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HIV/AIDS

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Women's Health and HIV

for Health Care Providers

Women's Health

Note: Some medications mentioned in this chapter may not be available on the VHA National Formulary. Consult VA pharmacists for alternatives.

Key Points

  • A Women Veterans Program Manager is available at every VA Medical Center to assist in providing care for women veterans.
  • Nearly one third of people living with HIV in the United States are women.
  • In the United States, HIV-infected women are less likely than HIV-infected men to receive ART.
  • General preventive strategies and health maintenance are all part of routine care for HIV-infected women.
  • Women should receive reproductive counseling.
  • For pregnant women and women who may become pregnant, avoid use of EFV.
  • Women with HIV have increased risk of developing abnormal cervical, vaginal, vulvar, and anal cytology, with possible progression to squamous carcinoma, especially if the CD4 count is <200 cells/µL.
  • Women with HIV have higher rates of persistence and recurrence of herpes simplex virus, human papillomavirus (HPV), bacterial vaginosis, and candidal genital tract infections compared with their HIV-uninfected counterparts.
  • Women with HIV are at increased risk of neuropsychiatric disease and should be screened accordingly.
  • All women veterans, including those with HIV, should be screened for military sexual trauma and exposure to domestic violence.
  • All women veterans, including those with HIV, should be screened for breast cancer and osteoporosis.

Background

Epidemiology

  • One half of the people living with HIV worldwide are women.
  • In the United States, according to the CDC:
    • Nearly one third of people living with HIV are women.
    • Heterosexual transmission is the main mode of HIV acquisition among women (80-90% 2008), followed by injection drug use.
    • Rates of HIV infection are increasing in rural and small metropolitan areas.
    • Women of color are disproportionately infected with HIV.
      • In 2010, the diagnosis rate of both HIV/AIDS and AIDS was 20 times higher for non-Hispanic black women than the rate for non-Hispanic white women; 64% of HIV-infected women were African American.
      • The diagnosis rate of both HIV/AIDS and AIDS was nearly 5 times higher among Hispanic/Latina women than non-Hispanic/Latina white women.
      • In 2010, 45% of women of color infected with HIV were from southern U.S. states. They are less likely to start ART than women and men from other regions of the United States, and they had the highest rate of HIV/AIDS events (81%).
    • HIV-infected women are less likely than their male counterparts to be on ART, largely because of decreased access to health care and because of priorities.

Veterans with HIV*

Women: 3%

*Veterans in the VA HIV Clinical Case Registry in care in 2007

Natural History

  • Women generally have lower viral loads than men at the time of seroconversion.
  • On average, HIV RNA levels are at least 50% lower in women than in men with the same CD4 cell counts and duration of HIV infection.
  • From seroconversion, the time to the development of AIDS and overall mortality are the same for women and men despite the difference in HIV RNA levels.
  • Virologic and CD4 responses to ART are the same for women and men.

Risks for Women with HIV

  • Women tend to be diagnosed later in the course of HIV infection than men, and they tend to seek care at more advanced disease stages.
  • Barriers to care include:
    • Child care or family care obligations, transportation limitations, lack of insurance, fear of disclosure (particularly to male partners, also to community and social networks), denial, and cultural mistrust of the health care system
    • Perception of their own need for medical care as being of low priority
  • Depression: A prospective cohort study showed that women who self-reported chronic depressive symptoms were twice as likely to have CD4 decline and to die than women with mild or no depressive symptoms.

Pharmacologic Considerations for Women with HIV

  • Limited pharmacokinetic studies show differences in ARV metabolism between women and men.
    • Women often have higher serum drug levels of certain ARVs, including EFV, NVP, IDV, LPV, and SQV.
    • Women have higher rates of adverse effects from certain ARVs, including:
      • Hepatotoxicity related to NVP, especially when NVP is initiated at CD4 counts of >250 cells/µL or during pregnancy
      • Rash related to NNRTIs and the PIs DRV and TPV
      • Nausea and vomiting related to PIs
      • ABC hypersensitivity (odds ratio: 1:4)
  • There is little information on dosage adjustment of ARVs for women (pregnant or nonpregnant).
  • Metabolism of ARVs may be altered during pregnancy.
  • Some ARVs should not be used by pregnant women or those who may become pregnant, because of potential teratogenicity or other toxicity.
  • Some ARVs have significant interactions with certain hormonal contraceptives; ARVs and contraceptives should be selected with this in mind (see Table 1).

Health maintenance: With prolonged survival in the era of ART, preventive strategies and health maintenance measures such as control of hypertension, smoking cessation, minimizing cardiovascular risk factors, and routine screening for osteoporosis and cancer (cervical, breast, and colon) are all part of routine care for HIV-infected women. See Hypertension, Dyslipidemia, and Smoking Cessation for further information on these topics.

