COMMENTARY

International Aids Conference: Novel Studies Compare ART Regimens

Paul E. Sax, MD

Disclosures

August 26, 2016

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Hello. This is Dr Paul Sax, from Brigham and Women's Hospital and Harvard Medical School in Boston. Today I'd like to summarize a few of the more interesting antiretroviral therapy (ART) studies presented at the recent International AIDS Conference in Durban, South Africa.

The first is the ARIA Study,[1] a trial performed in approximately 500 treatment-naive HIV-infected women randomly assigned to dolutegravir/abacavir/lamivudine (DTG/ABC/3TC) or ritonavir-boosted atazanavir plus tenofovir/emtricitabine (ATV+RTV+TDF/FTC) in an open-label design. At 48 weeks, the DTG/ABC/3TC arm was statistically significantly better, both because there were fewer discontinuations for adverse events, and fewer virologic failures. Notably, there were no cases of incident resistance in the DTG/ABC/3TC arm. This is yet another study cementing the first-line choices for ART now endorsed in the HIV treatment guidelines of both the US Department of Health and Human Services and the International Antiviral Society-USA.

The second analysis I'd like to talk about, the REALITY study,[2] was very interesting owing to its novel design and patient population. It was performed in sub-Saharan Africa in approximately 2000 individuals with a CD4 cell count < 100 cells/mm3. These antiretroviral-naive patients were randomly assigned to usual ART, predominantly efavirenz-based, or usual ART plus intensification with raltegravir for the first 12 weeks that they were on therapy. Not surprisingly, the people who got the raltegravir intensification had a faster HIV RNA decline and a greater CD4 cell count increase. However, the primary clinical endpoint did not demonstrate any benefit for this intensification. So once again, a four-drug regimen is proving no better than a three-drug regimen.

At the opposite extreme, what about a two-drug regimen? Updated data were presented from the PADDLE study,[3] a small, single-arm analysis in 20 treatment-naive patients with a screening HIV-1 RNA value less than< 100,000 copies/mL. They were given the two-drug dolutegravir/lamivudine regimen, and were followed for what has now been 48 weeks. At 48 weeks, 90% (18 out of 20) were successfully treated. Unfortunately, one patient died of suicide before the end of the study. Also, another patient experienced virologic failure. This patient started with screening HIV RNA <100,000 cells/mm3, but his entry HIV RNA was > 100,000 copies/mL. He ended up having low-level viremia toward the end of the study, and stayed in the study a bit longer—enough time so that he resuppressed, but is now on triple therapy.

One of this study's limitations, of course, is that it's very small, so we can't draw any conclusions about the relative performance of this two-drug strategy compared to the usual three-drug approaches. However, such larger studies are ongoing.

Please feel free to respond in the comment section on anything I've spoken about today. Once again, this is Dr Paul Sax. Thank you very much.

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