Jim Kling

September 19, 2013

DENVER — Switching from an antiretroviral regimen containing a boosted protease inhibitor to a once-daily, single-tablet regimen is safe and effective in black patients with HIV, according to a subgroup analysis from the SPIRIT trial.

Simplified antiretroviral regimens reportedly improve adherence and reduce the likelihood of virologic failure. They also lessen the risk for long-term drug toxicity. One single-tablet regimen — rilpivirine, emtricitabine, and tenofovir disoproxil fumarate — has been shown to be well tolerated and effective.

Black patients are underrepresented in trials of HIV therapies, and historically have been in all trials in the United States, said SPIRIT investigator Karam Mounzer, MD, medical director of Philadelphia FIGHT, a comprehensive AIDS service organization.

Dr. Mounzer presented the new subgroup analysis here at the 53rd Interscience Conference on Antimicrobial Agents and Chemotherapy.

The phase 3b SPIRIT trial was the first to evaluate the safety and efficacy of switching from an antiretroviral regimen of ritonavir plus 2 nucleoside/nucleotide reverse-transcriptase inhibitors with a boosted protease inhibitor to the single-tablet regimen in individuals infected with HIV-1 who were virally suppressed.

Study participants were randomized to undergo an immediate switch to the single tablet at baseline or to maintain their antiretroviral regimen with a boosted protease inhibitor for 24 weeks, and then switch to the single tablet for 24 weeks.

The primary end point was noninferiority of the single-tablet regimen at 24 weeks.

At week 24, there was no significant difference in viral suppression between the immediate-switch (single-tablet regimen) and delayed-switch (protease inhibitor regimen) groups (94% vs 90%; difference, 3.8%; 95% confidence interval [CI], –1.6% to 9.1%), indicating noninferiority. At week 48, when both groups had switched to the single tablet, there was also no significant difference (89% vs 92%).

When the researchers performed a subgroup analysis of black study participants, results were similar.

At week 48, there was no significant difference in viral suppression between the immediate-switch and delayed-switch groups (95% vs 91%; difference, 4.2%; 95% CI, –9.0% to 17.4%). At week 48, there was also no significant difference (89% vs 95%).

There was a significant improvement in lipid levels with the single-tablet regimen in the subanalysis.

Table. Mean Change From Baseline Lipid Levels in the Subgroup Analysis

Lipid Immediate Switch (Weeks 1–24) Delayed Switch (Weeks 1–24) Delayed Switch (Weeks 25–48) Immediate Switch (Weeks 1–48) P Value
Triglycerides (mg/dL) –26 +1 –33 –40 <.001
TC:HDL ratio –0.24 –0.17 –0.05 –0.32 .007
Cholesterol          
Total (mg/dL) –23 +2 –12 –25 <.001
Low-density lipoprotein (mg/dL) –19 –1 –6 –20 <.001
High-density lipoprotein (mg/dL) –3 +3 –2 –3 .027

 

In the subanalysis, the rate of grade 3/4 adverse events in the immediate-switch group was 8.2% over the 48-week period. In the delayed-switch group, the rate was 4.5% in the first 24 weeks (protease inhibitor regimen), and 5.0% in the second 24 weeks (single-tablet regimen).

The black study participants "had a fairly good response, compared with their white counterparts," Dr. Mounzer said.

It's encouraging that black patients who achieve viral suppression on "protease inhibitors can be switched to this fixed-dose combo — one pill once a day — and really have outstanding results," said Judith Aberg, MD, director of infectious diseases and immunology at the NYU School of Medicine, in New York City, who was not involved in the study.

The study has a small sample size, and "we don't want to overstate what it shows," said Dr. Aberg. Nevertheless, she said the results are encouraging, especially given that in some studies, black individuals have fared worse than white individuals when it came to viral failure rates. Such results "raise concerns, not only of disparities in healthcare, but that there could be a differential in the absorbance of medications. That has encouraged the pharmaceutical companies to look at how their antiretrovirals respond in the various subpopulations," she noted.

"The lipid data are important because we're treating people now for 20 or 30 years," Dr. Mounzer added. "A small improvement in lipids can translate over time into a substantial reduction in cardiovascular risk. We haven't established that, but that's the rationale."

"We're getting better at reaching this population," said Dr. Aberg. "It helps that we have a simpler, less-toxic combination therapy that improves adherence. This study reassures us that these medications work in all populations equally," she said.

Dr. Mounzer reports financial relationships with Gilead Sciences, Pfizer, GlaxoSmithKline, Merck, Boehringer Ingelheim, and Johnson & Johnson. Dr. Aberg reports being on the scientific advisory board for Janssen, Merck, and AbbVie.

53rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC): Abstract H-656. Presented September 11, 2013.

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