HIV and women

INTRODUCTION — Worldwide, women represent approximately 50 percent of the population with human immunodeficiency virus (HIV). While many of the clinical features of HIV in women are similar to those in men, there remain significant sex-based differences in the disease. These include:

●Differences in viral load early in infection

●Differences in selected opportunistic infections

●Difference in selected antiretroviral-related toxicities and side effects

●A number of female-specific complications

●Issues related to HIV and pregnancy

●The psychosocial impact and the environment in which HIV/acquired immunodeficiency syndrome (AIDS) occurs in women

●Access to and receipt of quality care

The epidemiology, clinical complications, natural history, and sex-specific management issues of HIV in nonpregnant women will be reviewed here. HIV in pregnant women is discussed separately. (See "Antiretroviral selection and management in pregnant individuals with HIV in resource-rich settings" and "Prenatal evaluation of women with HIV in resource-rich settings".)

EPIDEMIOLOGY

Prevalence — Globally, women comprise approximately half of the population with HIV [1]. This reflects the demographics in sub-Saharan Africa, where the majority of people with HIV live and where heterosexual exposure is the primary mode of transmission. In other parts of the world, such as the United States and Western Europe, sexual transmission among men who have sex with men is the most common route, and women make up a smaller proportion of the population with HIV. (See "Global epidemiology of HIV infection", section on 'Worldwide statistics'.)

As an example, in the United States, females made up 19 percent of the nearly 37,000 new HIV diagnoses in 2019 [2]. Since the initial reports of HIV in women in the United States, women from under-represented populations have been disproportionately affected. Among the 7190 women who received an HIV diagnosis in the United States in 2018, 58 percent were African American, 21 percent were White, and 17 percent were Hispanic/Latin American. Nevertheless, these rates represent a decline in HIV diagnoses among women compared with the past several years. Diagnoses declined by 20 percent among African American women, by 14 percent among Hispanic/Latin American women, and remained stable among White women.

Precise data regarding the burden of HIV among transgender women worldwide are lacking. In a meta-analysis of studies from the United States and countries in Asia, Latin America, and Europe between 2000 and 2011, the pooled prevalence of HIV among 11,066 transgender women worldwide was 19.1 percent [3]. The odds of HIV infection among transgender women were more than 48 times higher than among reproductive-age adults in those countries and did not differ between low- to middle-income and high-income settings. Similarly, HIV disproportionately affects transgender women in the United States, where an estimated 22 percent of transgender women have HIV [4]. Black transgender women are three times more likely than White transgender women to have HIV [5], and one 2018 review estimated that 44 percent of African American transgender women in the United States have HIV [6].

Risk factors for HIV acquisition

Sexual risk factors — Heterosexual contact is the most common reported risk factor for women, having overtaken injection drug use [2]. A number of risk factors for acquisition are shared between men and women, including presence of ulcerative sexually transmitted infections, higher viral loads, and unprotected sexual intercourse [7,8]. (See "HIV infection: Risk factors and prevention strategies" and "Management of nonoccupational exposures to HIV and hepatitis B and C in adults".)

It has been proposed that during the normal menstrual cycle, there is a period lasting approximately 7 to 10 days when innate, humoral, and cell-mediated immunity are suppressed by estradiol and/or progesterone, enhancing the potential for acquisition of HIV by women; this hypothesis requires further exploration [9]. However, even if this may represent a period of higher risk, primary prevention efforts for women should continue to emphasize the need for consistent adherence to safer sex practices regardless of timing in the menstrual cycle.

Risk associated with contraception — Some studies had raised concern that certain hormonal contraceptive methods, particularly depot medroxyprogesterone acetate (DMPA), are associated with an increased risk of HIV acquisition, but emerging data suggest that among non-condom contraceptive methods, the risks of HIV acquisition are largely comparable. Women at risk for HIV should choose among the contraceptive methods available to the general population (figure 1); they should also be advised to use condoms, regardless of other contraceptive use, to prevent transmission of other sexually transmitted infections (STIs) and be advised to undergo routine STI screening. This approach is consistent with the World Health Organization guidance on contraceptive use in women at high risk for HIV [10]. (See "Contraception: Counseling and selection" and "Screening for sexually transmitted infections", section on 'Females'.)

Several systematic reviews and meta-analyses of mainly observational studies that evaluated the risk of HIV with contraceptive use and also accounted for condom use had demonstrated an increased risk of HIV acquisition with DMPA compared with other forms of hormonal contraception [11-14]. However, a subsequent randomized trial of nearly 8000 African women at high risk of HIV did not demonstrate a difference in incident HIV infection with use of DMPA compared with the copper intrauterine device (IUD) or levonorgestrel implant (4.2 compared with 3.9 and 3.3 per 100 woman years, respectively) [15]. STIs were common, and nearly 50 percent of women reported no condom use with the last sexual act. Both levonorgestrel and copper IUDs appear to decrease HIV target cell populations in the female genital tract and may therefore decrease the risk of HIV acquisition [16]. (See "Intrauterine contraception: Candidates and device selection".)

Injection drug use — Increasing numbers of women are acquiring HIV through injection drug use. Worldwide, there has been a 33 percent increase in HIV acquired through injection drug use from 2011 to 2015 [17]. In the United States, the proportion of women acquiring HIV through injection drug use is comparable with that of men. However, prevalent routes of transmission differ by race. For example, while 92 percent of Black women in the United States acquire HIV through sex, only 68 percent of White women do.

Prevention of HIV infection — Potential interventions to reduce the risk of HIV acquisition include postexposure prophylaxis (PEP) following a high-risk exposure to HIV and pre-exposure prophylaxis (PrEP) for women who are at continued high risk of HIV (such as those in discordant sexual relationships, sex workers). These issues are discussed in detail elsewhere. (See "HIV infection: Risk factors and prevention strategies", section on 'Individuals at risk for HIV' and "HIV pre-exposure prophylaxis".)

NATURAL HISTORY

Morbidity and mortality — The understanding of the presence and extent of differences between the sexes in the natural history of HIV and the progression to AIDS continues to evolve. Early in the epidemic, a number of studies reported higher mortality and increased progression of HIV in women compared with men. However, more careful analyses incorporating other potential factors such as HIV risk, age, and the AIDS-defining condition showed that these differences were largely explained by decreased access to quality care and treatment rather than representing a more aggressive disease progression in women on biological grounds [18-21]. Women who receive care in more experienced clinics survive longer than women cared for by less experienced clinics [22]. However, even among established HIV clinics and adjusting for insurance rates, race and transmission, women were still less likely to be on antiretroviral therapy (ART) [23]. Delay in diagnosis is also common, with one-third of women in the United States either presenting with AIDS at the time of their HIV diagnosis or progressing to AIDS within the first 12 months [24].

