Bulletin of Experimental Treatments for AIDS, No. 26; September 1995
Leslie Hanna, Associate Editor of BETA.

Vaginitis may be caused by Candida (yeast), bacterial overgrowth (bacterial vaginosis), Trichomonas vaginalis (a protozoan, often sexually transmitted), atrophy (atrophic vaginitis, caused by lack of estrogen in tissues and usually following menopause) and herpes simplex virus (HSV). The cause of vaginitis cannot be determined on the basis of symptoms or physical examination alone. Usually, diagnosis involves examining a specimen of vaginal fluid under a microscope. Since various illnesses can cause symptoms of vaginitis, and mistreatment can cause new, secondary problems, accurate diagnosis is vital. For example, atrophic vaginitis, urethritis or sexually transmitted diseases (STDs), if mistakenly diagnosed and treated as vaginal candidiasis, can cause genital ulcerations, sores and progression of STDs.

Treatment of vaginitis in HIV positive women is generally similar to treatment in HIV negative women. Because pathogens in HIV positive women may disseminate more rapidly throughout the pelvic region, treatment should be initiated promptly and aggressively. Vaginal pathogens also may trigger other complications such as increased herpes simplex outbreaks or recurrences of genital warts. University of California at San Francisco researchers Abner Korn, MD, and Daniel Landers, MD, recently published an article in which they tentatively push the boundaries of standard treatment for HIV positive women, recommending "careful examination for and treatment of symptomatic and asymptomatic [emphasis added] vaginal infections in women with HIV infection." Their specific suggestions are discussed below, in the context of individual infections.

Three common conditions characterized by vaginitis are (vaginal) candidiasis, bacterial vaginosis and trichomoniasis. Neither candidiasis nor bacterial vaginosis is usually sexually transmitted or acquired. However, because they are commonly found in women undergoing STD evaluation, they are included in the guidelines on STD treatment published by the Centers for Disease Control and Prevention (CDC), the U.S. government agency that tracks disease occurrences and develops public health policies.

Ongoing research continues to develop a greater understanding of the complexity of the vaginal environment. Researchers and clinicians increasingly view the vagina as a delicate ecosystem in which many factors (normal bacteria, pH [acid-base concentration], infections) interact, at times predisposing a woman to specific complications. Currently researchers are studying a broad range of common genital tract infections including vaginitis in women with HIV, to better understand both the pathology of and relationships between different infections. Some preliminary data on these issues are presented in this article.

Another current research topic is the relationship of HIV infection to common gynecologic complaints such as vaginitis. In general, since vaginitis and other genital tract infections are seen among HIV negative as well as HIV positive women, the impact of HIV infection on incidence and pathogenesis has been difficult to determine. Of the types of vaginitis discussed here, only vaginal candidiasis thus far has been demonstrated to have an independent association with HIV infection.

Ongoing studies like the HIV Epidemiology Research Study (HERS) and the Women's Interagency HIV Study (WIHS), multicenter prospective studies that include both HIV positive women and HIV negative women at high risk for HIV infection (controls), should provide much-needed information. An improved understanding of the relationships between common gynecologic disorders and HIV infection has significant implications for health care. If HIV is causally associated with any genital or pelvic disease, screening recommendations can be altered for HIV positive women, and disease outcomes and quality of life improved.

Vaginal Candidiasis

Vaginal candidiasis may occur at any stage of HIV disease. This fungal infection presents a unique challenge in managing HIV disease for women. Candidiasis is the most common fungal infection in people with HIV/AIDS, and Candida, the yeast-like fungus that causes the infection, is the most common opportunistic pathogen. (For an overview of fungal infections relevant to all HIV-infected people, see the feature article in the June 1995 issue of BETA.)

Candida and other yeasts are normally present in 10-20% of women. Generally caused by the fungus C. albicans, vaginal candidiasis also may be caused by other Candida species. Nonspecific symptoms commonly include vulvar itching and a white vaginal discharge. Other possible symptoms include vaginal soreness, vulvar burning, painful sexual intercourse and difficult or painful urination. In severe cases, vulvar ulceration may occur.

Diagnosis is based on clinical observations and laboratory tests. Since yeast may be a normal part of a woman's vaginal flora, identification of Candida alone does not warrant treatment. A positive diagnosis is made when a potassium hydroxide preparation shows yeast or when a Pap smear or culture is positive for a yeast species, in combination with symptoms of vaginitis. In their article in the August 1995 Journal of Acquired Immunodeficiency Syndromes and Human Retrovirology, however, Korn and Landers suggest rethinking this standard guideline for application in HIV positive women.

