Chapter 46
Gynecologic Care of HIV-Infected Women
Deborah Cohan and Abner P. Korn
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Deborah Cohan, MD, MPH
Assistant Clinical Professor, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, Director of Bay Area Perinatal AIDS Center, San Francisco General Hospital, San Francisco, California (Vol 1, Chap 46)

Abner P. Korn, MD
Professor, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco; Director of Gynecology, San Francisco General Hospital, San Francisco, California (Vol 1, Chap 46)

 
GENERAL CONSIDERATIONS
GENDER DIFFERENCES IN HIV AND AIDS
LOWER GENITAL TRACT NEOPLASIA
INVASIVE CERVICAL CANCER
SUMMARY
SEXUALLY TRANSMITTED INFECTIONS
PELVIC INFLAMMATORY DISEASE
VAGINITIS
CONTRACEPTION
PRECONCEPTION COUNSELING
ASSISTED REPRODUCTION
MENSTRUAL DISORDERS
OSTEOPENIA AND OSTEOPOROSIS
CONCLUSION
REFERENCES

There are nearly 20 million women living with HIV worldwide, accounting for approximately half of all infections.1 Although the goal of this chapter is to describe the gynecologic care of the HIV-infected woman in industrialized settings, it is critical to understand that the burden of the epidemic lies within resource-limited areas, particularly sub-Saharan Africa.

In 2001, the Centers for Disease Control and Prevention reported 141,048 cumulative cases of AIDS among women in the United States The most common risk factor for HIV acquisition in women was heterosexual contact.2 In the United States, there is dramatic geographic variation in the prevalence of HIV/AIDS among women, with the highest prevalence of AIDS cases in the northeast and southeast regions of the country. In 2001, AIDS prevalence was 9.1 per 100,000 women in the United States. New York had the highest frequency, with 30.3 AIDS cases per 100,000 women.3 AIDS incidence and the proportion of AIDS cases are increasing yearly among American women, particularly women of color. Although most HIV infections in the United States are among men, an estimated 29% of infections are among women.3

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GENERAL CONSIDERATIONS

Gynecologic diseases are commonly encountered when caring for HIV-infected women.4 HIV infection may impact on the occurrence or clinical severity of a variety of gynecologic conditions. When encountered, clinical care for women with these conditions may prove to be challenging. In general, these conditions are more common and severe among more immunosuppressed women.5

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GENDER DIFFERENCES IN HIV AND AIDS

Women and men appear to have similar rates of disease progression and survival, once accounting for access to care, use of antiretrovirals, and stage of disease.6,7,8 Nonetheless, women appear to have less access to care and are less likely than men to receive antiretrovirals and opportunistic prophylaxis.9,10,11 Most studies addressing gender differences have found that women, on average, have lower plasma HIV RNA levels at any given CD4 count as compared with men.12,13 In their systematic review of the published literature, Gandhi and associates found that women's CD4-adjusted HIV RNA levels were approximately two-fold to six-fold (.13 to .78 log10) lower than those of men.13 The meta-analysis by Napravnik and associates confirmed this finding, calculating the CD4-adjusted HIV RNA summary estimate to be 41% lower (.23 log10) among women as compared with men.12 There are apparent cyclic alterations in viral load among women as well. Greenblatt and associates noted a .16-log10 decrease in median HIV RNA levels from the early follicular to mid luteal phase among ovulatory women.14 Nonetheless, menopause does not appear to have an impact on CD4 counts.15 Whereas the full implication of these findings remain uncertain, it suggests that decisions to initiate antiretrovirals using viral load levels should use different threshold values among women and that, perhaps, the timing of these viral loads in relation to the menstrual cycle should be noted.

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LOWER GENITAL TRACT NEOPLASIA

Prevalence

Women with HIV infection have approximately a four-fold to six-fold increased risk for squamous intraepithelial lesions (SIL) or cervical intraepithelial neoplasia (CIN) compared with uninfected women.16,17 In one of the ongoing, large, multicenter cohorts of HIV infected and uninfected women, SIL was detected in 17.4% (2.5% high-grade squamous intraepithelial lesions [HSIL]) of HIV-infected women compared with 3.5% of HIV-uninfected women (p < .001).18 With 5-year follow up, 73% of HIV-infected women had an abnormal Pap smear test result. Human papillomavirus infection (HPV) is also more commonly detected and more likely to be persistent in HIV-infected compared with uninfected women.18,19

Incidence

A 30-month prospective study of women with no evidence of cervical disease in New York City showed incident cases of SIL in 20% of HIV-infected and in 5% of HIV-uninfected women.20 No women had cervical cancer during the study. A multivariate analysis showed a significant association between HIV infection, transient and persistent HPV infection, and young age with development of SIL. Incidence of cervical disease is correlated both with low CD4+ cell count and increased HIV RNA level.16 Antiretroviral therapy (mostly zidovudine) was not protective against development of SIL (RR = 1.0; 95% confidence interval [CI]: .5, 2.0). In another study of 168 HIV-infected women, the 96 who received highly active antiretroviral therapy (HAART) had twice the likelihood of regression of CIN during a 12-month follow-up period compared with those who did not use HAART.21 In a larger study, the Pap smears of women who received HAART were less likely to have progression to a higher grade (OR = .68; 95% CI: .52 to .8) and more likely to have regression.22 Other studies have not shown a significant effect of HAART on regression of SIL.23

Vulvar, vaginal, and anal intraepithelial neoplasia appear to be prevalent among HIV-infected women. In a well-controlled prospective study, vulvar and vaginal condyloma were found in 5.6% of HIV-infected versus .8% of HIV-uninfected women. Vulvar intraepithelial neoplasia (VIN) was noted in only two of 396 (.5%).6 Incident vulvovaginal intraepithelial neoplasia lesions were 16-times more frequent in a prospective study of HIV-infected women compared with uninfected women.24 In this study, after a median follow-up of 3.2 years, 2% of all HIV-infected women had high-grade VIN and one patient had invasive vulvar carcinoma. Cigarette smoking and injection drug use were independently associated with vulvovaginal and perianal lesions in HIV-infected women.

Human papillomavirus (HPV) infection of the anus and epithelial abnormalities on anal Pap tests are common in persons with HIV infection.25,26 In a prospective study of 319 women, 26% of the HIV-infected women and 8% of the HIV-negative women had abnormal anal cytology.27 The likelihood of having abnormal anal cytology increased with the degree of abnormality of cervical cytology. Colposcopically directed biopsy showed high-grade lesions in 6% of the HIV-infected and in 2% of the HIV-negative women. HIV-infected women have a nearly eight-fold increased risk for in situ and a nearly seven-fold increased risk for invasive anal cancer compared with HIV-negative women.28

Although vulvar, vaginal, and anal cancers are infrequently reported in HIV-infected women, these conditions may become more common as improved medical care of HIV leads to women living with immunosuppression and intraepithelial neoplasia for longer periods of time. In women with immunosuppression after organ transplantations, a 100-fold increase in vulvar cancer has been reported occurring after an average of 107 months.29

Diagnosis

Most controlled studies have shown Pap smear sensitivity and specificity rates similar to those reported for HIV-negative women.30,31 Screening colposcopy does not appear to be warranted, at least in populations with a low prevalence of cervical disease.18 Some investigators, however, advocate screening colposcopy based on their findings in populations with a higher prevalence of dysplasia.32 A cost-effectiveness study comparing semi-annual cervical cytology with colposcopic screening of HIV-infected women in a Markov model showed that colposcopy added little and increased costs markedly.33 On the basis of the predominant findings, routine colposcopy is not recommended in published guidelines for screening of HIV-infected women.34,35 Because of the high prevalence of HPV in HIV-infected women, HPV typing (by polymerase chain reaction) may not be a useful means of triage of abnormal cervical smears.18 HPV testing by hybrid capture technique may be more useful in HIV-infected women. In a study from Hannover, Germany, HPV testing identified 16 of 17 (94%) of the lesions classified as CIN2 or higher with a specificity of 70%. Cervical cytology identified 11 of 17 (65%) of the lesions classified as CIN2 or higher with a specificity of 98%.36 The performance of HPV testing in a prospective study of a large cohort of HIV-infected women has yet to be reported.

Pap smears must be interpreted slightly differently among HIV-infected women than among uninfected women. Mild cytologic atypia and inflammation on Pap smear are more frequently associated with dysplasia in HIV-infected compared with HIV-uninfected women.37 Colposcopic examination is warranted after a single Pap showing cytologic atypia and may be warranted after a single smear showing severe inflammation. In the latter case, an alternative would be to search for an infectious cause of inflammation, such as Neisseria gonorrhea, Chlamydia trachomatis, herpes simplex virus (HSV), or Trichomonas vaginalis, and to perform colposcopy only if the inflammation fails to resolve after treatment of the infection. All HIV-infected women who have SIL on their Pap smears should have a colposcopic examination.