In 1996, declines in AIDS-related mortality began to be noted in resource-rich settings, attributed to improved HIV treatment with ART and improved prevention of opportunistic infections (OIs). However, the decline in AIDS-related mortality for women was initially less dramatic and lagged behind that of men (10 versus 25 percent) [25], although the rates of survival three years after diagnosis are now similar for men and women overall [24]. This delay in benefit has not been fully explained but, based upon the experiences earlier in the epidemic, is probably in part related to decreased access to or use of quality care [23,26,27], although ongoing work to understand the potential impact of biological differences continues. In contrast, emerging data from resource-limited settings suggests the opposite, with men having higher adjusted mortality rates than women [28].

Great strides have been made in reducing the mortality rates from AIDS among women. In the United States, approximately 94,000 women (15 years of age or older) died from HIV between 1987 (the first year HIV was listed as a cause of death on death certificates) and 2015. In 2015, 1667 women died from HIV, and AIDS was not among the top 10 causes of death among females regardless of race and ethnicity [29].

Impact of depression — Depression is common among women with HIV and may be a contributory factor to negative outcomes in this population [30,31]. In an analysis of data collected prospectively from a longitudinal cohort that included over 800 women with HIV followed for a median of five years, there was a dose-related association between cumulative days with depression and mortality; each additional 365 days of depressive symptoms were associated with a 72 percent increase in the mortality risk [31].

ACCESS TO QUALITY OF CARE — A large number of barriers to care exist for women, ranging from concrete needs (childcare, transportation, housing lack of insurance) to psychological and social barriers (fear of disclosure, denial, and cultural mistrust of the health care system) [32]. In addition, a large percentage of women with HIV/AIDS provide primary care for family members who may include children or other patients with HIV/AIDS. Thus, it is not uncommon for women to compromise their own care to provide care for others. Finally, there has been growing recognition of high rates of intimate partner and other violence against women, which may prevent women with HIV from accessing or remaining in medical care [33].

In the United States, the national HIV/AIDS Strategy emphasizes the importance of engaging and retaining people with HIV in care and treatment [34]. Extensive work has been done describing barriers and facilitators to entry and retention which exist at including personal, provider, clinic, and community levels [35-37]. Less is known about interventions which are effective at keeping women in care, but evidence suggests that women may now have similar rates of linkage into care and similar to higher rates of retention in care compared with men, after years of having lower rates [38]. Specific areas which have been important in helping women remain in care include ensuring that the clinic environment and services are responsive to the many socioeconomic and psychosocial challenges which may be more common for women including stigma, intimate partner violence, depression, legal, and childcare needs. Interdisciplinary team-based care is also important in ensuring continuity of care, ideally integrated at the site of HIV care.

Despite efforts to increase access and utilization of care, women with HIV continue to receive lower quality of care, even after adjusting for potential confounders, including race and HIV transmission risk [23,27,39,40].

SEX-RELATED BIOLOGICAL DIFFERENCES

Viral load differences — While sex-based differences in access and receipt of care exist, biological differences also exist. A natural cohort study of 812 specimens from 650 injection drug users (IDU) identified differences in viral load measurements between men and women; women had lower viral loads compared to men after controlling for CD4 counts (3365 copies/mL versus 8907 by branched deoxyribonucleic acid [DNA] assay and 45,416 copies/mL versus 93,130 by reverse transcriptase polymerase chain reaction assay) [41]. The time to the development of AIDS was not different between the sexes. Another way to look at this is that women had a 1.6-fold increased risk of progressing to AIDS compared with men with the same viral load and CD4 cell count.

Many other studies have also found this sex-based difference in HIV viral loads, with no difference in overall mortality; the difference appears to be occurring primarily in the years following seroconversion. One group found significantly lower viral loads at seroconversion in women compared with men (15,103 versus 50,766 copies/mL, respectively) without differences in CD4 cell count [42]. Initial viral load was a predictor of HIV progression for men but not for women, with women rapid progressors having a median initial HIV viral load of 17,149 copies/mL compared with 77,822 copies/mL for male progressors.

In a review of nine cross-sectional and four longitudinal studies, which included viral load measurements in males and females, women had greater than twofold lower levels of HIV-1 ribonucleic acid (RNA) than men, despite controlling for CD4 counts and time from seroconversion [43]. Although the initial level of HIV-1 RNA was lower in women than in men, the rates of disease progression appear similar [42,43]. (See "Techniques and interpretation of HIV-1 RNA quantitation".)

Acute HIV infection — The clinical manifestations of acute and early HIV infection are similar in women and men. However, a study looking at sex-based differences at the time of seroconversion from Kenya found that women were more likely to be infected with diverse variants of HIV, even at the time of initial infection in comparison to men [44]. Viral isolates were obtained during acute HIV infection and prior to seroconversion in both men and women. Both groups had similar frequency of sexual intercourse and sexually transmitted diseases. The difference was quite striking; 20 of 32 women had multiple variants of the virus compared to 0 of 10 for the men, although the clinical significance of this finding and impact on viral load at seroconversion remains unknown at this time.

Opportunistic infections — Pneumocystis jirovecii pneumonia is the most common AIDS-defining infection in women and men, and advanced immunosuppression (CD4 cell count <200/microL) is the most common AIDS-defining condition in both populations. Rates of other OIs do not differ with a few exceptions [45]. Kaposi's sarcoma (KS) remains more common in men in the United States, probably related to a higher prevalence of coinfection with the etiologic agent, human herpesvirus type 8. (See "Human herpesvirus-8 infection".)

In one study of 107 patients with KS in a large municipal hospital, 11 percent were women; birth outside of the United States was a significant risk factor [46]. Women with KS tended to present with more advanced and extensive disease, possibly related to delay in diagnosis.

A number of cohort studies have reported a higher incidence of esophageal candidiasis in women with HIV. Some studies have also found increased rates of bacterial infections and herpes simplex virus (HSV) infections in these women [21,40].

GYNECOLOGIC ISSUES — For many women, gynecologic complaints are the initial manifestation of HIV. These conditions, which also exist in uninfected women, may occur with higher frequency and severity in women with HIV.

●Vaginal candidiasis

●Abnormal cervical cytology

●Pelvic inflammatory disease

●Genital ulcer disease (eg, HSV, chancroid, syphilis, idiopathic)

●Menstrual disorders

A number of these conditions, including vaginal candidiasis and abnormal cervical cytology, occur at increased rates; others, including HSV and other genital ulcer diseases, may be more difficult to treat.

Women with HIV should receive a pelvic examination with appropriate studies including KOH and normal saline examination of any vaginal discharge, testing for chlamydial and gonococcal infections, regular Papanicolaou (pap) smears, and other studies as indicated by the complaints and clinical findings.