Korn and Landers suggest that clinicians consider treating HIV positive women with asymptomatic vaginal candidiasis, when a Pap smear is positive and inflammation is detected on close examination -- particularly if the inflammation is sufficient to cause mucosal breaks -- even if the patient is not aware of any symptoms of vaginitis. Dr. Korn told BETA that this suggestion arose primarily in relation to concerns about the potential for disease transmission that exists in the clinical scenario just described. First, the inflammatory cells may lead to increased shedding of HIV. Second, the patient herself is susceptible to exposure to more or new HIV as well as to numerous other pathogens. There also are associations between Candida-related vaginal inflammation and bacterial vaginosis. Still, Korn agrees that the risk/benefit ratio does not support treating based on Pap smears positive for yeast alone, in the absence of detectable vaginal inflammation and/or other pathogens.

Treatment Options for Candidiasis

Several topical treatments for vaginal candidiasis are available for intravaginal use, in cream or suppository (tablet or "troche") form. Topical "azole" drugs often relieve symptoms and effect negative cultures in women who complete the full course of therapy. Topical agents usually do not cause side effects, although mild local irritation may occur.

Initial treatment for vaginal candidiasis is usually a full 7-day course of therapy with regular-strength antifungal intravaginal creams or suppositories. These treatments are available both over-the-counter and by prescription. Usually, one night-time application is used for 7 consecutive nights. Since the topical agents are essentially equally effective, individual patient preferences as to form (cream, troche) as well as insurance company reimbursement policies may be used to guide physician recommendations. Miconazole (Monistat) and clotrimazole (Gyne-Lotrimin) are available over-the-counter. Some Medicaid and insurance plans will not reimburse these treatments. Out-of-pocket expenses may be avoided by using the prescription drugs Femstat (butoconazole) or Terazol (terconazole). Monistat is also available by prescription as Monistat DS; this regimen will treat in 3 days by use of 1 double-strength suppository application for 3 consecutive nights.

Another option would be a short course of an oral antifungal agent. The U.S. Food and Drug Administration (FDA) has approved a single dose of 150-200 mg fluconazole (Diflucan) for treatment of vaginal candidiasis. Another treatment option is 200 mg oral itraconazole (Sporanox) taken once daily for 3 days, although this indication is not FDA-approved. However, clinicians such as Lisa Bardaro, MD, of San Francisco, CA, increasingly regard this as aggressive first-line treatment, and prefer first to try an intravaginal agent such as Monistat DS, which cures in only 3 days.

Since vaginal candidiasis is not sexually transmitted, sex partners are not treated; however, Korn and Landers recommend considering partner treatment when the woman has symptomatic vaginal candidiasis. With regard to sexual activities during treatment, it is important to note that oil-based treatment creams and suppositories may weaken latex condoms and diaphragms. Creams used to treat vaginal candidiasis probably have a slightly greater proportion of oil ingredients than, e.g., the metronidazole gel (Metrogel) that may be used to treat bacterial vaginosis or trichomoniasis.

Follow-up to treatment is important. Vaginal candidiasis may fail to respond to topical treatment with creams or suppositories. Treatment failures should be evaluated individually, and may require aggressive treatment with systemic antifungal agents. It is important to distinguish between a true treatment failure, which may be defined as the persistence of symptoms in spite of completion of a 7-day course of therapy, and a recurrence, which may be defined as infection that recurs within 8 weeks following treatment. Recurrences should be confirmed by culture.

Recurrent Vaginal Candidiasis

HIV infection, diabetes mellitus, pregnancy and the use of broad-spectrum antibiotics or oral contraceptives are all independent risk factors for recurrent infection. HIV positive women are at increased risk for acute, recurrent and chronic vaginal candidiasis. One definition for recurrent vaginal candidiasis in immunosuppressed women is 2 or more full courses of treatment during a 6-month interval.