This chapter will address these commonly encountered issues for HIV-infected women:

  • Reproductive and hormonal issues
  • Interactions of ARVs with hormonal contraceptives
  • Screening for neuropsychiatric disorders
  • Screening for military sexual trauma and domestic violence
  • Screening for cancer, osteoporosis, and STD
  • Cervical dysplasia
  • Osteoporosis
  • Genital tract infections

HIV Prevention

Note: A Women Veterans Program Manager is available at every VA Medical Center to assist in providing care for women veterans, including those with HIV infection. See also Prevention for Positives.

Prevention of HIV transmission
RecommendationsComments
  • Evaluate each patient's need for HIV prevention strategies on a regular basis
  • Evaluate patient for high-risk behaviors (eg, alcohol misuse, substance use disorders) that may predispose to high-risk behaviors
  • Encourage use of condoms (male or female) during all sexual encounters
    • Other barriers: diaphragm, cervical cap -- limited efficacy in preventing HIV transmission
  • Screen regularly for STDs, and treat as needed
  • Use of nonoxynol-9 is not recommended: increased risk of HIV transmission resulting from vaginal irritation; lack of prevention of STDs
  • ART has been shown to reduce risk of HIV transmission to uninfected partners.
  • Preexposure prophylaxis (PrEP): two recent studies have shown efficacy and safety of daily oral TDF/FTC (as part of a comprehensive prevention strategy) in both women and men in heterosexual serodiscordant relationships; one of these also showed efficacy of daily oral TDF alone. Another study of TDF/FTC in women did not find a protective effect. Tenofovir vaginal gel has been shown to be effective; it is not available in the United States.
  • If used correctly and consistently, condoms are effective for reducing risk of transmission of HIV and other STDs, including HPV.
  • Condoms may also be effective for contraception, but only if used optimally (see below).
  • Abstinence is effective for preventing HIV, other STDs, and pregnancy.
  • Guidance on use of PrEP to prevent HIV infection in women is not yet available. Also, PrEP efficacy has not been studied in injection drug users.
  • In some women, HIV viral load may be substantially higher in vaginal secretions than in blood; thus risk of sexual transmission of HIV may not be predicted by plasma viral load.

Reproductive and Hormonal Issues

Contraception
Abbreviations: HERS = Heart and Estrogen/Progestin Replacement Study; USPHSTF = U.S. Public Health Services Task Force; WIHS = Women's Interagency HIV Study
* Public Health Service Task Force Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States; May 24, 2010.
RecommendationsComments
  • Condoms (male or female) during all sexual encounters; high failure rate if used suboptimally (consider second contraceptive method); if used correctly and consistently, effective also for prevention of HIV transmission
  • Intrauterine devices (IUDs), particularly the Mirena levonorgestrel-releasing (LNG) device and copper-T devices have been shown to be safe for use by HIV-infected women and do not increase HIV viral shedding
  • Other barriers: diaphragm, cervical cap
  • Spermicides (eg, nonoxynol-9) are not recommended: increased risk of HIV transmission resulting from vaginal irritation
  • Oral hormonal contraceptives: note drug-drug interactions with some ARVs (see Table 1)
  • Injectable contraceptives (medroxyprogesterone [DMPA, Depo-Provera]): appear to be effective for women on ARVs (however, see Table 1)
  • Transdermal/patch and intravaginal ring (NuvaRing): little information on interactions with ARVs but likely similar to those of oral hormonal contraceptives (see Table 1)
  • 50% of pregnancies in the United States are unplanned.
  • On a regular basis, evaluate each woman's pregnancy intent and need for contraceptive information and methods.
  • For women who intend or desire pregnancy, provide preconception counseling (see below).
  • Avoid use of EFV with women who use inadequate or inconsistent contraception (risk of teratogenicity in the first trimester).
  • Interactions between oral hormonal agents and many ARVs may decrease contraceptive efficacy (see Table 1. Fewer data are available for drug-drug interactions with other formulations.
  • Possible adverse effects of hormonal contraceptives include thrombosis, myocardial infarction (estrogen/progesterone), stroke, menstrual irregularities, breast tenderness, weight gain, mood changes, loss of bone mineral density (DMPA), increased risk of breast cancer. Smoking increases risk of thromboembolic events.
  • DMPA: data are conflicting, but possible increased risk of HIV transmission (from HIV-infected woman to male partner) or acquisition (by uninfected woman from HIV-infected man) for women on DMPA (note, study participants were not on ART).
  • For women in whom hormonal methods are contraindicated (eg, history of thrombosis, thrombophilia, or cancer), the copper-T IUD may be safe and effective.
Preconception
RecommendationsComments
Preconception counseling is needed for all women who intend to become or who may become pregnant; preconception counseling and care includes:

