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

Primary care physicians will provide an increasing amount of care for women with HIV. Increased identification and early initiation of treatment of HIV infection with simpler and more potent ART has resulted in increased longevity and decreased mortality. Sex-specific issues such as pregnancy, breast and cervical cancer screening and prevention, and menopause have become more important components of the overall care of women with HIV. As such, women with HIV will rely less on specialized care and more on primary care physicians. Therefore, primary care providers need to become more knowledgeable of critical management considerations for this population and more comfortable determining when specialty consultation is needed. In general, the management of women with HIV in the primary care setting shares many similarities with the management of women without HIV but with some important differences. This section of the module will highlight key aspects of care provision for women with HIV that should be considered in the primary care setting.

Routine clinical care for women with HIV should include all of the following:

• Immunizations: vaccine recommendations are generally similar between patients with and without HIV with the exclusion of live viral-based vaccines.
• Tuberculosis screening: screening for latent tuberculosis infection should be performed at the time of HIV diagnosis and annually thereafter in women with HIV with an ongoing risk for tuberculosis acquisition.
• Cardiovascular disease risk screening: patients with HIV should be screened for traditional modifiable risk factors, including cigarette smoking, hypertension, hyperlipidemia, diabetes, and obesity, because HIV infection itself may increase cardiovascular disease risk.^[23,24] These factors should be addressed at each physician visit with behavioral and pharmacologic interventions as appropriate.^[26]
• Breast cancer screening: women with HIV should follow standard age-based recommendations for regular mammograms and breast self-examinations established for all women, regardless of HIV status.
• Psychosocial assessment: psychosocial stressors should be evaluated on a regular basis in women with HIV as these factors can negatively affect adherence to ART and participation in clinical care. A multidisciplinary team that incorporates social services, mental health, and case management is often required to maintain ongoing clinical care and medication compliance in this population.^[35,36]
• Depression screening: patients with HIV should receive ongoing screening for depression, with referral for appropriate mental health intervention when indicated. This is especially important for women with HIV as the rate of depressive symptoms or disorders in this population is nearly double that in men with HIV.^[147,148] In addition, 1 in 5 women with HIV meet the classification for major depressive disorders compared with 1 in 20 women without HIV.^[149] Depression in women with HIV is associated with several negative sequelae, including increased rates of all-cause and AIDS-related mortality,^[163] potentially higher rates of STDs and substance abuse,^[164,165] and decreased cognitive function.^[166] In addition, depression has been linked to intimate partner violence necessitating inquiry into safe partnerships and living environments.
• STD screening: Sexually active women should receive routine screening for STDs, including for gonorrhea, chlamydia, trichomonas, syphilis, bacterial vaginosis, vulvovaginal candidiasis, herpes simplex virus, and HPV. STDs can facilitate HIV transmission by increasing genital shedding of HIV.^[80] STD screening should also be conducted after a new HIV diagnosis, with a new sexual partner, following a condom malfunction, after unprotected intercourse, or when there is a known exposure to an STD.
• Cervical cancer screening: Cervical cancer screening should be performed in women with HIV throughout their lifetimes.^[13] All women with HIV should undergo baseline screening by Pap test alone if younger than 30 years of age or Pap test alone or in combination with HPV DNA testing in women 30 years of age or older. Depending on the results of cervical cytology and/or HPV DNA testing, either repeat testing should be performed at 6 or 12 months or an immediate colposcopy should be offered. Testing intervals can be extended to 3 years following 3 consecutive normal Pap results or initial normal/negative Pap/HPV cotesting results.
• Anal cancer screening: Careful visual inspection of the vaginal, vulvar, and perianal region and digital examination of the anal canal should be performed routinely.^[13] Some specialists recommend anal cytologic screening for women with HIV, followed by high-resolution anoscopy in women with abnormal cytologic results, regardless of history of receptive anal intercourse.

The DHHS adult ART guidelines recommend that all people with HIV initiate ART regardless of CD4+ cell count to prevent sexual transmission of HIV in addition to preventing disease progression in the individual.^[77] Factors that should be considered when selecting an initial ART regimen for women with HIV include childbearing potential and use of hormonal contraceptives, HIV serostatus of partners, risk for adverse events of ARV agents, comorbidities, and anticipated ARV adherence. Despite recommendations for ART initiation, considerable numbers of women with HIV with clinical indications for treatment in the United States are not receiving ART. In addition, there are several notable differences between the course of ART in women with HIV vs that in men with HIV, including higher rates of treatment-associated adverse events^{[110,117,128,130-133]} and ART modification or discontinuation because of adverse events.^[127]

There are special considerations for reproductive health in women with HIV when compared with the general population. These include issues related to contraception, pregnancy, and menopause. Women with HIV infection often feel stigmatized by their diagnosis and, therefore, do not seek appropriate care, which can be detrimental to all facets of reproductive health. Primary care physicians can play an important role in addressing these issues by initiating discussions with women with HIV during routine primary care appointments.

