Clinicians should check women with HPV for HIV

Research: Focus on female genital ulcer infections

Researchers at the recent 6th Conference on Retroviruses and Opportunistic Infections highlighted new studies that show why HIV prevention efforts should focus on women who have sexually transmitted diseases, such as genital human papilloma virus (HPV).

Research presented at the Chicago conference follows two other studies investigating the prevalence of genital ulcers in women who are infected with HIV.

The body of evidence indicates that when clinicians examine a woman who has HPV or a genital ulcer, they also should suggest she be tested for HIV.

"Some studies show that patients with genital ulcers are at higher risk for HIV, perhaps because the ulcer provides a portal of entry for the virus," says Kristen Mertz, MD, medical epidemiologist with the Division of STD Prevention at the Centers for Disease Control and Prevention.

"Also we have a few studies that have detected HIV DNA in the ulcers, so we think HIV-positive patients with ulcers are more likely to transmit the virus," Mertz says.

HIV prevention efforts should target all patients — male and female — who have genital ulcers, she adds. Clinicians also should become aware of which diseases cause ulcers most commonly in their areas. For example, clinicians in Jackson, MS, found an outbreak of chancroid in 1994, which typically is far less common than genital herpes and syphilis. Because chancroid is so rare, clinicians often misdiagnose it.

"They should know if there’s chancroid around, or if all ulcers are caused by herpes or syphilis," Mertz advises. "It’s important to get the ulcers treated appropriately so they will heal quickly, and the message for patients is to abstain from sex when ulcers are present."

Five studies presented at the retrovirus conference focused on HPV, and a sixth compared syphilis serology between HIV-positive and HIV-negative women.

HIV clinical trials traditionally have overlooked women, but recent research is reversing this trend, according to Karin Nielsen, MD, MPH, a clinical instructor in the department of pediatrics at the University of California – Los Angeles School of Medicine and an attending physician at the UCLA Children’s Hospital in Los Angeles.

Nielsen, in an article for Medscape,1 describes the HPV and syphilis studies presented at the conference as follows:

Fifty-five percent of HIV-positive women in a study of vulvovaginitis had HPV, for a total of 171 out of 365 women studied. This compares to 33% of non-HIV infected women having HPV, for a total of 91 out of 335 seronegative women. Also, 26 or 7% of HIV-infected women had identifiable lesions at any site. Only two uninfected women had identifiable lesions. The study showed that risk factors for lesion development included CD4 absolute counts of less than 500 cells/mm3 and HPV seropositivity at entry.2

Another study of HPV persistence in HIV-infected women showed that 268 women who had been tested for HPV were re-evaluated. Of these, 22% had not had positive HPV tests at baseline. However, while 74% of non-HIV infected women cleared their HPV infection, only 16% of HIV-infected women with a CD4 T-cell count of less than 200 cells/mm3 were cleared of HPV infection.3

A study of 141 HIV-infected women conducted between March 1996 and January 1999 showed that HPV was more frequently detected in women with lower CD4 T-cell counts. As the women received more intensive antiretroviral therapy (ART), their CD4 T-cell counts increased and their HIV viral load decreased. The women were given Pap smears, and 45% had an abnormal Pap smear at their first visit. The study found that 82% of the women who had abnormal initial Pap smears had HPV, and half the women with normal Pap smears had the presence of HPV DNA.4

Study finds vitamin A deficiency

Another group of researchers found an association between vitamin A deficiency and HPV infection in HIV-positive women.5 Also, another study compared treating cervical lesions with topical 5-fluorouracil (5-FU). It found that using 5-FU as maintenance therapy for HIV-infected women with cervical lesions, class II or III, produced fewer incidents of recurrent dysplasia. Specifically, 50 women were given 5% 5-FU topical cream, 1 g every two weeks for six months. Another 51 women were observed as part of a control group. Local side effects were not significantly different from the treatment and control groups. But of the treated women, only 28% had recurrent dysplasia, as compared with 47% of the control group women observed.6

