Health Care of HIV-Infected Women Through the Life Cycle

Background

Women with HIV infection have the same reproductive and life cycle health needs and concerns as women without HIV infection. However, for women with HIV infection, certain gynecologic problems may be more common or more frequent. In addition, issues regarding antiretroviral therapy (ART), contraception, and preconception counseling require special attention. This chapter addresses some of the unique health care needs of HIV-infected women across the lifespan, from menarche through postmenopause, and describes the essential elements of care. For further information, see chapters Reducing Perinatal HIV Transmission, Care of HIV-Infected Pregnant Women, and Antiretroviral Medications and Hormonal Contraceptive Agents.

Epidemiology and Factors Affecting HIV Transmission

Heterosexual transmission of HIV is more efficient from man to woman than from woman to man. Transmission can occur through intact vaginal tissue; no damage to the vaginal lining is required. Women have specific risks of HIV acquisition at different phases of the lifespan:

  • Young adolescents have immature genital tracts and increased cervical ectopy (increased vulnerability to HIV and other sexually transmitted diseases [STDs])
  • Women of reproductive age may desire pregnancy and childbearing (potentially increasing risky sexual behaviors)
  • Married or partnered women may be monogamous with male partners who have risk factors for HIV infection (women may lack awareness of partner's risk behaviors)
  • Postmenopausal or posthysterectomy women may have vaginal atrophy (decreasing the anatomic barrier to HIV), or may have no fear of pregnancy or have a perception that they are at low risk of infection (increasing risky sexual behaviors)
  • Additionally, woman-to-woman transmission may occur if risk factors are present

Psychosocial/Emotional Factors Unique to Women

Women may inherit social roles and responsibilities as caretakers for extended family members and often for friends, and may not give sufficient priority to their own medical care. Furthermore, heterosexual women frequently are faced with unequal power and socioeconomic relationships with their male partners. These women may be more likely to exchange sex for money, less likely to successfully negotiate protected sex, and less likely to leave a relationship they perceive as risky. They may be fearful about disclosing their HIV status.

Sexual abuse appears to increase the risk of HIV transmission to HIV-uninfected women. For HIV-infected women, intimate partner violence and sexual coercion appear to occur at about the same rates as for HIV-uninfected women (>60% in one review). However, HIV-infected women appear to be subjected to more frequent and more severe abuse. HIV-infected women should be screened for intimate partner violence and referred to intervention services, if indicated. The U.S. Centers for Disease Control and Prevention (CDC) and the U.S. Preventive Services Task Force recommend several screening tools (see "References," below). The Abuse Assessment Screen (AAS) is one tool recommended by the CDC. It originally was intended for screening pregnant women but has since been used more widely.

Abuse Assessment Screen

  • Have you ever been emotionally or physically abused by your partner or someone important to you?
  • Within the last year, have you been hit, slapped, kicked, or otherwise physically hurt by someone? If yes, by whom? How many times?
  • Since you have been pregnant, have you been hit, slapped, kicked, or otherwise physically hurt by someone? If yes, by whom? How many times and where?
  • In the last year, has anyone forced you to have sexual activities? If so, whom? How many times?
  • Are you afraid of your partner or anyone you listed above?

ART Issues Particular to Women

In general, women on ART have virologic and immunologic responses comparable to those of men; however, several studies have shown that women discontinue ART more frequently than men. Women have higher rates of adverse effects from a number of antiretroviral (ARV) medications, in part because serum levels of at least some ARVs are higher in women. Pregnancy may require changes in ART, either because of pharmacokinetic changes or because of toxicity. See Table 1.

