Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV
Considerations for Antiretroviral Use in Special Patient Populations
Women with HIV
Last Updated: July 14, 2016; Last Reviewed: July 14, 2016
|Rating of Recommendations: A = Strong; B = Moderate; C = Optional
Rating of Evidence: I = Data from randomized controlled trials; II = Data from well-designed nonrandomized trials or observational cohort studies with long-term clinical outcomes; III = Expert opinion
This section discusses some unique issues to consider and basic principles to follow when caring for women living with HIV, including during pregnancy. Clinicians who care for pregnant women should consult the current 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 (Perinatal Guidelines) for a more in-depth discussion and guidance on managing these patients.
Gender Considerations in Antiretroviral Therapy
In general, studies to date have not shown gender differences in virologic responses to antiretroviral therapy (ART).1-4 However, there are limited data showing that pharmacokinetics (PKs) for some antiretroviral (ARV) drugs may differ between men and women, possibly because of variations between men and women in factors such as body weight, plasma volume, gastric emptying time, plasma protein levels, cytochrome P (CYP) 450 activity, drug transporter function, and excretion activity.5-7
Several studies have suggested that gender may influence the frequency, presentation, and severity of some ARV-related adverse events. Most notably, women are more likely to develop severe symptomatic hepatotoxicity with nevirapine (NVP) use,8,9 and are more likely to develop symptomatic lactic acidosis with prolonged use of older nucleoside reverse transcriptase inhibitors (NRTIs) such as zidovudine (ZDV), stavudine (d4T), and didanosine (ddI).10 These agents are no longer recommended for use in people with HIV in the United States; although ZDV is still administered intravenously (IV) to women during delivery, it is not generally recommended for long-term use.
Some studies have compared women and men in relation to metabolic complications associated with ARV use. Over 96 weeks following initiation of ART, women with HIV are less likely to have decreases in limb fat but more likely to have decreases in bone mineral density (BMD) than men with HIV.11,12 Women have an increased risk of osteopenia, osteoporosis, and fractures, particularly after menopause, and this risk is exacerbated by HIV and ART.13-16 ART regimens that contain tenofovir disoproxil fumarate (TDF), ritonavir-boosted protease inhibitors (PI/r), or both are associated with a significantly greater loss of BMD than regimens containing other NRTIs and raltegravir (RAL).17-20 Abacavir (ABC), NRTI-sparing regimens, and tenofovir alafenamide (TAF; a new oral tenofovir prodrug that induces less bone loss than TDF) may be considered as alternatives to TDF in patients who are at risk of osteopenia or osteoporosis. Recommendations for management of bone disease in people with HIV have been published.21
Women with HIV of Childbearing Potential
All women with HIV of childbearing potential should be offered comprehensive reproductive and sexual health counseling and care as part of routine primary medical care. Topics for discussion should include safe sex practices, reproductive desires and options for conception, the HIV status of sex partner(s), and use of effective contraception to prevent unintended pregnancy. Counseling should also include discussion of special considerations pertaining to ARV use when using hormonal contraceptives, when trying to conceive, and during pregnancy (see the Perinatal Guidelines).
Reproductive Options for Serodiscordant Couples
A women who wishes to conceive with a serodiscordant male partner should be informed of options to prevent sexual transmission of HIV while attempting conception. Interventions include screening and treating both partners for sexually transmitted infections (STIs), ART to maximally suppress and maintain the viral load of the partner with HIV, use of pre-exposure prophylaxis by the uninfected partner,22-24 male circumcision, and/or self-insemination with the HIV-uninfected partner’s sperm during the periovulatory period of the woman with HIV.25
Efavirenz (EFV) is teratogenic in nonhuman primates. Nonpregnant women of childbearing potential should have a pregnancy test before starting EFV and be advised of potential EFV-related risks to the fetus and the desirability of avoiding conception while on an EFV-based regimen (AIII). Regimens that do not include EFV should be considered in women who are planning to become pregnant or who are sexually active and not using effective contraception (BIII). The most vulnerable period in fetal organogenesis is early in gestation, usually before pregnancy is recognized. Efavirenz use after the first 8 weeks of pregnancy appears safe.
