Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV
The information in the brief version is excerpted directly from the full-text guidelines. The brief version is a compilation of the tables and boxed recommendations.
Considerations for Antiretroviral Use in Special Patient Populations
Women with HIV
Last Updated: October 25, 2018; Last Reviewed: October 25, 2018
|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 focuses on some unique clinical and therapeutic issues to consider and basic principles to follow when caring for cisgender women living with HIV. Cisgender women are defined as women who were assigned female at birth and who identify themselves as women. Some topics discussed in this section, such as contraception, drug-drug interactions between antiretroviral (ARV) drugs and hormonal therapy, and pregnancy, also apply to transgender men (men assigned female at birth), and individuals assigned female at birth who identify as nonbinary (gender identities that are not exclusively feminine or masculine) or gender fluid (gender identity is not fixed). A new section focused on transgender health and HIV is currently in development and will be added to the Special Patient Population section soon. Clinicians who care for pregnant patients should consult the current Perinatal Guidelines for a more in-depth discussion and guidance on managing these patients.
Sex Difference Considerations in Antiretroviral Therapy
In general, studies to date have not shown sex differences in virologic responses to antiretroviral therapy (ART).1-4 However, there are limited data showing that pharmacokinetics (PKs) for some ARV drugs may differ between men and women, possibly because of variations 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 with older ARV drugs have suggested that sex 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, and didanosine.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 some patients during delivery, it is not generally recommended for long-term use.
Some studies have investigated how metabolic complications associated with ARV use differ between women and men. 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.17-20 Abacavir, NRTI-sparing regimens, and tenofovir alafenamide (a new oral tenofovir prodrug that induces less bone loss than TDF) may be considered as alternatives to the use of 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
Adults and Adolescents with HIV Who Are of Childbearing Potential
All adults and adolescents with HIV who are 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 unplanned 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).
Antiretroviral Regimen Considerations When Trying to Conceive or For Individuals Who Cannot Use Effective Contraception
Efavirenz (EFV) is teratogenic in nonhuman primates. However, a meta-analysis that included data from 23 studies found no evidence for an increased risk of birth defects in infants born to women on EFV during the first trimester compared with infants born to women on other ARV drugs during the first trimester.22 EFV can be used in individuals of childbearing potential who are not using effective contraception or who are contemplating pregnancy. Individuals who become pregnant on EFV-containing regimens should continue their current regimens.
A preliminary report from an observational surveillance study of birth outcomes among pregnant women on ART in Botswana found an increase in the risk of in neural tube defects (NTDs) in infants born to women who received dolutegravir (DTG) prior to conception. In this report, four infants born to 596 women (0.67%) who initiated a DTG-based regimen prior to pregnancy and who were still receiving that regimen at the time of conception were affected compared to 0.1% of infants born to women who received other ARV drugs.23,24 This study is ongoing. By contrast, the same study identified no NTDs in the infants born to 116 women who initiated DTG-based regimens during the first trimester or the infants born to 396 women who initiated EFV-based regimens.25
DTG is not recommended for individuals who are pregnant and within 12 weeks post-conception. It is also not recommended if an individual of childbearing potential is sexually active and cannot use effective contraception or is contemplating pregnancy, unless there is no alternative option (AII). For those not known to be pregnant, a negative pregnancy test result should be documented prior to the initiation of DTG (AIII). Women who are currently receiving DTG or who wish to start DTG should be counseled about the potential risk of NTDs when DTG is taken near the time of conception. In a patient with multidrug-resistant HIV who has no alternatives to DTG, the decision of whether to use DTG should be made after careful consideration of the risk of NTDs in the infant if pregnancy occurs while a patient is taking DTG, and the risks of persistent viremia in the patient and potential HIV transmission to the fetus if pregnancy occurs while the patient is not on effective ART.