Systemic antifungal treatment with oral azole drugs may be needed to treat chronic, recurrent or refractory cases of vaginal candidiasis. Oral agents may cause nausea, abdominal pain and headache, and sometimes elevated liver enzymes. Liver function tests should be performed to establish baseline values before beginning prolonged therapy. Oral azoles may significantly interact with other drugs, including terfenadine (Seldane), rifampin (Rifadin), astemizole (Hismanal), phenytoin (Dilantin), cyclosporin A, coumarin-like agents or oral hypoglycemic agents. Pregnant women, in whom vaginal candidiasis is common, should avoid the use of oral azoles whenever possible, since there are insufficient data to rule out pregnancy-related complications. Note: for severe candidal infection, e.g., esophageal candidiasis, oral azoles are valid options for pregnant women. Abner Korn, MD, has successfully treated candidiasis that fails the standard first-line clotrimazole or miconazole intrava! ginal cream therapy with boric aci d suppositories, which are widely available, inexpensive and effective in resistant cases. Boric acid suppositories are used in 600 mg doses twice daily for 2 weeks.

For complicated vaginal candidiasis, Risa Denenberg, FNP, author of The Gynecological Care Manual for HIV Positive Women, recommends trying ketoconazole 200 mg/day for 14 days or fluconazole 100 mg/day for 7-14 days. To reduce the frequency of episodes of severe, recurrent vaginal candidiasis, the CDC currently recommends ketoconazole 100 mg daily for 6 months. For better absorption in the acid environment of the stomach, oral ketoconazole should be taken with orange juice or a cola beverage. Ketoconazole is often tried first because resistance develops less quickly than with fluconazole treatment, which may be reserved as a later option.

Other factors that may increase the general likelihood of vaginal candidiasis include chemical douches, vaginal ("feminine hygiene") sprays and tight, poorly ventilated clothing (pantyhose, nylon panties, tight pants and wet swimwear). Yeast infections in immunocompetent women often result from the introduction of fecal material into the vagina. Thus, healthcare practitioners should provide preventive information to their patients about hygiene. Other suggestions for preventing or minimizing candidiasis include daily ingestion of acidophilus yogurt and reduced dietary sugar.

Still other factors may contribute to imbalances of pH and/or flora in the vaginal environment, including poor nutrition, tampon use, sexual activity, stress and other infections. These imbalances cause epithelial cell susceptibility that contributes lead to tissue injury and vaginitis.

Clinical Trials for Candidiasis

Research is ongoing to determine better management and prevention strategies for candidiasis in HIV positive women. Two large studies currently underway through the Community Programs for Clinical Research on AIDS (CPCRA) research network are evaluating fluconazole as treatment and prophylaxis for candidiasis. Over 300 women are participating in CPCRA Women's Fungal Protocol 010, which compares fluconazole to placebo for preventing fungal infections in HIV positive women with fewer than 300 CD4 cells/mm3. Fluconazole is being evaluated for its ability to prevent primary and secondary mucosal candidiasis. The study, ongoing but closed to enrollment, is scheduled to conclude by the end of 1995. CPCRA 029 is evaluating fluconazole resistance in the same group of women participants (CPCRA 010).

Another ongoing open-label Phase I/II trial randomizes women to receive either 200 mg fluconazole a week or 100 mg daily as a treatment for vaginal candidiasis. Finally, a Phase I open-label trial randomizes women to receive either 200 mg weekly or 50 mg daily fluconazole as for prophylaxis. For more information about these and other clinical trials, call 1-800-TRIALS-A.

Treatment Issues

Recurrent vaginal candidiasis is the most frequent initial manifestation of HIV disease in women. Several studies emphasize that a history of recurrent or severe vaginal candidiasis often precedes a diagnosis of HIV infection or the development of symptoms of HIV disease. Research also has established that Candida infections occur in a hierarchical, usually progressive pattern in women with HIV; vaginal infection occurs at the relatively highest CD4 cell levels, oral infection at moderate levels and esophageal infection at the lowest levels (usually occurring when CD4 cell levels fall below 100 CD4 cells/mm3). Both site and severity of infection appear closely related to immune status at the time infection develops.

Chronic vaginal candidiasis that responds poorly to treatment is common in advanced disease; some studies link chronic refractory vaginal candidiasis to oral candidiasis and CD4 cell depletion. Another complication is persistent infection that fails to respond to drug treatment, caused by natural or acquired drug resistance on the part of the disease-causing organisms. Antifungal treatment and prophylaxis taken for various fungal infections potentially contribute to drug resistance and thus to vaginal candidiasis that resists standard treatments.