Safe and effective reproductive health and family planning services to prevent unintended pregnancies and perinatal transmission of HIV are an essential component of care for women with HIV of childbearing age. These women should receive ongoing counseling on reproductive issues. Regardless of hormonal contraceptive use, women with HIV should be advised to consistently use condoms (male or female) during sex and adhere to an HIV regimen that effectively maintains viral suppression. Both strategies are crucial to prevent transmission of HIV to uninfected partners and to protect against infection with other STIs. The following are some considerations when hormonal contraceptives are used.
PK interactions between ARV drugs and hormonal contraceptives may reduce contraceptive efficacy. However, there are limited clinical data regarding drug interactions between ARVs and hormonal contraceptives and the clinical implications of these interactions are unclear. The magnitudes of changes in drug levels that may reduce contraceptive efficacy or increase adverse effects are unknown.
- Combined Oral Contraceptives (COCs): Several PIs, EFV, and elvitegravir/cobicistat (EVG/c)-based regimens have drug interactions with COCs. Interactions include either a decrease or an increase in blood levels of ethinyl estradiol, norethindrone, or norgestimate (see Tables 18a, 18b, and 18d), which potentially decreases contraceptive efficacy or increases estrogen- or progestin-related adverse effects (e.g., thromboembolism). EFV can decrease etonogestrel bioavailability and plasma progestin concentrations of COCs containing ethinyl estradiol and norgestimate.26 Several PI/r and EVG/c decrease oral contraceptive estradiol levels.27-30 Several PK studies have shown that ETR, RPV, and NVP use did not significantly affect estradiol or progestin levels in women with HIV using COCs.31-33
- Injectable Contraceptives: Small studies of women with HIV receiving injectable depot-medroxyprogesterone acetate (DMPA) while on ART showed no significant interactions between DMPA and EFV, lopinavir/ritonavir (LPV/r), NVP, nelfinavir (NFV), or NRTI drugs.34-37
- Contraceptive Implants: Contraceptive failure of the etonogestrel implant in women on EFV-based therapy has been reported.38,39 Studies of women with levonorgestrel- and etonogestrel-releasing implants reported that participants receiving EFV-based ART had decreased bioavailability of levonorgestrel and etonogestrel.40,41 These PK studies did not identify any change in hormone concentrations when the implants were used in women taking NVP40 or LPV/r.41 Similarly, two retrospective cohort evaluations conducted in Swaziland and Kenya showed an increased risk of contraceptive failure in women using contraceptive implants and receiving EFV.42,43
Concerns about PK interactions between oral or implantable hormonal contraceptives and ARVs should not prevent clinicians from prescribing hormonal contraceptives for women on ART who prefer this contraceptive method. However, an alternative or additional effective contraceptive method is recommended when there are significant drug interactions between hormonal contraceptives and ARVs (see drug interaction Tables 18a, 18b, and 18d and the Perinatal Guidelines).
Risk of HIV Acquisition and Transmission
Studies have produced conflicting data on the association between hormonal contraception and the risk of acquisition of HIV.44 Most of the retrospective studies were done in the setting where the partners with HIV were not taking ART. A retrospective secondary analysis of two studies of serodiscordant couples in Africa in which the partner with HIV was not receiving ART found that women using hormonal contraception (the majority using injectable DMPA) had a two-fold increased risk of acquiring or transmitting HIV. Women with HIV using hormonal contraception had higher genital HIV RNA concentrations than those not using hormonal contraceptives.45 Oral contraceptive use was not significantly associated with transmission of HIV; however, the number of women using oral contraceptives in this study was insufficient to adequately assess risk. A World Health Organization expert group reviewed all available evidence regarding hormonal contraception and HIV transmission to a partner without HIV and recommended that women living with HIV can continue to use all existing hormonal contraceptive methods without restriction.46 Further research is needed to definitively determine if hormonal contraceptive use is an independent risk factor for acquisition and transmission of HIV, particularly in the setting of ART. Regardless, the potential association of hormonal contraception use and HIV transmission in the absence of ART underscores the importance of ART-induced viral suppression to reduce transmission risk.