A sixth study involved a comparison of syphilis serology between 855 HIV-positive and 434 HIV-negative but at-risk women. Researchers tested for syphilis via nontreponemal antibody tests and confirmed with a fluorescent treponemal antibody absorption test. They performed 4,064 syphilis tests over 24 months; 91% of these were negative according to the screening test, 7% were true-positive, and 2% were false-positive. The rate was the same for both groups, and HIV infection did not lead to an increase in false-positive syphilis serologies.7

Mertz and the CDC were involved in two studies, published last year in the Journal of Infectious Diseases, that looked at genital ulcers and HIV. Those studies’ findings were as follows:

In 1994, clinicians in Jackson, MS, noted an apparent outbreak of atypical genital ulcers. Of 143 patients with ulcers, 56 (39%) were positive for Haemophilus ducreyi (the bacterium that causes chancroid); 44 (31%) had herpes simplex virus; 27 (19%) had Treponema pallidum (the bacterium that causes syphilis); 12 (8%) were positive for more than one organism. Clinicians tested 136 of these patients for HIV and found that 14 (10%) were HIV-seropositive, compared with none of 200 patients without ulcers. Plus, HIV-1 DNA was detected by a multiplex polymerase chain reaction (PCR) assay in ulcers of six of the HIV-positive patients.8

Another study was conducted in 10 U.S. cities to determine the etiology of genital ulcers and to assess the prevalence of HIV infection in ulcer patients. Clinicians collected ulcer and serum specimens from about 50 ulcer patients at a STD clinic in each city. Herpes simplex virus (HSV) was detected in more than 50% of specimens from all cities except Memphis, TN, which had 42%. HIV seroprevalence in ulcer patients ranged from 0% to 18%.9

References

    1. Nielsen K. Women, HIV, HPV, and STDs. Medscape Feb. 12, 1999; www.medscape.com/Medscape/CNO/1999/retro/Story.cfm?story_id=492.

    2. Conley LJ, Ellerbrock TV, Bush TJ, et al. Incidence of HPV-associated vulvovaginal lesions in HIV-infected and uninfected women [abstract 462]. Presented at the 6th Conference on Retroviruses and Opportunistic Infections. Chicago; Feb. 1-5, 1999.

    3. Andieh L, Munoz A, Vlahov D, et al. Cervical neoplasia and the persistence of HPV infection in HIV+ women [abstract 463]. Presented at the 6th Conference on Retroviruses and Opportunistic Infections. Chicago; Feb. 1-5, 1999.

    4. Hoesly CJ, Jin G, Bragg S, et al. Molecular epidemiology of HPV infection in the genital tract of HIV seropositive women [abstract 465]. Presented at the 6th Conference on Retroviruses and Opportunistic Infections. Chicago; Feb. 1-5, 1999.

    5. French AL, Cohen MH, Semba RD, et al. Association of retinol deficiency with cervical squamous intra-epithelia lesions (SIL) in the HIV-infected women [abstract 464]. Presented at the 6th Conference on Retroviruses and Opportunistic Infections. Chicago; Feb. 1-5, 1999.

    6. Maiman M, Watts DH, Andersen J, et al. A phase three randomized trial of topical vaginal 5-fluorouracil maintenance therapy versus observation after standard treatment for high-grade cervical dysplasia in HIV infected women: ACTG 200 [abstract 466]. Presented at the 6th Conference on Retroviruses and Opportunistic Infections. Chicago; Feb. 1-5, 1999.

    7. Rompalo AM, Astenborsky J, Klein RS, et al. Syphilis serologic patterns among women with or at risk for HIV [abstract 468]. Presented at the 6th Conference on Retroviruses and Opportunistic Infections. Chicago; Feb. 1-5, 1999.

    8. Mertz KJ, Weiss JB, Webb RM, et al. An investigation of genital ulcers in Jackson, Mississippi, with use of a multiplex polymerase chain reaction assay: High prevalence of chancroid and human immunodeficiency virus infection. J Infect Diseases 1998; 178:1,060-1,066.

    9. Mertz KJ, Trees D, Levine WC, et al. Etiology of genital ulcers and prevalence of human immunodeficiency virus coinfection in 10 U.S. cities. J Infect Diseases 1998; 178:1,795-1,798.