Re-examining Treatment Recommendations for Women
HIV infection in the United States has increased among women and individuals of color, while decreasing among white men. Women and individuals of color now represent 67% of people newly diagnosed with AIDS, 62% of individuals living with AIDS, and 69% of newly reported diagnoses of HIV infection. The highest rates of AIDS, of HIV-infection and of HIV-related deaths are among African-American women and men. Nearly 80% of HIV infected women in the United States are African American or Latina. It is thus extremely important to know if the recommendations for treatment of HIV infected people, developed almost entirely from data in white men, are valid for women and individuals of color.
In the last year, new information has become available suggesting that the "natural history" of HIV-infection, that is, the way in which HIV can make people sick, may be different in women and in people of color, compared to white men. However, the recommendations followed by doctors to determine treatment for individuals with HIV-infection are based mostly on the results of studies of viral load and treatment in HIV infected white men. There are three areas in which there is evidence of differences between women and men. These include levels of viral load, T-cell counts in people with or without HIV infection, and the level of T-cell counts at which AIDS develops. The differences found between whites and people of color include viral load differences and differences in how fast T-cells decline.
There are now several studies in the United States which investigate the natural history of HIV infection in women. Two large studies include only women: the Women's Interagency HIV Study (WIHS), which has enrolled 2,059 HIV infected women and 569 HIV uninfected women, and the HIV Epidemiology Research Study (HERS), which includes about 800 HIV infected and 400 HIV uninfected women. Some studies include both men and women, usually with about four times as many men as women. This includes the ALIVE study (AIDS Link to Intravenous Experience) which follows the course of disease in women and men enrolled in a drug treatment program in Baltimore. Nearly all (96%) of the ALIVE participants are African American.
Recent studies suggest that viral load tends to be lower in women compared to men, in people of color compared to whites, and in those participants reporting a history of injection drug use. In addition, some data has suggested that for women with HIV infection, remaining alive is predicted better by the T-cell count than by the viral load. These findings have led some physicians and scientists to question whether it is appropriate to assume that the information gained from studies of white men should be used to develop the treatment recommendations for women and people of color.
In November of 1998, researchers from the ALIVE study published findings about the viral load levels of the women and men in the study. At every level of T-cells, the viral loads for the women were lower than in the men. For example in women the average level of viral load was 3,000 (copies/ml of blood) but in men it was 9,000. Similar results had been reported about a year earlier in a much smaller group of HIV infected women and men in the US military. In early 1999, the WIHS investigators also presented results which compared the viral loads in the WIHS women to the viral loads among the men in the Multicenter AIDS Cohort Study (MACS). These results indicated that the viral loads in women were 20% lower than in the men at any given level of T-cells. This information prompted other researchers to look at viral loads in women and men: some have found that there is a difference, and some have not found such a difference. The WIHS and MACS investigators also found that the viral load in people of color was 35% lower than in whites, an even larger difference than they found between women and men.
Although it is not often discussed, it has been known for some time that the "normal" T-cell levels in women and men are different. In people without HIV infection, the T-cell levels are about 100 cells higher in women than in men: on average, in people without HIV infection, women's T-cells are about 1100, and men's are about 1000 (cells/cubic mm of blood). This gender difference in T-cell counts is important when interpreting study results, as study groups of HIV infected individuals are often stratified by T-cell count in an attempt to adjust for duration of infection. It is assumed that people with similar T-cell counts have been infected for the same amount of time. That assumption may be incorrect when comparing groups of women and men. One study has shown that in people infected with HIV, the T-cells in the women remained about 100 cells higher than in the men for at least the first five years of infection. T-cells counts do not appear to differ by race however, at least across the Caucasian, African-American, and Latino groups in the United States.
The differences in T-cells may matter if they mean that women can develop AIDS or HIV related diseases at higher T-cell counts than in men. Alternatively, women's higher T-cell counts may "protect" them by preventing the development of AIDS for a longer period of time after becoming infected with HIV. Unfortunately, there are few studies that can help answer these questions, which are best answered in a study which includes people whose date of infection with HIV is known, or who have been followed for a long time before they develop AIDS. Most studies which have looked at gender differences in disease progression have followed people who are stratified by T-cell counts, as described above. Some studies have found no difference, some have found that women progress faster, and others have found that men progress faster. There is no study, however, that has been designed to answer this question, and the available data really leave the question unanswered. However, a very recently published study of a group of HIV infected women and men in Europe, had some disturbing findings. The investigators, using mathematical modeling of T-cells, demonstrated that the women developed AIDS at higher T-cell levels than the men.
Similarly, there is very little information to tell us if there is a difference in clinical disease between whites and people of color. Most studies have found no difference in rates of disease progression or death by race. However, the MACS study (a study of men only), which includes very few men of color, found that the rate at which the T-cells fell was much slower in the men of color compared to the white men -- suggesting that the men of color may do better clinically. Similarly, the WIHS investigators have preliminary findings that T-cells may fall more slowly in African American and Latina women, compared to white women.
There are three major measures that physicians or other providers use to recommend treatment to HIV infected individuals. These are: clinical disease (if the HIV infection is making the person sick), the T-cell count, and the viral load. It is clear that highly active antiretroviral therapy (HAART) should be recommended and provided to any person with clinical disease. It is less clear at what T-cell or viral load level treatment should be first recommended. The current recommendation is that HAART be recommended for any HIV infected person whose T-cells are less than 500 cells/mm3, or whose viral load is higher than 10,000 to 20,000 copies/ml. Although most people would not develop clinical disease at these high T-cell and low viral load levels, the purpose of treating early is to prevent the development of clinical disease. Because of the recent information suggesting gender and racial differences in T-cells and viral load, there has been concern that these recommendations may not be correct for women and people of color. However, two things must be kept in mind when considering changing the recommendations.
First, because of their lower viral loads when treatment is initiated (usually because of T-cell levels below 500 cells), it may be that women and people of color respond better to antiretroviral therapy. If this is the case, then the current recommendations may be appropriate, or it may even be that treatment could be initiated later for women and people of color. What is most important clinically is how different groups respond to treatment, not whether their viral loads are different in the absence of treatment. It is thus critically important to determine if the differences in viral load mean that women and people of color do better with treatment than white men, or worse. The scientific community is only beginning to be able to answer this question. Much more research is required.
Second, it is unclear whether the current treatment recommendations are "correct " even for white men. HAART has not been around long enough for us to know if people treated when the T-cells fall below 500 cells do better in the long run than people who wait until the T-cells fall below 350 or 300 cells/mm. A recent study from Europe found that HAART was initiated at lower T-cell counts in people with a history of injection drug use or who had completed less schooling, but, these groups were not any more likely to develop AIDS. This suggests that people who initiate treatment later may do just as well as those who initiate treatment by the current recommendations. Again, the optimal time to initiate treatment remains unanswered for all HIV infected individuals. It is thus premature to suggest a change in treatment recommendations for specific groups. It is not clear whether such a change would mean women or men of color would be treated earlier or later. Investigations of this question should clearly include enough women, and men of color, to allow informed decision making for those groups specifically.
In summary, much recently published information suggests that there are gender and/or racial differences in T-cell counts and in HIV viral loads. However, it is unclear whether these differences indicate that there are clinical differences by race or by gender, even in people not taking any treatment. The most important question is whether these differences in T-cell and viral load levels mean that treatment would be more or less effective in delaying or preventing clinical disease, including AIDS, for women and people of color. More study is needed to determine this.
This article was provided by AIDS Community Research Initiative of America. It is a part of the publication CRIA Update. Visit ACRIA's website to find out more about their activities, publications and services.