Sections

Sections Gynecologic Care of Women With HIV
WIHS and HERS Studies
Epidemiologic Data
Menstrual Abnormalities
Sexually Transmitted Infections
HIV Testing
Management Overview
Preconception Counseling
Gynecologic Surgery
Menopause
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References

Management Overview

WIHS and HERS Studies

As the human immunodeficiency virus (HIV) epidemic progressed and women represented an increasing proportion of cases, concerns arose about possible clinically significant gynecologic manifestations of HIV infection and acquired immunodeficiency syndrome (AIDS). To address those concerns, the National Institutes of Health (NIH) and the Centers for Disease Control and Prevention (CDC) funded 2 large, multisite, prospective cohort studies, respectively: the Women's Interagency HIV Study (WIHS)^[1]and the HIV Epidemiology Research Study (HERS).^[2]

WIHS and HERS have contributed greatly to the understanding of HIV infection in women. Findings from these and other studies indicate that there are subtle differences between HIV disease in men and women, although these differences are less pronounced than originally predicted.

WIHS, which began in 1994 and is ongoing, was established to follow the natural history of HIV infection and related health conditions among 2,058 women with HIV and 568 women without HIV.^[1]In HERS, 871 women with HIV and 439 women without infection who were at-risk, aged 16–55, were enrolled at 4 US sites between 1993 and 1995 and were followed prospectively until 2000 to evaluate medical and psychosocial events associated with the clinical course of HIV infection.^[2]

Epidemiologic Data

As therapies continue to improve, women with HIV can expect to live longer. Consequently, health care providers must be aware of the special needs of women with HIV/AIDS. The American College of Obstetricians and Gynecologists has released clinical management guidelines for practitioners who care for women infected with HIV.^[3]

Globally, nearly half of all adults living with AIDS are women. In the United States, women accounted for 19% of the new HIV cases in 2016.^[4]Black and Hispanic women account for 77% of HIV cases among women in the United States, although they represent less than 31% of people in the US; these disparities remain poorly explained.^{[5, 4, 6]}Approximately 12% of new HIV infections in women are related to injection drug use, but the number increases to 28% among White women.^[4]

Overwhelmingly, women who contract HIV infection are diagnosed during their reproductive years, and most (87%) become infected through high-risk heterosexual contact: sex with multiple partners, bisexual males, male injection drug users, or males with unidentified risk factors.^[4]

Disparities in survival by race and sex have been identified in studies: Blacks and women have poorer outcomes compared with Whites and men.^[7]

Among Black women in the United States, HIV/AIDS was the sixth leading cause of death among women aged 25-34 and the fourth leading cause of death among women aged 35–44 in 2014.^{[4, 8]}

Findings from several studies indicate that differential use of highly active antiretroviral therapy (HAART) explains much of the disparity.^[7]Lemly et al found that Black patients presented with more advanced stages of HIV infection, were slower to initiate HAART, and were less likely to receive HAART while in care.^[9]

Studies have clearly demonstrated sex and race differences in HAART prescription and use among patients with access to therapy. Other studies have demonstrated higher rates of discontinuation and virologic failure among Blacks and other minorities.^[10]Women have been found to be less likely to use HAART, but even after correction for HAART use, women still have poorer outcomes.^[9]

The reasons for differential use of HAART are unclear. Substance abuse, mental illness, gaps in public insurance coverage (ie, Medicaid), and psychosocial stressors may be contributing factors.

For other discussions on of HIV infection, see HIV Disease, Pediatric HIV Infection, and Antiretroviral Therapy for HIV Infection, as well as HIV in Pregnancy.

Menstrual Abnormalities

Menstrual dysfunction is relatively common in the general population of reproductive-aged women. Studies have not established a consistent association between HIV infection and menstrual abnormalities. Additionally, no clear relationship has been established between menstrual dysfunction (particularly amenorrhea) and the use of highly active antiretroviral therapy (HAART).

The few studies that have evaluated menstrual disorders or complaints in women with or without HIV have not found significant differences in amenorrhea, menstrual cycle length, or variability by HIV serostatus, unless advanced immunodeficiency (eg, CD4⁺ lymphocyte count < 200 cells/mL) is present.^[11]Women with HIV should receive the same workup and treatment for menstrual disorders (including evaluation of risk factors) as women without HIV.

