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 Management
Postpartum Follow-Up of HIV-Infected Women
(Last updated:9/14/2011)
Panel’s Recommendations :
- Contraceptive counseling should be included as a critical aspect of postpartum care (AIII).
- Decisions about continuing antiretroviral (ARV) drugs after delivery should take into account current recommendations for initiation of antiretroviral therapy (ART), current and nadir CD4 cell counts and trajectory, HIV RNA levels, adherence issues, whether the woman has an HIV-uninfected sexual partner, and patient preference (AIII).
- For women continuing ARV drugs 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).
- Women with a positive rapid HIV antibody test during labor require 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 ART and opportunistic infection (OI) prophylaxis (AII).
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The postpartum period provides an opportunity to review and optimize women’s health care. Comprehensive care and support services are particularly important for women with HIV infection and their families, who often face multiple medical and social challenges. Components of comprehensive care include the following medical and supportive care 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 the woman, her child(ren), and other family members.
Support services should be tailored to individual women’s needs and may 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. It is especially critical to ensure continuity of the antepartum ARV drug regimen when such treatment is required for a woman’s health . The decision about whether to continue ARV drugs after delivery should be discussed with a woman and made before delivery.
The postpartum period also is a critical time for addressing the issue of safer sex practices and contraception. Lack of breastfeeding is associated with earlier return of fertility; ovulation returns as early as 6 weeks postpartum, and even earlier in some women, putting them at risk of pregnancy shortly after delivery [1]. Interpregnancy intervals of less than 18 months have been associated with increased risk of poor perinatal and maternal outcomes in HIV-uninfected women [2]. 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 [3]. This is an important concern in women who are on an efavirenz-containing regimen because of the potential risk of teratogencity. A “dual-protection” strategy, such as use of condoms plus a second highly effective contraceptive, is ideal for women with HIV infection because it provides simultaneous protection against unintended pregnancy and HIV transmission or sexually transmitted infection (STI) acquisition or transmission [4]. 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 (OCs) and many ARV drugs (see Table 4 in Preconception Counseling). These interactions, however, do not necessarily rule out the use of hormonal contraceptives because there is no clear evidence of an effect on contraceptive or ARV efficacy or toxicity. OCs do significantly lower levels of amprenavir/fosamprenavir and, therefore, coadministration is not recommended; whether low-dose ritonavir boosting raises amprenavir levels sufficiently to allow coadministration is unknown. Depot medroxyprogesterone acetate (Depo-Provera, DMPA) pharmacokinetics (PKs) are not significantly affected by nevirapine, efavirenz, or nelfinavir, and levels of these drugs were not significantly altered by DMPA [5]. Adverse effects of DMPA are no different in HIV-infected women on ARV drugs than in HIV-uninfected women [6]. Other non-oral contraceptives, such as levonorgestrel implants, the combined contraceptive patch, the combined hormonal contraceptive vaginal ring, and the levonorgestrel IUD, are largely unstudied in combination with ARV drugs, but some data do exist on lopinavir/ritonavir interactions with the estrogen patch [7]. ARV drug interactions may be of less concern with contraceptive methods that exert primarily local activity and have minimal systemic absorption, but there is still a potential for interaction if metabolic or elimination pathways are shared [5, 8]. Permanent sterilization is appropriate only for women who are certain they do not desire future childbearing.
Women with nadir CD4 cell counts less than the currently recommended threshold for institution of ART [9] and/or symptomatic HIV infection should be encouraged to continue their ARV regimens postpartum without interruption. Decisions about whether to continue ARV drugs after delivery should be made in consultation with the HIV provider for women who began ARV drugs for prophylaxis of transmission with nadir CD4 cell counts greater than that currently recommended for treatment. Factors to be taken into consideration should include current recommendations for initiation of ART, current and nadir CD4 lymphocyte counts and trajectory, HIV RNA levels, adherence issues, partner HIV status, and patient preference. The risks versus benefits of stopping combination ARV drug regimens postpartum in women with high CD4 cell counts are being evaluated in the ongoing PROMISE study (clinical trial number NCT00955968).