Reproductive Options for Serodiscordant Couples
An individual who wishes to conceive with a serodiscordant 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), use of ART to maximally suppress and maintain the viral load of the partner with HIV, use of pre-exposure prophylaxis by the partner without HIV,26-28 male circumcision, and/or self-insemination with the sperm of the partner without HIV during the periovulatory period of the individual with HIV.29
Safe and effective reproductive health and family planning services to prevent unplanned pregnancies and perinatal transmission of HIV are an essential component of care for individuals with HIV of childbearing age. These individuals should receive ongoing counseling on reproductive issues. Regardless of hormonal contraceptive use, individuals 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 partners without HIV and to protect against infection with other STIs. The following sections describe some factors to consider 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 concentrations that may reduce contraceptive efficacy or increase the risk of adverse effects are not known for all forms of contraceptives.
- 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 19a, 19b, and 19d), which potentially decreases contraceptive efficacy or increases the risk of 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.30 Several regimens that include a cobicistat-boosted PI, PI/r, and EVG/c decrease oral contraceptive estradiol levels.31-34 One PK study showed that DTG did not affect ethinyl estradiol or norgestimate levels.35 Several studies have shown that use of etravirine, rilpivirine, and NVP did not significantly affect estradiol or progestin levels in individuals with HIV using COCs.36-38
- Injectable Contraceptives: Small studies of women with HIV who were 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.39-42
- Contraceptive Implants: Contraceptive failure of the etonogestrel implant in women on EFV-based therapy has been reported.43,44 Studies of women with levonorgestrel- and etonogestrel-releasing implants reported that participants receiving EFV-based ART had decreased bioavailability of levonorgestrel and etonogestrel.45-47 These studies did not identify any change in hormone concentrations when the implants were used in those taking NVP45,47 or LPV/r.46 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.48,49
Concerns about PK interactions between oral or implantable hormonal contraceptives and ARV drugs should not prevent clinicians from prescribing hormonal contraceptives for individuals 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 ARV drugs (see drug interaction Tables 19a, 19b, and 19d 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.50 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, compared to women who did not use hormonal contraception, those using hormonal contraception (with the majority of study participants using injectable DMPA) had a two-fold increased risk of acquiring or transmitting HIV. Higher genital HIV RNA concentrations have been found in women with HIV using hormonal contraception than in those not using hormonal contraceptives.51 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 use and HIV transmission to a partner without HIV and recommended that individuals living with HIV can continue to use all existing hormonal contraceptive methods without restriction.52 Further research is needed to definitively determine whether 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 individuals with HIV.53-55 Although studies have focused primarily on IUDs that do not contain hormones (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.56-58
Clinicians caring for pregnant adults and adolescents with HIV should review the Perinatal Guidelines. The use of combination ARV regimens is recommended for all pregnant persons with HIV, regardless of virologic, immunologic, or clinical parameters, for their own health and to prevent transmission of HIV to the fetus (AI). Pregnant individuals with HIV should be counseled regarding the known benefits and risks of ARV use during pregnancy to the woman, fetus, and newborn. They 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 them to adhere to care.
Prevention of Perinatal Transmission of HIV
The use of ART and the resultant reduction of HIV RNA levels decrease the risk of perinatal transmission of HIV.59-61 The goal of ART is to achieve maximal and sustained viral suppression throughout pregnancy. Long-term follow-up is recommended for all infants who were exposed to ART in utero, regardless of the infant’s HIV status (see the Perinatal Guidelines).
Antiretroviral Regimen Considerations
Pregnancy should not preclude the use of optimal ARV regimens. As in nonpregnant individuals, genotypic resistance testing is recommended for all pregnant persons before ARV initiation (AIII) and for those with detectable HIV RNA while on ART (AI). However, ART initiation should not be delayed pending genotypic resistance test results. The ARV regimen can be modified, if necessary, once the resistance test results are available (BIII). Unique considerations that influence recommendations on the ARVs to use during pregnancy include the following:
- Physiologic changes associated with pregnancy that potentially change the PKs of ARV drugs, which may affect ARV dosing at different stages of pregnancy;
- Potential ARV-associated adverse effects in pregnancy;
- Potential for nonadherence to a particular regimen during pregnancy; and
- Potential short-term and long-term effects of an ARV drug on the fetus and newborn, which are unknown for many drugs.
