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Gender Difference in Viral Load

April, 1999

In current medical practice, HIV levels and CD4+ cell counts are measured and interpreted and help guide anti-HIV therapy decision-making without regard to gender. Two recently reported studies are giving pause to this standard of practice. They suggest that women have progression of HIV disease at lower viral levels than men. A Federal Guidelines Panel, which provides guidance on the use of anti-HIV therapy in adults, recently held a meeting to review new information on gender differences in viral load. It concluded that presently these new data are not different enough to warrant recommendations for a different standard of care for women with HIV, nor should they be cause for alarm for women living with HIV. Nevertheless, women and their doctors should be aware of these data which may support initiating and switching therapy at a lower HIV levels than what is currently recommended in the Federal Guidelines document.


The A.L.I.V.E. Study Results

The first of two studies was presented at the 1998 World AIDS Conference in Geneva, Switzerland and was recently summarized in the scientific journal, The Lancet. Based on a large group of HIV-positive men and women with a history of injection drug use, involved in the A.L.I.V.E. study. It compared blood samples collected and stored from 527 participants since the late 1980s with 285 blood samples collected at least three years later.

HIV levels, CD4+ cell counts and information about the general health of the study participants at both time points were examined to see if there were unique differences according to gender and/or race. Differences based on gender did come forward. Women in the study had HIV levels 38 to 65% lower than what was observed in men. In general, women's HIV levels were half that of men in the study.

Viral load was consistently lower in women than men even after adjustments for CD4+ cell count differences were made. This difference persisted after accounting for other factors that the researchers felt could possibly influence the lower viral levels seen in women, such as race, current and previous use of anti-HIV therapy and use of street drugs. None of these factors explained the gender difference in HIV viral levels.

Researchers also looked at the association of viral load, CD4+ cell count and time to AIDS between men and women. They found that women and men with similar CD4+ cell counts had a similar progression time to AIDS. In addition, the differences in viral levels among men and women suggest that women appear to progress to AIDS with about half the viral load as men. In other words, women with half the viral load as men had a similar time to AIDS. Respectively, women with the same viral load as men had a higher risk of AIDS. What this probably means in is that for women with low CD4+ cell counts (e.g. below 200), CD4+ cell count is a more reliable indicator of general health and overall risk of HIV disease progression than is HIV levels. It also suggests that increases in HIV levels that are sustained, even modest ones, might be slightly more of concern to women than their male counterparts.


The WIHS Study Results

Similar findings were presented at the recent Conference on Retroviruses and Opportunistic Infections from a second study. Stored blood samples in 1984-85 from 1,511 HIV-positive men enrolled in the Multi-center AIDS Cohort Study (MACS) were compared with blood samples obtained in 1994-95 from 1,262 HIV-positive women enrolled in the Women's Interagency HIV Study (WIHS). When the original blood samples were collected, no one from either group was using anti-HIV therapies.

Like the ALIVE study, differences in viral load emerged. The degree of difference, however, was less dramatic. Also, differences were associated with specific CD4+ cell count levels. HIV levels were not different among men and women with CD4+ cell counts below 200. However, women whose CD4+ cell counts were 200-500 had a 40% lower viral level compared to men with the same CD4+ cell count. For CD4+ cell counts above 500, viral levels were 24% lower for women than for men. Thus, according to the WIHS/MACS comparison, women's overall viral load was approximately 20% lower than men's, with significant differences in the two CD4+ cell groupings shown below:


Differences in Viral Load
According to CD4+ Cell Count (WIHS/MACS)
CD4+ Cell Count Percent Lower Viral Level in Women
Less than 200 Insignificant
200-500 40%
Above 500 24%


Researchers from the WIHS/MACS cohort conclude that HIV load is lower in women than men, but only at CD4+ cell counts above 200. They suggest that theuse of the viral load tests, particularly when used as a starting point for beginning anti-HIV therapy, may need to be adjusted for gender to account for this difference. The largest impact of these findings is probably on how they affect women with CD4+ cell counts in the 200 to 500 range who are making decisions about therapy changes based on viral load.


Commentary on These Findings

While these findings are far from confirmed, they do raise important questions with regard to viral load in women and related risks of disease progression. These studies also remind us of two other points. CD4+ cell counts provide useful measures of the risk of disease progression and their meaning is not influenced by gender. Moreover, the decision to start, add or change therapy should never be decided solely on the basis of one laboratory measure (e.g. just viral load, just CD4+ cell counts, etc.).

"CD4+ cell counts provide useful measures of the risk of disease progression and their meaning is not influenced by gender."

Treatment decisions should factor in trends in viral load, trends in CD4+ cell counts, the number of available future options, side effects, ease of adherence, how one feels about anti-HIV therapy and measures of overall general health. Whether or not viral load differences according to gender should be considered a treatment decision point demands further study.

For more information on gender differences in viral load, call Project Inform's toll-free National HIV/AIDS Treatment Hotline at 1-800-822-7422 and request WISE Words, Issue #3.


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