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March 29, 2000

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Low Blood Levels of HIV Reduce Risk of Heterosexual Transmission

People with HIV infections are less likely to pass the virus to an opposite sex partner if they have low levels of the virus in their blood, according to a new study by researchers from Johns Hopkins, the National Institutes of Health, Makerere University (Kampala, Uganda), the Uganda Virus Research Institute (Entebbe, Uganda), and Columbia University. Results of the study, published in this week's New England Journal of Medicine, show viral load is the critical predictor of HIV transmission between men and women, regardless of which gender transmits the virus.

"With every 10-fold rise in the concentration of HIV in the bloodstream, transmission more than doubled. Just as drugs have helped reduce perinatal transmission, antiretroviral regimens that dampen HIV viral load should also be effective against heterosexual transmission of HIV," says Thomas Quinn, M.D., a professor of medicine at Johns Hopkins and senior investigator at the National Institute of Allergy and Infectious Diseases's Laboratory of Immunoregulation.

The researchers also found that circumcision was significantly associated with decreased HIV acquisition and that younger couples (ages 15 to 19) experienced the highest rates of infection. They did not find any statistical difference in the rate of transmission from male to female compared to female to male.

Heterosexual transmission is responsible for more than 80 percent of the estimated 50 million cumulative infections of HIV-1 worldwide, and it is the predominant mode of transmission in sub-Saharan Africa. It is also increasing throughout Asia and in many industrialized countries.

In an effort to better identify risk factors for heterosexual HIV transmission, the scientists followed 415 couples in which only one person was HIV positive at the beginning of the study. The couples, all residents of Uganda's rural Rakai district, received free condoms and HIV prevention education, as well as confidential HIV testing, counseling and treatment. They did not receive anti-HIV drugs because they are not available in this remote area of Uganda.

The research team visited the couples at 10-month intervals for up to 30 months, conducting private, same-sex interviews. Researchers assessed a variety of factors, such as condom use, numbers of sexual partners, intercourse frequency, general health history, AIDS-defining symptoms and circumcision. Study volunteers provided blood and urine samples, and women provided self-collected vaginal swabs for evaluation of HIV and sexually transmitted diseases.

Using polymerase chain reaction to measure viral load, the researchers discovered that, over the two-and-a-half year study, 22 percent of the previously uninfected partners became HIV positive and that as the volume of HIV rose in the blood, so did the likelihood that a person would infect his or her partner. Nearly 80 percent of the cases of new infections resulted from exposure to HIV-positive partners with more than 10,000 copies of HIV per milliliter of blood. Individuals who had less than 1,500 copies of the virus per milliliter of blood did not transmit the virus to their partner.

Researchers say drug therapies that suppress the virus could significantly reduce the spread of the disease. Thus, trials of such interventions should be considered a public health priority. For resource-poor areas like Uganda, extra effort is needed to develop low-cost methods of reducing viral load.

The study was funded by the National Institute of Allergy and Infectious Diseases (NIAID) and the National Institute of Child Health and Human Development (NICHD). Other authors of the study are Maria J. Wawer, M.D., and Mary O. Meehan from Columbia University's Joseph L. Mailman School of Public Health; Nelson Sewankambo, M.B., Fred Wabwire-Mangen, Ph.D., and David Serwadda, M.B., from Makere University; Thomas Lutalo, M.A., from Rakai Project Team; and Chuan Jun Li, M.D., and Ronald H. Gray, M.D., from Johns Hopkins University.


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