Hospital Practice
ISSN: 2154-8331 (Print) 2377-1003 (Online) Journal homepage: http://www.tandfonline.com/loi/ihop20
HIV Infection in Women: Presentations and Protocols Machelle H. Allen & Carola Marte To cite this article: Machelle H. Allen & Carola Marte (1992) HIV Infection in Women: Presentations and Protocols, Hospital Practice, 27:3, 155-162, DOI: 10.1080/21548331.1992.11705386 To link to this article: http://dx.doi.org/10.1080/21548331.1992.11705386
Published online: 17 May 2016.
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Date: 19 June 2016, At: 05:45
HIV Infection in Women: Presentations and Protocols
Downloaded by [La Trobe University] at 05:45 19 June 2016
MACHELLE H. ALLEN and CAROLA MARTE New York University and Beth Israel Medical Center, New York
In the 11th year of the AIDS epidemic in the United States, it is clear that more and more women are becoming infected with Hiv. Genital infections by other pathogens may be the first clue to the diagnosis. With progressive immunodeficiency, such infections may follow a protracted course or become recurrent, often requiring maintenance therapy.
HIV infection is becoming increasingly common in women throughout the United States. Yet there is generally little awareness of the problem in the medical community, and hardly any data on the primary gynecologic care of infected patients. Genital infections that resist standard therapy may be the first indication of immunodeficiency and are important to diagnose. In addition. because of the more aggressive and protracted course such conditions often take. HIV-infected women require heightened gynecologic surveillance, including more frequent Papanicolaou smears and liberal use of colposcopy.
Epidemiology As of December 1991, AIDS cases in the United States reported to the Centers for Disease Control totaled 202,921. Of these. 21,225 were in women and adolescent girls. Although this represents only a small percentage of all AIDS cases reported since 1981, the proportion of female patients has steadily risen-from 7% before 1985 to 10% in 1988 and 12.8% in 1991. including pediatric cases (Figure 1). The increase in the percentage of AIDS cases in women persists even after accounting for the 1987 revision of the CDC case definition. In New York City, AIDS now represents the leading cause of
Dr. Allen is Instructor, Department of Obstetrics and Gynecology, New York University School of Medicine. Dr. Marte is Instructor, Department of Medicine, Beth Israel Medical Center and Mount Sinai School of Medicine, New York.
death among women aged 25 to 34. Although poor women of color are disproportionately represented, the problem is not confined to inner-city populations but has invaded all strata of U.S. society. Perhaps most worrisome is the high rate of new HIV infections among adolescent females; in reports from some urban areas, the rate now approaches that among adolescent males. Heterosexual contact is often the only known risk factor for women. In a five-year, multicenter followup study of seropositive blood donors, 43 (57%) of 76 women interviewed reported sexual contact with a male partner at risk for HIV infection; 27 (36%) had no identified risk. In addition to reconfirming the prominent role of heterosexual transmission, these data suggest that many women are unaware of the infection status of their male sexual partners. Given the current system of hierarchical exposure categories, it is also likely that a high percentage of women listed as intravenous drug users actually acquired HIV through heterosexual transmission rather than needle sharing. According to the current CDC classification, a single experience with intravenous drugs is sufficient to remove an HIV-positive woman from the "heterosexual contact" or "no identified risk" category and place her in the "IV drug use" category. Yet seroprevalence studies of pregnant women indicate that fewer than one third of those who had been IV drug users and are currently on methadone are HIV-positive, compared with approximately half of female crack users (who typically become infected through heterosexual contact). These and similar surveys suggest that the number of women exposed Hospital Practice March 15. 1992
155
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Figure 1. Among all persons with AIDS in the United States, female patients are a steadily increasing minority. Before 1985, women and adolescent girls accounted for 7% of cases, with the number of younger children and infants negligible. In 1988, the proportion of female cases was 10%. Last year, 12.8% of U.S. AIDS patients were female, including many pediatric cases.
