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Early Antiretroviral Therapy Prevents Non-AIDS Outcomes in HIV-Infected People


According to an article published online in the New England Journal of Medicine (20 July 2015) based on new analysis of data from the Strategic Timing of AntiRetroviral Treatment (START) study, starting antiretroviral therapy early not only prevents serious AIDS-related diseases, but also prevents the onset of cancer, cardiovascular disease, and other non-AIDS-related diseases in HIV-infected people. Rates of both serious AIDS-related events and serious non-AIDS-related events were significantly reduced with early therapy.


The study’s composite endpoint had two components: serious AIDS events or death from AIDS, and serious non-AIDS events or non AIDS-related death. In May 2015, theSTART trial investigators released their initial groundbreaking findings that starting antiretroviral therapy early when immune systems are healthier, without waiting for CD4+ cell counts to decline, prevented the composite of serious AIDS events (such as AIDS-related cancers), serious non-AIDS-related events and death among HIV-infected individuals. The current results, which draw on more than two months of additional data since that announcement, show that starting treatment early significantly reduces the risk of both major components of this combined outcome: serious AIDS events and serious non-AIDS events. Non-AIDS-related events tracked by the study included cardiovascular disease, end-stage renal disease, liver disease, non-AIDS defining cancer or causes of death not attributable to AIDS. Serious AIDS events were reduced by 72% and serious non-AIDS events were reduced by 39%.


Based on the new data and analysis, the study now reports the overall risk of developing serious AIDS events, serious non-AIDS events, or death, was reduced by 57% among those in the early treatment group, compared to those in the deferred group. This reduction was seen regardless of age, gender, baseline CD4+ cell counts, geographic region or country income level. Other potentially life-threatening events and unscheduled hospitalizations for reasons other than AIDS were also assessed, and results did not differ between the immediate and deferred therapy groups, demonstrating the safety of early antiretroviral therapy.


The START study, which opened widely in March 2011, was conducted by the International Network for Strategic Initiatives in Global HIV Trials (INSIGHT). It enrolled 4,685 HIV-infected men and women ages 18 and older in 35 countries. Participants had never taken antiretroviral therapy and were enrolled with CD4+ cell counts in the normal range-above 500 cells per cubic millimeter (cells/mm3). Approximately half of the study participants were randomized to initiate antiretroviral treatment immediately (early treatment), and the other half were randomized to defer treatment until their CD4+ cell count declined to 350 cells/mm3. On average, participants in the study were followed for three years.


Although the median age of study participants was 36 – a relatively young group of participants – the most common events observed in the study were serious non-AIDS events, including many that typically affect older individuals. The two most common individual serious non-AIDS events in the immediate and deferred groups were cardiovascular disease (12 and 14 participants with events, respectively) and non-AIDS-defining cancer (9 and 18 participants with events, respectively).


To evaluate the safety of early treatment, potentially life-threatening symptomatic events not attributable to AIDS and unscheduled hospitalizations for reasons other than AIDS were assessed in both treatment groups. Rates for these events were similar in the two groups. When these events were combined with the serious AIDS and serious non-AIDS events, as an overall measure of clinical benefit for early treatment, the rate was 18% lower in the early treatment group, compared to the deferred treatment group.


The study was conducted in 215 sites across 35 countries, representing a diverse population of HIV-positive individuals. Specific outcomes differed by geographic region, though the benefits of immediate antiretroviral therapy were consistent. Most of the cancers and cardiovascular disease events occurred among participants from higher-income countries in Europe, and Australia, Israel and the United States (22 of 27 cancer diagnoses and 19 of 26 cardiovascular events, respectively). Most of the tuberculosis occurred among participants at study sites in Africa (16 of 26 events), where both TB and HIV/AIDS are endemic.


According to the study team, these findings are subject to some limitations. The patient population enrolled in START was younger than projected and experienced fewer overall events than were originally projected in the study’s design. This limited the ability to determine the effect of immediate antiretroviral therapy on specific serious non-AIDS conditions, such as the risk of cardiovascular disease. Further follow-up of this relatively young study population may help the better understand how early antiretroviral therapy impacts the cardiovascular system.


The HIV medicines used in the trial are approved medications donated by AbbVie, Inc., Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline/ViiV Healthcare, Janssen Scientific Affairs, LLC, and Merck & Co.



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