The optimum method of screening for noncervical lesions in HIV-infected women has not been determined. At a minimum, careful inspection of the vulva and perianal region should be performed during pelvic examinations. It may be possible to improve detection of VIN lesions by application of dilute acetic acid to the vulva followed by examination using low-power magnification (such as by hand-held magnifying glass). Optimally, the acetic acid must remain in contact with the vulva for approximately 5 minutes before examination.

High-resolution anoscopy (the use of a colposcope to examine the anal canal) is indicated for anal Pap smears that show atypical squamous cells, low-grade squamous intraepithelial lesions (LSIL) or HSIL. Approximately half of high-grade anal intraepithelial neoplasia (AIN) lesions will have only mild cytological abnormalities on cytology.27

Clinical Course and Treatment

The clinical course of CIN in HIV-infected women may be characterized by more progression and less regression than in HIV-negative women.38 A prospective study of women with SIL followed-up for 5 months in the Ivory Coast showed persistence in 76% of HIV-infected compared with only 18% of HIV-uninfected women (RR = 4.3; 95% CI: 2.4, 7.7).39 In the WIHS study, cytological progression was associated with HPV infection and with elevated HIV RNA level but not with HIV serostatus.16 Persistence of CIN after treatment is common in HIV-infected women.38 High recurrence rates (40% to 100%) of CIN after ablative or excisional therapy are reported in HIV-infected women, especially those with immunosuppression.30,40,41,42 Invasive cervical carcinoma has been reported 32 months after a cold-knife conization for CIN3 (with negative margins).40 A possible explanation for the increased treatment failure is the high likelihood of persistent HPV infection in HIV-infected women.19 The elevated HPV viral burden may lead to treatment failure.

HIV-infected women may also be more likely to have bleeding or infections after treatment for CIN than noninfected women.43 However, in this study, no patient required blood transfusion and all infections were vaginal, except for one case of pelvic inflammatory disease (PID).

Treatment of VIN in HIV-infected women is difficult. In one study, these women uniformly had recurrence of VIN after excisional or ablative therapy.44 The outcome of surgical treatment of AIN in HIV-infected patients appears to be similar, with approximately 80% having persistent or recurrent disease.45

While the high frequency of recurrence of intraepithelial neoplasia after therapy in HIV-infected women is concerning, it is important to keep in mind that the only clinically important treatment failure is that which leads to invasive cancer. Invasive cancer occurs rarely in HIV-infected women who are treated for cervical dysplasia. HIV-infected women with dysplasia need careful follow-up after treatment and often need second or third therapeutic procedures. Adjuvant 5-fluorouracil after excisional or ablative therapy for high-grade cervical dysplasia reduced the recurrence at 18 months from 47% to 28% in a randomized, controlled, clinical trial (ACTG 200).46 In this study, women in the treatment arm received 5% 5-fluorouracil cream twice weekly (2 grams per vagina) for 6 months. The 5-fluorouracil not only reduced the frequency of recurrence but also reduced the proportion of recurrences that were high-grade. An additional finding of this study was that women who were receiving antiretroviral therapy had less recurrence, whereas those with lower CD4+ cell counts had more recurrence. Only one of the treated women had signs or symptoms that could definitely be attributed to the 5-fluorouracil. Isotretinoin did not significantly prolong time to progression from LSIL to HSIL in a randomized, controlled trial.47 A randomized, controlled trial of topical 5% imiquimod cream, an immune-response modifier, in treatment of anogenital warts showed some efficacy in a group of mostly males with HIV-infection.48 Several small studies have shown a modest response of high-grade VIN to topical imiquimod.49

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INVASIVE CERVICAL CANCER

HIV infection is more clearly associated with invasive cervical cancer in studies performed in Europe and the United States than in most studies performed in Africa.50 The association noted could be confounded by factors such as injection drug use or lack of cervical cancer screening among HIV-infected women in the European and American studies.51 The prevalence of cervical cancer among more than 23,000 HIV-infected women in France, Italy, and Spain was 3.2% among those whose mode of HIV acquisition was injection drug use versus 1.8% among those who acquired HIV through sex.52 The CDC has detected no increase in the prevalence of invasive cervical cancer between 1992 and 1997 in their surveillance for AIDS-defining opportunistic illnesses in the United States.53 In contrast, in the United States Cancer Match Registry for 1978 to 1996, there was an increased risk for cervical cancer (RR = 5.5), vaginal and vulvar cancer (OR = .8), and anal cancer (OR = 6.8) among HIV-infected women.54 In the New York State AIDS Registry, the risk for invasive cervical cancer was found to be increased by a relative risk of 6.5 (95% CI: 4.1 to 9.7).55

Maiman and associates reported that HIV-infected women with cervical cancer were more likely to present at advanced clinical stage than were HIV-negative women.56 A review of invasive cervical cancer at two hospitals in New York City showed an HIV seroprevalence of 18%. Sixty-nine percent of HIV-uninfected women had stage I or II compared with 42% of HIV-infected women.57 In a multivariate analysis, risk factors associated with advanced cervical cancer were symptom duration more than 3 months and more than 3 years since last Pap smear. HIV infection was not correlated with advanced cervical cancer (OR = .8; 95% CI: .2 to 3.4). Thus, the advanced stage of cancer seems to reflect behavioral rather than biological factors.

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SUMMARY

Consideration should be given to counseling for HIV testing of women who have CIN, and those who have invasive cervical cancer and VIN. Most of the available evidence indicates that lower genital tract neoplasia in women with HIV is extremely common and in many cases may be refractory to standard treatment, especially in the presence of severe immunosuppression. Further investigation is needed to clarify optimum methods of screening for and treatment of lower genital tract neoplasia in HIV-infected women. We recommend frequent (semi-annual) Pap screening with colposcopic evaluation if the Pap shows dysplasia or atypia. After several normal Pap results, the screening interval may be increased.

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SEXUALLY TRANSMITTED INFECTIONS

Epidemiologic synergy describes the mutually amplifying epidemics of sexually transmitted infections (STIs) and HIV.58,59 In particular, the presence of an STI, particularly an ulcerative STI, increases the risk of HIV acquisition of HIV by two-fold to five-fold.58 The proposed mechanisms include the recruitment of HIV target cells, including CD4 cells, Langerhans cells, and macrophages, to the genital tract in the setting of an STI and the disruption of genital mucosa. There is also evidence of increased transmission of HIV in the presence of an STI, likely related to both increased genital viral load and increased plasma load associated with STIs.60 Several studies have now demonstrated that treatment of STIs decreases the likelihood of incident HIV acquisition and transmission.60,61 Mbopi-Kéou and colleagues found an association between HSV-2 DNA and genital HIV-1 RNA levels among co-infected women who shed HSV-2.62,63 Thus, all providers caring for HIV-infected women should obtain a thorough sexual history (including type and number of partners, specific sexual activities, condom and other barrier use, HIV-status of partner(s), reproductive desires, past STIs and current STI symptoms), and undergo routine screening for STIs and treatment as indicated.64 Appropriate STI screening should be guided by a woman's sexual behavior and local epidemiology in addition to standards of care established for HIV-infected individuals.65

Clinical management of STIs among HIV-infected women often differs from that of HIV-uninfected women. For instance, women co-infected with HIV and herpes simplex virus (HSV) may have more persistent and/or recurrent HSV as compared with HIV-negative women.64 Such women often benefit from suppressive therapy with acyclovir or valacyclovir.66 While acyclovir-resistant HSV is uncommon, it should be considered in HIV-infected women with persistent lesions despite adequate antiviral therapy. In such cases, a viral isolate should be obtained for sensitivity testing. Because valacyclovir has the same active metabolite as acyclovir, patients with verified acyclovir-resistant strains should be treated with foscarnet under the supervision of an expert in the field as recommended by the Centers for Disease Control.64 Similarly, HIV appears to alter the clinical course of granuloma inguinale and lymphogranuloma venereum (LGV).