Both the failure of standard regimens to be completely effective and infection that becomes chronic provoke questions about different regimens to try as secondary prophylaxis. However, the emergence of fluconazole-resistant candidiasis may prove to be a stumbling block to the development of effective antifungal prophylaxis regimens.

Fluconazole-resistant candidiasis is infection that fails to respond to treatment with fluconazole, an oral systemic drug used to treat a broad spectrum of HIV-related fungal infections and possibly the most important antifungal treatment option for people with HIV. The incidence of fluconazole-resistant candidiasis is increasing in women with HIV, primarily in those who have been repeatedly treated with fluconazole. When Candida that proliferate in one site develop resistance or are naturally resistant, infection becomes extremely hard to clear. The potential loss of fluconazole as a treatment option for a person with HIV is of serious concern.

At the HIV Infection in Women Conference in Washington, DC, in February 1995, Judith Feinberg, MD, of Johns Hopkins University, said that her growing concern about resistance has caused her to "backtrack away from oral drugs." Although research continues into the use of oral systemic drugs like fluconazole and itraconazole for first-line treatment, she favors topical forms of first-line treatment for both vaginal and oral candidiasis. Feinberg stresses the reservation of oral therapy for intravaginal treatment failures.

Bacterial Vaginosis

Bacterial vaginosis is caused by an overgrowth of anaerobic bacteria, including Gardnerella vaginalis, which overtake the normal Lactobacillus bacteria population in the vagina. (Until recently "Gardnerella" was the term commonly used to designate this infection.) A condition rather than a true infection, bacterial vaginosis represents an alteration of the normal environment of the vagina. It is associated with sexual activity but not considered sexually transmitted. Although an abnormal vaginal discharge and a strong ("fishy") odor usually occur, an estimated 50% of women have no symptoms. If present, the odor tends to be most pronounced directly after intercourse.

Generally, only women with symptoms are treated. Vaginal metronidazole gel (Metrogel) is increasingly used as the first-line treatment; it is safe, effective and relatively inexpensive. Metronidazole gel is used twice daily for 5 days. Previously, the traditional standard regimen had been 500 mg oral metronidazole (Flagyl) taken twice daily for 7 days. Alcohol use is to be avoided throughout treatment and for 24 hours after the last dose, due to possible severe nausea and vomiting. Alcohol use is less likely to be problematic if metronidazole gel is used because there is less absorption of metronidazole in the blood, but may still present some risk of side effects. An alternative regimen is a single dose of 2 g oral metronidazole. Use of metronidazole gel also will preclude mild gastrointestinal side effects that sometimes arise through oral metronidazole use. Male sex partners with balanitis (inflammation of the glans penis) should be treated.

Korn and Landers recommend treatment of women with HIV and bacterial vaginosis that is asymptomatic, following careful examination. Risa Denenberg, FNP, also suggests treating immunosuppressed women with asymptomatic bacterial vaginosis, with respect to the potential for complications that may arise. For example, there are some indications that bacterial vaginosis may increase the risk of pelvic inflammatory disease (PID), which is much more difficult to treat in HIV positive women.

Pregnant women are not advised to take any form of metronidazole (intravaginal gel or oral) during the first trimester, due to theoretical concern about adverse effects on fetuses. However, treatment during pregnancy is important. There have been suggestions that bacterial vaginosis and trichomoniasis may be associated with complications of pregnancy such as premature rupture of membranes and pre-term delivery. (The STDs gonorrhea, chlamydia and group B streptococcal infection remain more strongly associated with premature rupture of membranes and other complications of pregnancy.) Clindamycin vaginal cream (Cleocin) may safely be used by women in their first trimester of pregnancy, but should be used "only if clearly needed," according to the FDA. FDA has assigned clindamycin vaginal cream to their pregnancy category B, meaning that studies done in rats and mice using relatively high levels of drug showed no evidence of harm to the fetus. (Note: According to the 1995 Physic! ian's Desk Reference, 11% of women who are successfully treated with clindamycin vaginal cream actually develop Candida-related vaginitis as a side effect.) Clindamycin vaginal cream may be used as an alternative treatment in nonpregnant women as well. Pregnant women are sometimes treated on a case-by-case basis with oral clindamycin or intravaginal metronidazole gel. (There are no absolute contraindications.)

Recurrence of bacterial vaginosis is common but there are no long-term maintenance treatments, nor specific recommendations for women with HIV.