to HIV through heterosexual contact has consistently been underreported-and will continue to be underreported until the classification system is changed. For some time, investigators have observed that the interval between symptomatic HIV infection and death is shorter in women than in men. In a cohort of 5,833 New York City patients studied by Richard Rothenberg and colleagues in 1987, for example, mean survival from AIDS diagnosis to death was 298 days for women, compared with 374 days for men. In addition, although the clinical features of HIV-related Pneumocystis cartnil pneumonia are the same in Table 1. Common Gynecologic Conditions in HIV-Infected Women Candida vaginitis Genital herpes Syphilis Pelvic inflammatory disease Human papillomavirus disease
156
Hospital Practice March 15. 1992
both sexes. respiratory failure occurs more often in women and is more likely to be fatal. Reviewing deaths from AIDS in the United States between 1981 and 1988, Lisa M. Koonin and associates at the CDC and the New York City and New Jersey departments of health found that 16 of 20 pregnant women with AIDS had died of PCP. The mean interval between AIDS diagnosis and death was 113 days, with a median of 7 4 days. Ten of the women had used intravenous drugs, and the mean interval between AIDS diagnosis and death from PCP was only 59 days in these patients. The extent to which sex differences in survival may represent inherent host differences between men and women is unclear. It is probable, however, that external (and therefore modifiable) factors are at least partly responsible for the gender gap. These would include delayed diagnosis due to a low index of suspicion for HIV infection in women and use of diagnostic criteria that are based on
the gay white male population. Poor access to gynecologic (or general) health care and to research trials probably also contribute to lower survival in HIVinfected women. As community awareness of heterosexual HIV transmission increases and demands for counseling and testing are intensified, the number of asymptomatic women identified as seropositive will undoubtedly climb. The burden will thus be on physicians or other care providers to identify and treat gynecologic and other manifestations of HIV infection and to provide assistance with the complex medical, psychosocial, and ethical issues involved. At present, however, health care providers have scant resources on which to draw. Textbooks and manuals of care have not yet incorporated HIV-related gynecology, and little research has been devoted to the gynecologic problems and overall management ofHIV-infected women. For these reasons, the Ambulatory Care Division and the Department of Obstetrics and Gynecology of Bellevue Hospital Center recently collaborated in developing a series of management protocols summarized in this article. A brief review of HIVrelated gynecologic conditions most frequently encountered by primary care providers serves to put these protocols in context.
HIV-Related Gynecologic Conditions Candida vaginitis, genital herpes, syphilis, pelvic inflammatory disease. and human papillomavirus disease (condyloma acuminatum, cervical dysplasia, and cervical carcinoma) are of particular concern in the management ofHIV-infected women (Table 1). All occur with greater frequency and severity in this population,
Downloaded by [La Trobe University] at 05:45 19 June 2016
and all may demonstrate atypical manifestations, including lack of response to standard therapies. Nonsyphilitic genital ulcerschancroid and lymphogranuloma venereum-are also more common in women who are HIV infected than in women in general. However, the incidence of these disorders in the United States remains low compared with rates in developing countries. Cytomegalovirus is another pathogen that has been identified as a cause of both cervical and endometrial inflammation in HIV-infected women. Candida vaginitis. Although still widely neglected, this is the most common gynecologic disorder in HIV-infected women. In those who are severely immunocompromised, it may present as painful coalescing ulcerations requiring aggressive local treatment, followed by maintenance therapy with topical agents or an
oral imidazole such as ketoconazole or fluconazole. In women who are not otherwise symptomatic-including those in whom HIV infection has not yet been diagnosed-the presence of persistent or frequently recurrent vaginal candidiasis may be an early clue of immune suppression (sometimes earlier than oral thrush). Cases refractory to topical treatment frequently herald severe immune suppression and a rapid progression to AIDS. Herpes simplex virus, either type I or II, may similarly manifest as frequent, persistent, or severely ulcerating disease. If extensive areas of the perineum are involved or the lesions are atypical, definitive laboratory diagnosis will ensure effective treatment. Severe manifestations of herpes may require maintenance therapy with oral acyclovir for adequate suppression. Coexistent herpes simplex and Candi-
Figure 2. Since epithelial injury clearly compromises the
host defense, it is not surprising that genital ulcer disease heightens the risk of HIV infection and transmission. Nor is it surprising that HIV's tropism for lymphocytes and macrophages contributes to this correlation. In genital
da infections are relatively common, and bacterial superinfection may also be present. Apart from their morbidity, genital ulcer diseases such as herpes, syphilis, and chancroid have been repeatedly correlated with enhanced transmission of HN. In either sex, gross or microscopic bleeding and skin or mucosal injury increase the possibility of direct viral exposure. In addition, the body responds to genital ulcer disease with mobilization of activated lymphocytes and macrophages to the site of infection. These activated cells are highly vulnerable to HIV. Thus, a genital ulcer in an HIVinfected patient can serve as a source of infection for the patient's partner, and in an uninfected person. as a portal of entry for the virus (Figure 2). Both primary and secondary syphilis have increased dramatically in the United States in re-
ulcer disease due to herpes simplex virus infection, for example, both lymphocytes and macrophages are mobilized to combat HSV (left). With subsequent exposure to HIV, the effector cells recruited against HSV become targets of opportunity for HIV infection (right). Hospital Practice March 15, 1992
157
Downloaded by [La Trobe University] at 05:45 19 June 2016
general population and in heterosexual transmission of HIV, It has been hypothesized that the IUD string serves as a wick for ascending infection and that the inflamed endometrium provides a handy reservoir of leukocytes and lymphocytes for HIV to infect. The string may also be a source of penile abrasion and subsequent female-to-male HIV transmission.