For the treatment of granuloma inguinale among HIV-infected individuals, some experts recommend the addition of parenteral aminoglycoside to the typical 3-week regimen of oral doxycycline or trimethoprim-sulfamethoxazole.64 Similarly, women co-infected with HIV may experience prolonged disease course despite therapy. Treatment includes a 3-week regimen of oral doxycycline, which may need to be extended in cases of protracted LGV.64 However, treatment recommendations for gonorrhea, Chlamydia, trichomonas, pediculosis pubis, and scabies are the same for HIV-infected and uninfected women.64

For most co-infected individuals, HIV does not appear to alter the clinical course of syphilis. Nonetheless, HIV-infected individuals appear to be at slightly increased risk for both neurosyphilis and persistent disease despite treatment, although overall the absolute risk of these events is low.64 The CDC recommends treating HIV-infected patients with primary, secondary, and early latent syphilis with the standard single dose of 2.4 million units of intramuscular benzathine penicillin. In the absence of neurological signs or symptoms, pretreatment cerebral spinal fluid (CSF) assessment is not necessary. Because of the increased risk of treatment failure, it is important to monitor these patients clinically and serologically using a nontreponemal antibody titer at 3, 6, 9, 12, and 24 months after initial treatment. Cases in which nontreponemal titers do not decrease four-fold by 6 months after treatment should be considered treatment failures, undergo a CSF evaluation, and, if normal, treated with weekly benzathine penicillin injections for 3 weeks. Women with late latent or latent syphilis of unknown duration should undergo a pretreatment CSF examination and, if normal, receive weekly benzathine penicillin injections for 3 weeks. These women should be monitored clinically and serologically at 6, 12, 18, and 24 months. Neurological symptoms or a four-fold increase in nontreponemal titers necessitate a repeat CSF evaluation and treatment as indicated. Those women in whom the nontreponemal titer does not decrease by four-fold by 12 months should also undergo a repeat CSF evaluation and treated accordingly. Neurosyphilis may occur at any stage of syphilis. Treatment includes intravenous aqueous crystalline penicillin G 3 to 4 million units every 4 hours for 10 to 14 days. The CSF should be monitored at 6-month intervals until the cell count normalizes.

Hepatitis B (HBV) is a vaccine-preventable STI. Among those with HIV, HBV is more likely to proceed to chronic infection. It is, therefore, particularly important to vaccinate HIV-infected individuals against HBV with the three-part vaccination series over the course of 6 months (0, 1, and 6 months). Because immunization may be impaired in immunocompromised hosts, clinicians should obtain an HBV surface antibody (HBsAb) approximately 1 to 2 months after the third vaccine injection to confirm immunity. Those women found to be nonimmune despite a full series should undergo a second round of three HBV vaccinations with appropriate postvaccination surface antibody confirmation.

As with all STIs, sexual partners of infected patients should be evaluated and treated appropriately. For those clinicians who do not regularly treat STIs, the CDC maintains updated treatment guidelines that are easily accessible.35

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PELVIC INFLAMMATORY DISEASE

Because HIV and the organisms associated with PID are sexually transmitted, it is not surprising that these conditions are frequently coincident. Because HIV seroprevalence among women with PID ranges from 6.7% to 22%, serologic testing for HIV infection should be offered to women with a diagnosis of PID.67

HIV appears to alter the clinical presentation of PID. Recent studies have noted the following among HIV-infected women with PID when compared with HIV-uninfected women with PID: lower white blood cell counts, higher erythrocyte sedimentation rate, more syphilis, more frequent tubo-ovarian abscesses/adnexal masses, less gonorrhea, less Chlamydia, more bacterial vaginosis, and more plasma cell endometritis.68,69,70,71 The latter findings suggest that there is an impaired defense against ascent of vaginal flora to the upper genital tract in HIV-infected women. These data also suggest that an antibiotic regimen with strong anaerobic coverage would be optimal for treatment of PID in HIV-infected women. While these studies suggest a more severe presentation of PID among HIV-infected women, the prospective studies show little difference in response to antibiotic treatment (combined with drainage of abscesses greater than 4 cm in some of these studies) compared with HIV-uninfected women. Outpatient treatment of PID has been used with success in HIV-infected women.68,69,70,71 However, some degree of caution is in order in caring for HIV-infected women with PID; there is a significant minority among them (approximately 15%) who will require surgical means to diagnose or treat their infections. Inpatient treatment is indicated for a woman with PID who would be unlikely to adhere to a regimen of outpatient therapy.

The available data suggest that the clinical course of PID may be altered by symptomatic HIV infection and that such patients have blunted local immune defenses, resulting in slower or inadequate response to medical therapy. The current data support the use of the antibiotic treatment recommendations published by the CDC.35 We recommend vigilance for treatment failure in patients with severe immunosuppression and suggest use of antibiotic regimens with optimal anaerobic coverage in this group.

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VAGINITIS

Background

HIV-immune suppression can impact on frequency and/or severity of vaginal infections. In turn, these infections could influence HIV acquisition/transmission by several mechanisms, including altering HIV shedding, increasing inflammatory cells in the cervico/vaginal epithelia, or by adverse effects on protective vaginal microflora. Vaginal isolates of Candida albicans from HIV-infected women produce higher levels of secretory aspartyl proteinase, a virulence enzyme, than do those of HIV-uninfected women.72 A recent study from Providence, Rhode Island showed an association of HIV-RNA levels in cervico-vaginal secretions with bacterial vaginosis (BV) but not with Candida albicans infections.73 In contrast, a study performed in Mombassa, Kenya showed a decrease in cell-associated and cell-free HIV after treatment of Candida vaginitis, a decrease only in cell-free HIV after treatment of trichomonas vaginalis, and no effect on cell-free or cell-associated HIV after treatment of BV.74 In this report, the most significant decrease in genital-tract HIV occurred in women with Candida who had vulvar erythema and in women with trichomonas who had more than 10 neutrophils per high-power field on vaginal Gram stain.

Bacterial vaginosis has been associated with HIV seropositivity.59 With BV, the vagina has a higher pH, which is more favorable to HIV than the normal acidic pH. It is unclear whether bacterial vaginosis may increase female susceptibility to heterosexual transmission of HIV, whether immunosuppression may lead to increased susceptibility to bacterial vaginosis, or both.

Lower genital tract mucosal inflammation caused by trichomonas vaginalis infection could lead to increased shedding of HIV in seropositive women and increased susceptibility to infection with HIV in seronegative women. To date, studies show an inconsistent association between trichomonal infection and HIV.59 A study from South Africa showed an association between trichomonas vaginalis and a clinical diagnosis of PID in HIV-infected women.75 The authors postulated that proteases produced by trichomonas might degrade the cervical mucous barrier-facilitating ascent of microorganisms into the upper genital tract.

Prevalence and Incidence

The association between HIV infection and vaginal candidiasis is debated.76,77 A prospective cohort of HIV-infected and uninfected women showed no difference in prevalence of vaginal Candida albicans colonization, unless there was immunosuppression, in which case the rates of colonization and symptomatic infection tripled.78 The proportion of nonalbicans isolates did not differ among groups. In this study, candida colonization was not associated with antibiotic or oral contraceptive use. In contrast, in a cross-sectional study of patients referred to a vaginitis clinic, HIV was associated with nonalbicans Candida infection.79 In a 2-year follow-up study, there was a very slow incremental increase in nonalbicans yeast (mostly Candida glabrata) isolated from the vaginas of HIV-infected women.80 In this study, the HIV-infected women reported recent vaginal candidiasis approximately 50% more often than did the HIV-uninfected women. A large prospective study (HERS) with 4.5 years of follow-up showed a significantly higher incidence of vulvovaginal candidiasis among HIV-infected than among uninfected women.81 The 4.5-year cumulative frequency of vaginal candidiasis in the HIV-infected cohort who did not have VVC at the baseline visit was as high as 64.5% depending on how VVC was defined. The risk of acquiring VVC was elevated among women who had severe immunosuppression with CD4+ cells less than 200 cells/μL and for those with elevated HIV viral load. In addition, systemic antifungal use and older age were associated with reduced risk of VVC, whereas diabetes and pregnancy were most strongly associated with increased risk of VVC. Interestingly, antibacterial drug use did not increase the risk of VVC. In this study, VVC was more likely to persist among HIV-infected women but was no more severe than VVC in HIV-uninfected women. There is no evidence from controlled studies that the severity or clinical presentation of vaginal candidiasis is different in HIV-infected compared with HIV-uninfected women.

In a large cross-sectional study, there was a similar prevalence of trichomonas vaginalis and bacterial vaginosis among the HIV-infected and uninfected participants and no association with CD4+ cell count.82 A longitudinal study showed a higher prevalence and more persistence of BV among HIV-infected women than HIV-uninfected women.83 In this study, prevalence and severity, but not incidence, of BV were correlated with degree of immunosuppression.

