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Published in the Bulletin of Experimental Treatments for AIDS March 1997 issue, by the San Francisco AIDS Foundation. |
Women and AIDS: Recent News about Women and HIVby Leslie Hanna Epidemiology UpdateOn February 28, the Centers for Disease Control and Prevention (CDC) released new statistics on AIDS. Overall, the information is cause for celebration: in 1996, for the first time since the beginning of the AIDS epidemic, the number of AIDS deaths declined. That the decline is in part attributed to better treatments for HIV disease underscores the importance of access to health care, and hints at an explanation for the disparity of results (when viewed in terms of subgroups). While AIDS-related deaths declined overall by 12%, the numbers of deaths due to AIDS and new AIDS cases in U.S. women actually increased. The rate of AIDS-related deaths in women increased 3% in 1996, during which time women accounted for 20% of new AIDS cases. As of June 1996, a total of 540,806 AIDS cases had been reported in the U.S. Of these, women account for more than 78,000. Based on the CDC's estimate of 750,000 million persons living with HIV infection in the U.S. today, approximately 150,000 U.S. women are infected. The World Health Organization (WHO) reports that the proportion of women among adults and adolescents with AIDS around the world increased from 7% in 1985 to 19% in 1995. WHO estimates that the number of women infected will equal the number of men infected, worldwide, by the year 2000. In the U.S., AIDS is the third leading cause of death for women aged 25-44, and the number one cause of death for African American women aged 15-44. Women of color continue to be disproportionately affected by HIV/AIDS. Although African American and Latina women comprise only 21% of the adult female population, in 1995 they accounted for approximately 76% of women diagnosed with AIDS. In 1995, the rates of AIDS cases per 100,000 adolescent and adult women by racial/ethnic groups were as follows: 59.2 for non-Latina African Americans, 25.4 for Latinas, 5.2 for Native Americans, 3.8 for Caucasians and 2.0 for Asian/Pacific Islanders. In other words, the rates of AIDS for African American and Latina women were, respectively, 16 times and 7 times greater than for Causasian women. The number one cause of injuries to women aged 15-44 is domestic violence. Women in that age group experience domestic violence more frequently than automobile accidents, muggings and cancer, combined. Physical violence has been associated with risk for HIV acquisition. Other social factors associated with HIV acquisition in women include poverty, illegal substance use and homelessness. Financial and emotional dependence, poorer access to quality health care and a history of sexual abuse are also risk factors. HIV prevention and women. AIDS Information Exchange 13(2). January 1997. Kaposi's Sarcoma-Associated Herpesvirus in WomenBefore the advent of the AIDS epidemic, Kaposi's sarcoma (KS) was regarded as a rare tumor disorder. AIDS-associated KS may involve the skin, mucous membranes, lymph nodes and internal organs including the lungs, liver and spleen. It is both the most common AIDS-related cancer and an AIDS-defining condition. AIDS-related KS is found predominantly in men, particularly gay or bisexual men. KS has been associated with AIDS cases that involved sexual acquisition of HIV. While less common in women with AIDS, KS has occurred in women who report having had a bisexual male partner. These and other factors suggested that KS may itself be caused in part by a distinct, etiologic (disease-causing) agent, which is sexually transmitted. Researchers laboring to identify candidate agents recently succeeded in identifying Kaposi's sarcoma-associated herpesvirus (KSHV), or human herpesvirus 8 (HHV-8), in cells taken from KS tumors. Since that identification, studies have revealed that almost everyone with KS also has HHV-8 infection. Persons who have HHV-8 infection but not KS have been shown to have a 6 times higher risk of developing KS than those without HHV-8 infection. A team of researchers at the University of California at San Francisco (UCSF) developed a test for HHV-8 infection that permits screening of large numbers of people. The same group then used the test to study the prevalence of HHV-8 in women. According to investigators, this is one of the first published studies of HHV-8 prevalence in women with HIV. The study involved women with HIV or women at high risk for HIV, all of whom were also participants in the Women's Interagency HIV Study (WIHS). All participants gave consent, were extensively interviewed and had blood drawn for testing. The 2 groups -- HIV positive and HIV negative women -- were highly similar in terms of race and age. The mean ages for HIV positive women and HIV negative women were 39 and 37 years, respectively. The mean CD4 cell count for HIV positive women was 390 CD4 cells/mm3. HIV positive women were more likely than HIV negative women to report behaviors known to transmit viral pathogens, including injection drug use (60% vs 45%), sexual contact with a man who has used injection drugs (69% vs 57%), sexual contact with a man known to have had sex with men or who possibly had sex with men (41% vs 29%), and a greater median number of lifetime sex partners (median 20 vs 10). Among the 386 women in the study, 13 were found to be HHV-8 seropositive. Twelve of the 13 HHV-8 positive women were also HIV positive (92%); 2 were diagnosed with KS prior to or during the study. Only 1 of the 84 HIV negative women was HHV-8 seropositive. The difference in prevalence of HHV-8 on the basis of HIV serostatus was not statistically significant, due to the small sample size. Another limitation is that the test used (the latency-associated nuclear antigen, or LANA) does not always