What's the Difference?
DO WOMEN HAVE DIFFERENT types of problems from the disease than men experience? Do women respond to the drugs used to treat HIV differently from men? Even in 1997, the research of HIV infection in women lags behind what we know about the disease in men.
Women have been studied in the past primarily in the context of gaining more information about infants and as modes of transmission risks to infants and/or their partners. These delays have hindered assessment of viral expression in women, disease manifestations, prognosis and treatment issues. Obviously one major gender difference is the female specific gynecological complications of HIV infection; these will not be covered here.
Much of what we are beginning to learn about HIV in women is coming from 2 large natural history studies; the Women's Interagency HIV Study (WIHS) & the HIV Epidemiological Research Study (HERS). These studies have enrolled large numbers of infected and high risk women and are following these women at regular intervals to determine the course of disease.
One limitation of these studies is that they do not also follow a group of men so comparisons between men and women are difficult. Some of the issues identified so far that are problems for women include access to care, threats to family security, domestic violence and lack of social services. These studies are also focusing on learning more about the patterns of opportunistic infections in women, and about cervical dysplasia and cervical carcinoma.
Access to Care
Several studies indicate that women come for care at later stages of disease and that they may access fewer services than men (1). A study of a small *cohort of 200 women in a New York clinic indicated that women tend to seek treatment later in their clinical course of HIV disease and have a worse prognosis (2). The majority of the 200 HIV-infected women sought treatment at a relatively advanced stage of infection with a *CD4 count *<500. Most women were not tested until they or a child or partner developed symptoms.
A study of use of health services by women with HIV infection showed that even after being diagnosed and after having accessed the medical care system, women with AIDS received fewer services than men with AIDS (3). Use of health services by women was examined more closely in the HERS study. Among women enrolled in this study with <200 CD4 cells, 49% were taking antiviral therapy. PCP prophylaxis was only being used in 58% recommended for everyone with <200 T-cells (4).
Patterns of access to care vary in different areas of the country. In Seattle, research about the effect of gender and race on access and utilization of care for HIV-infected clients found that women entered the system at the same stage of disease as men but were significantly younger, indicating they were infected at a much earlier age (5).
Information on the natural history of women and HIV-infection is limited, especially in direct comparison to men. Earlier studies have suggested a reduction in survival for women. In most of these studies, the differences were explained by the fact that women had delayed accessing treatment (6). When only those who were receiving therapy were compared, the differences were no longer found. The earlier findings can probably be attributed to the difficulty women have accessing health care.
A research project at a university medical center followed a cohort of women and found that the clinical progression from HIV to AIDS and the length of survival for these women is similar to that of men. These women had equal access to quality medical care as well as access to research studies with potentially life-prolonging treatments. The women did however, have more frequent episodes of Candida Esophagitis (7).
Preliminary analysis on the comparison of HIV disease progression between men and women from serocon-version to severe immunodeficiency done by U.S. Army Medical Centers found no differences in progression in all analyses but one.
In the cohort that had >500 CD4s, differences in progression were found. In this cohort, differences in progression to CD4 <200, OI or death were higher in women than men but did not become apparent until after 3.5 years of follow-up (8). Another recent study evaluated predictors of survival in people with CD4 <50 and found that men had a 1.7 times risk of death when compared to women (9).
Information from several studies suggest that women are at increased risk for wasting syndrome, candida esophagitis, bacterial infections and death as a first event (10). Another study shows that women were one-third more likely than men to experience death as the first clinical event after study enrollment *(CPCRA). Several other groups report a high percentage of wasting syndrome as a presentation of AIDS in females.
A *retrospective study of clients of the Newark women's AIDS clinic looked at women who died in 1994, and found that wasting was the most common OI. In this group of women 78% had had oral candidiasis. Wasting syndrome and candida esophagitis were reported more frequently in women. Comparative analysis of HIV infection in men and women showed a decrease in PCP in females following introduction of Trimethoprim-Sulfa (Bactrim) (11). In another study, women appeared to be at increased risk of bacterial pneumonia compared to men (12). More recently, in a study of all bacterial infections in patients with CD4 <100, women were again found to be at increased risk compared to men.
A cohort of HIV infected women in Washington, D.C. which maintains data on 276 women since 1987 did a retrospective review looking at the cause of death and associated illnesses in 48 women. The list of the causes of each were multisystem failure in 32.5%: disseminated MAC in 44%, wasting in 37%, CMV retinitis 28%, Central Nervous System event in 23%, a respiratory event in 21%, malignancy in 16%, encephalitis in 14%, atypical mycobacterial (non-MAI) in 12%, TB-meningitis in 7%, & sepsis in 5%. The *mean CD4 count at death was 26. The primary cause of death was multisystem failure. Common organisms present at death were MAC and CMV (13).
