formula feeding beginning during the antenatal period.
Similarly, there are risks of HIV transmission via premastication (prechewing) of infant food.30
Centers for Disease Control and Prevention and Association of Public Health Laboratories. Laboratory testing for the diagnosis of HIV infection: updated recommendations. 2014. Available at http://stacks.cdc.gov/view/cdc/23447. Accessed January 17, 2015.
Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. 2014. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf. Accessed July 8, 2015.
Danel C, Gabillard D, Le Carrou J, et al. Early ART and IPT in HIV-infected African adults with high CD4 count (Temprano Trial). Presented at: 22nd Conference on Retroviruses and Opportunistic Infections. 2015. Seattle, WA.
National Institute of Allergy and Infectious Diseases. Starting antiretroviral treatment early improves outcomes for HIV-infected individuals. NIH News. 2015. Available at http://www.niaid.nih.gov/news/newsreleases/2015/Pages/START.aspx. Accessed July 8, 2015.
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.
Kreitchmann R, Harris R, Kakehasi F, et al. Adherence during pregnancy and post-partum: Latin America. Abstract 1016. 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. 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, et al. Adherence to antiretroviral therapy (ART) during and after pregnancy in low, middle and high income countries: a systematic review and meta-analysis. Abstract 1006. Presented at: 19th Conference on Retroviruses and Opportunistic Infections. 2012. Seattle, WA.
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.
Bonacquisti A, Geller PA, Aaron E. Rates and predictors of prenatal depression in women living with and without HIV. AIDS Care. 2014;26(1):100-106. Available at http://www.ncbi.nlm.nih.gov/pubmed/23750820.
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.
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-285, W-286, W-287, W-288, W-289, W-290, W-291, W-292, W-293, W-294. Available at http://www.ncbi.nlm.nih.gov/pubmed/22393036.
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, 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.
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.
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. 2010; Geneva.
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.
Haddad LB, Polis CB, Sheth AN, et al. Contraceptive methods and risk of HIV acquisition or female-to-male transmission. Curr HIV/AIDS Rep. 2014;11(4):447-458. Available at http://www.ncbi.nlm.nih.gov/pubmed/25297973.
Levison J, Weber S, Cohan D. Breastfeeding and HIV-infected women in the United States: harm reduction counseling strategies. Clin Infect Dis. 2014;59(2):304-309. Available at http://www.ncbi.nlm.nih.gov/pubmed/24771330.
Gaur AH, Dominguez KL, Kalish ML, et al. Practice of feeding premasticated food to infants: a potential risk factor for HIV transmission. Pediatrics. 2009;124(2):658-666. Available at http://www.ncbi.nlm.nih.gov/pubmed/19620190.