Treatment

When vaginal candidiasis is encountered in HIV-infected women, a variety of treatment options are available. These include topical antifungal agents such as clotrimazole, miconazole, terconazole, boric acid vaginal suppositories (600 mg twice daily for 2 weeks) and single-dose, oral fluconazole. For immunosuppressed women who have recurrent vaginal candidiasis, fluconazole (200 mg/week) is an effective means of prophylaxis.84 Unfortunately, there is evidence that this regimen leads to an increase in vaginal colonization with nonalbicans yeast85 and an increase in the proportion of fluconazole-resistant nonalbicans yeast over time.80 The decision to use long-term fluconazole, especially for primary prophylaxis, must be carefully considered because of the risk of development of resistance, the effectiveness of therapy for acute disease, the negligible incidence of serious invasive disease, and the possibility of drug–drug interactions.86 Clotrimazole powder (100-milligram capsules) used intravaginally once weekly reduced the rate of vaginal candidiasis in a cohort of HIV-infected women.87

A prospective study showed no difference in the treatment outcome of trichomonas but a significant decrease in cure rates of bacterial vaginosis among HIV-infected compared with HIV-uninfected women.88

Summary

Vaginal infections play an important role in transmission of HIV. Treatment of vaginal Candida infections can be challenging in HIV-infected women. Antifungal prophylaxis may be necessary but should be administered judiciously.

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CONTRACEPTION

A key element of providing care to an HIV-infected woman includes reproductive counseling with provision of contraception or preconception care. Most studies have found that individuals continue to be sexually active after receiving an HIV diagnosis.89,90,91,92,93,94 The reasons individuals and couples decide to use contraception, conceive, and continue or terminate a pregnancy are complex, particularly in the setting of HIV.91,95,96,97,98,99,100,101

While consistent hormonal contraception allows excellent pregnancy prevention, there are several issues relevant to the HIV-infected woman. Hormonal contraception appears associated with increased genital shedding of HIV-1.102,103,104 Mostad and colleagues found an association between hormonal contraceptives and cervical HIV-1 shedding.104 In particular, this study detected a significant association between cervical HIV-1 shedding and high-dose oral contraceptives (50 μg estradiol) (adjusted odds ratio [aOR]: 12.3; 95% CI: 1.5 to 101), low-dose oral contraceptives (aOR: 3.8; 95% CI: 1.4 to 9.9), and depot medroxyprogesterone acetate (DMPA) (aOR: 2.9; 95% CI: 1.5 to 5.7). More recently, Baeten reported an association between DMPA and both a higher baseline viral load and increased viral diversity.105 As a result, HIV-infected women using DMPA may be at increased risk for faster progression of HIV disease, although this has not been definitively studied. While no studies have evaluated Norplant and HIV shedding in humans, Marx and associates noted an increase in simian immunodeficiency virus (SIV) DNA-positive cells in the vaginal lamina propria of infected macaques with subcutaneous progesterone implants.106

In addition to biological implications, there may be behavioral consequences of hormonal contraceptives among HIV-infected women. Women using hormonal contraception, regardless of their HIV status, are often less likely to concurrently use condoms. Not surprisingly, one study found that HIV-infected women using oral contraceptives were significantly less likely to use condoms, putting them at risk for acquiring STIs and transmitting HIV to uninfected partners.107

Lastly, there are interactions between ethinyl estradiol (EE)/norethindrone acetate (NE) and some of the antiretrovirals. In particular, amprenavir, atazanavir, efavirenz, and indinavir all appear to increase levels of EE/NE.108 However, lopinavir/ritonavir, nelfinavir, nevirapine, and ritonavir decrease levels of EE/NE, likely by inducing CYP450 metabolism.108,109,110 There is also limited evidence that EE/NE may alter levels of antiretrovirals. Concurrent administration of 0.035 mg EE and 1 milligram NE with amprenavir 1200 milligram twice daily for 1 month, for instance, is associated with decreased levels of amprenavir.108

While there are theoretical concerns of the use of an intrauterine device (IUD) among HIV-infected women, no study has found an increase in viral shedding or incident infections associated with its use.111 Among 98 HIV-infected women in Kenya, there were no differences in HIV-1 DNA cervical shedding before and after IUD insertion.112 Sinei and associates found no significant differences in overall complications, incident pelvic inflammatory disease, and overall infection-related morbidity between 156 HIV-infected and 493 HIV-uninfected women who underwent IUD insertion.113 While it is often difficult to find the ideal method of contraception for any woman, it is crucial to assist the HIV-infected woman in weighing the risks and benefits of all options and choosing a realistic method for her circumstances.114

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PRECONCEPTION COUNSELING

Often overlooked is an HIV-infected woman's desire to conceive.115 Because people with HIV are living longer, healthier lives, and because antiretroviral therapy has dramatically decreased the likelihood of vertical transmission, some HIV-infected women choose to conceive.96,97 As with all women with chronic medical conditions, ideal pregnancies are planned while in care of a medical provider. While optimizing the HIV-specific needs of infected women is clearly outside the realm of most gynecologists, there are several issues that obstetricians/gynecologists can and should address with their HIV-infected patients considering pregnancy. Goals of preconception care include identifying risk factors for adverse maternal and neonatal outcomes, treating and stabilizing medical conditions and psychosocial problems before conception, and providing patient-specific health education. In particular, medications should be reviewed and teratogenic agents discontinued or changed. Medications with teratogenic potential include the antiretrovirals efavirenz and amprenavir and lipid-lowering agents such as HMG-CoA reductase inhibitors.116,117,118 Additionally, women using stavudine and/or didanosine should switch to another antiretroviral regimen, if possible, given the association between these medications and fatal maternal lactic acidosis.119,120,121,122,123 In addition to optimizing the medication profile, it is important to confirm that all vaccination series are up-to-date. Both hepatitis A and hepatitis B vaccines are safe among HIV-infected individuals. While measles-mumps-rubella (MMR) is a live-attenuated vaccine, the Advisory Committee on Immunization Practices (ACIP) recommends MMR vaccination for all susceptible, asymptomatic HIV-infected individuals in the absence of severe immunosuppression.124 There are limited data on the safety of varicella vaccination in the setting of HIV. Brady and associates reported on the safety of varicella vaccine among HIV-infected adults with CD4+ cell counts more than 400 who had been previously infected with varicella-zoster virus.125 There are no data specifically addressing the safety and efficacy of varicella vaccination in HIV-infected, susceptible women in the preconception period. Clearly, the provision of high-quality preconception care requires eliciting a thorough sexual and reproductive history, including goals for conception.

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ASSISTED REPRODUCTION

There is a growing body of literature addressing the ethics and science of providing assisted reproduction techniques to HIV-infected women and HIV-serodiscordant couples, both for infertility treatment and for HIV transmission prevention.126,127,128,129 Reasons for withholding infertility treatment among HIV-infected women and affected couples include the life-threatening nature of HIV and the unacceptably high risk of HIV transmission to the infant. In recent years, however, HIV has evolved into a chronic medication condition and transmission risk is less than 1% among women with maximally suppressed virus at the time of delivery.130 Infertility management is typically not withheld from women with other chronic conditions, such as diabetes, hypertension, and lupus, that may have more significant implications for the health of the woman or baby. Similarly, couples known to be carriers of autosomal recessive diseases, such as cystic fibrosis, Tay-Sachs and sickle-cell anemia, have at least a 25% chance of transmitting this condition, which is significantly higher than that for HIV.