Table 1: Special Considerations for Use of Antiretrovirals with Women
ARV Issues for WomenConsiderations
ARV adverse effectsSome ARV adverse effects may be more severe in women:
  • Abacavir hypersensitivity
  • Anemia (zidovudine)
  • Bone loss, especially after menopause
  • Hepatotoxicity (nevirapine)
  • Lactic acidosis (particularly with stavudine + didanosine)
  • Lipoaccumulation: central fat accumulation in breasts, abdomen; lipoatrophy: face
  • Neuropathy (stavudine, didanosine)
  • Severe rash (nonnucleoside reverse transcriptase inhibitors [NNRTIs], darunavir, tipranavir)
PregnancyTeratogenicity:
  • Efavirenz (EFV) is associated with neural tube defects in primates with in utero exposure. Consider alternatives, if feasible, in women who 1) are planning to become pregnant or 2) are sexually active with male partners and not using effective contraception. In women who become pregnant while taking EFV, EFV may be continued because the risk of neural tube defects is restricted to the first 5-6 weeks of pregnancy and pregnancy is rarely recognized before 4-6 weeks of pregnancy. Efavirenz is classified by the U.S. Food and Drug Administration (FDA) as a Pregnancy Category D drug.

Pharmacokinetic (PK) changes:

  • Serum levels of some ARVs may be decreased during pregnancy (e.g., unboosted protease inhibitors [PIs], and boosted PIs including atazanavir/ritonavir, darunavir/ritonavir, and lopinavir/ritonavir).
  • Some ARVs should be avoided and certain ARVs may require dosage adjustment in the third trimester.
  • PK studies in pregnancy are not available for some ARVs.

See chapter Reducing Perinatal HIV Transmission

ContraceptionThere are significant interactions between some hormonal contraceptive agents and certain ARVs; see "Contraception," below.

Baseline Reproductive History

Taking a careful reproductive history should be a part of routine primary care for any woman. Important information to gather includes the following:

  • Age of menarche
  • Menstrual history: last menstrual period (LMP), amenorrhea, menstrual irregularity, uterine fibroids, endometriosis
  • Obstetrical history: G-P-A-L
  • G (gravida, or number of pregnancies), P (parity, or number of births), A (abortion; number of miscarriages or terminations), L (number of living children)
    • Pregnancy complications and outcomes: full-term, premature births, mode of deliveries
    • Use of ART during pregnancy
    • HIV status of children
  • Sexual activity: vaginal, oral, anal; condom use; number of partners; sex of partners; HIV status of partners
  • Plans and desires for childbearing
  • Contraception, past and current
  • Date of last Papanicolaou (Pap) test and results; history of abnormal Pap test results
  • Gynecologic procedures: colposcopy/biopsy, loop electrosurgical excision procedure (LEEP), cervical surgery, tubal ligation, partial or total hysterectomy; and indication for these
  • History of STDs, bacterial vaginosis, vulvovaginal candidiasis, herpes, warts; especially recurrence
  • Current symptoms: vaginal discharge, vulvar/vaginal/anal pain, dysuria, dyspareunia (pain with intercourse), lesions, intermenstrual bleeding, postcoital bleeding

Elements of Gynecological Care

Women with HIV infection should receive routine screening for gynecologic cancers and infections. The incidence, prevalence, and persistence of human papillomavirus (HPV) infection and cervical, vaginal, vulvar, and anal dysplasia are more common in women with HIV infection, especially among women with low CD4 counts. It is not clear that initiation of suppressive ART improves clinical outcomes of women with dysplasia (see chapter Cervical Dysplasia). Other common gynecological problems include recurrent yeast vaginitis, pelvic inflammatory disease; vaginal, vulvar, and anal warts; and perineal/perianal herpes.