Recent data from the HPTN 052 clinical trial showed that earlier initiation of ARVs led to a significant reduction in sexual transmission of HIV to uninfected partners in serodiscordant couples (see Preconception Counseling). HPTN 052 evaluated immediate versus delayed initiation of ART to HIV-infected individuals with CD4 counts between 350 and 550 cells/mm3. Based on the results from that trial, continued administration of ARV drugs may be recommended for prevention of sexual transmission of HIV for postpartum women who have CD4 cell counts between 350 and 550 cells/mm3 and have HIV-uninfected sexual partners, and it may be considered for those with CD4 cell counts greater than 550 cells/mm3 with HIV-uninfected sexual partners. 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 should be continued.
Concerns have been raised about adherence to ARV regimens during the postpartum period. 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 [10-12]. Health care providers should be vigilant for signs of depression and illicit drug or alcohol use that may require assessment and treatment and interfere with adherence. Poor adherence has been shown to be associated with virologic failure, development of resistance, and decreased long-term effectiveness of ART [13-15]. Simplification of an ARV regimen (for example, to once-daily medications) can be considered. It may be preferable to temporarily interrupt ART in women who are unable to adhere to their regimens while they work with a 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 Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents).
For women whose antepartum regimen included a non-nucleoside reverse transcriptase inhibitor (NNRTI) and who plan to stop ARV prophylaxis 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 Therapy during Pregnancy and Prevention of Antiretroviral Drug Resistance). Women whose antepartum regimen did not include an NNRTI and who plan to stop ARV prophylaxis after delivery should stop all ARV drugs at the same time. Doses of some PIs may be increased during pregnancy. For women continuing therapy, available data suggest that standard doses can be used again, beginning immediately after delivery.
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 [16]. 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 ART and prophylaxis for OIs, as indicated. Other children and partner(s) should be referred for HIV testing.
References
1. Jackson E, Glasier A. Return of ovulation and menses in postpartum nonlactating women: a systematic review. Obstet Gynecol. 2011 Mar;117(3):657-662.
2. Sholapurkar SL. Is there an ideal interpregnancy interval after a live birth, miscarriage or other adverse pregnancy outcomes? J Obstet Gynaecol. 2010 Feb;30(2):107-110.
3. 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 Jan-Feb;12(1):9-23.
4. Cates W, Jr., Steiner MJ. Dual protection against unintended pregnancy and sexually transmitted infections: what is the best contraceptive approach? Sex Transm Dis. 2002 Mar;29(3):168-174.
5. Cohn SE, Park JG, Watts DH, et al. Depo-medroxyprogesterone in women on antiretroviral therapy: effective contraception and lack of clinically significant interactions. Clin Pharmacol Ther. 2007 Feb;81(2):222-227.
6. Watts DH, Park JG, Cohn SE, et al. Safety and tolerability of depot medroxyprogesterone acetate among HIV-infected women on antiretroviral therapy: ACTG A5093. Contraception. 2008 Feb;77(2):84-90.
7. Vogler MA, Patterson K, Kamemoto L, et al. Contraceptive efficacy of oral and transdermal hormones when co-administered with protease inhibitors in HIV-1-infected women: pharmacokinetic results of ACTG trial A5188. J Acquir Immune Defic Syndr. 2010 Dec 1;55(4):473-482.
8. Womack J, Williams A. Hormonal contraception in HIV-positive women. AIDS Read. 2008 Jul;18(7):372-377, 381.
9. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. 2011:1-174. http://aidsinfo.nih.gov/contentfiles/AdultandAdolescentGL.pdf.
10. 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 Jan;22(1):29-40.
11. 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 Jul 1;30(3):311-315.
12. Bardeguez AD, Lindsey JC, Shannon M, et al. Adherence to antiretrovirals among US women during and after pregnancy. J Acquir Immune Defic Syndr. 2008 Aug 1;48(4):408-417.
13. Paterson DL, Swindells S, Mohr J, et al. Adherence to protease inhibitor therapy and outcomes in patients with HIV infection. Ann Intern Med. 2000 Jul 4;133(1):21-30.
14. 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 Aug 1;27(4):372-376.
15. 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 Jun 1;24(2):123-128.
16. Centers for Disease Control and Prevention (CDC). Rapid HIV-1 antibody testing during labor and delivery for women of unknown HIV status: a practical guide and model protocol. 2004; www.cdc.gov/hiv/topics/testing/resources/guidelines/pdf/Labor&DeliveryRapidTesting.pdf.