Figure 3. From 1980 to 1990, the annual number of infants in the United States with congenital syphilis rose from less than 200 to more than 2,800. In part, the 1989 and 1990 values reflect an expanded CDC case definition. Even so, congenital syphilis tends to be underreported because it may not be diagnosed in liveborn infants or leads to spontaneous abortion or stillbirth.
cent years, and coinfection with HIV is common. In a survey of patients attending STD clinics in Baltimore, serologic evidence of prior syphilis was far more common in HIV-positive patients than in uninfected patients, even when analysis was limited to heterosexual men and women. As might be anticipated, the rising incidence of syphilis infections in sexually active adults has been accompanied by an equally rapid and alarming rise in the rate of congenital syphilis (Figure 3). Patients coinfected with HIV and Treponema are at particular risk for several reasons. First, it appears that treatment failures with benzathine penicillin G are not uncommon in this group. Second, HIV is known to increase susceptibity to neurosyphilis, which may be difficult to differentiate clinically from HIV dementia. If neurosyphilis cannot be ruled out in a patient 158
Hospital Practice March 15. 1992
who is coinfected with HIV, many physicians recommend spinal taps to attempt to confirm the diagnosis and intravenous administration of penicillin. Pelvic inflammatory disease is more likely to be refractory to antibiotic therapy and to require hospitalization in women who are HIV infected than in those who are not. Studies from anumber of cities hit hard by the AIDS epidemic indicate that PID and AIDS frequently coexist. The onset ofPID in HIV-infected women may be very subtle. The patient may experience a subacute infection with only nonspecific abdominal pain or no pain at all. Cervical motion tenderness or other signs considered classic for PID may be entirely absent. Still unresolved is the extent to which intrauterine devices may be a factor in both the high rate of PID in the
Human papillomavirus is the oncogenic agent thought to be responsible for most cervical carcinomas and is therefore the most potentially dangerous of the genital diseases common in HIV-infected women. Reports of frequently abnormal Pap smears in this group--often five to 10 times the expected ratedeserve particular attention. Increased cervical dysplasia and unusually aggressive HPV disease have been observed in other immunosuppressed populations. such as renal transplant recipients and cancer patients on chemotherapy. HIV-infected patients now have similar findings. Increased HPV infection rates, along with increased incidences of anal neoplasias, have been reported in men coinfected with Hiv. In women, HPV infections are multifocal and difficult to eradicate. Of particular concern in women is HPV-related cervical neoplasia, which may rapidly progre:;;:;; tomvasive cervical carcinoma. Nearly all care providers for HIV-infected women report significantly increased rates of abnormal Pap smears. Currently, there are no prospective data on HPV disease in HIV-infected women. Such studies are desperately needed, as even such basic information as how often to perform Pap smears (conltnues)
H IV INFECTION
(conttnued)
in women co-infected with HPV and HIV is lacking.
Downloaded by [La Trobe University] at 05:45 19 June 2016
When HIV Seropositivity Is Suspected Referral for HIV counseling and testing should be considered when any of the following is present: persistent or recurrent vaginal candidiasis (after two treatment courses or more than two episodes within six months); recurrent genital herpes simplex (more than two episodes within six months); severe or coalescing lesions of genital herpes simplex or candidiasis; genital ulcer diseases such as syphilis, chancroid, or lymphogranuloma venereum; condyloma acuminatum recalcitrant to conventional therapy or involving multiple sites; Pap smear evidence of moderate to severe cervical dysplasia, carcinoma in situ, or invasive carcinoma; recurrent or persistent PID despite appropriate nonsurgical treatment (Table 2). In addition, we strongly support the official New York State policy of offering HIV counseling and testing to all pregnant women, regardless of their (or their care provider's) perception of the actual risk of infection. Whatever a woman's views on abortion, she is entitled to make an informed decision based on full knowledge of her circum-
stances and the degree of risk to her unborn child. A woman's decision to be tested should be made freely after extensive discussion of such issues as risk factors for HIV infection, coexisting conditions-in particular, other sexually transmitted diseases-and their treatment, the importance of safer sex practices, and reproductive choice. Counseling is important not only to provide informed consent but also to give the medical team a sense of how the patient might handle the information provided by the test. Would she be able to accept the news of a positive serology without sinking into severe depression? How does she think her family would react? Is she capable of complying with a complex medical regimen, including daily antiviral medication and frequent follow-up visits for gynecologic examination and T-cell counts? Would she be willing to practice safer sex? The fact that a large percentage of women (and men) never return for the results of their HIV test suggests that insufficient time is being devoted to counseling at many test sites. Not only does the physician or other care provider need to be alert to possible gynecologic manifestations of HIV and ready to recommend testing if appropriate, he or she must also remain in touch with the support
Table 2. When to Refer for HIV Counseling and Testing Persistent, recurrent, or unusually severe vaginal candidiasis Recurrent or unusually severe genital herpes simplex
networks available to HIV-tnfected patients in the community. Knowing where to refer a woman who needs additional help with a specific issue (e.g., notifying a sex partner, kicking a drug habit, finding child care, choosing an appropriate contraceptive) may be as important in the long run as the more technical aspects of patient care.