Vaginal candidiasis — Recurrent vaginal candidiasis (at least four episodes in one year) may be the initial complaint of women with HIV and is the most common HIV-related gynecological symptom in women. It is also a common condition in women without HIV. One prospective study found a higher incidence and persistence but not severity of vaginal candidiasis among women with HIV compared with women at risk for HIV who did not have HIV [47].

Treatment is generally topical unless the infection does not respond or recurs frequently. Systemic treatment and suppression with imidazoles are effective, although long-term use can lead to colonization with resistant Candida species [48]. One study of 323 women with HIV and CD4 counts <300/microL found that intermittent suppression with fluconazole (200 mg PO once weekly) was effective as suppressive therapy without a high risk of resistance (under 5 percent in both the treatment group and control patients not receiving therapy) [49]. Weekly fluconazole prevented both vaginal and oropharyngeal candidiasis but not esophageal candidiasis. However, the need for preventive therapy has declined with the advent of more potent and durable ART regimens.

Other reasons for apparent treatment failure or breakthrough include a second etiologic agent (see below) and noninfectious conditions. These other diagnoses can be made after appropriate pelvic examination and cultures of vaginal and cervical discharge.

Bacterial vaginosis, genital ulcers, and pelvic inflammatory disease — Other gynecologic infections also occur in women with HIV.

Bacterial vaginosis may result in recurrent vaginal discharge. A prospective cohort study conducted over a five-year period found that bacterial vaginosis was both more prevalent and more persistent among women with HIV compared with those without HIV [50]. Women with HIV and CD4 cell counts <200/microL were more likely to have both persistent and severe bacterial vaginosis than those with CD4 counts >500/microL. Bacterial vaginosis may also be a risk factor for HIV acquisition [51]. Treatment of bacterial vaginosis is discussed elsewhere. (See "Bacterial vaginosis: Initial treatment".)

In comparison, genital HSV infections are increased in frequency and severity in women with HIV. Treatment with oral acyclovir or famciclovir and suppressive therapy for women with frequent recurrences is recommended. (See "Treatment of genital herpes simplex virus infection" and "Pathophysiology of TTP and other primary thrombotic microangiopathies (TMAs)".)

Genital ulcers can be caused by infectious agents other than HSV or may be idiopathic [52,53]. Chancroid (Haemophilus ducreyi infection) is especially common in women from resource-limited countries. (See "Approach to the patient with genital ulcers" and "Chancroid".)

Some studies of pelvic inflammatory disease (PID) in women with HIV have found increased risk of complications while others have not. Early in the epidemic, one study reported that women with HIV who had PID presented with fewer signs of acute infection, were more likely to have a delayed response to treatment, and more frequently required surgical intervention [54]. A second survey did not show any increased risk for complications but did document more disease severity on presentation and longer hospital stays for women with HIV [55]. However, a third prospective study of 207 women with PID (44 with HIV and 163 without) found no differences between women with and without HIV in severity of symptoms or response to therapy, regardless of CD4 counts [56]. Current recommendations are to hospitalize women with HIV who have PID and to use standard therapy. (See "Pelvic inflammatory disease: Treatment in adults and adolescents".)

Failure to respond, especially in women with advanced HIV, should prompt a change in treatment, ultrasonographic evaluation for tuboovarian abscess (TOA), and consideration of surgical intervention. As an example, in one study of 133 Kenyan women with PID verified by laparoscopy, the incidence of TOA was significantly higher in women with HIV (odds ratio [OR] 2.8) and was twice as frequent among women in whom the CD4 cell count was <14 percent (55 versus 28 percent) [57].

Cervical disease

Abnormal cervical cytology — Increased risk for low and high-grade squamous intraepithelial lesions (LSIL and HSIL), atypia (ASCUS), and carcinoma in women with HIV was first described early in the epidemic. As in women without HIV, high-risk types HPV-16 and HPV-18 are highly associated with abnormal cervical smears. (See "Cervical intraepithelial neoplasia: Terminology, incidence, pathogenesis, and prevention".)

The increased risk of cervical disease in women with HIV is related to the degree of immunosuppression (CD4 cell count), coinfection with moderate and high-risk human papilloma virus (HPV) genotypes [58,59], age [60,61], and cutaneous anergy [62].

A study prospectively evaluated a cohort of over 650 women with and without HIV who had no evidence of SIL by Pap smear or colposcopy for the development of SIL over a three-year period [63]. Women with HIV were more likely to develop SIL compared to the women without HIV (8.3 versus 1.8 cases per 100 person-years); 91 percent of these lesions were LSIL. None of the patients in either group developed cervical cancer during the follow-up period. Persistent HPV DNA, evidence of infection with multiple HPV types, and younger age were also associated with the appearance of SIL in a multivariate analysis.

HIV infection is associated with HPV infections, and the risk of HPV infection appears to increase with progressive immunosuppression and higher plasma viral loads [60,64-66]. Additionally, in one cohort study, high risk HPV types other than HPV-16 and HPV-18 were frequently identified among women with HIV and associated with abnormal cervical cytology [67]. Types most commonly associated with high-grade lesions were HPV-52 and HPV-58.

There is a low risk of cytologic abnormalities in women with HIV and relatively preserved CD4 counts who test negative for HPV [68,69]. Participants in the Women's Interagency HIV Study (WIHS) included 855 women with HIV (mean age, 36 years) and 343 women without HIV (mean age, 34 years) who had normal cervical cytology at baseline [68]. The participants underwent semi-annual examinations that included cytologic evaluation. At three years of follow-up, SIL was detected in 29 percent of women with HIV and a CD4 cell count <200 cells/microL and 14 percent of those with CD4 cell counts ranging from 200 to 500 cells/microL. Women with HIV and CD4 cell counts >500 cells/microL had low rates of SIL comparable to women without HIV (6 versus 5 percent). Similar findings were reported in a subsequent prospective analysis of a separate subset of women from the WIHS cohort [69].

The association between advancing immunosuppression and risk for cervical disease may be related to decreased rates of HPV clearance [70]. There are conflicting study results as to whether ART has any impact on the risk and natural history of ASCUS, LSIL, and HSIL, and carcinoma in women with HIV [71-74].

Screening for cervical disease is discussed elsewhere. (See "Screening for cervical cancer in patients with HIV infection and other immunocompromised states", section on 'Our approach to screening'.)

Cervical neoplasia — Women with HIV are more likely to present with multifocal cervical disease and to progress more rapidly to cervical cancer. One study found that cervical neoplasia was the leading indication for hysterectomy in women with HIV [75]. The HIV/AIDS Cancer Match Study (1980 to 2007) demonstrated that the proportion of cervical cancers among women with AIDS has increased from the pretreatment era to the ART era [74]. Furthermore, among females without AIDS, cervical cancer incidence was higher than other cancers that were evaluated in this study (eg, lymphoma). (See "Preinvasive and invasive cervical neoplasia in patients with HIV infection".)