ART is considered the standard of care for pregnant individuals with HIV, both to treat HIV infection and prevent perinatal transmission of HIV. Clinicians should review the Perinatal Guidelines for ARV recommendations for individuals who have recently received an HIV diagnosis or those who become pregnant while on ART.
Based on preliminary data from Botswana that reported neural tube defects in infants born to women who were taking a DTG-based regimen at the time of conception, DTG is currently not recommended for use in those who are pregnant and within 12 weeks post-conception (AII). Those who are pregnant and at 12 weeks post-conception or later may initiate or continue DTG-based regimens (CIII). Discontinuing DTG is unlikely to confer any benefit after the neural tube has formed, and medication changes during pregnancy could increase the risk of viremia and perinatal transmission.
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 infant delivery (AI). Administration of combination ART should continue during labor and before a cesarean delivery (oral medications can be administered with sips of water during this time).
Clinicians who are treating pregnant individuals with HIV are strongly encouraged to report cases of prenatal exposure to ARV drugs (either administered alone or in combinations) to the Antiretroviral Pregnancy Registry. The registry collects observational data regarding exposure to Food and Drug Administration-approved ARV drugs during pregnancy to assess potential teratogenicity.
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, individuals should be counseled to avoid breastfeeding.62 Persons 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.63 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.64-66 Clinicians should address ART adherence at each clinic visit postpartum, including an evaluation of specific facilitators of 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. 2007;21(7):835-843. Available at: https://www.ncbi.nlm.nih.gov/pubmed/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. 2006;7(8):520-529. Available at: https://www.ncbi.nlm.nih.gov/pubmed/17105511.
- Currier J, Averitt Bridge D, Hagins D, et al. Sex-based outcomes of darunavir-ritonavir therapy: a single-group trial. Ann Intern Med. 2010;153(6):349-357. Available at: https://www.ncbi.nlm.nih.gov/pubmed/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. 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: https://www.ncbi.nlm.nih.gov/pubmed/14744256.
- Ofotokun I, Chuck SK, Hitti JE. Antiretroviral pharmacokinetic profile: a review of sex differences. Gend Med. 2007;4(2):106-119. Available at: https://www.ncbi.nlm.nih.gov/pubmed/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. 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. 2004;35(5):538-539. Available at: https://www.ncbi.nlm.nih.gov/pubmed/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. 2008;46(6):933-940. Available at: https://www.ncbi.nlm.nih.gov/pubmed/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. 2007;21(18):2455-2464. Available at: https://www.ncbi.nlm.nih.gov/pubmed/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. 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. 2003;34(1):58-61. Available at: https://www.ncbi.nlm.nih.gov/pubmed/14501794.
- Yin M, Dobkin J, Brudney K, et al. Bone mass and mineral metabolism in HIV+ postmenopausal women. Osteoporos Int. 2005;16(11):1345-1352. Available at: https://www.ncbi.nlm.nih.gov/pubmed/15754081.
- Brown TT, Qaqish RB. Response to Berg et al. 'Antiretroviral therapy and the prevalence of osteopenia and osteoporosis: a meta-analytic review'. AIDS. 2007;21(13):1830-1831. Available at: https://www.ncbi.nlm.nih.gov/pubmed/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. 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. 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. 2010;51(8):963-972. Available at: https://www.ncbi.nlm.nih.gov/pubmed/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. 2009;49(10):1591-1601. Available at: https://www.ncbi.nlm.nih.gov/pubmed/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. 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. 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. 2015;60(8):1242-1251. Available at: http://www.ncbi.nlm.nih.gov/pubmed/25609682.
- Ford N, Mofenson L, Shubber Z, et al. Safety of efavirenz in the first trimester of pregnancy: an updated systematic review and meta-analysis. AIDS. 2014;28 Suppl 2:S123-131. Available at: https://www.ncbi.nlm.nih.gov/pubmed/24849471.
- Zash R, Makhema J, Shapiro RL. Neural-tube defects with dolutegravir treatment from the time of conception. N Engl J Med. 2018;379(10):979-981. Available at: https://www.ncbi.nlm.nih.gov/pubmed/30037297.