Gynecologic Management Until more information is available on the natural history ofHIV infection in women, routine gynecologic care should include a pelvic examination every six months, including syphilis serology, Pap smear, gonorrhea and Chlamydia assays, and wet mount and KOH preparation of any cervical or vaginal discharge (Table 3). Women known to be HIV infected should be followed by a primary care provider who can monitor CD4+ counts and recommend intervention when appropriate. This is particularly important now that early intervention in asymptomatic patients is recommended. Counseling should take place at the time of the initial pelvic examination, as discussed earlier. With respect to family planning, it should be pointed out that use of a latex condom containing nonoxynol-9-the best method, short of abstinence, of preventing heterosexual HIV transmission-is regarded by some as providing inadequate protection against pregnancy. Therefore, a backup form of contraception should be used.
Genital ulcer disease (e.g., syphilis, chancroid) Recalcitrant or multi site condyloma acuminatum Pap smear evidence of moderate-to-severe cervical dysplasia, carcinoma in situ, or squamous cell carcinoma Persistent or recurrent PID Pregnancy-regardless of the provider's perception of risk
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Hospital Practice March 15. 1992
Treatment ofHIV-Related Gynecologic Conditions Recurrent candidiasis. Patients should have an antifungal vaginal cream or suppository, such as clotrimazole or nystatin,
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available for self-administration. If candidiasis recurs or is not responsive to topical therapy. therapy with ketoconazole or another oral imidazole may be initiated. Concomitant antacids should be avoided if possible to optimize gastric absorption. Once the patient has been asymptomatic for two weeks, maintenance therapy may be instituted: 100 to 200 mg daily of oral ketoconazole for five days each month at onset of menses. Liver function tests must be monitored closely during the treatment period. Transaminases three times normal require evaluation for discontinuance of ketoconazole therapy. Ulcerative candidiasis may require higher initial doses ofketoconazole, up to 800 mgtday. Ifketoconazole is not fully effective or is contraindicated, oral fluconazole may be substituted at a starting dose of 200 mgtday, with a maintenance dose of 100 mgtday for five days per month. Liver function tests should be monitored as for ketoconazole. Recurrent herpes simplex. After confirmation by viral culture. therapy with oral acyclovir (400 mg four or five Urnes a day) should be instituted. This may be supplemented with acyclovir 5% ointment, applied at three-hour intervals. The oral agent may be maintained indefinitely at a lower dosage of 200 mg one or two times daily; however. renal function must be monitored closely and the dosing interval extended for renal insufficiency. Occasionally. resistant strains of herpes simplex will develop in a patient on long-term acyclovir therapy. Should this occur, a course of intravenous foscarnet (0.60 mgtkg. at eight-hour intervals, with reduced dosage in patients with renal impairment) has been reported to be effective.
Condyloma acuminatum. Trichloroacetic acid (95%) is the treatment of choice for vulvar and perianal lesions smaller than 2 em. Topical 5-fluorouracil is also available for cervical or vaginal lesions. Persistent or recurrent condylomata should be treated with cryosurgery, surgical excision, or C0 2 laser. Because viable HPV particles have been demonstrated in the smoke plume accompanying C0 2 laser therapy. vacuum suction is of utmost importance. Vaginal flat condylomata, especially recurrent lesions, may be treated with 5-FU cream, which is applied with a vaginal applicator in dosages ranging from once weekly (for 10 weeks) to daily (for five days unless local irritation prevents further application). Concomitant use of a petroleum-based cream may help prevent caustic irritation of the surrounding perineal area. Women should be advised that there may be a risk of increased HIV transmission after any biopsy or treatment procedures that result in open wounds. Abnormal Pap smear. If atypia persists after treatment for a specified inflammation. the patient should be referred for colposcopy and endocervical curettage and biopsy of any visible lesions. Cervical intraepithelial neoplasias or squamous intraepithelial lesions (all grades) should be colposcoped as soon as is possible. Treatment of lesions should not be altered because of HIV serostatus. If the biopsy is negative. colposcopy should be repeated in three months. Persistent ulcerative lesions. To ensure correct diagnosis and treatment. the following tests should be performed: syphilis serology and, if possible. dark-
Table 3. Gynecologic Management of HIVInfected Patients 1. Pelvic exam every 6 months (Pap smear, syphilis serology, gonorrhea/Chlamydia assay, wet mount, KOH prep) Further testing or treatment as appropriate
2. T-lymphocyte subsets > 500 Repeat at 3 to 6 months
ISSN: 2154-8331 (Print) 2377-1003 (Online) Journal homepage: http://www.tandfonline.com/loi/ihop20
HIV Infection in Women: Presentations and Protocols Machelle H. Allen & Carola Marte To cite this article: Machelle H. Allen & Carola Marte (1992) HIV Infection in Women: Presentations and Protocols, Hospital Practice, 27:3, 155-162, DOI: 10.1080/21548331.1992.11705386 To link to this article: http://dx.doi.org/10.1080/21548331.1992.11705386
Published online: 17 May 2016.
