During the first years of HIV infection, women have significantly lower amounts of the virus in their blood than do men, according to one of the largest studies ever to examine gender-specific differences of HIV infection. Despite their lower initial viral levels, women suffer the loss of immune cells and develop AIDS just as swiftly as men. The findings, reported in the March 8 issue of The New England Journal of Medicine, lend further support to recent changes in the criteria used to help doctors tailor anti-HIV drug therapy to delay the onset of AIDS.
Through a collaboration funded by the National Institute on Drug Abuse (NIDA), investigators from the National Institute of Allergy and Infectious Diseases (NIAID) and the Johns Hopkins University monitored more than 200 participants in the AIDS Linked to the Intravenous Experience (ALIVE) cohort.
"We established the ALIVE cohort in 1988 as a natural history study of HIV disease among injection drug users," explains NIDA Director Alan I. Leshner, Ph.D. "The current research evaluated the risk of progression to AIDS by measuring several factors, including the amount of virus in the blood, known as viral load."
The researchers found that the median initial viral load of the women who progressed to AIDS was almost five times lower than that of the men who progressed to AIDS.
"Despite early differences in viral load among men and women, as time went on, both men and women had a similar risk of developing AIDS," says Timothy Sterling, M.D., assistant professor of medicine and epidemiology at Hopkins and the first author on the study. "In addition, men and women experienced a similar rate of loss of their CD4+ T cells, the immune cells that decrease as a result of HIV infection."
Senior co-author Thomas C. Quinn, M.D., a senior investigator in NIAID's Laboratory of Immunoregulation and professor of medicine at Hopkins, says, "Previous studies in men have shown that initial viral load can be used to gauge their likelihood of progression to AIDS, but these data confirm that the initial viral load is much lower in women than in men and consequently not as predictive for women."
Between 1988 and 1998, the team followed a group of 156 men and 46 women who became HIV positive. During that time, 29 men and 15 women developed AIDS. The research team measured the volunteers' HIV load at regular intervals, starting from around the time they became infected with HIV and continuing for several years afterwards.
The investigators found that the women who developed AIDS had a median initial viral load of 17,149 copies of virus per milliliter (ml) of blood, about 4.5 times lower than the level found in men who progressed to AIDS, whose average was 77,822 copies/ml. Even men in the group who never developed AIDS had a higher median initial viral load of 40,634 copies/ml.
The women's lower levels meant that early after HIV infection a smaller percentage of them would have been eligible to start treatment with anti-HIV drugs. That calculation of eligibility relied upon clinical recommendations that were available at the time of the study. Such recommendations, which are reviewed regularly, have been updated recently.
"This research forms part of the body of data reviewed in forming the latest HIV treatment guidelines," says Anthony S. Fauci, M.D., director of NIAID. "It's important to conduct such studies that can give us a clearer picture of the unique challenges HIV/AIDS poses to women's health, because so many new cases of this disease are occurring among women, and among minority women in particular."
While the study sheds light on the effects of gender differences on viral load, Dr. Quinn notes that the best point at which to start anti-HIV drug treatments is still not known. Many other related questions remain - why are women's initial viral loads so much lower than men's? Are hormonal differences the key? Why do their levels rise after the initial years? "More studies on the dynamics of HIV infection could give us a better idea of when to start drug therapy to delay the onset of AIDS in people with HIV. Then we can help them have longer and healthier lives, which is our ultimate goal," says Dr. Quinn.
Reference: T Sterling et al. Initial plasma HIV-1 RNA levels and progression to AIDS in women and men. The New England Journal of Medicine 344(10):720-25 (2001).
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