  • Education regarding HIV and pregnancy, risk of transmission (to fetus or uninfected partners), measures to reduce this risk
  • Initiation of folate supplementation (higher dosage required for women who take TMP-SMX; see Pregnancy, below)
  • Screening tests: rubella titers, varicella titers in patients with no varicella history, HBV serologies, HCV antibody, Toxoplasma immunoglobulin G, cytomegalovirus, tuberculosis screening (purified protein derivative or Quantiferon), complete blood count; consider fasting glucose
  • Vaccinations as appropriate
  • Pap smear, STD screening (gonorrhea, chlamydia, syphilis, trichomoniasis)
  • Nutrition evaluation
  • Substance abuse and mental health screening and treatment as indicated
  • Referral to reproductive health specialist with experience in working with HIV-infected women (see Pregnancy, below)
  • Referral for prenatal genetic counseling
Assist women to become pregnant in ways that have lowest risk of HIV infection for partner (if HIV uninfected) and for fetus. Note that VA does not provide in vitro fertilization or other assisted reproduction services; patients must be referred to a non-VA provider for such services, which cannot be covered by VA on a fee basis.

  • For an HIV-infected woman with an HIV-uninfected male partner, advise methods of conception that avoid risk of HIV transmission to the partner (eg, home or office artificial insemination using partner's semen)
  • For an HIV-uninfected woman with an HIV-infected male partner, consider sperm washing, in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), pre-exposure prophylaxis, ART with virologic suppression for the infected partner, full disclosure of genetic and other risks of assisted reproduction should occur
  • Sperm washing results in sperm that is reported to be >99.9% free of HIV virus
  • Note that legal issues in some states may limit access to reproductive services
  • Maximize ART efficacy, selecting ARVs that are appropriate for use during pregnancy (see below)
  • Avoid potential teratogens, including EFV, ribavirin, hydroxyurea, thalidomide, some antiepileptic drugs
  • Optimize control of other medical conditions (eg, hypertension, diabetes)
  • Many HIV-infected women become pregnant, intentionally or unintentionally. It is important to discuss each patient's intentions and desire to bear children at entry to care and periodically thereafter.
  • Women with HIV infection have been noted to have increased rates of infertility compared with non-HIV infected women.
    • Tubal infertility is more common among women with HIV.
    • For women with difficulty conceiving, referral for evaluation of possible etiologies for infertility (including evaluation of endocrine, uterine, tubal, and male factors) should occur in advance of referral for assisted reproduction.
Pregnancy
RecommendationsComments
  • Refer to an obstetrician who has expertise working with HIV-infected women; for centers that do not have such expertise available, consultation is available through the (National Perinatal HIV Consultation and Referral ServiceLink will take you outside the VA website. VA is not responsible for the content of the linked site.; the number of the hotline for the service is 888-448-8765)
  • For pregnant women or women who may become pregnant, give 0.8 mg folate daily (folate dosage should be 4-5 mg QD for women who take TMP-SMX, to overcome the folate-antagonist effects of TMP-SMX)
  • ART during pregnancy:
    • Test for HIV resistance before initiating ART
    • Give combination ART with goal of maximal virologic suppression
    • Recommended agents for use during pregnancy*:
      • ZDV + 3TC, combined with NVP^, ATV/r or LPV/r
    • Alternative ARVs during pregnancy:
      • NRTIs: ABC,# FTC, TDF
      • NNRTIs: none
      • PIs: DRV/r, SQV/r
  • Use in special circumstances:
    • NRTIs: ddI, d4T
    • NNRTI: EFV
    • PIs: IDV/r, NFV
    • Integrase inhibitor: RAL
  • Insufficient data: ETR, RPV, FPV, TPV, ENF, MVC
  • Avoid use of EFV, DLV in the first trimester: risk of teratogenicity (pregnant women who are taking EFV as part of an effective ART regimen at the time they present for antenatal care may continue EFV)#

^Increased risk of hepatotoxicity during pregnancy; avoid initiating NVP in pregnant women with CD4 counts of >250 cells/µL
# If possible, check for HLA-B*5701 before treatment with ABC.

  • Goals include maximal suppression of HIV RNA to prevent HIV transmission and to optimize the patient's health.
  • Higher risk of perinatal transmission with:
    • High viral load
    • Low CD4 count
    • Advanced HIV infection
    • Poor nutrition
    • Drug use
    • STD
    • Vaginal delivery (if HIV RNA >1,000 copies/mL)
    • Invasive monitoring
    • Prolonged rupture of membranes
    • Chorioamnionitis
  • Without ART, risk of transmission is 25%; with PI-based ART, risk of transmission is 1% in the United States.
  • Pharmacokinetic changes during pregnancy may alter serum levels of some ARVs; check USPHSTF guidelines for recommended dosage adjustments; consult with pharmacologist.
    • Many experts recommend increase in LPV/r dosage to 600/150 mg BID during 3rd trimester.
  • Some evidence suggests ART may increase rates of preeclampsia.
  • Consider scheduled cesarean section delivery if HIV viral load is >1,000 copies/mL near time of delivery.
Breast-feeding
RecommendationsComments
  • Breast-feeding is not recommended in the United States (to avoid risk of HIV transmission through breast milk).
Menstrual irregularities and menopause
RecommendationsComments
Evaluate menstrual irregularities as in HIV-uninfected women. Initial considerations include:

  • For abnormal bleeding, seek to determine source of bleeding (bladder, urethra, vagina, uterus), with further evaluation depending on source
  • Pregnancy test
  • Consider polycystic ovarian syndrome (PCOS) in women with amenorrhea or hypomenorrhea and features suggestive of PCOS (clinical or serum hyperandrogenism, glucose intolerance, obesity)
  • Consider menopause (check follicle-stimulating hormone [FSH] to confirm)
  • Consider checking FSH and prolactin for secondary causes of amenorrhea
  • Consider hypothyroidism (check TSH)
  • For intermenstrual bleeding, evaluate for estrogen or progestin breakthrough on hormonal contraceptives, complications of intrauterine device, polyps, genital tract cancers, genital tract infections such as endometritis
  • For postcoital bleeding, evaluate for cervical malignancies and lesions, also for STDs
Treatment of menopausal symptoms: consider hormonal therapy as for HIV-uninfected women; keep in mind potential adverse effects, as well as drug-drug interactions between estrogens and some ARVs (see Table 1 below)
  • HIV-infected women more commonly experience irregular cycles and amenorrhea, but it is not entirely clear whether this is associated with HIV infection itself. Some research suggests associations between CD4 count and ovulatory status.
  • Confounders include weight loss, psychiatric medications, hormonal treatments, substance abuse, stress, and chronic disease.
  • Prolonged amenorrhea without ovarian failure in HIV-infected women is associated with low body mass index and low serum albumin.
  • Combined analysis of data from the HERS and WIHS cohorts showed that women on ART with good CD4 response had lower rates of menstrual irregularities than HIV-uninfected women.
  • In the WIHS study, the average age at onset of menopause was 48 for both HIV-infected women and HIV-uninfected women of similar demographics.
  • There is a blunted CD4 recovery to ART among postmenopausal women with HIV. This is postulated to be related to lower levels of estrogen and with decrease in thymic volume (associated with aging).
Sexual function
RecommendationsComments
Evaluate women's perceived level of and satisfaction with sexual function

Evaluate for factors related to perceptions of suboptimal sexual function:

  • Physical, sexual, emotional abuse
  • Relational problems
  • Depression
  • STDs
  • Medications
  • Pelvic pain
  • Constitutional symptoms
  • Peripheral and autonomic neuropathy
  • Hypogonadism
  • Other medical and psychiatric comorbidities
Sexual function in HIV-infected women is a neglected area of study.

Discuss patient's concerns candidly.

  • Patient-reported sexual dysfunction is associated with nonadherence to ART.
  • Sexual dysfunction may be a marker for depression, worsening health status including pain syndromes, or intimate partner violence.
  • A wide variety of medications, especially psychiatric, antiepileptic, and cardiovascular drugs, are associated with sexual dysfunction.
Table 1. Potential ARV Interactions: Hormonal Contraceptives

Print table

Drug interactions between oral contraceptive agents and many PIs and NNRTIs may affect the serum levels of either the hormonal agent or the ARV. In some cases, contraceptive efficacy or the potential for side effects may be affected significantly. Dosage adjustments may be required, and some combinations are contraindicated. See table below for details.

There are very few data on potential interactions between ARVs and nonoral hormonal contraceptives. Transdermal (patch) and transvaginal (intravaginal ring) contraceptive devices contain ethinyl estradiol (EE); thus caution should be used on a theoretical basis with ARVs that increase the serum estradiol levels. DMPA (Depo-Provera) is a progestin; thus, its interactions with ARVs may mirror those of norethindrone (NE). This may be cause for concern if DMPA is used with ARVs that increase NE levels, because DMPA is long-acting and has sustained serum levels.

There are no significant known interactions between hormonal contraceptives and NRTIs, integrase inhibitors, or CCR5 antagonists.