Trichomoniasis

Trichomoniasis, often referred to as "trich" (pronounced "trick"), is caused by the single-celled protozoan Trichomonas vaginalis. Approximately 2-3 million persons in the U.S. are affected each year. Research suggests that trichomoniasis may facilitate HIV transmission; mucosal inflammation due to the infection may increase the amount of viral shedding. Women often develop a yellow-green, strong-smelling vaginal discharge, and vulvar itching and irritation. There may be discomfort during intercourse and urination.

Patients are always treated for trichomoniasis when the organism is detected, even if the patient is not particularly disturbed by or even aware of symptoms. The recommended treatment is 2 g oral metronidazole (Flagyl) in a single dose. An alternative is 500 mg metronidazole twice daily for 7 days. Sex partners should receive the same treatment. (Infection in men is often asymptomatic.) The CDC recommends avoiding sexual activity until treatment is completed and symptoms resolve. Again, persons taking this drug are advised to refrain from alcohol use.

The metronidazole regimen is highly effective. To avoid either pregnancy-related complications, clindamycin cream may be tried. Again, to avoid mild gastrointestinal side effects that may arise through metronidazole use, vaginal metronidazole gel may be tried.

Recent Research from the HIV Infection in Women Conference At the HIV Infection in Women Conference in Washington, DC, in February 1995, several researchers presented interim findings from studies of genital tract infections in women with HIV-related immunosuppression. The remainder of this article presents preliminary data which may be of interest relating to vaginal candidiasis, bacterial vaginosis and trichomoniasis.

Carol Brosgart, MD, from the University of California at San Francisco presented preliminary data on the prevalence of Candida and other genital tract infections in HIV positive women at the February conference. The women in this particular study were all participants in a primary study of screening methods (Pap smear vs colposcopy) for cervical intraepithelial neoplasia (CIN).

Data was collected from 66 HIV positive women. Baseline data reflects a history of genital tract infections, as reported by the women. There were 2 study visits, each of which included a physical exam, laboratory blood tests, tests for genital tract infections and additional tests as needed, such as biopsies. Interim data was collected as well during non-scheduled study visits from women who had some reason(s) to visit the clinic between visits.

The women were 51% African-American, 32% Caucasian, 11% Latina, 5% Native American and 1% Asian American. The median age was 35 and the median CD4 cell count was 401 cells/mm3. Risk factors for HIV acquisition were 54% injection drug use (IDU), 72% partners of injection drug users and 19% transfusion. (Some women had multiple risk factors for HIV acquisition.) Fifty-two percent (52%) reported more than 10 lifetime sex partners and 39% more than 25 lifetime sex partners.

The women were screened for vaginal candidiasis (VC), bacterial vaginosis (BV) and trichomoniasis (TV). (They also were screened for other genital tract infections -- gonococcal cervicitis, nongonococcal cervicitis, pelvic inflammatory disease, genital warts, genital herpes, syphilis and chlamydiasis -- not discussed in this article.)

Researchers preliminarily concluded that vaginal candidiasis, bacterial vaginosis and trichomoniasis were indeed common cervical/vaginal infections among women in the study. Development of infection(s) appears related to immunodeficiency, opportunistic infections and history of (prior) infection.

Susan Cu-Uvin, MD, presented data on prevalence of genital tract infections including vaginal candidiasis, bacterial vaginosis and trichomoniasis in HERS participants. By comparing data collected among HIV positive women to data from HIV negative women, researchers attempted to determine the impact of HIV infection on these infections. The median CD4 cell count of the 382 HIV positive women was 398 cells/mm3. The control group consisted of 273 HIV negative women.

The predominant type of genital tract infection seen was vaginitis. Vaginal candidiasis was associated with HIV infection after adjusting for age, current drug use, number of sexual partners, ever trading sex for money, condom use and antimicrobial use. Bacterial vaginosis and trichomoniasis occurred at similar rates in HIV positive and negative women, and were not associated with HIV infection.

These data suggest that vaginal candidiasis may be more frequent in HIV positive women, but that other lower genital tract infections occur at relatively similar rates in HIV positive and HIV negative women. (Note: IDU was independently associated with increased BV and TV.) Since many women with genital tract infections neither reported nor apparently detected symptoms or abnormal discharge, researchers emphasize the importance of regular gynecologic care.

