Inclusion in START Trial Continues UNC’s History of HIV Research Informing Treatment Guidelines

David Wohl, MD, leads UNC's AIDS Clinical Trials Unit.

David Wohl, MD, leads UNC’s AIDS Clinical Trials Unit, and spoke about the START Trial results on WRAL. Click photo to watch the Health Team’s segment.

The Strategic Timing of AntiRetroviral Treatment (START) study released findings recently that may possibly change worldwide treatment guidelines. The University of North Carolina at Chapel Hill was one of three sites in the state that participated in this clinical trial, which found that starting people living with HIV on treatment earlier in their disease course protects them from death as well as co-morbid conditions related and unrelated to AIDS. The study is expected to influence the World Health Organization (WHO), who is meeting this month to review its global HIV treatment guidelines. Inclusion in this trial is just one of the many examples of how UNC Chapel Hill researchers have continued to be at the forefront of improving the lives of people living with HIV and preventing transmission of the virus to uninfected people.

START, conducted through the International Network for Strategic Initiatives in Global HIV Trials (INSIGHT), included 215 sites in 35 countries.  The trial enrolled and randomized 4,685 men and women who were infected with HIV and whose CD4 cell counts were above 500/mm3  (normal CD4 cell count is 1,000) to start HIV therapy immediately or to defer treatment until when their counts fell to 350 cells/mm3 or there was a clinical indication for HIV therapy.  After approximately three years of on-study follow-up, an independent data and safety monitoring board review found that there was a highly statistically significant difference between the early HIV therapy and deferred arms for the composite primary outcome of AIDS events, serious non-AIDS events, or death that favored the early treatment arm.

At UNC, 16 patients were enrolled in the trial. David Wohl, MD, Site Leader of the UNC AIDS Clinical Trials Unit at Chapel Hill, says the trial should be the end of a debate regarding the timing of HIV therapy that has raged since the first HIV medications became available.

“While other studies have suggested a benefit of antiretroviral treatment (ART) early in the course of HIV disease, the START study is the last word on ART, and we at UNC keep showing that early antiretroviral therapy is not only better and safer for the person living with HIV, but also for infection control,” Wohl says.

Wohl recently completed a six-year term on the U.S. Department of Health and Human Services (DHHS) ART guideline panel, serving on a subgroup advising exactly when to begin ART. These guidelines eliminated CD4 count thresholds for starting HIV therapy in 2013 and recommend ART to all with HIV regardless of CD4 cell count. Wohl notes that the WHO will look at the START trial’s results and could be motivated to change its current recommendation to include more people living with HIV. Currently, the WHO recommends ART for those with a CD4 cell counts of 500 cells/mm3 or less.

The results of the START Trial complement the findings of the HIV Prevention Trials Network (HPTN) 052 study. That trial was led by UNC’s Myron Cohen, MD, Co-Principal Investigator of the HPTN and Chief of UNC’s Division of Infectious Diseases. Dubbed the ‘Breakthrough of the Year’ by the prestigious medical journal Science in 2011, HPTN 052 demonstrated that ART was effective in preventing sexual transmission of the virus. An analysis of clinical outcomes also showed that ART given earlier also protected the health of those treated. Cohen’s four-year follow up confirmed the durability of treatment during the International AIDS Society’s meeting in Vancouver in July 2015.

UNC's Kevin Robertson, PhD, leads the neurology substudy of the START trial.

UNC’s Kevin Robertson, PhD, leads the neurology substudy of the START trial.

These results influencing treatment guidelines are just a few examples of notable HIV findings to come out of UNC. A substudy of the START trial is a neurological trial being led by UNC Neurologist Kevin Robertson, PhD, which seeks to further study the connection of ART on the brain and cognitive function.

“Based on studies that we have been a major part of at UNC, we know that HIV gets into the brain early, and also that antiretroviral treatment improves neurocognitive functioning – how people think and remember – later in the disease,” says Robertson. “What we hope to document in the START Neurology substudy is that early antiretroviral treatment will protect the brain over the long term, so individuals with HIV can have productive lives, as we continue to follow these participants over the years.”

The START neurology substudy is still in analysis and results are forthcoming.

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