reliably detect HHV-8 infection in people with KS. However, results can be compared across different studies that have used the LANA test. To more accurately gauge HHV-8 prevalence among women, larger numbers of women will need to be studied. According to epidemiologic data, KS occurs in 1-3% of women with HIV in developed countries. Researchers note a strong correlation between HHV-8 seropositivity and the subsequent development of KS; thus, the 4% HHV-8 seroprevalence rate found in this study is considered consistent with the estimated 1-3% risk of KS in women with HIV. Similarly, prevalence of KS in HIV positive hemophiliac men is 1%, and HHV-8 seropositivity is 1-3%; prevalence of KS in gay and bisexual HIV positive men is 15-30% and HHV-8 seropositivity is 30-35%. This correlation provides further support for the hypothesis that HHV-8 plays a causal role in KS. The investigators of this study suggest that studying HHV-8 in women, along with other key groups such as injection drug users and adolescents, will clarify risk factors for HHV-8 infection and, ultimately, help to find methods to prevent it. Kedes DH and others. The prevalence of serum antibody to human herpesvirus 8 (Kaposi sarcoma-associated herpesvirus) among HIV-seropositive and high-risk HIV-seronegative women. The Journal of the American Medical Association 277(6): 478-481. February 12, 1997. Vaginal MicrobicidesThe call for the immediate development of an effective vaginal microbicide was issued loudly and clearly last summer in Vancouver, BC, at the XI International Conference on AIDS. There is widespread consensus that an effective female-controlled method for preventing HIV infection is urgently needed. The female condom is the single female-controlled method available today, but it is expensive and not always acceptable to either male partners or to women. Many microbicide candidates are currently at the laboratory stage of study. In February, a Phase I clinical trial of an antiviral compound and vaginal microbicide known as PRO 2000 began in London. Manufactured by Procept, Inc., of Cambridge, MA, PRO 2000 is both the name of the intravaginal gel and the name of the active ingredient, shown in laboratory studies to be active against multiple strains of HIV. Data are still being gathered on the compound's effectiveness against other sexually transmitted diseases. Approximately 36 women have been enrolled so far in the London study, which will assess primarily the safety and tolerability of the gel in healthy women. The study is largely funded by the British Medical Research Council, which pledged over $1 million dollars for safety studies of microbicide candidates, and which is actively designing Phase II and III clinical trials. A Phase I study of PRO 2000 is also underway in Antwerp, Belgium. In other microbicide news, a candidate microbicide technology, known as BufferGel, received U.S. patent approval in January. The manufacturer, Ultrafem, Inc., of New York, contends that the approval will facilitate the continued development of the compound and its progression through clinical trials. Currently, the compound is being studied in a Phase I trial involving 20 women in Providence, RI. BufferGel is an "acidic-buffer technology" that operates by maintaining normal vaginal pH. Normal vaginal pH is acidic, which is naturally protective against invading, foreign organisms. Studies indicate that HIV and other pathogens that cause sexually transmitted diseases, as well as sperm, are acid-sensitive, and cannot survive in the normal vaginal environment. Semen, on the other hand, is alkaline, and normally functions to disrupt vaginal pH, rendering the vagina less acidic and more receptive to sperm as well as more vulnerable to infections. Another promising feature is that, unlike nonoxynol-9, BufferGel is not a detergent, and thus is not expected to irritate vaginal tissues. Patent awarded for BufferGel technology to prevent STDs. AIDSWeekly: 15. February 3, 1997. Phase I topical microbicide clinical trial initiated in London. AIDSWeekly: 17. February 3, 1997. Erck S. Personal communication. February 1997. Anal HPV Infection and NeoplasiaAnogenital neoplasia signifies a precancerous change in cells and tissues in the genitals or anus. Cervical, vulvar, vaginal, penile and anal neoplasias all are considered anogenital neoplasias. Most anogenital neoplasia is related to infection with the human papillomavirus (HPV), which may manifest as warts. Increased rates of HPV infection, anogenital warts and cervical intraepithelial neoplasia (CIN) have been reported in women with HIV. Researchers and clinicians increasingly report elevated incidences of anal HPV infection, which may ultimately lead to anal cancer, in both women and men with HIV. A recent study evaluated the prevalence of anal HPV infection and the incidence of related anal cellular abnormalities in women with HIV. The cross-sectional study involved a group of women who were already enrolled in a study of the gynecologic manifestations of HIV disease. All participants in this substudy (102 HIV positive and 96 HIV negative women) were interviewed; they also received a gynecologic examination that included Pap smears of the cervix and of the anus. Anal swabs were tested for HPV DNA. Anal tests were evaluated using the same criteria for interpretation of cervical Pap smears, and results were reported using a similar system that ranks any significant observed cellular abnormalities as low-grade (mild dysplasia) or high-grade (moderate dysplasia and severe dysplasia, or cancer). (See Cervical Intraepithelial Neoplasia in the June 1996 issue of BETA.) Both groups of women were similar in terms of age and demographics (income, history of smoking, illicit drug use and prostitution). However, HIV positive women were more likely than HIV negative women to have a history of current or previous genital