Intrauterine devices (IUDs) appear to be a safe and effective contraceptive option for women with HIV.47-49 Although studies have focused primarily on nonhormone-containing IUDs (e.g., copper IUD), several small studies have found that levonorgestrel-releasing IUDs are also safe and not associated with increased genital tract shedding of HIV.50-52
Clinicians caring for pregnant women with HIV should review the Perinatal Guidelines. The use of combination ARV regimens is recommended for all pregnant women with HIV, regardless of virologic, immunologic, or clinical parameters, for their own health and to prevent transmission of HIV to the fetus (AI). Pregnant women with HIV should be counseled regarding the known benefits and risks of ARV use during pregnancy to the woman, fetus, and newborn. Women should be counseled and strongly encouraged to receive ART for their own health and that of their infants. Open, nonjudgmental and supportive discussion should be used to encourage women to adhere to care.
Prevention of Perinatal Transmission of HIV
The use of ART and the resultant reduction of HIV RNA levels decrease perinatal transmission of HIV.53-55 The goal of ART is to achieve maximal and sustained viral suppression throughout pregnancy. Long-term follow-up is recommended for all infants born to women who receive ART during pregnancy, regardless of the infant’s HIV status (see the Perinatal Guidelines).
ARV Regimen Considerations
Pregnancy should not preclude the use of optimal ARV regimens. As in nonpregnant individuals, genotypic resistance testing is recommended for all pregnant women before ARV initiation (AIII) and for pregnant women with detectable HIV RNA while on ART (AI). However, ART initiation should not be delayed in pregnant women pending genotypic resistance testing results. The ARV regimen can be modified, if necessary, once the resistance testing results are available (BIII). Unique considerations that influence recommendations on ARVs to use to treat pregnant women with HIV include the following:
- Physiologic changes associated with pregnancy that potentially result in changes in PKs, which may affect ARV dosing at different stages of pregnancy;
- Potential ARV-associated adverse effects in pregnant women and the potential for adherence to a particular regimen during pregnancy; and
- Potential short- and long-term effects of an ARV on the fetus and newborn, which are unknown for many drugs.
ART is considered the standard of care for pregnant women with HIV, both to treat HIV infection and prevent perinatal transmission of HIV. If a pregnant woman receiving an EFV-based regimen presents to prenatal care during the first trimester with suppressed HIV RNA, EFV can be continued. This is because the risk of fetal neural tube defects is restricted to the first 5 to 6 weeks of pregnancy and pregnancy is rarely recognized before 4 to 6 weeks of pregnancy. Unnecessary changes in ARV drugs during pregnancy may be associated with loss of viral control and increased risk of perinatal transmission. Detailed recommendations on ARV choice in pregnancy are discussed in detail in the Perinatal Guidelines.
If maternal HIV RNA is ≥1,000 copies/mL (or unknown) near delivery, IV infusion of ZDV during labor is recommended regardless of the mother’s antepartum regimen and resistance profile, and the mode of delivery (AI). Administration of combination ART should continue during labor and before a cesarean delivery (oral medications can be continued with sips of water).
Clinicians who are treating pregnant women with HIV are strongly encouraged to report cases of prenatal exposure to ARVs (either administered alone or in combinations) to the Antiretroviral Pregnancy Registry (http://www.apregistry.com). The registry collects observational data regarding exposure to Food and Drug Administration (FDA)-approved ARV drugs during pregnancy to assess potential teratogenicity. Analysis of the Antiretroviral Pregnancy Registry data indicates that there is no clear association between first-trimester exposure to any ARV drug and increased risk of birth defects. For more information regarding selection and use of ART during pregnancy, refer to the Perinatal Guidelines.
Following delivery, clinical, immunologic, and virologic follow-up should continue as recommended for nonpregnant adults and adolescents. Because maternal ART reduces but does not eliminate the risk of transmission of HIV in breast milk and postnatal transmission can occur despite maternal ART, women should be counseled to avoid breastfeeding.56 Women with HIV should not premasticate food and feed it to their infants because the practice has been associated with mother-to-child transmission of HIV.57 ART is currently recommended for all individuals with HIV (AI), therefore maternal ART should be continued after delivery. For more information regarding postpartum management, refer to the Perinatal Guidelines.
Several studies have demonstrated that adherence to ART may decline in the postpartum period.58-60 Clinicians caring for postpartum women who are receiving ART should address adherence, including an evaluation of specific facilitators and barriers to adherence. Clinicians may recommend an intervention to improve adherence (see Adherence to the Continuum of Care).