Women also should be evaluated for risk of breast cancer, for contraceptive needs, and for preconception counseling

Table 2: Routine Gynecologic Screening and Counseling for Women
Medical ServiceComments
Cervical and anal cancer screeningWomen with HIV infection should have more frequent screening than uninfected women:
  • Screen all HIV-infected women for cervical cancer (cervical Pap test) at initial visit, at 6 months, then annually unless abnormal.
  • For HIV-infected women (any age) with ASCUS or higher-grade abnormality, colposcopy generally is recommended; alternatively, the Pap can be repeated in 6-12 months.
  • Consider anal cancer screening (anal Pap test) for all HIV-infected women if high resolution anoscopy is available to evaluate abnormal findings.
  • See chapters Cervical Dysplasia and Anal Dysplasia
  • Perform pelvic examination.
    • Include vulvar and anal examination
    • Assess for potentially dysplastic lesions
  • CDC recommendations for HPV vaccination of children and young women should be followed.
STD screeningGonorrhea, chlamydia, syphilis at least annually, and more frequently depending on risk factors or symptom exam findings
Breast cancer screeningMammography
  • Mammogram every 1-2 years recommended for women 50-69 years of age
  • Consider annual mammogram for women 40-50 years of age
  • Consider starting earlier if risk factors are present
  • For women ≥70 years of age, decisions about whether to continue screening should take into account the woman's life expectancy and clinical status

Clinical breast examination

  • Annually
  • Breast self-examination (BSE) monthly (assess technique)
Contraceptive counseling
  • Assess life dynamics and need for contraception at every visit.
  • Stop only after hysterectomy or sterilization.
  • See "Contraception," below.
Preconception counselingAnnually or more often for all women of reproductive age
  • Ask about pregnancy desires at every visit
  • See "Preconception Counseling," below

Contraception

Many contraceptive choices are available for HIV-infected women; some considerations are presented in the table below. For more information about interactions between ARVs and hormonal agents, see chapter Antiretroviral Medications and Hormonal Contraceptive Agents. Depending on the woman's (and her partner's) risk factors, consistent condom use should be emphasized, with or without other methods of contraception, to prevent the transmission of HIV and the acquisition or transmission of other STDs. Dual contraception (e.g., use of condoms plus additional contraception) is the optimal contraceptive strategy for serodiscordant heterosexual couples since it reduces the risk of transmission of HIV and other STDs as well as providing effective contraception.

Table 3: Advantages and Disadvantages of Various Contraceptives
Contraceptive TypeDisadvantages

*See chapter Antiretroviral Medications and Hormonal Contraceptive Agents and Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Accessed December 1, 2013.

Barrier Methods
Male and female condom
  • Only contraceptive method that also protects against transmission of HIV and STDs
  • Requires partner cooperation and correct technique
  • High failure rate when used incorrectly or inconsistently
Diaphragm and cervical cap 
  • Requires correct technique
  • High failure rate when used incorrectly or inconsistently
  • Use of diaphragms with spermicide can disrupt the cervical mucosa, which may increase risk of HIV transmission to uninfected sex partners
Hormonal Methods*
  • Do not prevent STD or HIV transmission
Oral
  • Very effective contraception if used as prescribed
  • Lighter menstrual flow
  • May have significant drug-drug interactions with PIs, some NNRTIs, and elvitegravir/cobicistat that may affect the efficacy and toxicity of estradiol or the progestin, and of certain PIs*
  • Alternative or additional methods recommended for women taking certain PIs or NNRTIs, or elvitegravir/cobicistat.
Injectable depot medroxyprogesterone acetate (DMPA, Depo-Provera)
  • Effective contraception for 3 months
  • May cause amenorrhea
  • Concern about osteoporosis with long-term use
  • Irregular bleeding, especially initially
  • Weight gain
  • Limited and conflicting data show possible increased risk of HIV transmission (from HIV-infected woman to male partner) or acquisition (by uninfected woman from HIV-infected man) for women on DMPA (note: no study participants were on ART)
Transdermal (patch)
  • Effective contraception if used as prescribed
  • Lighter menstrual flow
  • No data on pharmacokinetic interactions with ARVs, but of possible significance; use same precautions as with oral hormonal agents (see above)
Vaginal ring
  • Effective contraception if used as prescribed
  • Lighter menstrual flow
  • No data on pharmacokinetic interactions with ARVs, but of possible significance; use same precautions as with oral hormonal agents (see above)
Intrauterine devices (IUDs) (copper IUD and levonorgestrel-containing IUD)
  • Effective for long-term use
  • No evidence of increased HIV viral shedding
  • Progestin-releasing IUD may cause lighter menstrual flow
  • Possible blood loss with Copper T IUD
  • Insertion of IUD not recommended for women with advanced immunosuppression
Etonogestrel implant
  • Effective
  • Amenorrhea
  • No data on pharmacokinetic interactions with ARVs, but of possible significance; Use same precautions as with oral hormonal agents (see above)
Emergency contraception:
  • Levonorgestrel
  • Ulipristal acetate
  • Effective
  • Efavirenz lowers levonorgestrel levels; use alternative method
  • No data on pharmacokinetic interactions with ARVs, but of possible significance; use same precautions as with oral hormonal agents (see above)
Copper T IUD
  • Appropriate for women who present 4-5 days after intercourse
  • Heavy blood loss
Surgical Methods
Bilateral tubal ligation (female)
  • Effective; permanent
  • Does not prevent transmission of HIV or other STDs
  • No future fertility (usually not reversible)
Vasectomy (male)
  • Effective; permanent
  • Does not prevent transmission of HIV or other STDs
  • No future fertility (usually not reversible)
Spermicides
Spermicides 
  • Not currently recommended
  • Nonoxynol-9 causes mucosal damage to vagina
  • Do not prevent transmission of HIV or other STDs