Submit your article to this journal
View related articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ihop20 Download by: [La Trobe University]
Date: 19 June 2016, At: 05:45
HIV Infection in Women: Presentations and Protocols
Downloaded by [La Trobe University] at 05:45 19 June 2016
MACHELLE H. ALLEN and CAROLA MARTE New York University and Beth Israel Medical Center, New York
In the 11th year of the AIDS epidemic in the United States, it is clear that more and more women are becoming infected with Hiv. Genital infections by other pathogens may be the first clue to the diagnosis. With progressive immunodeficiency, such infections may follow a protracted course or become recurrent, often requiring maintenance therapy.
HIV infection is becoming increasingly common in women throughout the United States. Yet there is generally little awareness of the problem in the medical community, and hardly any data on the primary gynecologic care of infected patients. Genital infections that resist standard therapy may be the first indication of immunodeficiency and are important to diagnose. In addition. because of the more aggressive and protracted course such conditions often take. HIV-infected women require heightened gynecologic surveillance, including more frequent Papanicolaou smears and liberal use of colposcopy.
Epidemiology As of December 1991, AIDS cases in the United States reported to the Centers for Disease Control totaled 202,921. Of these. 21,225 were in women and adolescent girls. Although this represents only a small percentage of all AIDS cases reported since 1981, the proportion of female patients has steadily risen-from 7% before 1985 to 10% in 1988 and 12.8% in 1991. including pediatric cases (Figure 1). The increase in the percentage of AIDS cases in women persists even after accounting for the 1987 revision of the CDC case definition. In New York City, AIDS now represents the leading cause of
Dr. Allen is Instructor, Department of Obstetrics and Gynecology, New York University School of Medicine. Dr. Marte is Instructor, Department of Medicine, Beth Israel Medical Center and Mount Sinai School of Medicine, New York.
death among women aged 25 to 34. Although poor women of color are disproportionately represented, the problem is not confined to inner-city populations but has invaded all strata of U.S. society. Perhaps most worrisome is the high rate of new HIV infections among adolescent females; in reports from some urban areas, the rate now approaches that among adolescent males. Heterosexual contact is often the only known risk factor for women. In a five-year, multicenter followup study of seropositive blood donors, 43 (57%) of 76 women interviewed reported sexual contact with a male partner at risk for HIV infection; 27 (36%) had no identified risk. In addition to reconfirming the prominent role of heterosexual transmission, these data suggest that many women are unaware of the infection status of their male sexual partners. Given the current system of hierarchical exposure categories, it is also likely that a high percentage of women listed as intravenous drug users actually acquired HIV through heterosexual transmission rather than needle sharing. According to the current CDC classification, a single experience with intravenous drugs is sufficient to remove an HIV-positive woman from the "heterosexual contact" or "no identified risk" category and place her in the "IV drug use" category. Yet seroprevalence studies of pregnant women indicate that fewer than one third of those who had been IV drug users and are currently on methadone are HIV-positive, compared with approximately half of female crack users (who typically become infected through heterosexual contact). These and similar surveys suggest that the number of women exposed Hospital Practice March 15. 1992
155
Downloaded by [La Trobe University] at 05:45 19 June 2016
Figure 1. Among all persons with AIDS in the United States, female patients are a steadily increasing minority. Before 1985, women and adolescent girls accounted for 7% of cases, with the number of younger children and infants negligible. In 1988, the proportion of female cases was 10%. Last year, 12.8% of U.S. AIDS patients were female, including many pediatric cases.