- Collazos J, Asensi V, Carton JA. Sex differences in the clinical, immunological and virological parameters of HIV-infected patients treated with HAART. AIDS. Apr 23 2007;21(7):835-843. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17415038.
- Fardet L, Mary-Krause M, Heard I, Partisani M, Costagliola D. Influence of gender and HIV transmission group on initial highly active antiretroviral therapy prescription and treatment response. HIV Med. Nov 2006;7(8):520-529. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17105511.
- Currier J, Averitt Bridge D, Hagins D, et al. Sex-based outcomes of darunavir-ritonavir therapy: a single-group trial. Ann Intern Med. Sep 21 2010;153(6):349-357. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20855799.
- Rosin C, Elzi L, Thurnheer C, et al. Gender inequalities in the response to combination antiretroviral therapy over time: the Swiss HIV Cohort Study. HIV Med. May 2015;16(5):319-325. Available at http://www.ncbi.nlm.nih.gov/pubmed/25329751.
- Gandhi M, Aweeka F, Greenblatt RM, Blaschke TF. Sex differences in pharmacokinetics and pharmacodynamics. Annu Rev Pharmacol Toxicol. 2004;44:499-523. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14744256.
- Ofotokun I, Chuck SK, Hitti JE. Antiretroviral pharmacokinetic profile: a review of sex differences. Gend Med. Jun 2007;4(2):106-119. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17707845.
- Venuto CS, Mollan K, Ma Q, et al. Sex differences in atazanavir pharmacokinetics and associations with time to clinical events: AIDS Clinical Trials Group Study A5202. J Antimicrob Chemother. Dec 2014;69(12):3300-3310. Available at http://www.ncbi.nlm.nih.gov/pubmed/25159623.
- Baylor MS, Johann-Liang R. Hepatotoxicity associated with nevirapine use. J Acquir Immune Defic Syndr. Apr 15 2004;35(5):538-539. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15021321.
- Wit FW, Kesselring AM, Gras L, et al. Discontinuation of nevirapine because of hypersensitivity reactions in patients with prior treatment experience, compared with treatment-naive patients: the ATHENA cohort study. Clin Infect Dis. Mar 15 2008;46(6):933-940. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18271750.
- Lactic Acidosis International Study Group LAISG. Risk factors for lactic acidosis and severe hyperlactataemia in HIV-1-infected adults exposed to antiretroviral therapy. AIDS. Nov 30 2007;21(18):2455-2464. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18025882.
- McComsey GA, Kitch D, Sax PE, et al. Peripheral and central fat changes in subjects randomized to abacavir-lamivudine or tenofovir-emtricitabine with atazanavir-ritonavir or efavirenz: ACTG Study A5224s. Clin Infect Dis. Jul 15 2011;53(2):185-196. Available at http://www.ncbi.nlm.nih.gov/pubmed/21690627.
- Galli M, Veglia F, Angarano G, et al. Gender differences in antiretroviral drug-related adipose tissue alterations. Women are at higher risk than men and develop particular lipodystrophy patterns. J Acquir Immune Defic Syndr. Sep 1 2003;34(1):58-61. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14501794.
- Yin M, Dobkin J, Brudney K, et al. Bone mass and mineral metabolism in HIV+ postmenopausal women. Osteoporos Int. Nov 2005;16(11):1345-1352. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15754081.
- Brown TT, Qaqish RB. Response to Berg et al. Antiretroviral therapy and the prevalence of osteopenia and osteoporosis: a meta-analytic review. AIDS. Aug 20 2007;21(13):1830-1831. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17690589.
- Sharma A, Shi Q, Hoover DR, et al. Increased fracture incidence in middle-aged HIV-infected and HIV-uninfected women: updated results from the Women's Interagency HIV study. J Acquir Immune Defic Syndr. Sep 1 2015;70(1):54-61. Available at http://www.ncbi.nlm.nih.gov/pubmed/26322667.
- Grant PM, Kitch D, McComsey GA, et al. Low baseline CD4+ count is associated with greater bone mineral density loss after antiretroviral therapy initiation. Clin Infect Dis. Nov 2013;57(10):1483-1488. Available at http://www.ncbi.nlm.nih.gov/pubmed/23943825.