Furthermore, there is evidence that assisted reproductive therapy, such as sperm washing with intrauterine insemination (IUI) or in vitro fertilization (IVF) with or without intracytoplasmic sperm injection (ICSI), may decrease the risk of HIV acquisition in HIV-uninfected women attempting pregnancy with HIV-infected male partners.131,132,133,134,135,136,137,138 Several clinical programs, most notably in Europe and New York, offer these techniques to discordant couples to increase the likelihood of conception with HIV transmission to the uninfected woman. To date, more than 2800 sperm washing per IUI cycles have been performed on nearly 1100 patients, leading to 470 pregnancies and no cases of perinatal HIV transmission.133,134,135,139,140,141,142,143 Similarly, 93 cycles of IVF have been performed on 75 patients, resulting in 28 pregnancies and no cases of HIV transmission.140,143 Moreover, nearly 250 cycles of IVF-ICSI have been performed on 164 patients with 90 resultant pregnancies and, again, no cases of HIV transmission.136,138,140,143

Recently, the Ethics Committee of the American Society for Reproductive Medicine stated, “Unless health care workers can show that they lack the skill and facilities to treat HIV-positive patients safely or that the patient refused reasonable testing and treatment, they may be legally as well as ethically obligated to provide requested reproductive assistance.”144

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MENSTRUAL DISORDERS

Menstrual abnormalities are prevalent among women infected with HIV.145,146,147,148,149 It is not clear, however, whether HIV, per se, is a risk factor for such disorders. Several studies have found no difference in menstrual patterns between HIV-infected and uninfected women.147,150 However, one study demonstrated a higher prevalence of amenorrhea among 248 HIV-infected versus 82 high-risk HIV-uninfected women, after adjusting for age, ethnicity, and drug use (aOR: 7.1; 95% CI: 1.1 to 1000).145 Another study found a higher frequency of amenorrhea among HIV-infected women with late wasting (38%), defined as less than 90% ideal body weight, as compared with infected women without wasting (17%).151 In the large combined HERS and WIHS prospective cohorts, polymenorrhea, defined as fewer than 19 days between cycles, was seen more often among HIV-infected women (aOR: 1.45; 95% CI: 1.00 to 2.11) as compared with HIV-uninfected women, adjusting for age, ethnicity, body mass index, psychotropic medication, and drug use.150 Polymenorrhea was particularly evident among women with HIV viral load values above 168,000 copies/mL. A separate analysis of the same cohort found an independent association between psychotropic medication and both amenorrhea and polymenorrhea.152 Not surprisingly, they also found an association between both methadone maintenance and injection drug use and amenorrhea. Regardless of whether HIV is independently associated with menstrual disorders, prevalence of such menstrual irregularities is high; therefore, it is crucial to inquire about menstrual function among HIV-infected women seeking care.

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OSTEOPENIA AND OSTEOPOROSIS

There is a growing body of literature addressing metabolic alterations among HIV-infected individuals. While most of the attention has focused on changes in central fat accumulation and peripheral subcutaneous fat loss, researchers are now turning their attention to altered bone metabolism.153,154,155,156,157,158 Some authors report an association between HIV and diminished bone density.159 Other authors attribute this apparent bone loss to antiretroviral therapy, most likely protease inhibitors, not HIV infection.160,161 The epidemiology of osteopenia and osteoporosis among HIV-infected women is a rapidly evolving field and much of the research thus far has generated more questions than answers. Nonetheless, as HIV-infected women live longer lives and more of these women reach menopause, the clinical management of osteopenia and osteoporosis in this population will become only more relevant.

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CONCLUSION

Recent well-designed prospective studies have shed some light on the interactions between HIV and gynecological diseases, but our understanding is far from complete. The most significant challenges ahead seem to be the development of microbicidal agents that could prevent HIV transmission and development of better treatment methods for lower genital tract neoplasia. Gynecological diseases are frequently encountered when caring for HIV-infected women, especially those with greater degrees of immunosuppression. Most gynecological conditions in HIV-infected women will respond to standard therapy but require increased vigilance for treatment failure. Some will require multiple courses of treatment or use of innovative treatment methods. All HIV-infected women deserve careful evaluation for and treatment of gynecological diseases.

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REFERENCES

1. UNAIDS: AIDS Epidemic Update. Geneva: Joint United Nations Programme on HIV/AIDS (UNAIDS), pp 1-40, 2002

2. U.S. HIV and AIDS cases reported through December 2001: HIV/AIDS Surveill Rep 13, 2002

3. CDC: HIV/AIDS Surveillance Report. Atlanta: Centers for Disease Control and Prevention 1-44, 2001

4. Frankel RE, Selwyn PA, Mezger J, et al: High prevalence of gynecologic disease among hospitalized women with human immunodeficiency virus infection. Clin Infect Dis 25:706-712, 1997

5. Watts DH, Spino C, Zaborski L, et al: Comparison of gynecologic history and laboratory results in HIV-positive women with CD4+ lymphocyte counts between 200 and 500 cells/microl and below 100 cells/microl. J Acquir Immune Defic Syndr Hum Retrovirol 20:455-462, 1999

6. Chaisson RE, Keruly JC, Moore RD: Race, sex, drug use, and progression of human immunodeficiency virus disease. N Engl J Med 333:751-756, 1995

7. von Overbeck J, Egger M, Smith GD, et al: Survival in HIV infection: Do sex and category of transmission matter? Swiss HIV Cohort Study AIDS 8:1307-1313, 1994

8. Suligoi B: The natural history of human immunodeficiency virus infection among women as compared with men. Sex Transm Dis 24:77-83, 1997

9. Gollub EL: Human rights is a US problem, too: The case of women and HIV. Am J Public Health 89:1479-82, 1999

10. Anderson KH, Mitchell JM: Differential access in the receipt of antiretroviral drugs for the treatment of AIDS and its implications for survival. Arch Intern Med 160:3114-3120, 2000

11. Shapiro MF, Morton SC, McCaffrey DF, et al: Variations in the care of HIV-infected adults in the United States: Results from the HIV Cost and Services Utilization Study. JAMA 281:2305-2315, 1999

12. Napravnik S, Poole C, Thomas JC, et al: Gender difference in HIV RNA levels: A meta-analysis of published studies. J Acquir Immune Defic Syndr 31:11-19, 2002

13. Gandhi M, Bacchetti P, Miotti P, et al: Does patient sex affect human immunodeficiency virus levels? Clin Infect Dis 35:313-322, 2002

14. Greenblatt RM, Ameli N, Grant RM, et al: Impact of the ovulatory cycle on virologic and immunologic markers in HIV-infected women. J Infect Dis 181:82-90, 2000

15. van Benthem BH, Vernazza P, Coutinho RA, et al: The impact of pregnancy and menopause on CD4 lymphocyte counts in HIV-infected women. AIDS 16:919-924, 2002

16. Massad LS, Ahdieh L, Benning L, et al: Evolution of cervical abnormalities among women with HIV-1: Evidence from surveillance cytology in the women's interagency HIV study. J Acquir Immune Defic Syndr 27:432-442, 2001

17. Mandelblatt JS, Fahs M, Garibaldi K, et al: Association between HIV infection and cervical neoplasia: implications for clinical care of women at risk for both conditions. AIDS 6:173-178, 1992

18. Massad LS, Riester KA, Anastos KM, et al: Prevalence and predictors of squamous cell abnormalities in Papanicolaou smears from women infected with HIV-1. Women's Interagency HIV Study Group J Acquir Immune Defic Syndr 21:33-41, 1999

19. Sun XW, Kuhn L, Ellerbrock TV, et al: Human papillomavirus infection in women infected with the human immunodeficiency virus [see comments]. N Engl J Med 337:1343-1349, 1997

20. Ellerbrock TV, Chiasson MA, Bush TJ, et al: Incidence of cervical squamous intraepithelial lesions in HIV-infected women. JAMA 283:1031-1037, 2000

21. Heard I, Tassie J, Kazatchkine MD, et al: Highly active antiretroviral therapy enhances regression of cervical intraepithelial neoplasia in HIV-seropositive women. AIDS 16:1799-1802, 2002

22. Minkoff H, Ahdieh L, Massad LS, et al: The effect of highly active antiretroviral therapy on cervical cytologic changes associated with oncogenic HPV among HIV-infected women. AIDS 15:2157-2164, 2001

23. Lillo F, Ferari D, Veglia F, et al: Human papillomavirus infection and associated cervical disease in human immunodeficiency virus-infected women: Effect of highly active antiretroviral therapy. J Infect Dis 184:547-551, 2001

24. Conley LJ, Ellerbrock TV, Bush TJ, et al: HIV-1 infection and risk of vulvovaginal and perianal condylomata acuminata and intraepithelial neoplasia: A prospective study. Lancet 359:108-113, 2002

25. Hillemanns P, Ellerbrock TV, McPhillips S, et al: Prevalence of anal human papillomavirus infection and anal cytologic abnormalities in HIV-seropositive women. AIDS 10:1641-1067, 1996

26. Williams AB, Darragh TM, Vranizan K, et al: Anal and cervical human papillomavirus infection and risk of anal and cervical epithelial abnormalities in human immunodeficiency virus-infected women. Obstet Gynecol 83:205-211, 1994

27. Holly EA, Ralston ML, Darragh TM, et al: Prevalence and risk factors for anal squamous intraepithelial lesions in women. J Natl Cancer Inst 93:843-849, 2001

28. Frisch M, Biggar RJ, Goedert JJ: Human papillomavirus-associated cancers in patients with human immunodeficiency virus infection and acquired immunodeficiency syndrome. J Natl Cancer Inst 92:1500-1510, 2000

