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Staying Positive

Jon Reinfurt

Staying Positive (continued)

From nearly the beginning of the AIDS epidemic in 1981, Hopkins epidemiologists have relied on unique cohorts of patients to help them define, control and treat HIV infection. What sets the researchers’ approach apart is that instead of comparing people with HIV to those in the general population—a study practice that, in many epidemiologists’ opinions, leads to misleading results—the epidemiologists have intensely studied HIV-positive and HIV-negative people from the same backgrounds for decades.

In the MACS study, that’s been almost entirely men who have sex with men. The ALIVE study (AIDS-Linked to the Intravenous Experience) has looked at some 4,000 injection drug users in East Baltimore since 1988, while WIHS (the Women’s Interagency HIV Study) has enrolled more than 3,700 women since it began in 1993. In each case, the participants have given greatly of their time and bodies. In the MACS cohort, for example, some people travel several hours to keep their semi-annual commitment.

“I can’t say enough positive things about the participants,” says Jacobson, who helps create statistical models to make sense of the mass of MACS data coming in from sites in Baltimore, Chicago, Los Angeles and Pittsburgh. “In addition to extensive medical questionnaires and the physical, we have exams to observe things like frailty, so we have them do timed walking and hand gripping. For kidney function we had a subgroup that went through infusions (they had an intravenous solution of Iohexol, which the kidneys normally quickly excrete), and had blood taken five times over four hours. We have another sub-study on cardiovascular disease where a group goes for IV contrast (injection) and cardiovascular scanning.

Not long after being diagnosed as HIV-positive in 1994, Mike Willis nearly died. But since then, he has stabilized on a modest two-drug HAART regimen. “I don’t have a lot to complain about,” he says. “I’ve done really well, and I’m grateful.”

“It’s incredible,” she continues. “We’re learning so much. We just pulled stored blood [from] 12,000 person visits over 25 years, to look at markers of inflammation and co-infections. In the MACS, we have over 600 men who became infected while under observation, who contributed specimens before and after infection, as well as before and after initiation of treatment. So we can see how biomarkers (such as those that can measure presence of heart disease, inflammation and cancer) are affected from both HIV and treatment. They also go through neuropsychological testing so we can see the effects of infection on cognition and memory.”

Given this level of scrutiny, the cohorts have yielded a treasure trove of findings; some 1,100 published papers from MACS, and 365 from ALIVE, according to its PI, epidemiologist Gregory Kirk, MD, PhD ’03, MPH ’95. Historically, those MACS papers helped confirm the mechanism for how HIV replicates and destroys key CD4 immune cells in the process; the relationship between high HIV viral load, low CD4 cell counts and the progression of illness; and the point at which so-called HAART (highly active antiretroviral therapy) should be started to maximize its effectiveness.

Now those data are being used to determine long-term consequences of HIV infection and treatments on aging. When an April 2011 Journal of the National Cancer Institute paper highlighted the U.S. cancer burden among HIV-infected individuals, it set off alarm bells among many older patients and clinicians, especially when its authors noted, “HIV-infected people are at an increased risk of many non-AIDS defining cancers... In a meta-analysis, these risks were estimated to be increased threefold for lung cancer, 29-fold for anal cancer, fivefold for liver cancer and 11-fold for Hodgkin’s lymphoma.”

Bloomberg School researcher Joseph Margolick, MD, PhD, suggests taking these concerning numbers with a grain of salt. Margolick, who is the PI of the MACS Baltimore site, says many studies attempt to draw conclusions without having cohorts that contain large numbers of HIV-negative and HIV-positive persons from the same at-risk populations. He notes that people at risk for HIV are different from the general public in terms of exposure to many infectious agents. For example, injection drug users have a much higher rate of hepatitis C infection than the general population. So in that case, to assess the effects of HIV infection, it’s important to compare HIV-positive injection drug users to HIV-negative injection drug users rather than the general public, he says.

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  • SnO-FlAkE

    leland ms 09/18/2012 11:49:30 AM

    very very gd info

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