The Community Based Clinical Trial Network's Observational Data Base enrolled 4080 persons and looked at opportunistic infections in HIV disease. Cryptococcal infection (fungus) was the OI found in this particular study to be significantly higher in women at 20%, compared to men at 8% (14). Another study done by Georgetown University Hospital presented data that PCP was the most common AIDS defining event for women as well as men (15). In one study which looked at the gender differences in HIV related cyto-megalovirus, women were found to be at risk, yet significantly lower risk than men, for invasive CMV disease (16).
Little information on response to therapy is available. One study on CMV showed women with CMV retinitis treated with ganciclovir did not survive as long as men. However, no difference was seen when foscarnet was used (17).
Response to Therapy
Women's response to drug therapies an area where the least amount of information is available. Too few women are enrolled in most clinical trials to be able to tell if there are important differences.
A retrospective study looking at ACTG enrollment showed women accounted for 24% (1106/4635) of adult study entrants compared to 14% in '91 and 6.7% in '86-'90 (18). Hypothetically, in a large clinical trial greater than 15% of the enrolled participants must be women in order to detect clinically significant gender differences in toxicities and response to therapy (19).
The main reason to be concerned about differences is that on average women weigh less than men. For most drugs this will not make a difference. Potentially important gender differences in response to new therapies may not become evident before drugs are introduced into practice unless larger numbers of women can be enrolled in clinical trials.
Editorial note: The government funded research effort systematically excludes women by design; based mostly on inclusion and exclusion criteria. Statistically significant numbers of women will never be enrolled in these research projects unless we aggressively pressure them to drastically redesign this system to include women.
A *prospective study of gender differences in response to antiretroviral therapy showed that women appeared to dose reduce their antiretrovirals more frequently and report more symptoms. Men were more likely to have severe blood test abnormalities during follow-up (20). Another study showed that menstruation did not affect the levels of AZT in the blood streams of women in this trial (21).
Review of available information on women and prevention reveals a key message; we need to change our approach in reaching and educating women about their potential risk of HIV-infection. More intensive prevention efforts are needed for women. Studies of women's sexuality and HIV prevention show that women disclosed shame, fear of their partners, rejection, fear of losing their partners, obedience to accepted sexual behavior and that sex was considered as a marital obligation were the most common barriers to overcome (22). Another survey found that the more religouse women were, the more judgemental they were toward sexuality & AIDS. The threat of violence by their sexual partners also seems to account for a significant incidence of unsafe sexual encounters (23).
Regional workshops were held in six U.S. cities across the country where Latina women leaders met to discuss a variety of critical HIV/AIDS issues including prevention, care, treatment, research, clinical trials, legal and ethical issues affecting Latinas and their families. The results were that the women left these workshops feeling empowered by the process and are now developing network chapters in their own communities (24).
In conclusion, differences in access to care and social issues influence our understanding of gender differences in the natural history of HIV infection. Information from several studies suggest that women are more likely than men to experience fungal infections, bacterial infections and wasting.
To date there is no strong evidence to suggest that there is any gender difference in response to antiretroviral therapy. Several clinical trials are ongoing to address antiretroviral therapy and response to specific OIs: wasting, candida vaginitis, cervical dysplasia.
More information is clearly needed to address ongoing questions about women & HIV. Research is one of the pathways to obtaining this information. (It is increasingly difficult to get funding for research projects which study women that aren't ghetto-ized into the female genital tract.)
Article Glossaryantiretroviral therapy:
drugs used against HIV. CD4: same as a T-cell. cervical carcinoma: full blown cancer of the cervix. cervical dysplasia: pre-cancer of cervix. cohort: a group of people with similarities. CPCRA: a research program of NIAID. Epidemiolgic Research: natural history. et.al: and others. intermittently: not on a regular basis. manifestations: symptoms of HIV. mean: average. natural history: observing disease progression. opportunistic infections: diseases that come with AIDS. PCP prophylaxis: medicine to prevent pneumonia prognosis: forecast. prospective: likely to happen. retrospective: looking at previously collected data. <500: less than 500 < : less than. > : greater than.
(1) Zanetta, 1995. (2) LaTrenta, 1992. (3) Hellin, 1993. (4) Solomon, 1996. (5) Farrell, 1996. (6) LaTrenta, 1992. (7) Benson, 1992. (8) Levin, 1993. (9) Spino, Retrovirus 96. (10) Ciesielaski, 1995. (11) Hoyt, 1995. (12) Brosgart, 1995. (13) Young, 1995. (14) Cohen, 1992. (15) Young, 1990. (16) Brosgart, 1995. (17) Murphy, 1996. (18) Pearl, 1992.(19) Currier, 1996. (20) Currier, 1996. (21) Cordaro, 1993. (22) Villar, 1996. (23) Jadack, 1995. (24) Alvarado, 1996.
This article was provided by Women Alive. It is a part of the publication Women Alive Newsletter.