29. Penn I: Cancers of the anogenital region in renal transplant recipients. Cancer 58:611-616, 1986

30. Wright TC, Ellerbrock TV, Chiasson MA, et al: Cervical intraepithelial neoplasia in women infected with human immunodeficiency virus: Prevalence, risk factors, and validity of Papanicolaou smears. New York Cervical Disease Study Obstet Gynecol 84:591-597, 1994

31. Korn AP, Autry M, DeRemer PA, et al: Sensitivity of the Papanicolaou smear in human immunodeficiency virus-infected women. Obstet Gynecol 83:401-404, 1994

32. Maiman M, Fruchter RG, Sedlis A, et al: Prevalence, risk factors, and accuracy of cytologic screening for cervical intraepithelial neoplasia in women with the human immunodeficiency virus. Gynecol Oncol 68:233-239, 1998

33. Goldie SJ, Weinstein MC, Kuntz KM, et al: The costs, clinical benefits, and cost-effectiveness of screening for cervical cancer in HIV-infected women. Ann Intern Med 130:97-107, 1999

34. el-Sadr W, Oleske JM, Agins BD: Managing early HIV infection. Agency for Health Care Policy and Research. Clinical Practice Guideline Quick Reference Guide for Clinicians 105:1-37, 1994

35. Sexually transmitted diseases treatment guidelines 2002. Centers for Disease Control and Prevention MMWR Recomm Rep 51:1-78, 2002

36. Petry KU, Böhmer G, Iftner T, et al: Human papillomavirus testing in primary screening for cervical cancer of human immunodeficiency virus-infected women, 1990–1998. Gynecol Oncol 75:427-431, 1999

37. Wright TC, Moscarelli RD, Dole P, et al: Significance of mild cytologic atypia in women infected with human immunodeficiency virus. Obstet Gynecol 87:515-519, 1996

38. Heard I, Bergeron C, Jeannel D, et al: Papanicolaou smears in human immunodeficiency virus-seropositive women during follow-up. Obstet Gynecol 86:749-753, 1995

39. La Ruche G, Leroy V, Mensah-Ado I, et al: Short-term follow up of cervical squamous intraepithelial lesions associated with HIV and human papillomavirus infections in Africa. Int J STD AIDS 10:363-368, 1999

40. Fruchter RG, Maiman M, Sedlis A, et al: Multiple recurrences of cervical intraepithelial neoplasia in women with the human immunodeficiency virus. Obstet Gynecol 87:170-174, 1996

41. Maiman M, Fruchter RG, Serur E, et al: Recurrent cervical intraepithelial neoplasia in human immunodeficiency virus-seropositive women. Obstet Gynecol 82:170-174, 1993

42. Holcomb K, Matthews RP, Chapman JE, et al: The efficacy of cervical conization in the treatment of cervical intraepithelial neoplasia in HIV-positive women. Gynecol Oncol 74:428-431, 1999

43. Cuthill S, Maiman M, Fruchter RG, et al: Complications after treatment of cervical intraepithelial neoplasia in women infected with the human immunodeficiency virus. J Reprod Med 40:823-828, 1995

44. Korn A, Abercrombie A, Foster: Vulvar intraepithelial neoplasia in women infected with human immunodeficiency virus 1. Gynecol Oncol 61:384-386, 1996

45. Chang G, Berry J, Jay N, et al: Surgical treatment of high-grade anal squamous intraepithelial neoplasia lesions: A prospective study. Dis Colon Rectum 45:453-458, 2002

46. Maiman M, Watts DH, Andersen J, et al: Vaginal 5-fluorouracil for high-grade cervical dysplasia in human immunodeficiency virus infection: A randomized trial. Obstet Gynecol 94:954-961, 1999

47. Robinson WR, Andersen J, Darragh TM, et al: Isotretinoin for low-grade cervical dysplasia in human immunodeficiency virus-infected women. Obstet Gynecol 99:777-784, 2002

48. Gilson RJ, Shupack JL, Friedman-Kien AE, et al: A randomized, controlled, safety study using imiquimod for the topical treatment of anogenital warts in HIV-infected patients. Imiquimod Study Group AIDS 13:2397-2404, 1999

49. Todd RW, Etherington IJ, Luesley DM: The effects of 5% Imiquimod on high-grade vulvar intraepithelial neoplasia. Gynecol Oncol 85, 2002

50. Parkin DM, Wabinga H, Nambooze S, et al: AIDS-related cancers in Africa: maturation of the epidemic in Uganda [see comments]. AIDS 13:2563-2570, 1999

51. Serraino D, Napoli PA, Zaccarelli M, et al: High frequency of invasive cervical cancer among female injecting drug users with AIDS in Italy [letter] [see comments]. AIDS 10:1041-1042, 1996

52. Dal Maso L, Serraino D, Francheschi S: Epidemiology of AIDS-related tumours in developing and developed countries. Eur J Cancer 37, 2001

53. Jones JL, Dworkin MS, Alderton DL, et al: Surveillance for AIDS-defining opportunistic illnesses. MMWR Morb Mortal Wkly Rep 48:1-22, 1999

54. Frisch M, Biggar RJ, Engels E: Association of cancer with AIDS-related immunosuppression in adults. J Acquir Immune Defic Syndr 285:1736-1745, 2001

55. Gallagher B, Wang Z, Schymura MJ, et al: Cancer incidence in New York State Acquired immunodeficiency syndrome patients. Am J Epidemiol 154:544-556, 2001

56. Maiman M, Fruchter RG, Guy L, et al: Human immunodeficiency virus infection and invasive cervical carcinoma. Cancer 71:402-406, 1993

57. Fruchter RG, Maiman M, Arrastia CD, et al: Is HIV infection a risk factor for advanced cervical cancer? J Acquir Immune Defic Syndr Hum Retrovirol 18:241-245, 1998

58. Wasserheit J: Epidemiological synergy. Interrelationships between human immunodeficiency virus infection and other sexually transmitted diseases Sex Transm Dis 19:61-77, 1992

59. Fleming DT, Wasserheit JN: From epidemiological synergy to public health policy and practice: The contribution of other sexually transmitted diseases to sexual transmission of HIV infection. Sex Transm Infect 75:3-17, 1999

60. Rothenberg RW, St Louis ME, Douglas JM: The effect of treating sexually transmitted diseases on the transmission of HIV in dually infected persons: A clinic-based estimate. Ad Hoc STD/HIV Transmission Group Sex Transm Dis 27:411-416, 2000

61. Grosskurth HM, Todd J, Mwijarubi E, et al: Impact of improved treatment of sexually transmitted diseases on HIV infection in rural Tanzania: Randomised controlled trial. Lancet 346:530-536, 1995

62. Mbopi-Keou FX, Robinson NJ, Mayaud P, et al: Herpes simplex virus type 2 and heterosexual spread of human immunodeficiency virus infection in developing countries: Hypotheses and research priorities. Clin Microbiol Infect 9:161-171, 2003

63. Mbopi-Keou FX, Legoff J, Gresenguet G, et al: Editorial: Genital shedding of Herpes Simplex virus-2 DNA and HIV-1 RNA and proviral DNA in HIV-1- and Herpes Simplex virus-2-coinfected African women. J Acquir Immune Defic Syndr 33:121-124, 2003

64. Sexually transmitted diseases treatment guidelines. MMWR Morb Mortal Wkly Rep 51:1-84, 2002

65. Guidance for STD clinical preventive services for persons infected with HIV. Sex Transm Dis 28:460-463, 2001

66. Corey L, Tyring S, Beutner K, et al: Once daily valacyclovir reduces transmission of genital herpes. Abstract LB-3. 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy. San Diego 2002

67. Safrin S, Dattel BJ, Hauer L, et al: Seroprevalence and epidemiologic correlates of human immunodeficiency virus infection in women with acute pelvic inflammatory disease. Obstet Gynecol 75:666-670, 1990

68. Bukusi EA, Cohen CR, Stevens CE, et al: Effects of human immunodeficiency virus 1 infection on microbial origins of pelvic inflammatory disease and on efficacy of ambulatory oral therapy. Am J Obstet Gynecol 181:1374-1381, 1999

69. Barbosa C, Macasaet M, Brockmann S, et al: Pelvic inflammatory disease and human immunodeficiency virus infection. Obstet Gynecol 89:65-70, 1997

70. Cohen CR, Sinei S, Reilly M, et al: Effect of human immunodeficiency virus type 1 infection upon acute salpingitis: A laparoscopic study. J Infect Dis 178:1352-1358, 1998

71. Irwin KL, Moorman AC, O'Sullivan MJ, et al: Influence of human immunodeficiency virus infection on pelvic inflammatory disease. Obstet Gynecol 95:525-534, 2000