to HIV through heterosexual contact has consistently been underreported-and will continue to be underreported until the classification system is changed. For some time, investigators have observed that the interval between symptomatic HIV infection and death is shorter in women than in men. In a cohort of 5,833 New York City patients studied by Richard Rothenberg and colleagues in 1987, for example, mean survival from AIDS diagnosis to death was 298 days for women, compared with 374 days for men. In addition, although the clinical features of HIV-related Pneumocystis cartnil pneumonia are the same in Table 1. Common Gynecologic Conditions in HIV-Infected Women Candida vaginitis Genital herpes Syphilis Pelvic inflammatory disease Human papillomavirus disease
156
Hospital Practice March 15. 1992
both sexes. respiratory failure occurs more often in women and is more likely to be fatal. Reviewing deaths from AIDS in the United States between 1981 and 1988, Lisa M. Koonin and associates at the CDC and the New York City and New Jersey departments of health found that 16 of 20 pregnant women with AIDS had died of PCP. The mean interval between AIDS diagnosis and death was 113 days, with a median of 7 4 days. Ten of the women had used intravenous drugs, and the mean interval between AIDS diagnosis and death from PCP was only 59 days in these patients. The extent to which sex differences in survival may represent inherent host differences between men and women is unclear. It is probable, however, that external (and therefore modifiable) factors are at least partly responsible for the gender gap. These would include delayed diagnosis due to a low index of suspicion for HIV infection in women and use of diagnostic criteria that are based on
the gay white male population. Poor access to gynecologic (or general) health care and to research trials probably also contribute to lower survival in HIVinfected women. As community awareness of heterosexual HIV transmission increases and demands for counseling and testing are intensified, the number of asymptomatic women identified as seropositive will undoubtedly climb. The burden will thus be on physicians or other care providers to identify and treat gynecologic and other manifestations of HIV infection and to provide assistance with the complex medical, psychosocial, and ethical issues involved. At present, however, health care providers have scant resources on which to draw. Textbooks and manuals of care have not yet incorporated HIV-related gynecology, and little research has been devoted to the gynecologic problems and overall management ofHIV-infected women. For these reasons, the Ambulatory Care Division and the Department of Obstetrics and Gynecology of Bellevue Hospital Center recently collaborated in developing a series of management protocols summarized in this article. A brief review of HIVrelated gynecologic conditions most frequently encountered by primary care providers serves to put these protocols in context.
HIV-Related Gynecologic Conditions Candida vaginitis, genital herpes, syphilis, pelvic inflammatory disease. and human papillomavirus disease (condyloma acuminatum, cervical dysplasia, and cervical carcinoma) are of particular concern in the management ofHIV-infected women (Table 1). All occur with greater frequency and severity in this population,
Downloaded by [La Trobe University] at 05:45 19 June 2016
and all may demonstrate atypical manifestations, including lack of response to standard therapies. Nonsyphilitic genital ulcerschancroid and lymphogranuloma venereum-are also more common in women who are HIV infected than in women in general. However, the incidence of these disorders in the United States remains low compared with rates in developing countries. Cytomegalovirus is another pathogen that has been identified as a cause of both cervical and endometrial inflammation in HIV-infected women. Candida vaginitis. Although still widely neglected, this is the most common gynecologic disorder in HIV-infected women. In those who are severely immunocompromised, it may present as painful coalescing ulcerations requiring aggressive local treatment, followed by maintenance therapy with topical agents or an
oral imidazole such as ketoconazole or fluconazole. In women who are not otherwise symptomatic-including those in whom HIV infection has not yet been diagnosed-the presence of persistent or frequently recurrent vaginal candidiasis may be an early clue of immune suppression (sometimes earlier than oral thrush). Cases refractory to topical treatment frequently herald severe immune suppression and a rapid progression to AIDS. Herpes simplex virus, either type I or II, may similarly manifest as frequent, persistent, or severely ulcerating disease. If extensive areas of the perineum are involved or the lesions are atypical, definitive laboratory diagnosis will ensure effective treatment. Severe manifestations of herpes may require maintenance therapy with oral acyclovir for adequate suppression. Coexistent herpes simplex and Candi-
Figure 2. Since epithelial injury clearly compromises the
host defense, it is not surprising that genital ulcer disease heightens the risk of HIV infection and transmission. Nor is it surprising that HIV's tropism for lymphocytes and macrophages contributes to this correlation. In genital
da infections are relatively common, and bacterial superinfection may also be present. Apart from their morbidity, genital ulcer diseases such as herpes, syphilis, and chancroid have been repeatedly correlated with enhanced transmission of HN. In either sex, gross or microscopic bleeding and skin or mucosal injury increase the possibility of direct viral exposure. In addition, the body responds to genital ulcer disease with mobilization of activated lymphocytes and macrophages to the site of infection. These activated cells are highly vulnerable to HIV. Thus, a genital ulcer in an HIVinfected patient can serve as a source of infection for the patient's partner, and in an uninfected person. as a portal of entry for the virus (Figure 2). Both primary and secondary syphilis have increased dramatically in the United States in re-
ulcer disease due to herpes simplex virus infection, for example, both lymphocytes and macrophages are mobilized to combat HSV (left). With subsequent exposure to HIV, the effector cells recruited against HSV become targets of opportunity for HIV infection (right). Hospital Practice March 15, 1992
157
Downloaded by [La Trobe University] at 05:45 19 June 2016
general population and in heterosexual transmission of HIV, It has been hypothesized that the IUD string serves as a wick for ascending infection and that the inflamed endometrium provides a handy reservoir of leukocytes and lymphocytes for HIV to infect. The string may also be a source of penile abrasion and subsequent female-to-male HIV transmission.