Decreased EE or NE levels
PIs:
  • ATV/r
  • DRV/r
  • LPV/r
  • NFV
  • RTV
  • TPV/r
Risk of contraceptive failure; use alternative (or additional) contraceptive method

(If oral contraceptive used with ATV/r, it should contain ≥35 mcg of EE.)
NNRTIs:
  • NVP
Risk of contraceptive failure; use alternative (or additional) contraceptive method.
Increased EE or NE levels
PIs (without RTV):
  • ATV
  • FPV
  • IDV
  • ATV: Risk of EE or NE adverse effects (eg, deep vein thrombosis). Use alternative method of contraception or lowest effective dosage with careful monitoring for adverse effects. If given concurrently, oral contraceptive should contain ≤30 mcg of EE; however, doses <25 mcg have not been studied.
  • FPV: Risk of EE or NE adverse effects; also, ↓ FPV levels; avoid, or use lowest effective dosage of EE/NE with careful monitoring for adverse effects and for ARV efficacy.
  • IDV: No dosage adjustment.
NNRTIs:
  • EFV
Risk of EE or NE adverse effects; alternative contraceptive method is recommended.
No data
PIs:
  • SQV
Alternative method of contraception is recommended.
Mixed effects
NNRTIs:
  • ETR
↑ EE, ↓ NE; no dosage adjustment.

Neuropsychiatric Disorders

RecommendationsComments
Screen for neuropsychiatric disorders in HIV-infected women

  • Depression
  • Dementia
  • Posttraumatic stress disorder (PTSD)
  • Personality disorders
Perform neuropsychiatric testing as needed
Neuropsychiatric disorders are common in HIV-infected individuals:

  • Direct effects of HIV on neuronal function
  • Underlying psychiatric disease
  • Affective disorders
  • Prior trauma
  • Social comorbidities
  • Personality disorders
Women with HIV are at increased risk of HIV-associated psychiatric disease, especially HIV-related dementia, but also at risk of underdiagnosis and undertreatment of depression.

Neuropsychiatric testing is recommended to establish diagnosis.

Owing to increased rates of depression and PTSD in women veterans, aggressive screening and treatment of depression in HIV-infected women is recommended.

Substance abuse is often comorbid with PTSD and depression.

For women with HIV infection, especially those with multiple responsibilities, psychosocial needs may be complex, requiring multidisciplinary team care. Research suggests that case management can improve outcomes, care, and treatment adherence.

For further information, see Depression.

Military Sexual Trauma and Domestic Violence (Intimate Partner Violence)

Military sexual trauma (MST)
RecommendationsComments
Screen all veterans, including female veterans, for MST.

Refer veterans with MST to the designated MST Counselor or team; referral to a local Vet Center may be an appropriate alternative based on available services.
  • All VA Medical Centers have designated MST Coordinators.
  • 30-45% of female veterans have been exposed to MST.
  • Effects of MST include:
    • Avoidance of places or objects that recall memories of the traumatic incident
    • Anxiety
    • Depression
    • Suicidal thoughts
    • Misuse of alcohol and other substance
    • Recurring and intrusive thoughts and dreams about the trauma incident
    • Nonspecific health problems
    • Problems with interpersonal relationships
Domestic violence
RecommendationsComments
Consider screening with the HITS scale:

  • Hurt: How often does your partner physically hurt you?
  • Insult: How often does your partner insult or talk down to you?
  • Threaten: How often does your partner threaten you with physical harm?
  • Scream: How often does your partner scream or curse at you?

Each question is answered on a 5-point scale: 1 = never; 2 = rarely; 3 = sometimes; 4 = fairly often; 5 = frequently. The score ranges from 4 to a maximum of 20. A score of ≥10 is considered diagnostic of abuse.

Look for evidence of physical abuse (bruises, fractures, injuries accompanied by implausible explanation).

If abuse is documented or suspected:

  • Consult Social Work Service
  • Refer the patient to community domestic violence agencies
Work with the patient to develop an emergency safety plan.
  • Domestic violence is prevalent among both female veterans and women living with HIV infection.
  • Screening instruments such as the HITS scale have been validated.
  • There is weak evidence for the efficacy of interventions in the health care setting.

Screening: Cancer, Osteoporosis, and STDs

Note: For other routine cancer screening, see Cancer Screening.