- Stellbrink HJ, Orkin C, Arribas JR, et al. Comparison of changes in bone density and turnover with abacavir-lamivudine versus tenofovir-emtricitabine in HIV-infected adults: 48-week results from the ASSERT study. Clin Infect Dis. Oct 15 2010;51(8):963-972. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20828304.
- Martin A, Bloch M, Amin J, et al. Simplification of antiretroviral therapy with tenofovir-emtricitabine or abacavir-lamivudine: a randomized, 96-week trial. Clin Infect Dis. Nov 15 2009;49(10):1591-1601. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19842973.
- Duvivier C, Kolta S, Assoumou L, et al. Greater decrease in bone mineral density with protease inhibitor regimens compared with nonnucleoside reverse transcriptase inhibitor regimens in HIV-1 infected naive patients. AIDS. Apr 27 2009;23(7):817-824. Available at http://www.ncbi.nlm.nih.gov/pubmed/19363330.
- Brown TT, Moser C, Currier JS, et al. Changes in bone mineral density after initiation of antiretroviral treatment with tenofovir disoproxil fumarate/emtricitabine plus atazanavir/ritonavir, darunavir/ritonavir, or raltegravir. J Infect Dis. Oct 15 2015;212(8):1241-1249. Available at http://www.ncbi.nlm.nih.gov/pubmed/25948863.
- Brown TT, Hoy J, Borderi M, et al. Recommendations for evaluation and management of bone disease in HIV. Clin Infect Dis. Apr 15 2015;60(8):1242-1251. Available at http://www.ncbi.nlm.nih.gov/pubmed/25609682.
- Heffron R, Pintye J, Matthews LT, Weber S, Mugo N. PrEP as peri-conception HIV prevention for women and men. Curr HIV/AIDS Rep. Mar 18 2016. Available at http://www.ncbi.nlm.nih.gov/pubmed/26993627.
- Vernazza PL, Graf I, Sonnenberg-Schwan U, Geit M, Meurer A. Preexposure prophylaxis and timed intercourse for HIV-discordant couples willing to conceive a child. AIDS. Oct 23 2011;25(16):2005-2008. Available at http://www.ncbi.nlm.nih.gov/pubmed/21716070.
- Whetham J, Taylor S, Charlwood L, et al. Pre-exposure prophylaxis for conception (PrEP-C) as a risk reduction strategy in HIV-positive men and HIV-negative women in the UK. AIDS Care. 2014;26(3):332-336. Available at http://www.ncbi.nlm.nih.gov/pubmed/23876052.
- Lampe MA, Smith DK, Anderson GJ, Edwards AE, Nesheim SR. Achieving safe conception in HIV-discordant couples: the potential role of oral preexposure prophylaxis (PrEP) in the United States. Am J Obstet Gynecol. Jun 2011;204(6):488 e481-488. Available at http://www.ncbi.nlm.nih.gov/pubmed/21457911.
- Sevinsky H, Eley T, Persson A, et al. The effect of efavirenz on the pharmacokinetics of an oral contraceptive containing ethinyl estradiol and norgestimate in healthy HIV-negative women. Antivir Ther. 2011;16(2):149-156. Available at http://www.ncbi.nlm.nih.gov/pubmed/21447863.
- 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. Dec 2010;55(4):473-482. Available at http://www.ncbi.nlm.nih.gov/pubmed/20842042.
- Zhang J, Chung E, Yones C, et al. The effect of atazanavir/ritonavir on the pharmacokinetics of an oral contraceptive containing ethinyl estradiol and norgestimate in healthy women. Antivir Ther. 2011;16(2):157-164. Available at http://www.ncbi.nlm.nih.gov/pubmed/21447864.
- Food and Drug Administration. Stribild (package insert). Available at http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203100s000lbl.pdf. Accessed May 16, 2016. 2016.
- Food and Drug Administration. Genvoya (package insert). Gilead. Available at http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/207561s000lbl.pdf. Last accessed May 16, 2016.
- Scholler-Gyure M, Kakuda TN, Woodfall B, et al. Effect of steady-state etravirine on the pharmacokinetics and pharmacodynamics of ethinylestradiol and norethindrone. Contraception. Jul 2009;80(1):44-52. Available at http://www.ncbi.nlm.nih.gov/pubmed/19501215.