Preconception Counseling

As discussed above, every visit with an HIV-infected woman in her reproductive years presents an opportunity to discuss pregnancy desires and options, including gathering information about her partner. It is important to assess the couple's sexual history, sexual decision making, and control of reproductive options. The goals of preconception counseling are to improve the health of the woman prior to conception and identify, and when possible intervene around, risk factors for adverse maternal and fetal outcomes. When a woman desires pregnancy, it is important to discuss the topics listed below, with the goals of educating her and decreasing risk of HIV transmission to an HIV-uninfected partner or to the fetus. Ideally, the partner will take part in the discussion.

  • Options for conception that decrease risk of HIV transmission to an HIV-uninfected partner (see below)
  • Recommendations for ART before and during pregnancy, at delivery, and postpartum
  • Optimization of maternal health status and suppression of HIV viral load before pregnancy
  • Effect of HIV and ARVs on pregnancy and outcomes
  • Effect of non-HIV-related factors (e.g., age, drug use) and other medical conditions (e.g., hypertension, diabetes, depression) on pregnancy course
  • Counseling on safer sexual practices
  • Counseling on other aspects of health promotion (e.g., smoking and alcohol cessation, drug treatment)
  • Perinatal HIV transmission risk and prevention: ARVs for mother and infant, mode of delivery, avoidance of breast-feeding
  • Treatment and care of an HIV-exposed or HIV-infected infant
  • Long-term planning including advance directives and guardianship of a child if one or both parents were to become ill or die

Any history of infertility or low fertility in either the patient or her partner should be evaluated and options for having children should be discussed, including current information on gamete donation, other assisted reproductive techniques, and adoption.

If the heterosexual couple is serodiscordant, techniques to minimize the risk of transmission to the uninfected partner should be discussed. These same techniques should be explained to couples when both partners are HIV infected, if there is a risk of transmitting different HIV "strains." Some of the recommended techniques include the following:

  • If the male partner is HIV uninfected: the woman does self-insemination of ejaculate using a syringe (no HIV exposure risk to the male partner)
  • Maximal suppression of the HIV viral load of the infected partner with ART
  • Screening for and treatment of STDs
  • Assisted reproductive technology
    • Sperm washing with polymerase chain reaction (PCR) testing and intrauterine insemination (IUI), in vitro fertilization (IVF), or intracytoplasmic sperm injection (ICSI), if the male partner is HIV infected and the female partner is HIV uninfected