Sexually Transmitted Infections

The HIV Epidemiology Research Study (HERS)^[2]and other studies have not found significant differences in the prevalence of chlamydial infection, gonorrhea, trichomoniasis, or syphilis in women by HIV serostatus.^{[12, 13]}However, the presence of new or recurrent sexually transmitted infections (STIs) indicates high-risk behavior and warrants further counseling. Because the presence of STIs increases HIV shedding (which may increase the risk of HIV transmission to partners),^[14]STIs should be treated aggressively in women with HIV.

Many STIs are asymptomatic; therefore, sexually active women with HIV should be screened at least annually for curable STIs (eg, syphilis, trichomoniasis, gonorrhea, chlamydia).^{[15, 16]}More frequent STI screening may be indicated based on symptoms and risk behaviors.

The diagnosis and treatment of gonorrhea, chlamydial infection, and trichomoniasis are the same diagnosed and treated in HIV-positive women as in HIV-negative women. However, closer monitoring after treatment for syphilis is warranted for HIV-infected women.^{[15, 16]}

Genital ulcer disease from herpes simplex virus type 2

Herpes simplex virus type 2 (HSV2) is the most common cause of genital ulcer disease worldwide. While the prevalence of HSV2 varies by geographic location, it is consistently present in high percentages (50–90%) among persons infected with HIV. Among those co-infected with HIV and HSV2, more shedding of HSV2 and HIV in the genital tract occurs than in those infected with HIV or HSV2 alone.^[17]

Co-infection with HSV increases the risk of HIV acquisition by nearly twofold. Women with HIV may have recurrent problems with herpetic outbreaks and may benefit from episodic or suppressive therapy. highly active antiretroviral therapy (HAART) may decrease HSV shedding, although the data are inconsistent. The CDC’s Sexually Transmitted Diseases Treatment Guidelines provide recommendations for both episodic and suppressive HSV therapy in women with HIV.^[15]

Vulvovaginal candidiasis

Vulvovaginal candidiasis (VVC) is a common cause of vaginitis among women. In both women with and without HIV, the most common cause of VVC is Candida albicans. Studies have consistently found that both vaginal colonization and VVC are more frequent among women with HIV infection.^{[18, 19]}The clinical spectrum of signs and symptoms and the severity of disease, however, do not appear to differ between those infected and those uninfected with HIV.

The frequency of vaginal yeast colonization is inversely related to CD4⁺ counts, which may predispose the subgroup of women with HIV and low CD4⁺ counts to more frequent or severe infections.^[20]Since the clinical and microbiological spectrum of VVC appears similar for women with and without HIV, the treatment decision should be based on the clinical indications.^{[15, 20, 21]}VVC is associated with increased HIV cervicovaginal shedding; in women with HIV, however, the effect of treatment for VVC on HIV transmission is unknown.

Bacterial vaginosis

Bacterial vaginosis (BV) is the most common cause of vaginal discharge among women of reproductive age. Several clinical studies have found that the prevalence of BV in women with HIV is similar to that among women without HIV.^{[22, 23]}However, evaluation of HERS concluded that BV is more prevalent among women with HIV, primarily because of more persistent infections rather than more incident (ie, frequent) infections.^[22]

Women who are immunocompromised (CD4⁺ T-cell count < 200 cells/mL) have a higher prevalence of BV than women with HIV with higher CD4⁺ counts. Women with HIV may require longer or more frequent treatment. Otherwise, the treatment regimens for BV in women with HIV infection are the same as for those not infected.

Pelvic inflammatory disease

Few data suggest that the course of pelvic inflammatory disease (PID) in women with HIV is worse than that in women without HIV. Thus, women should be managed according to the standard treatment criteria. Tubo-ovarian abscesses may be more common in women infected with HIV, but these appear to respond equally as well as uninfected women to standard IV and oral antibiotic therapies.^[15]

Human papillomavirus infection and cervical disease

Human papillomavirus (HPV) causes cervical cytologic abnormalities (such as atypical squamous cells of undetermined significance [ASCUS] and squamous intraepithelial neoplasia [SIL]) and cervical cancer. More than 40 types of HPV cause genital infection; the types are typically grouped as low-risk (eg, 6, 11) or high-risk (eg, 16, 18) for development of cervical cancer. Persistent infection with a high-risk HPV type is necessary for progression to high-grade SIL and invasive cervical cancer, while both low-risk and high-risk HPV types can cause ASCUS and low-grade SIL. Nearly 70% of invasive cervical cancer is caused by HPV types 16 and 18.