Women with HIV also have worse treatment outcomes for cervical neoplasia compared with the general population. In a meta-analysis of 40 studies, the pooled rate treatment failure (defined as residual or recurrent high grade lesions post-treatment) was 21 percent, which was higher than that among women without HIV (OR 2.7, 95% CI 2.0-3.5) [76]. Neoplasia is more likely to recur in women with HIV if their CD4 cell counts decline [77]. The management of cervical neoplasia is discussed in detail elsewhere. (See "Cervical intraepithelial neoplasia: Choosing excision versus ablation, and prognosis and follow-up after treatment".)

Screening and prevention — Since women with HIV overall have a much higher risk of HPV infection and cervical cancer than do women without HIV, cervical screening is of paramount importance worldwide. Screening for cervical cancer in women with HIV is discussed in detail elsewhere. (See "Screening for cervical cancer in patients with HIV infection and other immunocompromised states", section on 'Our approach to screening'.)

Prevention of HPV-associated disease through HPV vaccination is also an important aspect of care of young women with HIV. Recommendations on HPV vaccination are discussed elsewhere. (See "Human papillomavirus vaccination", section on 'Administration'.)

Vulvar and perianal pathology — Women with HIV are at greater risk for vulvar and perianal pathology compared with women without HIV [78]. As with cervical pathology, HPV infection and HIV status are associated with vulvovaginal and perianal lesions.

●A prospective cohort study of 1562 women with HIV and 469 women without HIV found an increased incidence of genital warts and vulvar intraepithelial neoplasia among those with HIV [79]. The administration of potent ART decreased the risk of developing these conditions.

Monitoring and evaluation of vulvar pathology in women with HIV is discussed separately. (See "Screening for cervical cancer in patients with HIV infection and other immunocompromised states".)

●In a retrospective United States study of 745 women with HIV who underwent screening with anal Papanicolaou test, 39 percent had abnormal anal cytology [80]. Of the 147 women who underwent high-resolution anoscopy following an abnormal initial screening Papanicolaou test, 26 percent had high-grade squamous intraepithelial lesions (HSIL) and one woman had anal cancer on biopsy. Rates of HSIL were not significantly different between those who did and did not meet national expert guidelines criteria for screening (history of anogenital condylomata, prior abnormal cervical or vulvar histology, and receptive anal intercourse). Cigarette smoking, however, was associated with a more than doubled risk of HSIL. In a separate prospective study, poorly controlled HIV infection was associated with HSIL on biopsy (61 versus 5 percent in those with viral suppression) [81].

There is uncertainty with regards to optimal screening for anal intraepithelial neoplasia in women with HIV. Some experts recommend screening with anal Papanicolaou test for women with HIV who engage in anal intercourse or have abnormal cervical cytology or genital warts, whereas other experts recommend more broad screening for all women with HIV. (See "Anal squamous intraepithelial lesions: Epidemiology, clinical presentation, diagnosis, screening, prevention, and treatment".)

Menstrual abnormalities and menopause — Menstrual abnormalities, including early menopause, have been described in a number of women with HIV, but the rates and patterns are not well studied [82]. Data from small studies evaluating the age of onset of menopause among women with HIV compared with women without HIV have been conflicting and inconclusive. HIV-related inflammatory effects on the neuroendocrine axis have the potential to alter the natural history and symptomatology of menopause [83]. However, one cohort study found no difference in menstrual patterns between 197 women with and 189 controls [84].

Amenorrhea in a woman with HIV warrants a standard work-up for other gynecologic and endocrine etiologies, as well as a pregnancy test, as it does not necessarily indicate menopause. HIV infection is associated with amenorrhea [85]. As an example, in a Women's Interagency HIV Study (WIHS), prolonged amenorrhea without ovarian failure was more likely among 1139 women with HIV compared with 292 women without HIV when adjusted for age [86]. Body mass index (BMI), serum albumin, and parity were all negatively associated with ovarian failure in women with HIV. Providers were correct about the diagnosis of menopause among women with HIV in only 37 percent of cases. (See "Evaluation and management of secondary amenorrhea".)

As the population with HIV ages, the number of women approaching and experiencing menopause is growing. As in the general population, menopause is associated with a number of symptoms in women with HIV, including muscle aches and pains, fatigue, and difficulty falling asleep [87]. In an analysis of the PRIME study of 710 women with HIV, aged 45 to 60 years, post-menopausal status was associated with higher rates of anxiety, depression, and urogenital symptoms [88]. Factors that can influence these and other menopausal symptoms, such as smoking, stress, drug use, low BMI, and under-represented race/ethnicity, are also prevalent among women with HIV [89]. Severe menopausal symptoms in this population have been associated with lower adherence to antiretrovirals [90].

Hormone replacement therapy is an option for treating menopausal symptoms in women with HIV. Menopausal women should be given adequate information of symptomatology, lifestyle modification, and treatment options [91]. The risk-benefit ratio of hormonal replacement for these women remains to be described, as well as potential pharmacologic interactions between protease inhibitors and estrogen replacement. At this time, the decision about hormonal replacement should be made individually after education and counseling of the woman and determination of risk factors for cardiac disease, osteoporosis, cancer, and other conditions [92]. (See "Menopausal hormone therapy: Benefits and risks".)

GENITAL TRACT SHEDDING OF HIV — Despite the occasional presence of HIV in female genital tract secretions, women on antiretroviral therapy (ART) with consistently undetectable plasma HIV RNA levels do not transmit HIV to their sexual partners [93]. (See "HIV infection: Risk factors and prevention strategies", section on 'Treatment as prevention'.)

Several studies have detected HIV-1 proviral DNA, cell-free RNA, and/or cell-associated RNA in the female genital tract with variable rates of detection [94,95]. In one study of 97 women, paired plasma and cervical lavage specimens were collected to determine the patterns and predictors of genital tract HIV RNA during a 36-month period [96]. The strongest predictor of HIV RNA detection in cervicolavage fluid was a plasma viral load of more than 2.6 log (10) copies/mL. Studies have demonstrated that genital tract shedding can still occur even when plasma viral load is suppressed [97,98]. As an example, in a study of 1114 African women on ART who were enrolled in several clinical studies, genital shedding was detected during 5.8 percent of visits when the patient had an undetectable viral load and during 23.6 percent of visits when the patient had a detectable viral load [99]. Genital shedding was associated with HIV disease stage, antiretroviral regimen, and genital ulcers or cervical tenderness. Potential risk factors in other studies for shedding of HIV in the genital tract may include herpes simplex virus infection. (See "Epidemiology, clinical manifestations, and diagnosis of genital herpes simplex virus infection", section on 'Immunosuppressed patients'.)