- Zash R, Holmes L, Makhema J, et al. Surveillance for neural tube defects following antiretroviral exposure from conception. Presented at: 22nd International AIDS Conference. 2018. Amsterdam.
- Zash R, Jacobson DL, Diseko M, et al. Comparative safety of dolutegravir-based or efavirenz-based antiretroviral treatment started during pregnancy in Botswana: an observational study. Lancet Glob Health. 2018;6(7):e804-e810. Available at: https://www.ncbi.nlm.nih.gov/pubmed/29880310.
- Heffron R, Pintye J, Matthews LT, Weber S, Mugo N. PrEP as peri-conception HIV prevention for women and men. Curr HIV/AIDS Rep. 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. 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. 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. 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.
- Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarat (Stribald) [package insert]. Gilead. 2017. Available at: http://www.gilead.com/~/media/Files/pdfs/medicines/hiv/stribild/stribild_pi.pdf.
- Evitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (Genvoya) [package insert]. Gilead. 2017. Available at: http://www.gilead.com/~/media/files/pdfs/medicines/hiv/genvoya/genvoya_pi.pdf.
- Song IH, Borland J, Chen S, Wajima T, Peppercorn AF, Piscitelli SC. Dolutegravir Has No Effect on the Pharmacokinetics of Oral Contraceptives With Norgestimate and Ethinyl Estradiol. Ann Pharmacother. 2015;49(7):784-789. Available at: https://www.ncbi.nlm.nih.gov/pubmed/25862012.
- Scholler-Gyure M, Kakuda TN, Woodfall B, et al. Effect of steady-state etravirine on the pharmacokinetics and pharmacodynamics of ethinylestradiol and norethindrone. Contraception. 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. 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. 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. 2007;81(2):222-227. Available at: https://www.ncbi.nlm.nih.gov/pubmed/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. 2008;90(4):965-971. Available at: https://www.ncbi.nlm.nih.gov/pubmed/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. 2008;77(2):84-90. Available at: https://www.ncbi.nlm.nih.gov/pubmed/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. 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. 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. 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. 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. 2014;66(4):378-385. Available at: http://www.ncbi.nlm.nih.gov/pubmed/24798768.
- Chappell CA, Lamorde M, Nakalema S, et al. Efavirenz decreases etonogestrel exposure: a pharmacokinetic evaluation of implantable contraception with antiretroviral therapy. AIDS. 2017;31(14):1965-1972. Available at: https://www.ncbi.nlm.nih.gov/pubmed/28692531.
- 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. 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. 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. 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. 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 statment. 2014. Geneva, Switzerland. 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. 2007;197(2):144 e141-148. Available at: https://www.ncbi.nlm.nih.gov/pubmed/17689627.
- Curtis KM, Nanda K, Kapp N. Safety of hormonal and intrauterine methods of contraception for women with HIV/AIDS: a systematic review. AIDS. 2009;23 Suppl 1:S55-67. Available at: https://www.ncbi.nlm.nih.gov/pubmed/20081389.
- Centers for Disease Control and Prevention. U.S. medical eligibility criteria for contraceptive use. 2010. Adapted from: The World Health Organization Medical Eligibility Criteria for Contraceptive Use, 4th edition. MMWR Morb Mortal Wkly Rep. 2010;59(RR04):1-6. Available at: https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5904a1.htm?s_cid=rr5904a1_e.
- 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. 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. 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. 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. 2001;183(4):539-545. Available at: https://www.ncbi.nlm.nih.gov/pubmed/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. 1999;341(6):385-393. Available at: https://www.ncbi.nlm.nih.gov/pubmed/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. 1999;341(6):394-402. Available at: https://www.ncbi.nlm.nih.gov/pubmed/10432324.
- Panel on Treatment of Pregnant Women with HIV Infection and Prevention of Perinatal Transmission. Recommendations for the use of antiretroviral drugs in pregnant women with HIV infection and interventions to reduce perinatal HIV transmission in the United States. 2018. 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. 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. 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. 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). 2010;19(10):1863-1867. Available at: https://www.ncbi.nlm.nih.gov/pubmed/20831428.