HPV infections are common, frequent, and generally transient and asymptomatic in the general population of sexually active young women. Approximately 70% of new HPV infections in young women without HIV clear spontaneously within 1 year, and up to 91% clear within 2 years.^[24]

Among women with HIV, HPV infection is more prevalent and persistent, the distribution of high-risk types is different, and cytologic abnormalities are more prevalent. High-risk HPV types have been found to have lower clearance rates than low-risk types, but there does not appear to be a difference by HIV serostatus.^[25]The degree of immunosuppression correlates inversely with the frequency and severity of cytologic abnormalities.

The relationship between HIV infection and invasive cervical cancer is less clear. Some studies have reported that although HIV infection increases the risk of abnormal cervical cytology, most abnormalities are low-grade. High-grade lesions and invasive cancers are rare (ie, similar to that among women without HIV)^{[26, 27]}; however, it appears that women with HIV and invasive cervical cancer have a greater degree of immunosuppression than women with HIV who are immunocompetent.^[28]

Highly active antiretroviral therapy (HAART) has improved the length and quality of life among women with HIV infection. Consequently, researchers have hypothesized that HAART could reduce the risk of cervical dysplasia and progression to invasive cervical cancer by decreasing HIV replication, but this hypothesis has not been proven. A 2009 HERS publication reported that HAART was associated with enhanced HPV clearance but not with Papanicolaou test abnormality regression.^[29]

HIV Testing

More than 20% of people who are infected with HIV in the United States are estimated to be unaware of their HIV status. The CDC and ACOG recommend HIV screening in health care settings for all patients aged 13-64 years.^{[30, 31]}

Because they often provide primary health care for women, obstetrician-gynecologists are well positioned to encourage HIV screening for women. The CDC recommends that all pregnant women be screened with consent for HIV infection as part of routine prenatal testing as early in the pregnancy as possible.^{[15, 30]} Retesting is recommended in the third trimester (preferably ≤ 36 weeks' gestation) in pregnant women at high-risk of HIV infection.^[15]

Unless she declines, perform rapid HIV screening for women in labor who have an undocumented HIV status.^[15] For women with positive rapid HIV test results, administer antiretroviral prophylaxis without waiting for results from more confirmatory tests.^[15] In the absence of antiretroviral therapy, the risk of HIV transmission to the neonate is about 30%.^[15]

Management Overview

After initial diagnosis, women with HIV should provide a complete history of previous cervical disease, and they should receive a comprehensive gynecologic examination.^{[15, 16]}

Papanicolaou testing

A Papanicolaou test should be performed twice during the first year. If the results of both tests are normal, subsequent Papanicolaou tests should be performed annually. Otherwise, subsequent care should be administered according to the American Society of Colposcopy and Cervical Pathology (ASCCP) 2006 Consensus Guidelines for Management of Abnormal Cervical Cytology.^[32]

Management for cytologic abnormalities

Women infected with HIV who have cytologic abnormalities, regardless of CD4⁺ count or antiretroviral treatment status, should undergo colposcopy and directed biopsy. Conversely, women with HIV with normal cervical cytology should not receive colposcopy and biopsy.

Because of the increased prevalence of abnormal cervical cytology, more women with HIV may undergo hysterectomy for high-grade squamous intraepithelial neoplasia (SIL) or carcinoma in situ. HERS found that 63% of women with HIV with evidence of cervical intraepithelial neoplasia (CIN) before or at hysterectomy experienced SIL vaginal cytology during follow-up, a level that is significantly higher than in women in the general population.^[33]Low CD4⁺ counts and high viral load appear to also be predictors of SIL during follow-up.

Women with HIV have higher rates of intraepithelial neoplasia of the vulvar, vaginal, and anal regions than women without HIV, and these lesions may be present in the absence of squamous intraepithelial lesions of the cervix. Risk factors for development of vulvar, vaginal, and anal intraepithelial neoplasia include CD4⁺ counts less than 200 cells/mL, HPV positivity, and high-risk HPV positivity.