Cervical cancer screening:
Abbreviations: ASCUS = atypical squamous cells of undetermined significance; CT = Chlamydia trachomatis; GC = Neisseria gonorrhea; HSIL = high-grade squamous intraepithelial lesion; LSIL = low-grade squamous intraepithelial lesion; NAAT = nucleic acid amplification test
TestRecommendationsComments
  • Cervical Pap test (smear or liquid cytology)
  • Baseline
  • Repeat in 6 months
  • If both Pap results are normal and CD4 count is >200 cells/µL, repeat annually
  • If both Pap results are normal and CD4 count is <200 cells/µL, repeat every 6 months
  • If any Pap smear result is abnormal, additional testing should be done; see Cervical Dysplasia and Management of Abnormal Pap Smear Results, below
  • HIV-infected women are more likely than HIV-uninfected women to be infected with HPV, especially with oncogenic HPV types.
  • Dysplasia may involve the cervix, vulva, vagina, or anus.
  • Abnormalities on cervical colposcopy are seen in 64% of women with CD4 counts of <200 cells/µL and 34% of those with CD4 counts of >400 cells/µL.
  • HIV-infected women have decreased rates of clearance of HPV; as a result, they have an increased risk of disease progression and recurrence.
  • For management of abnormal results, see Cervical Dysplasia and Management of Abnormal Pap Smear Results, below.
Vulvar and vaginal cancer screening:
TestRecommendationsComments
  • Visual and manual inspection
  • Evaluate at times of cervical Pap test
  • Suspicious lesions: colposcopy; biopsy
  • HIV-infected women have elevated rates of vulvar and vaginal neoplasia.
  • Lesions may be multifocal, extensive, and recurrent, and may have an unusual appearance; sometimes progressing rapidly, especially in women with CD4 counts of <200 cells/µL.
  • Apparent condylomata that are resistant to treatment and unusual vulvar lesions should be referred for biopsy; also check RPR.
Anal cancer screening:
TestRecommendationsComments
  • Digital rectal examination (DRE)
  • Anal Pap test
No national guidelines for anal cancer screening; consider:
  • Baseline
  • Annual DRE and anal Pap screening if patient is sexually active and baseline result was normal
  • Use polyester swab and liquid cytology method, if available
  • Anal dysplasia and anal cancer rates among HIV-infected women are not fully known but appear to be higher than those for HIV-uninfected women.
  • Anal dysplasia is seen in women with and without a history of receptive anal sex.
  • ART has not been shown to prevent or alter the course of anal dysplasia.
  • ASCUS, LSIL, HSIL: Refer for high-resolution anoscopy with biopsy.
  • Screening was cost-effective in a small study; no large-scale clinical trials on cost-effectiveness have been conducted.
  • See Anal Dysplasia.
Breast cancer screening:
TestRecommendationsComments
  • Mammogram
  • Age 40-69: every 1-2 years
  • Age ≥70: discuss and take into account estimated life expectancy and presence of comorbid disease
  • HIV-infected women do not appear to have elevated risk of breast cancer.
  • See Cancer Screening.
Osteoporosis/osteopenia screening:
TestRecommendationsComments
  • Dual-energy X-ray absorptiometry (DEXA) bone densitometry
  • Baseline for patients at risk and all women >65 years of age
  • Also consider for thin female smokers >40 years of age
  • Every 1-2 years for patients with osteoporosis who are treated with bisphosphonates
  • Age and previous fracture are the most significant risk factors.
  • See Osteoporosis, below, for more information and treatment recommendations.
STD screening:
TestRecommendationsComments
  • RPR, VDRL
  • Cervical GC and CT (NAAT or culture of first-void urine or cervical specimen)
  • Rectal or pharyngeal testing for GC and CT, based on possible risks or exposures (NAAT or culture of swab)
  • Trichomonas (wet-mount examination or culture of vaginal secretions)
  • HBV, HCV
  • HSV IgG (type specific)
  • Perform at baseline, repeat according to risks or exposures (eg, every 3-6 months for women with new sex partners since previous examination)
  • STDs should be treated to prevent health complications for the patient, and also to prevent perinatal transmission or transmission to sex partners.
  • Inflammatory STDs may increase risk of HIV transmission to uninfected sex partners.
  • See Prevention for Positives.

Print table

Cervical Dysplasia and Management of Abnormal Pap Smear Results

Epidemiology and DiagnosisManagement and Treatment
  • HPV prevalence is higher among HIV-infected women than among HIV-uninfected women.
  • In the WIHS cohort, prevalence of genital HPV among HIV-infected women is approximately 64%, compared with 30% among HIV-uninfected women.
  • HIV-infected women have increased persistence of HPV and greater likelihood of high-risk oncogenic types of HPV.
  • Women with low CD4 counts tend to harbor high-risk HPV types.
  • HIV-infected women are at greater risk of cervical dysplasia and cervical cancer.
  • The time between diagnosis of carcinoma in situ and development of invasive disease is shorter among HIV-infected women who are not on ART than among HIV-uninfected women (3.2 vs 15.7 years).
  • However, ART has not been shown consistently to prevent or alter the course of cervical dysplasia in HIV-infected women.
  • See Screening: Cancer, Osteoporosis, and STDs, above, for screening recommendations.
  • Most experts recommend more aggressive management of HIV-infected women than HIV-uninfected women. The American Society for Colposcopy and Cervical Pathology (ASCCP) recommends managing HIV-infected women no differently than HIV-uninfected women.
  • ASCUS: There is controversy about management of ASCUS in HIV-infected women:
    • Most authorities recommend that HIV-infected women with ASCUS be referred for colposcopy.
    • In HIV-infected women, there are insufficient data to recommend HPV DNA testing for oncogenic HPV types as part of management of ASCUS.
  • ASC-H (atypical squamous cells, cannot exclude HSIL), LSIL, HSIL, and atypical glandular cells: Refer all patients with these findings for colposcopy. Note that some laboratories use the cervical intraepithelial neoplasia (CIN) 1, 2, 3 classification; these patients should also be referred for colposcopy.