When counseling women with HIV on the use of safe and effective contraception, primary care physicians can explain the importance of dual forms of contraception: barrier (condom) and hormonal (or sterilization). Dual mechanisms are necessary because ARV agents may alter the clinical effectiveness of many of the available contraceptive choices, and contraceptive agents may alter the efficacy of some ARV agents. In addition, barrier (condom) contraception is also important to reduce the risk of sexual transmission of HIV to intimate partners. Virologic responses to ART should be monitored closely when used in combination with nonbarrier contraceptives. Pharmacokinetic interaction should be considered when combined oral contraceptives and ARVs are used together and certain agents should not be used concurrently. Limited data exist regarding the use of implantable or intravaginal contraception in women with HIV. However, the CDC’s Medical Eligibility Criteria for Contraceptive Use lists all combined hormonal contraceptive methods (including the patch and vaginal ring) as Category 1 (no restriction for use) for women at high risk for HIV or with HIV or AIDS.^[72] Both the copper-containing intrauterine device (Tcu-380A IUD) and the levonorgestrel-releasing intrauterine contraceptive system are acceptable choices for women with HIV and do not appear to be associated with increased genital tract shedding of HIV.^[77]

The DHHS recommends the use of ART by all pregnant women with HIV to reduce the risk of mother-to-child transmission of HIV regardless of CD4+ cell count.^[52] In many cases, HIV infection may be initially diagnosed during pregnancy. The CDC, the American College of Obstetrics and Gynecology, and the DHHS all recommend routine prenatal HIV screening in the first trimester for all pregnant women, with repeat testing at other times during pregnancy in women who are at increased risk of acquiring HIV.^[184] In addition, women who present to labor and delivery with unknown HIV status or who are at risk for HIV acquisition should undergo rapid HIV testing. If the results of the rapid test are positive or unknown, intravenous zidovudine should be administered without waiting for confirmation of HIV status. Primary care physicians should involve both obstetrical providers and HIV specialists in the medical care of pregnant women with HIV throughout the entire gestational period especially regarding selection of appropriate ART, management of prenatal care and delivery, and treatment of infants exposed to HIV. Key management strategies for pregnant women with HIV include the following^[52]:

• Pregnant women with HIV should follow the same vaccination schedule as nonpregnant patients with HIV, with particular attention to the need for hepatitis A and B vaccination (if antibodies are not present) and influenza virus vaccine, inactivated
• Pregnant women with HIV should be monitored with greater frequency for ARV treatment response and complications
• Intravenous zidovudine administered near delivery is recommended for pregnant women with HIV with HIV-1 RNA > 1000 copies/mL or unknown HIV-1 RNA levels unless there is evidence of resistance or toxicity
• Women whose HIV-1 RNA remains > 1000 copies/mL near the time of delivery should be advised to undergo Cesarean section
• Women should continue their oral ART regimen as prescribed before and during labor and delivery
• ART should be continued postpartum unless a contraindication exists
  • However, decisions regarding ART continuation postpartum should be made with consultation between the woman and her HIV provider, preferably before delivery
• Breastfeeding is currently not recommended in any women with HIV with access to clean water and formula, regardless of HIV-1 RNA level
• Mothers should be discharged with a prescription for ART for themselves and for their infants and instructions for follow-up^[52]

Based on the success of ART, the proportion of women with HIV who are 50 years of age or older continues to increase, with a concomitant increase in the need for effective management of menopausal symptoms in this group. All postmenopausal women, including those with HIV infection, should undergo routine health screening, including Pap smears and screening for STDs, breast cancer, colon cancer, osteoporosis, cardiovascular risk factors, and depression.^[230] Evidence suggests that several important interactions may occur between HIV infection and menopause, and primary care physicians may be better able to assist women with HIV experiencing complications of menopause if they have an understanding of this potential interplay. Several potential associations that may be useful to consider include:

• Earlier menopause in women with HIV may be associated with lower CD4+ cell count, low physical activity, and injection drug use^[227]
• Women with HIV may be at increased risk for conditions linked with estrogen deficiency^[220-223]
• Severity of menopause symptoms may be altered in women with HIV^[228,229]

Current evidence supports the use of hormone replacement therapy for relief of menopausal symptoms, especially vasomotor effects. However, there are no available data demonstrating safety in the HIV population.