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Special Considerations in the Management of HIV in Women, Including During Conception and Pregnancy

Joseph J. Eron, Jr., MD
Program Director
Daniel R. Kuritzkes, MD
Program Director
Judith S. Currier, MD, MSc
Sigal Yawetz, MD
Released: May 21, 2020

Overview of Health Considerations: Reproductive Health

There are special considerations for reproductive health in women with HIV when compared with the general population. Issues surrounding contraception are multifaceted for women with HIV. These women often feel stigmatized by their diagnosis and, therefore, may not seek appropriate care. In general, contraception options offered to women with HIV are similar to those of the general population, but barrier contraception should be used conjunctively. There is minimal evidence-based guidance to direct practitioners in this arena.

Oral Contraceptives
The studies that have evaluated whether the use of hormonal contraceptives has any effect on chronic HIV infection have demonstrated conflicting results. Some studies have not observed an association between hormonal contraception and HIV disease progression.[37-41] In a study of Zambian women not yet receiving ART, the use of depomedroxyprogesterone acetate or oral contraceptives was associated with an accelerated HIV disease progression and death.[42] A systematic review of randomized clinical trials and cohort studies found no evidence that hormonal contraceptives increase a woman’s risk of HIV disease progression. [37,43] Therefore, hormonal contraceptive choices should be based on each woman’s needs rather than possible effects on HIV progression.[43,44] The WHO recommends that women infected with HIV or at high risk of HIV can continue to use hormonal contraceptives to prevent pregnancy.[45]

The primary concern in women with HIV should be focused on effects the ARV agents may have on the clinical effectiveness of available contraceptive choices (Table 1). Therefore, any nonbarrier contraceptive should be used in conjunction with a barrier (condom) device, not only for pregnancy prevention but also to prevent HIV transmission. In addition, contraceptive agents may alter the pharmacokinetics and efficacy of certain ARVs. Virologic responses to ART should be monitored closely when used in combination with nonbarrier contraceptives. Pharmacokinetic interaction should be considered when combined oral contraceptives and ARVs are used together and certain agents should not be used concurrently (Table 1).[46-56] Specifically, data have demonstrated a negative effect on both progesterone and ARV levels when efavirenz and combined oral contraceptives are coadministered.[57] Elvitegravir/cobicistat increased norgestimate exposures, which may potentially increase the risk of complications including insulin resistance, dyslipidemia, acne, and venous thrombosis.[58] The potential risks and benefits of using norgestimate-containing contraceptives in combination with cobicistat and elvitegravir should be considered, particularly in women who have risk factors for these complications.

Table 1. Effects of Coadministration of ART and Combined Oral Contraceptives

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Injectable Contraceptives
There are no clinically important pharmacokinetic interactions that occur when progestin injectable contraceptives, such as depot-medroxyprogesterone acetate (DMPA), are used with ARVs.[59-61] DMPA may be associated with an elevated HIV-1 RNA set point when used at the time of HIV acquisition,[62] and this could result in more rapid disease progression. Women with HIV and women without HIV experience similar adverse events when using injectable hormonal contraceptives.

Whether DMPA use is associated with HIV acquisition or transmission is controversial and additional studies are needed to provide clarity.[63] Currently available data include a retrospective analysis from a prospective cohort,[64] a systematic review[65] and a preplanned secondary analysis of data from the VOICE trial[66] suggesting that there may be an increased risk of HIV acquisition and/or transmission with the use of hormonal contraceptive pills and/or DMPA. However, these analyses each have limitations and do not provide irrefutable evidence that contraception and HIV transmission or acquisition are linked. Other publications do not find an association between injectable contraceptive use and HIV acquisition or transmission.[67-70] Following the publication of data demonstrating an increased risk of HIV acquisition with DMPA, the WHO conducted a review of the available evidence and concluded that women living with HIV can continue to use all existing hormonal contraceptive methods without restriction.[45] The guidance statement notes that “women at high risk of acquiring HIV can use progestogen-only injectables but should be advised about concerns that these methods may increase risk of HIV acquisition, about the uncertainty over whether there is a causal relationship, and about how to minimize their risk of acquiring HIV.”[71] Therefore, patients and their partners should be counseled regarding the continued use of barrier contraception (condoms) in addition to other contraceptive choices.

Implantable, Intravaginal, and Intrauterine Contraceptives
Limited data exist regarding the use of implantable or intravaginal contraception in women with HIV. However, the CDC’s Medical Eligibility Criteria for Contraceptive Use lists all combined hormonal contraceptive methods (including the patch and vaginal ring) as Category 1 (no restriction for use) for women at high risk for HIV or with HIV or AIDS.[72,73] There is some indication that use of efavirenz may decrease levonorgestrel levels attained from the levonorgestrel implant leading the DHHS panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission to recommend considering an alternative method of contraception in addition to this method.[52,74] A randomized clinical trial of Ugandan women with HIV using the subdermal levonorgestrel implant demonstrated a high 15% rate (3/20) of unintended pregnancies among those who were receiving efavirenz-based ART vs a 0% pregnancy rate among 17 women not receiving ART.[75] The significantly reduced efficacy of the levonorgestrel implant was attributed to a drug–drug interaction between levonorgestrel and efavirenz, as demonstrated by an estimated 45% to 57% reduced levonorgestrel concentration in samples obtained over 48 weeks in women receiving efavirenz-based ART vs women not receiving ART. In a retrospective study of 24,560 women with HIV in Kenya, patients receiving an efavirenz-based regimen had a 3 times higher risk of unintended pregnancy than patients receiving a nevirapine-based regimen, although this rate was still lower than for women using other hormonal contraception.[76]

Some ritonavir-boosted PIs may affect contraceptive hormone levels (including decreasing progestin), and guidance from the DHHS states that patients receiving ritonavir-boosted darunavir and using implantable contraceptives may consider an alternative or additive method of contraception.[52]

Both the copper-containing intrauterine device (Tcu-380A IUD) and the levonorgestrel-releasing intrauterine contraceptive system are acceptable choices for women with HIV and do not appear to be associated with increased genital tract shedding of HIV.[77]

Barrier Contraceptives
Barrier methods of contraception, such as condoms, should be encouraged in all individuals with HIV even when other forms of contraception are used. Condoms must be used consistently and correctly for effective contraception, for the prevention of sexually transmitted diseases (STDs), and for the prevention of HIV transmission. Spermicides containing nonoxynol 9 topical should not be used for the prevention of HIV or STD transmission; products containing nonoxynol 9 topical may increase the risk of HIV transmission.[78]

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