Osteoporosis

Epidemiology and DiagnosisManagement and Treatment
* Calcium and other divalent cations may lower serum levels of integrase inhibitors; calcium should be taken ≥2 hours apart from integrase inhibitors.
Background

  • In small cohort studies, HIV-infected women had twice the rate of osteopenia (by DEXA) as HIV-uninfected women matched for age, race, and BMI.
  • HIV infection itself appears to be independently associated with reduced bone mineral density.
  • Exposure to ARVs, specifically PIs, has not been found to be associated with osteoporosis.
Risk factors

  • History of fracture as an adult
  • Age
  • Female sex
  • Race (Asians and Caucasians at higher risk)
  • Family history
  • Low body weight (<58 kg, 127 lb) or weight loss
  • Estrogen deficiency at early age (amenorrhea >1 year, early menopause)
  • Lifestyle: current cigarette smoking, alcohol misuse, inadequate physical activity
  • Poor health/nutrition (eg, low calcium intake)
  • Medications (eg, corticosteroids, anticonvulsants, gonadotropin-releasing hormone [GnRH] agonists, lithium)
  • Medical conditions (eg, hyperthyroidism, gastrectomy, COPD, hyperparathyroidism, multiple myeloma, celiac disease, eating disorder)
  • Recurrent falls, dementia
Evaluation

  • DEXA screening for women with risk factors or age >65 (see above):
    • Normal = T-score above -1
    • Osteopenia = T-score between -1 and -2.5
    • Osteoporosis = T-score less than -2.5 (a fracture-threshold)
Prevention (for all women)

  • Calcium* 1,000 mg per day for premenopausal women; 1,500 mg per day for postmenopausal women, in divided doses
  • Vitamin D 400-800 IU QD (800-1,000 IU in women age >50 years)
  • Exercise: 30 minutes of weight-bearing exercise ≥4 times per week
  • Smoking cessation, limited alcohol intake, adequate diet, careful sun exposure
  • Women taking calcium and vitamin D supplements in the Women's Health Initiative had a 1% gain in hip bone mineral density and a slight but statistically nonsignificant reduction in hip fracture (hazard ratio: 0.71; 95% confidence interval: 0.52-0.97 [for women with ≥80% adherence]).
Treatment

Treat women with:

  • T-score below -2.0 in the absence of risk factors
  • T-score below -1.5 + risk factors
  • Age >70 + multiple risk factors
Treatment options

  • Bisphosphonates offer the most clinically significant benefit. Randomized controlled studies show a 56% reduction in hip fractures in patients treated with alendronate. Options include:
    • Alendronate 70 mg PO once weekly
    • Ibandronate 150 mg PO once monthly
    • Zoledronic acid 5 mg IV once yearly
Plus:

  • Calcium* 1,500 mg per day in divided doses
  • Vitamin D 800-2,000 IU QD
  • Smoking cessation
  • Limited alcohol intake
  • Exercise: 30 minutes of weight-bearing exercise ≥4 times per week

Genital Tract Infections

HSV
* STD treatments reflect current CDC guidelines.
Epidemiology and DiagnosisManagement
  • Risk factor for HIV acquisition and transmission
  • Of HIV-infected women, 50-90% have concurrent HSV infection
  • In the HERS study, there was no difference in rates between HIV-infected and high-risk HIV-uninfected women
  • Chronic suppressive therapy with acyclovir may increase survival for HIV/HSV-coinfected women who do not take ARVs; this benefit is not demonstrated in patients on ART
  • Infection can be primary, nonprimary first episode, or recurrent
  • Most genital HSV infections occurring in HIV coinfection reflect reactivation syndromes; symptomatic episodes may be more severe, more frequent, and longer in duration than in HIV-negative women
  • Genital HSV in HIV-infected women ranges in appearance from small confined ulcers to painful extensive necrotic lesions accompanied by constitutional symptoms
  • Complications seen more commonly in advanced HIV infection include aseptic meningitis, sacral radiculopathy, transverse myelitis, scarring, rectovaginal fistulae
Diagnosis: swab base of lesion for testing via viral culture, direct fluorescent-antibody assay, HSV PCR, or Tzanck prep (less sensitive)