warts (16% vs 3%) or a history of CIN or cervical cancer (19% vs 1%). Results of the anal cytology (cell study) smears indicated that 27% of 99 smears taken from HIV positive women had some sort of cellular abnormality. Of these, 22 were classified as mild cytologic atypia, or mild cellular changes, while 5 were classified aslow-grade anal intraepithelial neoplasia (AIN). Only 6 (6%) of smears from HIV negative women had any cellular abnormality; 5 were classified as mild cytologic atypia, and one was considered low-grade AIN. None of the samples in this study were found to be moderate or high-grade AIN, and there were no cases of anal cancer. The difference in prevalence of anal cellular abnormalities between the 2 groups was statistically significant. A high prevalence of anal HPV infection was found in HIV positive women in this study -- in 29% of HIV positive women, compared to 2% of HIV negative women. A related increase in anal cellular abnormalities was also found in HIV positive women. Researchers note that they did not perform anoscopy (examination of the anal canal and rectum), which might have detected more cases of AIN. Anal HPV infection was shown to be associated with some risk factors already known for HPV infection of the cervix -- history of prostitution, CIN and cigarette smoking -- but not for others, such as number of lifetime sexual partners and age. This study, like previous studies, failed to find an association between a history of anal intercourse and anal HPV or cancer. The most significant risk factor for both anal HPV infection and for anal cellular abnormalities was HIV infection. Hillemanns P and others. Prevalence of anal human papillomavirus infection and anal cytologic abnormalities in HIV-seropositive women. AIDS 10(14):1641-1647. December 1996. New Studies of Methods for Preventing Perinatal HIV TransmissionA host of new AIDS Clinical Trials Group (ACTG) studies that will evaluate methods for preventing perinatal HIV transmission (PHT) have recently begun. Inspired by research over the past year showing that triple combinations of anti-HIV drugs have efficacy superior to double combinations or monotherapy for HIV treatment, 4 trials will evaluate the safety and pharmacokinetics of triple regimens for prophylaxis of PHT. Each triple combination prophylaxis trial involves a combination of 3 potent anti-HIV drugs to be used by the mother during pregnancy, labor and delivery, and after birth by the infant, as well. Three of the different combinations involve a protease inhibitor plus AZT (Retrovir) and 3TC (Epivir). The fourth triple combination trial combines Glaxo Wellcome's nucleoside analog 1592U89 with AZT and 3TC. Ideally, these potent antiretroviral combinations will significantly reduce the risk of perinatal HIV transmission. Each study generally requires that women begin the prophylaxis regimens during the latter part of pregnancy. Intrapartum (during delivery) dosing involves intravenous infusions of AZT , and continued oral doses of the other 2 agents, except in the trial that involves indinavir (Crixivan), which is discontinued at the first sign of labor. Generally, infants receive AZT treatment for 6 weeks, as well as single or multiple doses of the other study agents. Exclusion criteria for these trials generally include obstetrical complications such as fetal growth retardation, intolerance to study agents on the part of the mother or use of drugs contraindicated with the study drugs (particularly for the studies involving ritonavir and nelfinavir). The triple combination trial protocol numbers and agents are:
Though powerful and promising, antiretroviral regimens involving multiple drugs are not without disadvantages, including an increased risk of side effects, high cost and complicated dosing schedules. Therefore, other key studies will look at simpler regimens. ACTG 332 will evaluate the safety and pharmacokinetics of combination d4T (Zerit) and 3TC in women during pregnancy, then in infants. ACTG 316 is a new, placebo-controlled trial of nevirapine (Viramune) for preventing perinatal transmission from women beginning in their third trimester of pregnancy. Finally, ACTG 324 will study a simpler, shorter AZT regimen than the regimen used in ACTG 076, which subsequently became what is now the sole approved PHT prevention regimen. ACTG 324 will evaluate the pharmacokinetics and tolerance of an oral AZT regimen given to HIV positive women only during labor and delivery. New York State Begins Mandatory HIV Testing of NewbornsOpen mandatory HIV testing of all newborns began in New York state in February, despite the strong objections of leading HIV experts and national organizations including the CDC, which urges mandatory prenatal counseling and voluntary testing. Since the CDC abandoned their national anonymous testing of newborns in 1996, New York state hospitals have continued testing, but have first asked mothers for their consent. However, on February 1, mandatory disclosure of test results began. Since HIV test results take at least 2 weeks and often longer to return, and since most women and newborns are released from the hospital much sooner than that, it is likely that hospital counselors will be forced to spend much time and effort tracking down women and their infants after they have already left the hospital -- with no guarantee that they can be found. This method bypasses the important window of opportunity that can be opened by prenatal testing, counseling and treatment. Since most perinatal HIV transmission occurs in utero, during delivery or within the first few weeks of life (from breast-feeding), testing newborns is not an efficient way to prevent pediatric HIV infection. AIDS/STD News Report: 14. February 19, 1997. Leslie Hanna is Associate Editor of BETA. Page last updated 1 April 1997 |
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