ANTIRETROVIRAL MANAGEMENT

Evaluation prior to initiation — In individuals of childbearing potential, the fertility desires and preferred method of birth control should be addressed. Pregnancy testing should be done prior to the initiation of antiretroviral therapy (ART), as pregnancy impacts the selection of ART and the use of other drugs potentially indicated in HIV infection. (See "Antiretroviral selection and management in pregnant individuals with HIV in resource-rich settings".)

Other pre-selection testing is the same as in the general population. (See "Initial evaluation of adults with HIV".)

Selection of antiretroviral regimens

Individuals of childbearing potential — Individuals of childbearing potential include premenopausal female adults and adolescents as well as transgender or gender-fluid individuals capable of pregnancy. The approach to regimen selection in sexually active individuals of childbearing potential differs somewhat from that in the general population with HIV, since it takes into account data on maternal and fetal safety with use during pregnancy in addition to the typical considerations for regimen selection. (See "Selecting antiretroviral regimens for treatment-naïve persons with HIV-1: General approach", section on 'Considerations prior to initiating treatment'.)

Thus, our approach to regimen selection or management in individuals of childbearing potential depends on their intentions for conception and use of contraception:

●For those who have no plans to conceive in the near future – The approach to regimen selection is the same as in the general population with HIV; patients who are already taking effective ART should continue unless there are other reasons to switch. These issues are discussed in detail elsewhere. (See "Selecting antiretroviral regimens for treatment-naïve persons with HIV-1: General approach" and "Switching antiretroviral therapy for adults with HIV-1 and a suppressed viral load".)

●For those who are actively trying to conceive

•Initiating ART − For individuals who are actively trying to conceive and initiating ART, we suggest one of the following preferred regimens:

-Dolutegravir

Plus, one of the following:

-Tenofovir alafenamide-emtricitabine (TAF-FTC), tenofovir disoproxil fumarate-emtricitabine (TDF-FTC), TAF-lamivudine (TAF-3TC), TDF-lamivudine (TDF-3TC), or abacavir-lamivudine (ABC-3TC)

For patients who have had exposure to cabotegravir from pre-exposure prophylaxis or who cannot take dolutegravir for another reason, we substitute ritonavir-boosted darunavir for dolutegravir in the regimens listed above.

There is a small difference in the rate of neural tube defects in infants exposed to dolutegravir around the time of conception (0.11 percent) compared with infants born to women without HIV (0.07 percent) in a setting where folate supplementation of food is not routine; however, the risk with dolutegravir exposure is not statistically different compared with exposure to non-dolutegravir-containing antiretroviral therapy around the time of conception (0.11 percent) [100]. Dolutegravir has many advantages, including its high and durable virologic potency, ease of use, and overall safety. Thus, we and others suggest dolutegravir as one of the preferred medications in those who are trying to conceive and throughout pregnancy. We counsel our patients about these data and the fact that there is more information about the safety of dolutegravir during pregnancy and around the time of conception than most other antiretroviral regimens. Dolutegravir should not be administered within two hours of ingesting any preparation that contains such minerals as calcium or iron, including prenatal vitamins. Data on the risk of neural tube defects are discussed in detail elsewhere. (See "Safety and dosing of antiretroviral medications in pregnancy", section on 'Dolutegravir'.)

For individuals trying to conceive who cannot take one of the preferred regimens above, other regimens that have well-established safety and efficacy during pregnancy that are reasonable alternatives (as long as resistance is not an issue) include raltegravir or ritonavir-boosted atazanavir plus a dual-NRTI backbone. In general, we favor integrase inhibitor-based ART because it is well tolerated; dosing of protease inhibitors may warrant adjustment during pregnancy, as discussed elsewhere. (See "Safety and dosing of antiretroviral medications in pregnancy", section on 'Integrase inhibitors' and "Safety and dosing of antiretroviral medications in pregnancy", section on 'Protease inhibitors'.)

Although bictegravir is commonly used in the general population as a component of the fixed-dose combination bictegravir-emtricitabine-tenofovir alafenamide (BIC/FTC/TAF), data on the safety and efficacy of bictegravir in pregnancy are relatively limited. In the United States, the Department of Health and Human Services Panel on Treatment of HIV During Pregnancy and Prevention of Perinatal Transmission notes insufficient data for bictegravir [101]. Pending more data, we generally do not initiate bictegravir-containing regimens in individuals actively trying to conceive unless one of the above regimens cannot be used. (See "Safety and dosing of antiretroviral medications in pregnancy", section on 'Tenofovir alafenamide' and "Safety and dosing of antiretroviral medications in pregnancy", section on 'Bictegravir'.)

We also avoid initiating a cobicistat-containing regimen in individuals who are trying to conceive because decreased drug levels during pregnancy and associated loss of virologic control have been described with cobicistat-boosted regimens [102,103]. (See "Safety and dosing of antiretroviral medications in pregnancy", section on 'Cobicistat'.)

•On suppressive ART − For individuals who are trying to conceive and are already on a suppressive ART regimen with an agent for which there are limited data in pregnancy (eg, bictegravir, doravirine, oral two-drug regimens, injectable cabotegravir-rilpivirine regimen), the decision to remain on their regimen or switch to a different one should be individualized. We discuss the limited safety data for these agents during pregnancy as well as the risk of switching therapy (eg, difficulty with adherence with a different regimen, loss of virologic control). Some women may reasonably decide that the uncertain safety profile does not outweigh the risks of switching.

For women taking a cobicistat-containing regimen, however, we suggest switching to a different regimen due to decreased levels of the antiretroviral the cobicistat is boosting during pregnancy and the potential for loss of virologic suppression.

All individuals with HIV who are trying to conceive should receive folic acid supplementation, as recommended for the general population. (See "Preconception and prenatal folic acid supplementation", section on 'Folic acid supplementation for preventing NTDs'.)

●For those who are not actively trying to conceive but are sexually active and not using reliable contraception – We discuss the lack of data on certain regimens in pregnancy and individualize regimen selection through shared decision-making. For patients concerned about these uncertainties, we suggest one of the regimens above that are preferred for patients actively trying to conceive. However, some patients may prefer the benefits and convenience of certain regimens, such as bictegravir-emtricitabine-tenofovir alafenamide or long-acting cabotegravir-rilpivirine, despite understanding the limited safety data in the setting of a possible unplanned pregnancy, and reasonably choose a regimen containing these agents.

Individuals who conceive while taking ART should generally continue their regimen, with rare exception. In some cases, dosing adjustments may be warranted. These issues are discussed in detail elsewhere. (See "Antiretroviral selection and management in pregnant individuals with HIV in resource-rich settings" and "Prevention of vertical HIV transmission in resource-limited settings".)