The couple should be fully educated about other options, including the following:

  • Preexposure prophylaxis (PrEP) for the uninfected partner
  • Estimating the time of ovulation and limiting unprotected intercourse to this period, with or without use of PrEP. This approach should be considered only if HIV viremia is maximally suppressed and intercourse is limited to times when conception is most likely.
  • Postexposure prophylaxis for an uninfected partner

The CDC has issued interim guidelines on use of PrEP by heterosexually active individuals as well as a fact sheet on PrEP (see "References,"). Both address the use of PrEP during attempts to conceive. Few clinical data are available at this time to guide practice; when treating serodiscordant couples who wish to conceive using PrEP, providers should review current guidelines and consult with experts in the field.

If an HIV-infected woman who is considering pregnancy initiates ART, an appropriate regimen should be started before pregnancy, avoiding agents with increased risk of teratogenicity (e.g., efavirenz), hepatotoxicity (e.g., nevirapine, in women with CD4 counts of >250 cells/µL), or metabolic complications such as lactic acidosis (e.g., didanosine and stavudine). see chapter Reducing Maternal-Infant HIV Transmission and the U.S. Department of Health and Human Services Perinatal HIV Guidelines (see "References," below). It should be noted that most fetal organogenesis occurs in the early weeks of pregnancy, before most women know that they are pregnant. Thus, any medication with potential teratogenicity or fetal toxicity, whether an ARV or another drug, should be avoided for use by women who are intending to become pregnant or who may become pregnant. Certain medications (e.g., ribavirin) should be avoided by male partners of women who may become pregnant.

Folate supplementation to reduce the risk of neural tube defects in the developing fetus should be started at least 1 month before conception, if possible, because the neural tube forms in the early weeks of pregnancy (see chapter Care of HIV-Infected Pregnant Women).

Menopause

There is evidence that HIV-infected women may be more likely to undergo premature physiologic menopause. Earlier onset of menopause also is associated with non-HIV factors such as ethnicity and a history of intravenous drug use. Menopausal women are more at risk of premature bone loss, osteopenia, and osteoporosis; this risk may be increased by HIV infection and certain ARVs. If indicated, bone density screening (DEXA) should be considered.

Hormone replacement therapy (HRT), especially of long duration, has been associated with an increased risk of breast cancer and cardiovascular and thromboembolic events, and its routine use is not recommended. HRT may be considered for women who experience severe vasomotor symptoms and vaginal dryness, but should be used only for a limited period of time and at the lowest effective dosage.

References

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  • ACOG Committee on Practice Bulletins - Gynecology. ACOG Practice Bulletin No. 117: Gynecologic care for women with Human Immunodeficiency Virus. (2010). ACOG Practice Bulletin No. 117. Obstet Gynecol, 2010 Dec;116(6):1492-509. (December 2010; Reaffirmed 2012).
  • Aberg JA, Gallant JE, Ghanem KG et al.; HIV Medicine Association of the Infectious Diseases Society of America. Primary care guidelines for the management of persons infected with human immunodeficiency virus: 2013 update by the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis. 2014 Jan;58(1):e1-e34.
  • Centers for Disease Control and Prevention. Interim guidance for clinicians considering the use of preexposure prophylaxis for the prevention of HIV infection in heterosexually active adults. MMWR Morb Mortal Wkly Rep. 2012 Aug 10;61(31):586-9.
  • Centers for Disease Control and Prevention, CDC Fact Sheet. PrEP: A New Tool for HIV Prevention. August 2012. Accessed January 15, 2014.
  • Centers for Disease Control and Prevention, Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion. U.S. Selected Practice Recommendations for Contraceptive Use, 2013: Adapted from the World Health Organization selected practice recommendations for contraceptive use, 2nd edition. MMWR Recomm Rep. 2013 Jun 21;62(RR-05):1-60.
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