Tedd Ellerbrock, MD, from the CDC also presented data on the prevalence of genital tract infections among HIV positive women. Participants in this study were recruited from STD, methadone and HIV clinics, interviewed and tested for yeast such as Candida albicans as well as bacterial vaginosis and trichomoniasis. A control group of HIV negative women was matched for age (median equal to 35 years), income and race. Since use of antibiotics and sexual exposure are both independently associated with vaginitis, researchers collected data on these 2 factors for extra, comparative information. During the past 3 months 39% of HIV positive and 19% of HIV negative women had used antibiotics; 77% and 59% of HIV positive and HIV negative women, respectively, had either not had sexual intercourse or always used condoms.

In this study, none of these infections were prevalent in either group. For example, 28% of HIV positive women and 20% of HIV negative women had yeast (such as Candida) on culture, a difference that was not statistically significant. Ellerbrock therefore agrees with CDC recommendations that clinicians continue to use the same screening procedures for HIV positive women as for HIV negative women. However, Ellerbrock added, more and better information is needed to ensure that these screening guidelines are appropriate for HIV positive women.

Sources

American Foundation for AIDS Research (AmFAR) AIDS/HIV Treatment Directory 7(4). January 10, 1995.

Brosgart CL and others. Genital tract infection and cervical disease in women with HIV infection: implications for screening. HIV Infection in Women Conference: the First National Scientific Meeting on HIV Infection in Adult and Adolescent Women. Washington, DC. February 22-24, 1995. FC1-175.

Cu-Uvin S. Prevalence of genital tract infection in HIV seropositive women. HIV Infection in Women Conference: the First National Scientific Meeting on HIV Infection in Adult and Adolescent Women. Washington, DC. February 22-24, 1995. FC1-178.

Denenberg R. Gynecological Care Manual for HIV Positive Women. Essential Medical Information Systems, Inc., Durant, OK. 1993.

Diseases characterized by vaginal discharge. Morbidity and Mortality Weekly Report 42(RR-14): 67-75. September 24, 1993.

Ellerbrock T. Genital tract infections in HIV-infected women. HIV Infection in Women Conference: the First National Scientific Meeting on HIV Infection in Adult and Adolescent Women. Washington, DC. February 22-24, 1995. FC1-180.

Feinberg J. Treatment and prophylaxis of opportunistic infections: systemic fungal infections. HIV Infection in Women Conference: the First National Scientific Meeting on HIV Infection in Adult and Adolescent Women. Washington, DC. February 22-24, 1995. WC2-41.

Iman N and others. Hierarchical pattern of mucosal candida infections in HIV-seropositive women. The American Journal of Medicine 89(2): 142-146. August 1990.

Korn AP. Personal communication. August 17, 1995.

Korn AP and Landers DV. Gynecologic disease in women infected with human immunodeficiency virus type 1. Journal of Acquired Immunodeficiency Syndromes and Human Retrovirology 9(4): 361-370. August 1, 1995.

McCarthy KH and Norman SG. Gynecological problems in women infected with the human immunodeficiency virus. from HIV Infection in Women. Johnson and Johnstone, eds. Churchill Livingstone. 1993.

1993 Revised Classification System for HIV Infection and Expanded Surveillance Case Definition for AIDS Among Adolescents and Adults. Morbidity and Mortality Weekly Report 41(RR-17). December 18, 1992.

[sidebar] Azoles The "azoles" are a group of drugs that are used for a wide range of fungal infections. There are 2 classes of azole drugs, the imidazoles and the triazoles. The imidazole class is the original class, and includes clotrimazole (Lotrimin, Mycelex), miconazole (Monistat) and ketoconazole (Nizoral). The newer class of triazoles includes fluconazole (Diflucan) and itraconazole (Sporanox).

[sidebar] Candidiasis and HIV Disease Candidiasis is an important indicator of HIV disease severity, according to the Centers for Disease Control and Prevention (CDC). CDC publishes a classification system for HIV disease that is used for public health purposes such as AIDS case reporting. Under the CDC definition, 3 clinical categories (A, B and C) serve as clinical indices of the severity of HIV disease. Clinical category A includes asymptomatic disease or new infection; category B consists of symptomatic conditions related to immune deficiencies; category C consists of more serious conditions or opportunistic infections that constitute an AIDS diagnosis.

Under the 1993 CDC definitions in use today, vaginal candidiasis is a category B condition. Candidiasis of the bronchi, trachea or lungs are all AIDS-defining conditions belonging to clinical category C.

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