Individuals without childbearing potential — There are no sex-specific recommendations for selection of antiretroviral regimens, and thus recommended regimens for nonpregnant individuals who do not have childbearing potential are generally the same as those for the general population with HIV [103,104]. (See "Selecting antiretroviral regimens for treatment-naïve persons with HIV-1: General approach" and "Selecting an antiretroviral regimen for treatment-experienced patients with HIV who are failing therapy".)

However, treatment-associated side effects appear to be more common in women, and these could potentially impact efficacy. Thus, potential toxicity should be taken into account when selecting a regimen. (See 'Side effects' below.)

Additional considerations for transgender women — Antiretroviral regimen selection and management in transgender women who are using gender-affirming hormone therapy (eg, estrogen, androgen inhibitors) should take into consideration the potential for drug interactions. Otherwise, antiretroviral selection is the same as for cisgender women. (See 'Individuals of childbearing potential' above and 'Individuals without childbearing potential' above.)

Unboosted integrase inhibitors, nucleoside reverse transcriptase inhibitors (NRTIs), and certain non-nucleoside reverse transcriptase inhibitors (NNRTIs; ie, rilpivirine and doravirine) are not expected to have drug interactions with hormone therapy. Estradiol used for gender-affirming hormone therapy has been observed to decrease the level of tenofovir, although the clinical significance of this decrease is uncertain [105,106].

Other NNRTIs (ie, efavirenz, etravirine, and nevirapine) may decrease the levels of estradiol, and concurrent use may warrant an increase in the estradiol dose for clinical effect. As an example, in a study of 20 transgender women who started hormone therapy three weeks before starting efavirenz plus TDF-FTC, estradiol concentrations were lower following initiation of ART [105].

The impact on ritonavir or cobicistat-boosting agents on estradiol used for gender-affirming hormone therapy is uncertain; if concurrent use is necessary, monitoring for therapeutic drug levels, toxicity, and clinical estradiol effect can be used to guide estradiol dose adjustments [106].

Efficacy — Overall, the efficacy of ART in women appears comparable to that in men [107-111]. As an example, in a large multicenter cohort of individuals initiating ART, there were no significant sex differences in virologic, immunologic, or clinical outcomes after controlling for potential confounders [108]. However, the efficacy of specific antiretrovirals may be different in women and men.

As an example, in a subset analysis of a trial of 1857 individuals (322 of whom were women), women who were randomly assigned to initiate a ritonavir-boosted atazanavir-based regimen were more likely to experience virologic failure compared with those who received an efavirenz-based regimen, regardless of the nucleoside inhibitor backbone [112]. Additionally, women on atazanavir were more likely than men on atazanavir to experience virologic failure, but the same gender difference was not observed for efavirenz.

The reason for decreased efficacy with certain antiretroviral agents among women is unclear, although may be related to drug toxicity, pharmacokinetics, or other causes. In one analysis that suggested a higher risk of virologic failure among women following initiation of one of three regimens (tenofovir-emtricitabine plus ritonavir-boosted atazanavir, raltegravir, or ritonavir-boosted darunavir), the excess risk in women was attenuated when the analysis was adjusted for race [113]. At this point, there are not enough data to support recommending particular regimens in women because of superior efficacy.

Nevertheless, these data highlight the importance of evaluating the efficacy of specific antiretroviral regimens in women rather than extrapolating the data from studies of men. The feasibility of this has been demonstrated in several large studies [114-116], including a large randomized trial of nearly 600 women, in which an elvitegravir-cobicistat-based regimen resulted in higher rates of virologic suppression at one year compared with a boosted-atazanavir-based regimen (87 versus 81 percent) [115]. Similarly, a large randomized trial confirmed that switching from a suppressive regimen to bictegravir-emtricitabine-tenofovir alafenamide is an effective option for women, specifically [117].

Side effects — Women appear to experience more adverse effects from ART regimens than men [107,118-123]. In particular, women tend to gain more weight than men with newer ART regimens (eg, integrase strand transfer inhibitor [INSTI]-based and/or TAF-based regimens). This has been observed among individuals initiating ART as well as those switching to a new regimen. Nevertheless, other advantages of the newer regimens generally outweigh these side effects.

●Weight gain − In a pooled analysis of eight randomized clinical trials of ART-naïve individuals initiating ART, female sex was an independent risk factor for ≥10 percent weight gain (odds ratio 1.54, 95% CI 1.21-1.96) [120]. Black women were more likely to experience ≥10 percent weight gain compared with non-Black women (19.7 versus 12.4 percent). The ≥10 percent weight gain was associated with a nonstatistically significant increase in diabetes- and hyperglycemia-related adverse effects. Another randomized clinical trial was the ADVANCE study, which compared dolutegravir plus TAF-FTC, dolutegravir plus TDF-FTC, and efavirenz-TDF-FTC among 1053 ART-naïve individuals in South Africa [121]. Women were more likely to experience weight gain in all three treatment groups at 96 weeks (12 to 28 percent versus 3 to 5 percent among men), and weight gain among women was greatest with dolutegravir plus TAF-FTC (mean 8.1 kg versus 4.8 kg and 3.2 kg with dolutegravir plus TDF-FTC and efavirenz-TDF-FTC, respectively). Women also gained more fat than lean body mass than men (with fat concentrating in the limbs and trunk).

Observational studies of virally suppressed women have also noted excess weight gain associated with switching to INSTI-based regimens, which in some cases was greater than that observed in men [122,123].

●Bone density loss − Limited studies suggest that women experience more bone density loss after initiation of ART compared with men [103,124]. This is one of the reasons that TAF is preferred over TDF. (See "Selecting antiretroviral regimens for treatment-naïve persons with HIV-1: General approach", section on 'Approach for most patients' and "Bone and calcium disorders in patients with HIV", section on 'Risk with specific agents'.)

●Other metabolic effects − There is no clearly established sex difference in the frequency of lipodystrophy or diabetes due to ART. However, some studies have found increased risk of fat accumulation versus lipoatrophy in women and decreased risk of hyperlipidemia compared with men [125].

Sex-based differences may reflect differences in pharmacokinetics due to body weight or drug metabolism, hormonal differences, or other factors. As an example, in a study that suggested greater virologic failure with a ritonavir-boosted atazanavir-based regimen in women compared with men, women had slower clearance and higher trough concentrations of atazanavir than men [112]. Of note, self-reported side effects were not more frequent among women in this study.

Adherence — Adherence is a major barrier to success with ART for women and men. Several observational studies have suggested higher rates of nonadherence among women compared with men [126]. Reasons for this may include competing needs of other family members with HIV and other infections, fear of disclosure in their own household, lack of social services (eg, food, housing, and transportation), poor patient-provider relationships, and side effects [127,128]. Racial barriers may also play a role, as Black and Hispanic American women had lower adherence rates compared with White women [129].