Figure 3. From 1980 to 1990, the annual number of infants in the United States with congenital syphilis rose from less than 200 to more than 2,800. In part, the 1989 and 1990 values reflect an expanded CDC case definition. Even so, congenital syphilis tends to be underreported because it may not be diagnosed in liveborn infants or leads to spontaneous abortion or stillbirth.
cent years, and coinfection with HIV is common. In a survey of patients attending STD clinics in Baltimore, serologic evidence of prior syphilis was far more common in HIV-positive patients than in uninfected patients, even when analysis was limited to heterosexual men and women. As might be anticipated, the rising incidence of syphilis infections in sexually active adults has been accompanied by an equally rapid and alarming rise in the rate of congenital syphilis (Figure 3). Patients coinfected with HIV and Treponema are at particular risk for several reasons. First, it appears that treatment failures with benzathine penicillin G are not uncommon in this group. Second, HIV is known to increase susceptibity to neurosyphilis, which may be difficult to differentiate clinically from HIV dementia. If neurosyphilis cannot be ruled out in a patient 158
Hospital Practice March 15. 1992
who is coinfected with HIV, many physicians recommend spinal taps to attempt to confirm the diagnosis and intravenous administration of penicillin. Pelvic inflammatory disease is more likely to be refractory to antibiotic therapy and to require hospitalization in women who are HIV infected than in those who are not. Studies from anumber of cities hit hard by the AIDS epidemic indicate that PID and AIDS frequently coexist. The onset ofPID in HIV-infected women may be very subtle. The patient may experience a subacute infection with only nonspecific abdominal pain or no pain at all. Cervical motion tenderness or other signs considered classic for PID may be entirely absent. Still unresolved is the extent to which intrauterine devices may be a factor in both the high rate of PID in the
Human papillomavirus is the oncogenic agent thought to be responsible for most cervical carcinomas and is therefore the most potentially dangerous of the genital diseases common in HIV-infected women. Reports of frequently abnormal Pap smears in this group--often five to 10 times the expected ratedeserve particular attention. Increased cervical dysplasia and unusually aggressive HPV disease have been observed in other immunosuppressed populations. such as renal transplant recipients and cancer patients on chemotherapy. HIV-infected patients now have similar findings. Increased HPV infection rates, along with increased incidences of anal neoplasias, have been reported in men coinfected with Hiv. In women, HPV infections are multifocal and difficult to eradicate. Of particular concern in women is HPV-related cervical neoplasia, which may rapidly progre:;;:;; tomvasive cervical carcinoma. Nearly all care providers for HIV-infected women report significantly increased rates of abnormal Pap smears. Currently, there are no prospective data on HPV disease in HIV-infected women. Such studies are desperately needed, as even such basic information as how often to perform Pap smears (conltnues)
H IV INFECTION
(conttnued)
in women co-infected with HPV and HIV is lacking.
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When HIV Seropositivity Is Suspected Referral for HIV counseling and testing should be considered when any of the following is present: persistent or recurrent vaginal candidiasis (after two treatment courses or more than two episodes within six months); recurrent genital herpes simplex (more than two episodes within six months); severe or coalescing lesions of genital herpes simplex or candidiasis; genital ulcer diseases such as syphilis, chancroid, or lymphogranuloma venereum; condyloma acuminatum recalcitrant to conventional therapy or involving multiple sites; Pap smear evidence of moderate to severe cervical dysplasia, carcinoma in situ, or invasive carcinoma; recurrent or persistent PID despite appropriate nonsurgical treatment (Table 2). In addition, we strongly support the official New York State policy of offering HIV counseling and testing to all pregnant women, regardless of their (or their care provider's) perception of the actual risk of infection. Whatever a woman's views on abortion, she is entitled to make an informed decision based on full knowledge of her circum-
stances and the degree of risk to her unborn child. A woman's decision to be tested should be made freely after extensive discussion of such issues as risk factors for HIV infection, coexisting conditions-in particular, other sexually transmitted diseases-and their treatment, the importance of safer sex practices, and reproductive choice. Counseling is important not only to provide informed consent but also to give the medical team a sense of how the patient might handle the information provided by the test. Would she be able to accept the news of a positive serology without sinking into severe depression? How does she think her family would react? Is she capable of complying with a complex medical regimen, including daily antiviral medication and frequent follow-up visits for gynecologic examination and T-cell counts? Would she be willing to practice safer sex? The fact that a large percentage of women (and men) never return for the results of their HIV test suggests that insufficient time is being devoted to counseling at many test sites. Not only does the physician or other care provider need to be alert to possible gynecologic manifestations of HIV and ready to recommend testing if appropriate, he or she must also remain in touch with the support
Table 2. When to Refer for HIV Counseling and Testing Persistent, recurrent, or unusually severe vaginal candidiasis Recurrent or unusually severe genital herpes simplex
networks available to HIV-tnfected patients in the community. Knowing where to refer a woman who needs additional help with a specific issue (e.g., notifying a sex partner, kicking a drug habit, finding child care, choosing an appropriate contraceptive) may be as important in the long run as the more technical aspects of patient care.