- Crauwels HM, van Heeswijk RP, Buelens A, Stevens M, Hoetelmans RM. Lack of an effect of rilpivirine on the pharmacokinetics of ethinylestradiol and norethindrone in healthy volunteers. Int J Clin Pharmacol Ther. Feb 2014;52(2):118-128. Available at http://www.ncbi.nlm.nih.gov/pubmed/24161160.
- Stuart GS, Moses A, Corbett A, et al. Combined oral contraceptives and antiretroviral PK/PD in Malawian women: pharmacokinetics and pharmacodynamics of a combined oral contraceptive and a generic combined formulation antiretroviral in Malawi. J Acquir Immune Defic Syndr. Oct 1 2011;58(2):e40-43. Available at http://www.ncbi.nlm.nih.gov/pubmed/21921726.
- 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. Feb 2007;81(2):222-227. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17192768.
- Nanda K, Amaral E, Hays M, Viscola MA, Mehta N, Bahamondes L. Pharmacokinetic interactions between depot medroxyprogesterone acetate and combination antiretroviral therapy. Fertil Steril. Oct 2008;90(4):965-971. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17880953.
- 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. Feb 2008;77(2):84-90. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18226670.
- Luque AE, Cohn SE, Park JG, et al. Depot medroxyprogesterone acetate in combination with a twice-daily lopinavir-ritonavir-based regimen in HIV-infected women showed effective contraception and a lack of clinically significant interactions, with good safety and tolerability: results of the ACTG 5283 study. Antimicrob Agents Chemother. Apr 2015;59(4):2094-2101. Available at http://www.ncbi.nlm.nih.gov/pubmed/25624326.
- Leticee N, Viard JP, Yamgnane A, Karmochkine M, Benachi A. Contraceptive failure of etonogestrel implant in patients treated with antiretrovirals including efavirenz. Contraception. Apr 2012;85(4):425-427. Available at http://www.ncbi.nlm.nih.gov/pubmed/22036046.
- McCarty EJ, Keane H, Quinn K, Quah S. Implanon(R) failure in an HIV-positive woman on antiretroviral therapy resulting in two ectopic pregnancies. Int J STD AIDS. Jul 2011;22(7):413-414. Available at http://www.ncbi.nlm.nih.gov/pubmed/21729965.
- Scarsi KK, Darin KM, Nakalema S, et al. Unintended Pregnancies Observed With Combined Use of the Levonorgestrel Contraceptive Implant and Efavirenz-based Antiretroviral Therapy: A Three-Arm Pharmacokinetic Evaluation Over 48 Weeks. Clin Infect Dis. Mar 15 2016;62(6):675-682. Available at http://www.ncbi.nlm.nih.gov/pubmed/26646680.
- Vieira CS, Bahamondes MV, de Souza RM, et al. Effect of antiretroviral therapy including lopinavir/ritonavir or efavirenz on etonogestrel-releasing implant pharmacokinetics in HIV-positive women. J Acquir Immune Defic Syndr. Aug 1 2014;66(4):378-385. Available at http://www.ncbi.nlm.nih.gov/pubmed/24798768.
- Patel RC, Onono M, Gandhi M, et al. Pregnancy rates in HIV-positive women using contraceptives and efavirenz-based or nevirapine-based antiretroviral therapy in Kenya: a retrospective cohort study. Lancet HIV. Nov 2015;2(11):e474-482. Available at http://www.ncbi.nlm.nih.gov/pubmed/26520927.
- Perry SH, Swamy P, Preidis GA, Mwanyumba A, Motsa N, Sarero HN. Implementing the Jadelle implant for women living with HIV in a resource-limited setting: concerns for drug interactions leading to unintended pregnancies. AIDS. Mar 13 2014;28(5):791-793. Available at http://www.ncbi.nlm.nih.gov/pubmed/24401645.
- Morrison CS, Nanda K. Hormonal contraception and HIV: an unanswered question. Lancet Infect Dis. Jan 2012;12(1):2-3. Available at http://www.ncbi.nlm.nih.gov/pubmed/21975268.
