Table of Contents:

• Gender Difference in Viral Load?
  • The A.L.I.V.E. Study
  • The WIHS/MACS Study
  • Differences in Viral Load According to CD4+ Cell Count (WIHS/MACS)
• Practical Questions for Women:
  • The Federal Guidelines for Starting and Switching Therapy
• The Basics of Viral Load Testing
  • The How and Why of Testing
  • Interpreting the Results
  • Undetectability: To Be or Not To Be?
  • Getting Viral Load Tests
• Treatment Notes
  • New Anti-HIV Drug Approved by the FDA - Abacavir
  • Possible Side Effects
  • Abacavir Recommended Dosing
  • While Another Awaits Approval - Amprenavir
  • Dosing Concerns
• Glossary of Concepts and Terms

In current medical practice, HIV levels and CD4+ cell counts are measured, interpreted and used to help guide anti-HIV therapy without regard to gender. Two recently reported studies give pause to this standard of practice. They suggest that there may be differences in the way HIV viral levels (viral load) relate to the risk of HIV disease progression among men and women. Essentially, the studies suggest that women have progression of HIV disease (at least as measured by CD4+ counts) at lower viral levels than men. The question of how much lower, or what a lower viral level means, remains a bit unclear.

The Federal Guidelines Panel -- the decision-making body which creates the guidelines for the use of anti-HIV therapy -- recently reviewed the new information on gender differences in viral load. It concluded that, for the time being, no changes should be made in the guidelines with regard to the use of anti-HIV therapies in women. They concluded that these new data are not markedly different enough to warrant changing strategies for treating HIV, nor should they be cause for alarm for women living with HIV.

Still, some people remain concerned about the implications of these studies. They add fuel to the already controversial debate of when is the most effective time to start or switch anti-HIV therapy. This article walks through these two studies and discusses some of the questions they have raised. No doubt you will be hearing more about this issue in the future.

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

The first of the two main studies was presented at the 1998 World AIDS Conference in Geneva, Switzerland and was recently summarized in the scientific journal, The Lancet. It is based on a large group of HIV-positive men and women with a history of injection drug use. Blood samples from 527 participants which have been collected since the late 1980s were compared to 285 blood samples collected at least three years later. Researchers examined levels of HIV and CD4+ cell counts at both time points. In addition, they gathered information about the general health of the study participants and looked 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 38-65% lower than those observed in men with similar CD4+ counts. In general, women's HIV levels were half that of men in the study.

To try to better understand this difference more thoroughly, researchers examined viral load with CD4+ cell counts (0-200, 200-499 and greater than 500). Again, viral load was consistently lower in women than men across CD4+ cell count groupings.

This difference persisted after accounting for other factors that the researchers felt might influence the lower viral levels seen in women. Factors such as race, current and previous use of anti-HIV therapy and use of street drugs were analyzed. None of these factors could explain the gender difference in HIV viral levels.

So, What Does this Mean?

According to this study, it seems that -- despite having a lower viral load -- women appear to progress to symptoms of HIV disease at a similar rate as men. To verify if this was indeed the case, researchers looked at the association of viral load, CD4+ cell count and time to AIDS between men and women.

What they found was that women and men with similar CD4+ cell counts had a similar time to AIDS. The differences in viral levels among men and women suggest women appear to progress to AIDS with approximately half the viral load as men. Respectively, women with the same viral load as men had a higher risk of AIDS. What is consistent between men and women, however, is the predictive value of CD4+ cell counts. When CD4+ cell counts decline, people are at similar risk of HIV disease progression, regardless of gender.

Now, these findings are far from confirmed nor does everyone agree on how they should be interpreted. Nevertheless, they do raise important questions -- like whether the relationship between HIV levels and progression to HIV disease is different among women and men. Several explanations for this difference have been proposed, including different biological dynamics of the virus in men and women, behavioral differences that might influence viral load and/or hormonal differences.

At this point, however, explanations seem premature. More information is needed to truly understand what the difference in viral load between men and women actually is, and even more information is needed to understand what this difference means.

The WIHS/MACS Study

A study presented at the recent Conference on Retroviruses and Opportunistic Infections adds dimension to these questions. Like the A.L.I.V.E. study, it compared viral levels and CD4+ cell counts between men and women.

Stored blood samples in 1984-85 from 1,511 HIV-positive men enrolled in the Multicenter 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. Additionally, 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 between 200 and 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. However, this study found significant differences between women in three different CD4+ cell groupings, which is contrary to the findings of the A.L.I.V.E study.

Now, How Should One Interpret These Results?

The researchers conclude that HIV load is lower in women than men, but only at CD4+ cell counts above 200. They suggest that the use 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. However, the Federal Treatment Guidelines discourage making initial treatment decisions solely on the basis of viral load numbers and always recommend that the CD4+ count also be a factor in the decision. In the case of women with CD4+ counts below 200, almost all sources recommend treatment regardless of viral load. Thus, the real impact of these findings, if they prove to be further confirmed, is how they affect women with CD4+ cell counts in the 200 to 500 range, who are making decisions about therapy based on viral load.