MACS passes 15-year mark and is still going strong

Long-time participant reflects on study’s meaning

One of the richest sources of AIDS research information will keep up its work, thanks to a recent government grant.

The Bethesda, MD-based National Institute of Allergy and Infectious Diseases (NIAID) recently awarded a five-year grant to extend the research work of the Multicenter AIDS Cohort Study (MACS), which reached a milestone of 15 years this spring.

MACS research has resulted in more than 600 published papers, and it’s the longest continuous study of HIV-infected people. Volunteer participants are men who have sex with men and who are willing to be evaluated every six months through a questionnaire about their health status, a physical exam, and blood samples. All of these data are processed through the Center for the Analysis and Management of the Data from MACS under the direction of an investigator at the Johns Hopkins School of Public Health in Baltimore.

Since 1984, the study has followed 5,622 homosexual and bisexual men nationwide to determine if, when, and how they contract HIV. The MACS sites are located at Johns Hopkins School of Public Health, Northwestern Univers ity Medical School Howard Brown Clinic in Chicago, the University of California Schools of Public Health and Medicine in Los Angeles, and the University of Pittsburgh Graduate School of Public Health.

The study originally enrolled 1,150 men, and more than 100 of those have attended all 30 MACS visits.

Program identified primary risk behaviors

"MACS made a big contribution to understanding the primary risk behaviors of spreading HIV," says Joseph Margolick, MD, PhD, associate professor in the department of molecular microbiology and immunology at the Johns Hopkins School of Public Health. Margolick, who is the director of MACS, has been involved in the study since its inception.

"One of the ideas people had in the 1980s was that you couldn’t change people’s sexual behavior, but it turned out that when people found out that a specific type of sexual behavior was communicating the disease, they did change their sexual behavior," Margolick says.

For example, once research showed that unprotected anal sex resulted in a high HIV transmission rate, men in the gay community began to use condoms during sex more frequently.

MACS research has helped public health officials develop prevention strategies, says Chris Camp, MA, chair of the Community Advisory Board of the Study to Help in AIDS Research Effort, which is part of the Baltimore MACS. Camp also works for the state of Maryland’s Department of Health and Mental Hygiene in the AIDS Administration as a training specialist.

Camp, who is HIV-positive, is a participant in the study. (See related article on Camp’s personal story, p. 94.)

"As part of the interview process when you come in every six months for a visit, they go through a whole series of questions about different behaviors you might engage in and what efforts you’re taking to reduce your risk of transmission to both yourself and others," Camp explains. "The study is divided between HIV-positive and -negative men."

Camp actually found out about his HIV status because of another government study. In 1982, he was involved in a hepatitis study in Texas. Researchers kept his blood samples, and then the government decided in the mid-1980s to do a retrospective study of the blood samples from the earlier study to see how many also showed antibodies to HIV. Camp, unfortunately, had the HIV antibodies, and was notified in 1986 of his infection.

"I’ve never been sick with anything HIV-related — not ever," he says. "I’ve had the joys of side effects from HIV drugs, but never had anything AIDS-related."

Camp became involved with the study in 1988 along with his partner at the time, who also was HIV-positive. They were part of a concordant couples group and were identified by the numbers 13218 and 13219, he recalls.

Camp’s partner died in 1992, his but participation with MACS has continued posthumously. "Even though he has passed away, they can go back and use his blood cells, culture from them, and take into consideration his samples," Camp says.

Margolick counts among MACS’ greatest accomplishments these two developments:

MACS researchers quickly learned the levels of T-cell counts that indicated a person was at risk for AIDS-defining illnesses.

"The question was, at what point are you so compromised that you’re at risk for getting this stuff?" Margolick says. Because of drug side effects, clinicians don’t want to treat everyone with prophylactic antibiotics, so it’s helpful to know the point at which the benefits outweigh the risks.

"We found that when the CD-4 cell count was 200 cells per milliliter of blood, that’s when a person started being at risk, and now that’s when they start taking prophylactic antibiotics to prevent pneumocystis pneumonia," Margolick explains.

MACS research has influenced guidelines regarding the use of viral load as a treatment criterion.

Using MACS blood samples from the early years of the HIV infection, researchers measured the virus in plasma to categorize them as low-load, intermediate-load, and high-load. Then they compared these viral load findings with what they knew of how quickly the disease had progressed in the people who had provided the samples.

"It turned out that the higher your viral load, the greater your chance of getting AIDS," says Margolick. "That influenced national guidelines that say when your viral load reaches a certain level in your blood, you should start taking [antiretroviral therapy]."

MACS research also has contributed to the study of people who have been infected with HIV but do not progress to AIDS. "There are a few people who have been infected the whole time, and we’re still trying to figure out why these people don’t progress to AIDS," Margolick says.

Another mystery MACS researchers are trying to unravel has to do with how T-cells are produced in response to HIV infection and why the immune system collapses.

"We’ve learned a lot about suppressor responses that inhibit the virus, but we need to learn much more," Margolick says.

As the study heads toward its 20th year in 2004, AIDS researchers have more cause for optimism than they did in the mid-1980s, Margolick notes. "Until 1995, when the protease inhibitors came along, people were dying at a pretty high rate, and we thought the study would end because there would be nobody left."

(Editor’s note: For more information about MACS, visit the Johns Hopkins School of Public Health Web site at www.statepi.jhsph.edu.)