When women with HIV receive routine pelvic examinations, the vulva, vagina, and anus should be carefully examined. When colposcopy is indicated, the entire lower genital tract should be evaluated, including biopsies as needed.^[34]

Preconception Counseling

The CDC,^{[15, 30]} the American Congress of Obstetricians and Gynecologists (ACOG),^[35]and several other national organizations recommend preconception counseling for all women of childbearing age, including women who are HIV positive.^{[36, 37]}The goals of preconception care are to provide education and counseling targeted to the individual's needs, identify risk factors for adverse maternal or fetal outcomes, and initiate interventions to optimize outcomes.

Most women with HIV infection are of reproductive age, and 70-80% are sexually active. With highly active antiretroviral therapy (HAART), women with HIV are living longer, healthier lives; consequently more women with HIV may desire their own biologic children.

By suppressing viral load, HAART significantly decreases mother-to-child transmission. To maximize outcomes and minimize risk, physicians should encourage women to plan their pregnancies, to use an effective form of contraception until they are ready to conceive, and to reduce risky behaviors (ie, smoking, substance use) and use folic acid.

In addition, physicians should counsel women regarding the risk of transmitting infection through unprotected intercourse with an uninfected male partner. Intravaginal or intrauterine insemination may be feasible to reduce the risk of HIV transmission to an uninfected male partner.

Contraception

Nearly 50% of all pregnancies in the United States are unintended. Women with HIV should be counseled regarding the need to avoid unintended pregnancy as well as the need to protect themselves against sexually transmitted infections (STIs) and to protect their uninfected male partner(s) from infection.^[38]

Highly effective contraceptive methods (eg, hormonal methods, intrauterine devices [IUDs]) should be recommended when appropriate. Depomedroxyprogesterone acetate (DMPA) is considered safe and effective in women with HIV without known interactions with antiretroviral therapy.^{[39, 40]}

Combined oral contraceptives (COCs) are not recommended for women with HIV on certain HAART regimens because of potential alterations in safety and effectiveness of both the hormonal contraceptive and the antiretroviral drug.^{[41, 42]}Specifically, for women taking ritonavir-boosted protease inhibitors, COCs are generally not recommended.^[42]Women on HAART who are interested in using COCs should consistently use condoms (ie, dual method).

IUDs are considered safe and effective for women with HIV,^[43]but IUD insertion is not recommended for women with AIDS unless they are clinically stable on antiretroviral therapy.^[42]Although data on surgical sterilization of women with HIV are scant, no specific recommendations or concerns different from those regarding women without HIV have been described.

Correct, consistent condom use is essential for protection of an uninfected male partner and for protection of the woman from STIs, which can increase viral shedding. Studies have reported decreased condom use among women with HIV on HAART^[44], and among women without HIV whose partners have HIV.^[45]

Gynecologic Surgery

There is little published information on gynecologic surgery in women with HIV; most information is from studies of postoperative complications after cesarean section. The limited available data on gynecologic surgery suggest that no differences in the clinical management of women with HIV undergoing routine gynecologic procedures are required.

Two limited studies found no significant differences in postoperative complications between immunocompetent women with HIV and women without HIV.^{[46, 47]}A larger, retrospective study concluded that women with HIV who undergo abdominal surgery or uterine curettage appear to be at risk for increased infectious morbidity such as postoperative fever (either transient or fever requiring antibiotic therapy).^[48]Complications are more likely in women with HIV who are immunocompromised.^{[47, 48]}

In a more recent study at a single institution, investigators reported that low preoperative levels of serum albumin in HIV-infected women were associated with an increased risk of surgical site infections following abdominal hysterectomy.^[49]

Menopause

Because of improved antiretroviral therapies, women with HIV are living longer, healthier lives. In addition, the HIV/AIDS epidemic is maturing in the United States. As a result, increasing numbers of women with HIV are reaching menopause. However, data on menopause in women with HIV are very limited. Menopause in the general US population occurs at a median age of 51.4 years; a few studies have found that menopause occurs 2-3 years earlier in women with HIV. Menopause has also been found to occur earlier among African-American women, cigarette smokers, and drug users; and each of these groups is overrepresented among women with HIV.

A prospective study of the natural history of menopause among 302 women with HIV and 269 high-risk women without HIV found an average age of menopause of 46 and 47 years, respectively. In addition, this study found that HIV infection, use of cocaine or opioids, and physical inactivity were independently associated with age-adjusted onset of menopause.^[50]

The degree to which a women with HIV experiences menopausal symptoms may relate to her immune status.^[51]While hormone replacement therapy (HRT) has been studied extensively among the general population, it has not been studied in women with HIV.

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