Social and community adherence support programs should be designed to address the multiple challenges for women on HIV therapy. Providing basic social services, establishing trust within the patient-provider relationship, and recognizing underlying mental health disorders or HIV-related cognitive deficits is critical in improving the adherence to ART in women.

Monitoring — There are no sex-based differences in recommendations for monitoring CD4 cell counts and plasma viral load or for the prevention and treatment of opportunistic infections [103,130,131]. (See "Techniques and interpretation of HIV-1 RNA quantitation" and "Techniques and interpretation of measurement of the CD4 cell count in people with HIV".)

CHOICE OF CONTRACEPTION — The choice of contraception for a woman with HIV is often complicated and must incorporate issues related to:

●Specific contraceptives and their efficacy in preventing pregnancy

●Change in risk of transmission of HIV and other sexually transmitted infections (STIs)

●Drug interactions between certain antiretroviral agents and hormonal contraceptives

General considerations for contraception selection are discussed elsewhere (see "Contraception: Counseling and selection"). The following sections discuss the considerations specific to HIV infection and treatment.

Although transmission of HIV does not occur if a person with HIV is on antiretroviral therapy (ART) and consistently virally suppressed, a form of barrier contraception is always recommended because of the risk of other STI transmission. Other factors may also influence a woman's choice of contraception, including whether she has been able to disclose her HIV status, fear of domestic violence, and other medical conditions. The best practice is dual contraception with a hormonal agent to prevent pregnancy and condoms to reduce the transmission of STIs.

Hormonal contraceptives — Hormonal contraceptives (eg, oral, injectable, implants) are effective reversible agents for the prevention of pregnancy in women.

Drug interactions — While reliability does not appear to be reduced by HIV infection, efficacy can be compromised by drug interactions between estrogen/progesterone and certain antiretroviral agents and other medications commonly used in individuals with HIV [132] including:

●Non-nucleoside reverse transcriptase inhibitors (specifically efavirenz)

●Protease inhibitors

●Pharmacologic boosters (eg, ritonavir, cobicistat)

●Other medications (including rifampin) that may be needed to treat HIV-related complications or comorbidities

In particular, certain protease inhibitors (including ritonavir-boosted darunavir and lopinavir/ritonavir) decrease ethinyl estradiol and norethindrone levels; alternative or additional contraceptive methods should be used for patients taking these agents [131]. Similar precautions are advised for the cobicistat-boosted protease inhibitors and cobicistat-boosted elvitegravir. Unboosted integrase inhibitors, such as dolutegravir, raltegravir, and bictegravir, can be safely prescribed with hormonal contraceptives.

Efavirenz has also been implicated in significant drug interactions with certain hormonal contraceptives, in particular progestin-releasing implants (both levonorgestrel and etonogestrel), resulting in decreased contraceptive efficacy [133-135]. In a prospective study of women with HIV in Uganda who received a levonorgestrel implant, levonorgestrel levels were lower and unintended pregnancies were higher among the 20 women who were on an efavirenz-containing ART regimen compared with the 20 on a nevirapine-containing regimen and 17 ART-naïve women (three versus zero unintended pregnancies within 48 weeks of follow-up) [133]. Similarly, in a large retrospective study in Kenya, the adjusted pregnancy incidence among over 6000 women using progestin-releasing implants was three times higher in those using an efavirenz- versus nevirapine-based regimen [135]. Nevertheless, the adjusted pregnancy rate with concomitant efavirenz use and progestin-releasing implants remained lower compared with other forms of contraception apart from intrauterine devices or permanent methods, regardless of ART regimen used. In the United States, efavirenz-based regimens are no longer preferred regimens for treatment initiation [103]. In settings where equally effective non-efavirenz-containing regimens are not available, an additional or alternative form of birth control with equal efficacy should be used for women on efavirenz-containing regimens. This challenge highlights the need for better ART regimens for women of childbearing age, as well as alternate strategies for long-acting contraceptive agents.

Providers are cautioned to check for new information as research continues. A number of online resources are available which provide up-to-date information on drug interactions [103,136,137].

Effect on HIV disease progression — Conflicting results have been published on the effects of hormonal contraception on HIV disease progression [138]. In two large studies, hormonal contraception was associated with more rapid CD4 T-cell depletion [139,140]; however, other smaller studies did not support these findings [141,142]. All of these trials were performed in women who were not taking ART.

Intrauterine contraceptive device — The intrauterine contraceptive device also provides effective contraception and appears to be safe to use in women with HIV. One large randomized controlled trial in Zambia, which compared the safety and effectiveness of a copper IUD versus hormonal contraception, demonstrated that only one patient developed pelvic inflammatory disease during the two-year follow-up [139]. Furthermore, women assigned to the IUD arm were significantly less likely to become pregnant. There is also no evidence of increased cervical shedding of HIV and no increased risk of viral transmission from a woman using an IUD [143,144]. (See "Contraception: Counseling and selection" and 'Hormonal contraceptives' above and "Intrauterine contraception: Candidates and device selection", section on 'Immunocompromise'.)

Other effective forms of birth control — Use of male condoms, although less efficacious for the prevention of pregnancy, has been proven to reduce transmission of HIV and other STIs [145,146]. Acceptance of male condom use may be limited by fear of disclosure, refusal by the partner, and many other issues. Although the data are limited, it is likely that the female condom, when used properly, has similar efficacy as the male condom and is attractive as a woman-controlled method [147]. While cost, convenience and esthetics have limited the widespread use of the female condom, effective interventions to increase the use of barrier methods in women and men are increasingly available. The diaphragm and cervical cap are associated with a decreased risk of gonorrhea, chlamydia, trichomoniasis, and PID [148,149]. Much of the protective effect is probably due to the concomitant use of spermicides, and no impact on HIV transmission has been consistently shown.

Microbicides — Vaginal microbicides, which are also spermicidal, have generally had disappointingly minimal effect in preventing STIs and are thus not routinely recommended. This is discussed in detail elsewhere. (See "Prevention of sexually transmitted infections", section on 'Limited efficacy of topical microbicides'.)

OTHER PRIMARY CARE ISSUES — Primary care for women with HIV raises some special issues. General primary care issues for persons with HIV are discussed elsewhere. (See "Primary care of adults with HIV".)

Screening for sexually transmitted infections — Ongoing screening for sexually transmitted infections among sexually active women with HIV is important for both the woman's own health and from a public health perspective, similar to all sexually active women. This is discussed in detail elsewhere. (See "Primary care of adults with HIV", section on 'Sexually transmitted infections' and "Screening for sexually transmitted infections", section on 'Patients with HIV infection'.)