- Heffron R, Donnell D, Rees H, et al. Use of hormonal contraceptives and risk of HIV-1 transmission: a prospective cohort study. Lancet Infect Dis. Jan 2012;12(1):19-26. Available at http://www.ncbi.nlm.nih.gov/pubmed/21975269.
- World Health Organization. Hormonal contraceptive methods for women at high risk of HIV and living with HIV: 2014 guidance statement. Geneva, Switzerland. 2014. Available at http://apps.who.int/iris/bitstream/10665/128537/1/WHO_RHR_14.24_eng.pdf?ua=1.
- Stringer EM, Kaseba C, Levy J, et al. A randomized trial of the intrauterine contraceptive device vs hormonal contraception in women who are infected with the human immunodeficiency virus. Am J Obstet Gynecol. Aug 2007;197(2):144 e141-148. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17689627.
- Curtis KM, Nanda K, Kapp N. Safety of hormonal and intrauterine methods of contraception for women with HIV/AIDS: a systematic review. AIDS. Nov 2009;23 Suppl 1:S55-67. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20081389.
- U.S. Medical Eligibility Criteria for Contraceptive Use. Recommendations and Reports June 18, 2010 / 59(RR04);1-6; Prepared by Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion: (http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5904a1.htm?s_cid=rr5904a1_e). 2010.
- Heikinheimo O, Lehtovirta P, Aho I, Ristola M, Paavonen J. The levonorgestrel-releasing intrauterine system in human immunodeficiency virus-infected women: a 5-year follow-up study. Am J Obstet Gynecol. Feb 2011;204(2):126 e121-124. Available at http://www.ncbi.nlm.nih.gov/pubmed/21035781.
- Lehtovirta P, Paavonen J, Heikinheimo O. Experience with the levonorgestrel-releasing intrauterine system among HIV-infected women. Contraception. Jan 2007;75(1):37-39. Available at http://www.ncbi.nlm.nih.gov/pubmed/17161122.
- Coleman JS, Mwachari C, Balkus J, et al. Effect of the levonorgestrel intrauterine device on genital HIV-1 RNA shedding among HIV-1-infected women not taking antiretroviral therapy in Nairobi, Kenya. J Acquir Immune Defic Syndr. Jun 1 2013;63(2):245-248. Available at http://www.ncbi.nlm.nih.gov/pubmed/23446496.
- Ioannidis JP, Abrams EJ, Ammann A, et al. Perinatal transmission of human immunodeficiency virus type 1 by pregnant women with RNA virus loads <1000 copies/ml. J Infect Dis. Feb 15 2001;183(4):539-545. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11170978.
- Mofenson LM, Lambert JS, Stiehm ER, et al. Risk factors for perinatal transmission of human immunodeficiency virus type 1 in women treated with zidovudine. Pediatric AIDS Clinical Trials Group Study 185 Team. N Engl J Med. Aug 5 1999;341(6):385-393. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10432323.
- Garcia PM, Kalish LA, Pitt J, et al. Maternal levels of plasma human immunodeficiency virus type 1 RNA and the risk of perinatal transmission. Women and Infants Transmission Study Group. N Engl J Med. Aug 5 1999;341(6):394-402. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10432324.
- Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission. 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. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/PerinatalGL.pdf.
- Gaur AH, Freimanis-Hance L, Dominguez K, et al. Knowledge and practice of prechewing/prewarming food by HIV-infected women. Pediatrics. May 2011;127(5):e1206-1211. Available at http://www.ncbi.nlm.nih.gov/pubmed/21482608.
- Bardeguez AD, Lindsey JC, Shannon M, et al. Adherence to antiretrovirals among US women during and after pregnancy. J Acquir Immune Defic Syndr. Aug 1 2008;48(4):408-417. Available at http://www.ncbi.nlm.nih.gov/pubmed/18614923.
- Mellins CA, Chu C, Malee K, et al. Adherence to antiretroviral treatment among pregnant and postpartum HIV-infected women. AIDS Care. Sep 2008;20(8):958-968. Available at http://www.ncbi.nlm.nih.gov/pubmed/18608073.
- Rana AI, Gillani FS, Flanigan TP, Nash BT, Beckwith CG. Follow-up care among HIV-infected pregnant women in Mississippi. J Womens Health (Larchmt). Oct 2010;19(10):1863-1867. Available at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20831428.