Gynecologic Management Until more information is available on the natural history ofHIV infection in women, routine gynecologic care should include a pelvic examination every six months, including syphilis serology, Pap smear, gonorrhea and Chlamydia assays, and wet mount and KOH preparation of any cervical or vaginal discharge (Table 3). Women known to be HIV infected should be followed by a primary care provider who can monitor CD4+ counts and recommend intervention when appropriate. This is particularly important now that early intervention in asymptomatic patients is recommended. Counseling should take place at the time of the initial pelvic examination, as discussed earlier. With respect to family planning, it should be pointed out that use of a latex condom containing nonoxynol-9-the best method, short of abstinence, of preventing heterosexual HIV transmission-is regarded by some as providing inadequate protection against pregnancy. Therefore, a backup form of contraception should be used.
Genital ulcer disease (e.g., syphilis, chancroid) Recalcitrant or multi site condyloma acuminatum Pap smear evidence of moderate-to-severe cervical dysplasia, carcinoma in situ, or squamous cell carcinoma Persistent or recurrent PID Pregnancy-regardless of the provider's perception of risk
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Hospital Practice March 15. 1992
Treatment ofHIV-Related Gynecologic Conditions Recurrent candidiasis. Patients should have an antifungal vaginal cream or suppository, such as clotrimazole or nystatin,
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available for self-administration. If candidiasis recurs or is not responsive to topical therapy. therapy with ketoconazole or another oral imidazole may be initiated. Concomitant antacids should be avoided if possible to optimize gastric absorption. Once the patient has been asymptomatic for two weeks, maintenance therapy may be instituted: 100 to 200 mg daily of oral ketoconazole for five days each month at onset of menses. Liver function tests must be monitored closely during the treatment period. Transaminases three times normal require evaluation for discontinuance of ketoconazole therapy. Ulcerative candidiasis may require higher initial doses ofketoconazole, up to 800 mgtday. Ifketoconazole is not fully effective or is contraindicated, oral fluconazole may be substituted at a starting dose of 200 mgtday, with a maintenance dose of 100 mgtday for five days per month. Liver function tests should be monitored as for ketoconazole. Recurrent herpes simplex. After confirmation by viral culture. therapy with oral acyclovir (400 mg four or five Urnes a day) should be instituted. This may be supplemented with acyclovir 5% ointment, applied at three-hour intervals. The oral agent may be maintained indefinitely at a lower dosage of 200 mg one or two times daily; however. renal function must be monitored closely and the dosing interval extended for renal insufficiency. Occasionally. resistant strains of herpes simplex will develop in a patient on long-term acyclovir therapy. Should this occur, a course of intravenous foscarnet (0.60 mgtkg. at eight-hour intervals, with reduced dosage in patients with renal impairment) has been reported to be effective.
Condyloma acuminatum. Trichloroacetic acid (95%) is the treatment of choice for vulvar and perianal lesions smaller than 2 em. Topical 5-fluorouracil is also available for cervical or vaginal lesions. Persistent or recurrent condylomata should be treated with cryosurgery, surgical excision, or C0 2 laser. Because viable HPV particles have been demonstrated in the smoke plume accompanying C0 2 laser therapy. vacuum suction is of utmost importance. Vaginal flat condylomata, especially recurrent lesions, may be treated with 5-FU cream, which is applied with a vaginal applicator in dosages ranging from once weekly (for 10 weeks) to daily (for five days unless local irritation prevents further application). Concomitant use of a petroleum-based cream may help prevent caustic irritation of the surrounding perineal area. Women should be advised that there may be a risk of increased HIV transmission after any biopsy or treatment procedures that result in open wounds. Abnormal Pap smear. If atypia persists after treatment for a specified inflammation. the patient should be referred for colposcopy and endocervical curettage and biopsy of any visible lesions. Cervical intraepithelial neoplasias or squamous intraepithelial lesions (all grades) should be colposcoped as soon as is possible. Treatment of lesions should not be altered because of HIV serostatus. If the biopsy is negative. colposcopy should be repeated in three months. Persistent ulcerative lesions. To ensure correct diagnosis and treatment. the following tests should be performed: syphilis serology and, if possible. dark-
Table 3. Gynecologic Management of HIVInfected Patients 1. Pelvic exam every 6 months (Pap smear, syphilis serology, gonorrhea/Chlamydia assay, wet mount, KOH prep) Further testing or treatment as appropriate
2. T-lymphocyte subsets > 500 Repeat at 3 to 6 months