Health maintenance — The care of women with HIV must incorporate primary care into their HIV care [150]. As women survive longer with HIV, other comorbid conditions will increase with age. Furthermore, HIV infection and treatment may increase the risk of many of these conditions, including diabetes, cardiovascular disease (CVD) [151,152], cognitive dysfunction [153], renal insufficiency, liver disease, osteoporosis, and psychiatric disease [154]. There appear to be sex differences in interventions to address such conditions. As an example, although women (n = 12,955) were generally at lower CVD risk than men (n = 36,094) in the large observational D:A:D cohort study, they were less likely to receive appropriate CVD interventions, except for anti-hypertensive treatment [155].

In the United States, it is estimated that half of all pregnancies are unplanned. Given that congenital anomalies occur in very early stages of pregnancy, even before women may be aware they are pregnant, women of childbearing potential should be advised to maintain good nutrition. This includes recommendations to consume 400 micrograms of folic acid daily to prevent two common and serious congenital anomalies, spina bifida and anencephaly [156-159]. (See "Preconception and prenatal folic acid supplementation", section on 'Rationale for universal prophylaxis in females of childbearing potential'.)

HIV infection is variably associated with the risk of non-AIDS-defining malignancies. Higher rates of some cancers, such as lung and anal cancer, have been reported among individuals with HIV, whereas lower age-adjusted rates have been observed for other cancers, such as colon and breast cancer [160]. Whether these differences are related to differences in risk or rates of screening compared with the overall population is not known at this time.

Thus, close attention to screening for comorbidities, reducing their risk, and effectively managing them is critical to the care of the person with HIV [161]. Moreover, clinicians should recognize that not all complaints are necessarily HIV-related. (See "Overview of preventive care in adults".)

The complex psychosocial needs of many women with HIV often requires a multidisciplinary team to address issues such as housing, substance abuse, and mental illness, either on-site or by linkage with other institutions or community-based organizations. One group found that case management significantly improved care and use of HIV therapies for individuals with HIV [162].

HIV AND PREGNANCY — Since many women with HIV are diagnosed during pregnancy and women with HIV may choose to become pregnant, primary care providers should have a basic understanding of the current state of knowledge regarding HIV and pregnancy. The use of combination antiretroviral therapy during pregnancy has reduced the HIV transmission rate from approximately 20 to 30 to <1 percent in resource-rich settings [163-165]. The general and antiretroviral management of pregnant women with HIV is discussed in detail elsewhere. The approach differs by resource-rich versus resource-limited settings.

●(See "Prenatal evaluation of women with HIV in resource-rich settings" and "Antiretroviral selection and management in pregnant individuals with HIV in resource-rich settings" and "Intrapartum and postpartum management of pregnant women with HIV and infant prophylaxis in resource-rich settings".)

●(See "Prevention of vertical HIV transmission in resource-limited settings" and "Prevention of HIV transmission during breastfeeding in resource-limited settings".)

●(See "Safety and dosing of antiretroviral medications in pregnancy".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: HIV treatment in nonpregnant adults and adolescents" and "Society guideline links: HIV treatment in pregnant patients" and "Society guideline links: Primary care of adults with HIV" and "Society guideline links: Cervical cancer screening, prevention, and management".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Beyond the Basics topic (see "Patient education: HIV and pregnancy (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Epidemiology − Heterosexual contact is the most commonly reported risk factor for HIV acquisition in women worldwide. (See 'Epidemiology' above.)

●Natural history − Early in the epidemic, several studies reported higher mortality and increased progression of HIV in women compared with men. However, subsequent data demonstrated that these differences were largely explained by decreased access to care by women rather than greater disease progression compared to men. (See 'Natural history' above.)

●Genital infections − Certain genital infections, such as vaginal candidiasis and herpes simplex virus, appear to be more persistent and severe in women with HIV than in women without HIV, although some of these differences have been reduced in women on effective ART. (See 'Vaginal candidiasis' above and 'Bacterial vaginosis, genital ulcers, and pelvic inflammatory disease' above.)

●Cervical disease − Women with HIV have an increased risk for cervical dysplasia and cervical cancer compared with women without HIV. Risk of severe cervical disease is related to the degree of immunosuppression (as measured by the CD4 cell count), response to ART, and coinfection with moderate and high-risk human papilloma virus genotypes. (See 'Abnormal cervical cytology' above.)

●Antiretroviral regimens − Selection of antiretroviral regimens for individuals of childbearing potential warrants special consideration. In particular, although bictegravir is commonly used in the general population, there is limited data on its’ safety and dosing in pregnancy. (See 'Individuals of childbearing potential' above.)

•For individuals who are actively planning to conceive and are initiating antiretroviral therapy, we suggest one of the following regimens rather than a regimen containing bictegravir (Grade 2C):

-Dolutegravir

Plus

-Tenofovir alafenamide-emtricitabine (TAF-FTC) or tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) or TAF-lamivudine (TAF-3TC) or TDF-lamivudine (TDF-3TC) or abacavir-lamivudine (ABC-3TC)

For patients who have had exposure to cabotegravir from pre-exposure prophylaxis or who cannot take dolutegravir for another reason, we substitute ritonavir-boosted darunavir for dolutegravir in the regimens listed above.

•For individuals who are actively planning to conceive and are already on a suppressive ART regimen with limited data on use in pregnancy (eg, bictegravir-containing regimens, two-drug oral regimens, injectable cabotegravir-rilpivirine regimen), the decision to switch to a different regimen should be individualized based on uncertainties with use during pregnancy, the small possibility of loss of virologic control with switching, and the treatment history.

•For individuals who are actively planning to conceive, we also suggest not initiating a cobicistat-boosted regimen (eg, elvitegravir-cobicistat, darunavir-cobicistat, atazanavir-cobicistat) because of concerns about adequate levels during pregnancy (Grade 2C).

•For individuals of childbearing potential who are not actively planning to conceive but are sexually active and not using reliable contraception, we individualize regimen selection through shared decision-making, weighing limited data on safety should an unplanned pregnancy occur against the benefits and convenience of certain regimens, such as bictegravir-emtricitabine-tenofovir alafenamide.

●HIV and pregnancy − Management of pregnant women with HIV is discussed in detail elsewhere. (See "Antiretroviral selection and management in pregnant individuals with HIV in resource-rich settings", section on 'On ART with viral suppression'.)

●Choice of contraception − The choice of contraception for a woman with HIV remains complex and must incorporate issues related to the prevention of transmission of HIV and other sexually transmitted diseases and to drug interactions with antiretroviral medications and future conception plans. (See 'Choice of contraception' above.)

ACKNOWLEDGMENTS — The UpToDate editorial staff acknowledges Lisa Hirschhorn, MD, MPH, who contributed to an earlier version of this topic review.

UpToDate also gratefully acknowledges John G Bartlett, MD (deceased), who contributed as Section Editor on earlier versions of this topic and was a founding Editor-in-Chief for UpToDate in Infectious Diseases.