72. de Bernardis F, Mondello F, Scaravelli G, et al: High aspartyl proteinase production and vaginitis in human immunodeficiency virus-infected women. J Clin Microbiology 37:1376-1380, 1999

73. Cu-uvin S, Hogan JW, Caliendo AM, et al: Association between bacterial vaginosis and expression of human immunodeficiency virus type 1 RNA in the female genital tract. Clin Infect Dis 33:894-896, 2001

74. Wang CC, McClelland RS, Reilly M, et al: The effect of treatment of vaginal infections on shedding of human immunodeficiency virus type 1. J Infect Dis 183:1017-1022, 2001

75. Moodley P, Wilkinson D, Connolly C, et al: Trichomonas vaginalis is associated with pelvic inflammatory disease in women infected with human immunodeficiency virus. Clin Infect Dis 34:519-522, 2002

76. Sobel JD: Vulvovaginal candidiasis: a comparison of HIV-positive and -negative women. Int J Sex Transmit Dis AIDS 13:358-362, 2002

77. White MH: Is vulvovaginal candidiasis an AIDS-related illness? Clin Infect Dis 22:S124-S127, 1996

78. Duerr A, Sierra MF, Feldman J, et al: Immune compromise and prevalence of Candida vulvovaginitis in human immunodeficiency virus-infected women. Obstet Gynecol 90:252-256, 1997

79. Spinillo A, Capuzzo E, Gulminetti R, et al: Prevalence of and risk factors for fungal vaginitis caused by non-albicans species [see comments]. Am J Obstet Gynecol 176:138-141, 1997

80. Sobel JD, Ohmit SE, Schuman P, et al: The evolution of Candida spp And fluconazole susceptibility among oral and vaginal isolates recovered from human immunodeficiency virus (HIV) seropositive and at-risk HIV-seronegative women. J Infect Dis 183:286-293, 2000

81. Duerr A, Helig CM, Meikle SF, et al: Incident and persistent vulvovaginal candidiasis among human immunodeficiency virus-infected women: Risk factors and severity. Obstet Gynecol 101:548-556, 2003

82. Greenblatt RM, Bacchetti P, Barkan S: Lower genital tract infections among HIV-infected and high-risk uninfected women. Findings of the Women's Interagency HIV Study (WIHS) Sex Transm Dis 26:143-151, 1999

83. Jamieson DJ, Duerr A, Klein RS: Longitudinal analysis of bacterial vaginosis: Findings from the HIV epidemiology research study. Obstet Gynecol 98:656-663, 2001

84. Schuman P, Capps L, Peng G, et al: Weekly fluconazole for the prevention of mucosal candidiasis in women with HIV infection. A randomized, double-blind, placebo-controlled trial. Terry Beirn Community Programs for Clinical Research on AIDS [see comments] Ann Intern Med 126:689-696, 1997

85. Vazquez JA, Sobel JD, Peng G, et al: Evolution of vaginal Candida species recovered from human immunodeficiency virus-infected women receiving fluconazole prophylaxis: The emergence of Candida glabrata? Terry Beirn Community Programs for Clinical Research in AIDS (CPCRA) Clin Infect Dis 28:1025-131, 1999

86. Reef SEAM KH: Opportunistic candidal infections in patients infected with human immunodeficiency virus: Prevention issues and priorities. Clin Infect Dis 21:S99-S102, 1995

87. Williams AB, Yu C, Tashima K, et al: Evaluation of two self-care treatments for prevention of vaginal candidiasis in women with HIV. J Assoc Nurses AIDS Care 12:51-57, 2001

88. Moodley P, Wilkinson D, Connolly C, et al: Influence of HIV-1 coinfection on the effective management of vaginal discharge. Sex Transm Dis 30:1-5, 2003

89. Van Devanter N, Cleary PD, Moore J, et al: Reproductive behavior in HIV-discordant heterosexual couples: implications for counseling. AIDS Patient Care STDS 12:43-49, 1998

90. Bova C, Durante A: Sexual functioning among HIV-infected women. AIDS Patient Care STDS 17:75-83, 2003

91. Wilson TE, Massad LS, Riester KA, et al: Sexual, contraceptive, and drug use behaviors of women with HIV and those at high risk for infection: Results from the Women's Interagency HIV Study. AIDS 13:591-598, 1999

92. Zierler S, Mayer K, Moore J, et al: Sexual practices in a cohort of US women with and without human immunodeficiency virus. HERS Study. HIV Epidemiology Research Study J Am Med Womens Assoc 54:79-83, 1999

93. Kennedy M, Moore J, Schuman P, et al: Sexual behavior of HIV-infected women reporting recent sexual contact with women. JAMA 280:29-30, 1998

94. Heckman TG, Silverthorn M, Waltje A, et al: HIV transmission risk practices in rural persons living with HIV disease. Sex Transm Dis 30:134-136, 2003

95. Sowell RL, Misener TR: Decisions to have a baby by HIV-infected women. West J Nurs Res 19:56-70, 1997

96. Sowell RL, Murdaugh CL, Addy CL, et al: Factors influencing intent to get pregnant in HIV-infected women living in the southern USA. AIDS Care 14:181-191, 2002

97. Richter DL, Sowell RL, Pluto DM: Factors affecting reproductive decisions of African American women living with HIV. Women Health 36:81-96, 2002

98. De Vincenzi I, Jadand C, Couturier E, et al: Pregnancy and contraception in a French cohort of HIV-infected women. SEROCO Study Group AIDS 11:333-338, 1997

99. Wilson TE, Minkoff H: Brief report: Condom use consistency associated with beliefs regarding HIV disease transmission among women receiving HIV antiretroviral therapy. J Acquir Immune Defic Syndr 27:289-291, 2001

100. Hankins C, Tran T, Lapointe N: Sexual behavior and pregnancy outcome in HIV-infected women. Canadian Women's HIV Study Group. J Acquir Immune Defic Syndr Hum Retrovirol 18:479-487, 1998

101. Hankins C, Gendron S, Tran T, et al: Sexuality in Montreal women living with HIV. AIDS Care 9:261-271, 1997

102. Clemetson DB, Moss GB, Willerford DM, et al: Detection of HIV DNA in cervical and vaginal secretions. Prevalence and correlates among women in Nairobi, Kenya JAMA 269:2860-2864, 1993

103. Mostad SB: Prevalence and correlates of HIV type 1 shedding in the female genital tract. AIDS Res Hum Retrovirus 14:S1:S11-S15, 1998

104. Mostad SB, Overbaugh J, DeVange DM, et al: Hormonal contraception, vitamin A deficiency, and other risk factors for shedding of HIV-1 infected cells from the cervix and vagina. Lancet 350:922-927, 1997

105. Baeten JM: The influence of vitamin A and hormonal contraception on HIV transmission and disease progression in women: Abstract #116. 10th Conference on Retroviruses and Opportunistic Infections. Boston 2003

106. Marx PA SA, Gettie A, Dailey PJ, et al: Progesterone implants enhance SIV vaginal transmission and early virus load. Nat Med 2:1084-1049, 1996

107. Diaz T, Schable B, Chu SY: Relationship between use of condoms and other forms of contraception among human immunodeficiency virus-infected women. Supplement to HIV and AIDS Surveillance Project Group. Obstet Gynecol 86:277-82, 1995

108. McNicholl I: Database of antiretroviral drug interactions: Interactions between hormonal agents and antiretrovirals: HIV InSite. 2003

109. Mildvan D, Yarrish R, Marshak A, et al: Pharmacokinetic interaction between nevirapine and ethinyl estradiol/norethindrone when administered concurrently to HIV-infected women. J Acquir Immune Defic Syndr 29:471-477, 2002

110. Ouellet D, Hsu A, Qian J, et al: Effect of ritonavir on the pharmacokinetics of ethinyl oestradiol in healthy female volunteers. Br J Clin Pharmacol 46:111-116, 1998

111. Grimes DA: Intrauterine device and upper-genital-tract infection. Lancet 356:1013-1019, 2000

112. Richardson BA, Morrison CS, Sekadde-Kigondu C, et al: Effect of intrauterine device use on cervical shedding of HIV-1 DNA. AIDS 13:2091-2097, 1999

113. Sinei SK, Morrison CS, Sekadde-Kigondu C, et al: Complications of use of intrauterine devices among HIV-1-infected women. Lancet 351:1238-1241, 1998

114. Curtis KM, Chrisman CE, Peterson HB: Contraception for women in selected circumstances. Obstet Gynecol 99:1100-1112, 2002

115. Lai KK: Attitudes toward childbearing and changes in sexual and contraceptive practices among HIV-infected women. Cleve Clin J Med 61:132-136, quiz 161 1994

