An ongoing dialogue on HIV/AIDS, infectious diseases,
August 31st, 2012
“PEARLS” Study a Massive, Impressive Accomplishment
One of the most frequent criticisms of randomized clinical trials of HIV therapy is that certain patient groups — in particular gay men — are over represented compared to the HIV population as a whole. For example, in the recently published and presented clinical trials of the Quad and dolutegravir, women accounted for < 20% of the study population, despite representing approximately 50% of those living with HIV worldwide.
Now along comes the The Prospective Evaluation of Antiretrovirals in Resource Limited Settings (PEARLS) study, and let no one criticize this trial as not being representative! Conducted in Brazil, Haiti, India, Malawi, Peru, South Africa, Thailand, the United States, and Zimbabwe, the study enrolled 1,571 HIV-1-infected treatment-naive patients, of whom 47% were women. They were randomized to one of three treatments:
- ZDV/3TC + EFV
- TDF/FTC/EFV
- ddI + FTC + ATV
50% were African race, 23% Asian, and 20% Hispanic — remarkably diverse demographics.
A DSMB stopped the study early after observing a greater number of virologic failures in the ATV arm, and a lower than expected number of failures with the other two regimens. Furthermore, while the two EFV arms were comparably effective from a virologic perspective — a finding similar to the prior 934 study, where virologic failures were not significantly different — the safety of TDF/FTC/EFV was significantly better than ZDV/3TC + EFV, particularly in women. Interestingly, women also did better than men on the atazanavir regimen; the reason for this difference is being investigated, and may be related to fact that levels of PIs can be higher in women than men.
The importance of this study is that it greatly strengthens the evidence that TDF/FTC/EFV is truly our gold standard for HIV treatment across a broad range of patients and in multiple settings. It also demonstrates a research collaboration on a massive scale, involving the NIH, several pharmaceutical companies, literally hundreds of investigators at dozens of study sites, and 9 countries!
Additional analyses from this impressive trial are eagerly awaited.
2 Responses to ““PEARLS” Study a Massive, Impressive Accomplishment”
Paul E. Sax, MD
Contributing Editor
NEJM Journal Watch
Infectious Diseases
Biography | Disclosures | Summaries
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Paul, how did this study get past an IRB in the US? ddI/FTC and unboosted ATV??
Lenny,
The key is the start date of the study — way back in 2005, and the study planned at least a year before this. At that time the combination of ddI + 3TC was considered a reasonable alternative once-daily NRTI combination (largely due to this study), and unboosted ATV had the advantage of being metabolically friendly and NOT requiring ritonavir, which required cold storage, etc.
In 2012, I completely agree with you — I personally wouldn’t use ddI in anyone, especially a treatment-naive patient where we have so many safer choices!
Paul