  • Differential diagnosis includes: syphilis, chancroid, drug eruptions, Behçet syndrome
  • Initial episode or severe mucocutaneous outbreak: hospitalize and treat with IV acyclovir (5 mg/kg IV Q8H) for 7-14 days, changing to PO therapy when lesions improve
  • Episodic therapy for outbreaks: valacyclovir 1,000 mg BID, acyclovir 400 mg TID, or famciclovir 500 mg BID for 5-14 days
  • Suppressive therapy: consider for patients with frequent recurrences, especially those with CD4 counts of <100 cells/µL and severe protracted outbreaks:
    acyclovir 400 mg BID, valacyclovir 500 mg BID, or famciclovir 500 mg BID
  • During pregnancy, refer to OB/GYN specialist for management
  • Counsel use of latex barriers to prevent HSV transmission to uninfected partners
Genital ulcers
Epidemiology and DiagnosisManagement
  • Risk factor for HIV acquisition and transmission
  • Research indicates prevalence as high as 14% in an urban population, with recurrence rate of 19%
  • Only 40% of cases had identifiable pathogen
  • Differential diagnosis includes syphilis, chancroid, HSV (see above); may be caused by atypical pathogens identified (CMV, Chlamydia trachomatis, Gardnerella vaginalis)
  • In women, genital ulcers often are not noticed
  • Lesions may be large, requiring multiple admissions and surgical procedures
Initial episode:
  • Attempt to establish a diagnosis: laboratory testing (viral, bacterial culture, serology) or biopsy
  • For severe or erosive lesions, prompt evaluation and management, possibly including hospitalization and surgery, may be needed to prevent scarring, vaginal or urethral stricture, or fistulae
  • Follow up carefully to evaluate for recurrence
Bacterial vaginosis (BV)
Epidemiology and DiagnosisManagement
  • Risk factor for HIV acquisition and transmission
  • HIV-infected women have increased persistence of BV, especially with CD4 counts of <200 cells/µL
Diagnosis (3 of 4 Amsel criteria):

  • Homogeneous, thin, grayish-white discharge that smoothly coats the vaginal walls
  • Vaginal pH >4.5
  • Positive whiff-amine test, defined as the presence of a fishy odor when 10% KOH is added to a sample of vaginal discharge
  • Clue cells on saline wet mount
  • Metronidazole 500 mg BID for 7 days
    Alternatives:
  • Topical vaginal therapy
    • Metronidazole gel 0.75%, 5 g QD for 5 days
    • Clindamycin cream 2%, 5 g QD for 7 days
  • Clindamycin 300 mg PO BID for 7 days (less evidence for efficacy; higher risk of Clostridium difficile)
Vaginal candidiasis
Epidemiology and DiagnosisManagement
  • HIV-infected women may have higher rates of persistence and recurrence (≥4 episodes per year)

    Diagnosis: budding yeast and hyphae on 10% KOH wet mount of vaginal discharge
  • Single episode:
    • Topical azoles for 3-7 days
    • Fluconazole 150 mg PO for 1 dose
    • Itraconazole 200 mg PO BID for 1 day or QD for 3 days
  • Recurrent episodes (≥4 episodes per year):
    • Fluconazole 150 mg PO for 3 doses 72 hours apart, followed by fluconazole 150 mg PO once a week for 6 months
Pelvic inflammatory disease (PID)
Epidemiology and DiagnosisManagement
  • Among women with HIV infection, risk for severe morbidity and mortality is increased and PID may be more severe at time of presentation
  • A Kenyan study showed increased incidence of tuboovarian abscesses in HIV-infected women
  • HIV-infected women with PID respond to the same antibiotics as HIV-uninfected women but may need surgical interventions more frequently
  • Causative organisms include Chlamydia trachomatis, Neisseria gonorrhea, Streptococcus spp, Escherichia coli, Klebsiella spp, Proteus spp, and BV flora
  • Risk factors: multiple partners, partner with an STD or STD symptoms, prior STD, IUD in situ
  • Clinical presentation: bilateral lower abdominal pain, often <2 weeks' duration, worse with coitus or jarring movements
Clinical diagnosis:

  • Lower abdominal pain, plus one of the following:
    • Cervical motion tenderness or uterine/adnexal tenderness
    • Temperature >101°F (>38.3°C)
    • Leukocytosis
    • Abnormal cervical or vaginal mucopurulent discharge
    • Presence of WBCs on saline microscopy of vaginal secretions
    • Elevated erythrocyte sedimentation rate
    • Elevated C-reactive protein
  • An adnexal mass suggests tuboovarian abscess
  • Laparoscopic evaluation is recommended for:
    • Strongly suspected competing diagnosis (eg, appendicitis)
    • Acutely ill patients for whom outpatient treatment of PID has failed
    • Patients not clearly improving after 72 hours of inpatient treatment for PID
Consider hospitalization in event of severe illness, pregnancy, or inability to take oral therapy

Outpatient treatment:

  • Ceftriaxone 250 mg IM for 1 dose, plus doxycycline 100 mg PO BID for 14 days, with or without metronidazole 500 mg PO BID for 14 days
  • Cefoxitin 2 g IM for 1 dose with probenecid 1 g PO for 1 dose, plus doxycycline 100 mg PO BID for 14 days, with or without metronidazole 500 mg PO BID for 14 days
  • Consultation with OB/GYN is recommended as treatment failures, delayed diagnosis, and loss to follow-up are common

References