116. De Santis M, Carducci B, De Santis L, et al: Periconceptional exposure to efavirenz and neural tube defects. Arch Intern Med 162:355, 2002

117. Bristol-Myers-Squibb Company: Sustiva Prescribing Information 6495-07. Revised April 2002. www.sustiva.com 2002

118. Fundaro C, Genovese O, Rendeli C, et al: Myelomeningocele in a child with intrauterine exposure to efavirenz. AIDS 16:299-300, 2002

119. Mandelbrot L, Kermarrec N, Marcollet A, et al: Case report: nucleoside analogue-induced lactic acidosis in the third trimester of pregnancy. AIDS 17:272-273, 2003

120. Bristol-MyersSquibb: Important Drug Warning. 2001

121. Sarner L, Fakoya A: Acute onset lactic acidosis and pancreatitis in the third trimester of pregnancy in HIV-1 positive women taking antiretroviral medication. Sex Transm Infect 78:58-59, 2002

122. Lactic acidosis and anti-retroviral drugs. Prescrire Int 11:113-115, 2002

123. Hill JB, Sheffield JS, Zeeman GG, et al: Hepatotoxicity with antiretroviral treatment of pregnant women. Obstet Gynecol 98:909-911, 2001

124. Measles, mumps, and rubella–Vaccine use and strategies for elimination of measles, rubella and congenital rubella syndrome and control of mumps. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 47:1-57, 1998

125. Brady KA, Levin M, Weinberg A, et al: Safety and immune response to varicella vaccine in HIV-infected adults previously infected with varicella. 9th Conference on Retroviruses and Opportunistic Infections. Seattle 2002

126. Anderson DJ: Assisted reproduction for couples infected with the human immunodeficiency virus type 1. Fertil Steril 72:592-594, 1999

127. Human immunodeficiency virus and infertility treatment. Fertil Steril 77:218-222, 2002

128. Drapkin Lyerly A, Anderson J: Human immunodeficiency virus and assisted reproduction: Reconsidering evidence, reframing ethics. Fertil Steril 75:843-58, 2001

129. Peterman TA, Cates W Jr., Curran JW: The challenge of human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) in women and children. Fertil Steril 49:571-581, 1988

130. Shapiro DE, Tuomala R, Samelson R, et al: Mother-to-Child HIV Transmission Rates According to Antiretroviral Therapy, Mode of Delivery, and Viral Load (PACTG 367): Abstract #114. 9th Conference on Retroviruses and Opportunistic Infections. Seattle, WA. 2002

131. Sauer MV, Chang PL: Establishing a clinical program for human immunodeficiency virus 1-seropositive men to father seronegative children by means of in vitro fertilization with intracytoplasmic sperm injection. Am J Obstet Gynecol 186:627-633, 2002

132. Pena JE, Thornton MH 2nd, Sauer MV: Complications of in vitro fertilization with intracytoplasmic sperm injection in human immunodeficiency virus serodiscordant couples. Arch Gynecol Obstet 2003

133. Semprini AE: Insemination of HIV-negative women with processed semen of HIV-positive partners. Lancet 341:1343-1344, 1993

134. Semprini AE, Fiore S, Pardi G: Reproductive counselling for HIV-discordant couples. Lancet 349:1401-1402, 1997

135. Semprini AE, Levi-Setti P, Bozzo M, et al: Insemination of HIV-negative women with processed semen of HIV-positive partners. Lancet 340:1317-1319, 1992

136. Loutradis D, Drakakis P, Kallianidis K, et al: Birth of two infants who were seronegative for human immunodeficiency virus type 1 (HIV-1) after intracytoplasmic injection of sperm from HIV-1-seropositive men. Fertil Steril 75:210-212, 2001

137. Marina S, Marina F, Alcolea R, et al: Human immunodeficiency virus type 1–serodiscordant couples can bear healthy children after undergoing intrauterine insemination. Fertil Steril 70:35-39, 1998

138. Marina S, Marina F, Alcolea R, et al: Pregnancy following intracytoplasmic sperm injection from an HIV-1-seropositive man. Hum Reprod 13:3247-3249, 1998

139. Bujan L, Daudin M, Pasquier C: Reproductive options for HIV-serodiscordant couples. Perspect Sex Reprod Health 34:104, 2002

140. Weigel MM, Gentili M, Beichert M, et al: Reproductive assistance to HIV-discordant couples–the German approach. Eur J Med Res 6:259-262, 2001

141. Pasquier C, Daudin M, Righi L, et al: Sperm washing and virus nucleic acid detection to reduce HIV and hepatitis C virus transmission in serodiscordant couples wishing to have children. AIDS 14:2093-2099, 2000

142. Tur R, Buxaderas C, Martinez F, et al: Comparison of the role of cervical and intrauterine insemination techniques on the incidence of multiple pregnancy after artificial insemination with donor sperm. J Assist Reprod Genet 14:250-253, 1997

143. Sauer MV: Addressing the Fertility Needs of HIV Serodiscordant Couples. Presented at Fertility Regulation and Systemic Hormones in HIV-Infected and At-Risk Women McLean, VA, 2003

144. Human immunodeficiency virus and infertility treatment: Ethics Committee of the American Society for Reproductive Medicine. Fertil Steril 77:218-222, 2002

145. Chirgwin KD, Feldman J, Muneyyirci-Delale O, et al: Menstrual function in human immunodeficiency virus-infected women without acquired immunodeficiency syndrome. J Acquir Immune Defic Syndr Hum Retrovirol 12:489-494, 1996

146. Ellerbrock TV, Wright TC, Bush TJ, et al: Characteristics of menstruation in women infected with human immunodeficiency virus. Obstet Gynecol 87:1030-1034, 1996

147. Shah PN, Smith JR, Wells C, et al: Menstrual symptoms in women infected by the human immunodeficiency virus. Obstet Gynecol 83:397-400, 1994

148. Shah PN, Smith JR, Iatrakis GM, et al: HIV infection and menstrual abnormalities. Genitourin Med 68:425-426, 1992

149. Clark RA, Mulligan K, Stamenovic E, et al: Frequency of anovulation and early menopause among women enrolled in selected adult AIDS clinical trials group studies. J Infect Dis 184:1325-1327, 2001

150. Harlow SD, Schuman P, Cohen M, et al: Effect of HIV infection on menstrual cycle length. J Acquir Immune Defic Syndr 24:68-75, 2000

151. Grinspoon S, Corcoran C, Miller K, et al: Body composition and endocrine function in women with acquired immunodeficiency syndrome wasting. J Clin Endocrinol Metab 82:1332-1337, 1997

152. Harlow SN SD, Cohen M, Ohmit SE, et al: Substance use and psychotherapeutic medications: A likely contributor to menstrual disorders in women who are seropositive for human immunodeficiency virus. Am J Obstet Gynecol 188:881-886, 2003

153. Cheonis N: Osteoporosis and HIV disease. Beta 14:26-34, 2001

154. McDermott AY, Shevitz A, Knox T, et al: Effect of highly active antiretroviral therapy on fat, lean, and bone mass in HIV-seropositive men and women. Am J Clin Nutr 74:679-686, 2001

155. Mora S, Sala N, Bricalli D, et al: Bone mineral loss through increased bone turnover in HIV-infected children treated with highly active antiretroviral therapy. AIDS 15:1823-1829, 2001

156. Knobel H, Guelar A, Vallecillo G, et al: Osteopenia in HIV-infected patients: is it the disease or is it the treatment? AIDS 15:807-808, 2001

157. HAART and bone loss. AIDS Patient Care STDS 14:226, 2000

158. Stephens EA, Das R, Madge S, et al: Symptomatic osteoporosis in two young HIV-positive African women. AIDS 13:2605-2606, 1999

159. Aukrust P, Haug CJ, Ueland T, et al: Decreased bone formative and enhanced resorptive markers in human immunodeficiency virus infection: Indication of normalization of the bone-remodeling process during highly active antiretroviral therapy. J Clin Endocrinol Metab 84:145-150, 1999

160. Tebas P, Powderly WG, Claxton S, et al: Accelerated bone mineral loss in HIV-infected patients receiving potent antiretroviral therapy. Abstract #114. 7th Conference on Retroviruses and Opportunistic Infections. Alexandria, VA 2000

161. Hoy J, Hudson J, Law M, et al: Osteopenia in a randomized, multicenter study of protease inhibitor substitution in patients with the lipodystrophy syndrome and well-controlled HIV viremia. Abstract #208. 7th Conference on Retroviruses and Opportunistic Infections. San Francisco 2000

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