HIV Viral Load is Lower in Women than Men

Current Treatment Guidelines Result in a Sex Difference in Treatment Eligibility Despite No Sex Difference in AIDS Risk

A ten-year study of injection drug users infected with the human immunodeficiency virus (HIV) has conclusively confirmed that women have lower viral load (the number of HIV particles present in blood) than men, particularly in the first few years after infection. HIV-infected women, however, progress to AIDS at the same rate as men. These results clarify how candidates for anti-retroviral therapy should be chosen. The report appears in the March 8th issue of the New England Journal of Medicine. In the study, by scientists at the Johns Hopkins Schools of Public Health and Medicine, median viral loads were initially more than three times lower in women than in men, but women went on to develop AIDS at the same rate as men.

Twenty-nine men and 15 women in the study progressed to AIDS. Among the 29 men who progressed to AIDS, the median initial viral load was 77,822 copies per milliliter (ml) of blood, compared to 40,634 copies/ml among the 127 men who did not progress to AIDS. Among women, the corresponding figures were 17,149 copies/ml and 12,043 copies/ml, respectively. The risk of AIDS was comparable for women and men; that is, no statistically significant sex difference was detected in the rate of disease progression. Viral loads continued to be lower in women than men for several years after HIV-1 seroconversion.

Lead author Timothy R. Sterling, MD, assistant professor of medicine, Division of Infectious Diseases, at the Johns Hopkins University School of Medicine, says, "This sex difference in initial viral load means that the same viral load measurement does not convey the same risk of AIDS in women and men. For example, in this study an initial viral load of 17,149 copies/ml was associated with progression to AIDS in women but not in men. In men, a viral load as high as 40,634 copies/ml was not associated with progression to AIDS."

This distinction is important, said the authors, because of guidelines for the initiation of antiretroviral therapy. Until recently, the treatment guidelines recommended initiation of antiretroviral therapy when the viral load was greater than 20,000 copies/ml. Using this cutoff, 74 percent of men and 37 percent of women in the current study would have been eligible for therapy shortly after seroconversion.

The authors noted, however, that when treatment eligibility was based on the number of CD4+ cells there was no sex difference in treatment eligibility. CD4+ cells are immune cells produced by the body to fight infection; lower numbers of CD4+ cells indicate more advanced HIV infection.

"The results of this study suggest that greater emphasis should be placed on CD4+ count than viral load when deciding when to initiate treatment," says senior author Thomas C. Quinn, professor of medicine, Division of Infectious Diseases, at the Johns Hopkins University School of Medicine. "These findings are consistent with the revised new guidelines, which recommend that antiretroviral therapy be initiated for both men and women when the CD4+ lymphocyte count is less than 350 cells/mm3," adds Dr. Quinn, who is also a professor of Molecular Microbiology and Immunology at the Johns Hopkins School of Public Health.

From 1988 to 1998, at approximately six-month intervals, the 202 HIV-positive injection drug users (156 male and 46 female) participating in the study returned to the clinic for a physical exam and to have blood drawn for HIV serologic testing. Any participants identified as HIV-seropositive were asked to return and give another blood sample so that viral load and CD4+ cell levels could be measured. Plasma was also frozen for future studies.

These results, say the authors, underscore the need for further studies of the implications of the sex difference in plasma viral load on initiation of antiretroviral therapy, as well as studies to assess whether there is a viral load cutoff that predicts progression to AIDS.

The study's other authors were David Vlahov, PhD, Jacquie Astemborski, MHS, Donald R. Hoover, PhD, MPH, and Joseph B. Margolick, MD, PhD.

Support for this study was provided by the National Institute on Drug Abuse and the National Institute of Allergy and Infectious Diseases.