Here, in bite-sized form, is our run-through of some of the clinically noteworthy studies on HIV antiretrovirals that were presented at IAS 2015 in Vancouver, British Columbia. We'll be adding to this article as we continue to review conference presentations, posters and abstracts.
Women-Only Stribild Study Shows Superiority -- and Proves a Point
One of the conference's most important presentations never even made it to a stage, though it was frequently mentioned by other presenters. WAVES (short for "Women Antiretroviral Efficacy and Safety") is the first major head-to-head study of commonly used HIV antiretroviral regimens in which the participants were all female -- you read that right, and yes, we are indeed two decades into the combination antiretroviral treatment era. It pitted elvitegravir/cobicistat/emtricitabine/tenofovir (Stribild) against a regimen of ritonavir (Norvir)-boosted atazanavir (Reyataz) plus tenofovir/emtricitabine (Truvada). The results were presented in a poster by Kathleen Squires of Thomas Jefferson University.
The international, randomized, double-blind trial of 575 women demonstrated Stribild's virologic superiority over the boosted atazanavir regimen through 48 weeks, regardless of baseline viral load and CD4 count. There were no real surprises on the safety front based on what we already know about these drugs, and no one on the Stribild regimen developed resistance.
Boosted atazanavir has been relegated to an also-ran in U.S. first-line treatment recommendations, thanks to the relatively recent rise of integrase inhibitors and one-pill regimens such as Stribild. As much as anything, this study's value lies in its ability to prove a point that many researchers have long tried to make: It is an entirely feasible endeavor to construct and execute a robust HIV clinical trial that does not consist mostly of men.
As TAF Nears Approval, Solid Switch Study Results
A pair of oral abstract presentations highlighted the potential benefits -- or, less commonly, pitfalls -- of switching from the "current" tenofovir to the "new" tenofovir once U.S. Food and Drug Administration approval arrives (likely later this year). The "new" tenofovir, of course, is tenofovir alafenamide fumarate (TAF), a tenofovir prodrug with a friendlier toxicity profile than the current standard-of-care tenofovir dipivoxil fumarate (TDF).
Tony Mills of the Southern California Men's Medical Group presented 48-week data from GS-292-0109, a very large study (1,436 participants!) that enrolled people who had been fully suppressed on a TDF-containing regimen for at least the prior 96 weeks. The participants (89% male, roughly 68% white) were randomized 2:1 to either receive a formulation of Stribild with the 300 mg of TDF replaced with 10 mg of TAF or to continue on their current TDF regimen.
Virologic outcome through 48 weeks heavily favored the Stribild-TAF arm, regardless of age, race or adherence level. (Gauging outcome by sex was more challenging due to the low percentage of women enrolled.) However, it wasn't sheer virologic efficacy that drove the difference; the culprit here was adverse events leading to treatment discontinuation. People in the Stribild-TAF arm exhibited significantly less osteopenia and osteoporosis, significant improvements in bone mineral density of the hip and spine, and significantly better renal function compared to people in the TDF arm.
Of note, fasting lipids (i.e., total cholesterol, HDL, LDL, TC:HDL ratio and triglycerides) all significantly increased among people in the Stribild-TAF arm relative to the TDF arm, highlighting the long-established tendency for free-circulating TDF to reduce lipid levels.
A follow-up presentation by Samir Gupta of the Indiana University School of Medicine highlighted TAF's benefits relative to TDF in patients with established renal impairment. His small (242-patient), open-label study enrolled virologically suppressed patients with a stable, but low, estimated glomerular filtration rate and switched them from their current therapy to Stribild-TAF. At week 48, participants generally saw significant improvements in renal function. Among participants who had switched from a TDF-containing regimen to Stribild-TAF, there were statistically significant reductions in clinically significant albuminuria and proteinuria.
Reduced Atazanavir Dose Appears Safer, Retains Activity
Lowering the dose of once-daily atazanavir from 300 mg to 200 mg in a ritonavir-boosted regimen significantly reduces toxicity without hurting the regimen's virologic efficacy in Thai patients, according to results from the LASA study.
The study grew out of earlier findings that the standard 300-mg dose of atazanavir with 100 mg of ritonavir led to significantly higher drug exposure levels in Thai patients relative to their U.S. counterparts. The 48-week results of this randomized trial of 560 participants (about half of whom were women) already on a boosted protease inhibitor regimen, presented by Torsak Bunupuradah of the HIV Netherlands Australia Thailand Research Collaboration, found that viral suppression rates were very similar (and very high) between the two arms -- that is, until one looked at the data using an NC=F (non-complete equals failure) analysis. At which point the lower-dose regimen looked significantly better, thanks to dramatically lower discontinuation rates overall (including discontinuations due to clinical jaundice or rash). Rates of grade 3 to 4 hyperbilirubinemia were also significantly lower in the study's reduced-dose arm.
One must be cautious when assessing the applicability of these study results outside of Thai patients. But they are interesting both from the standpoint of potential toxicity reduction (perhaps especially in patients with low body weight) and treatment cost reduction -- that is, assuming a clinician treating a patient with atazanavir-related toxicities does not decide to switch to a different regimen entirely.
Myles Helfand is the editorial director of TheBody.com and TheBodyPRO.com.
Follow Myles on Twitter: @MylesatTheBody.