HIV Drugs Getting Better (CME/CE)
The efficacy of HIV drugs in clinical trials has increased markedly over time, according to a meta-analysis of 144 studies with more than 40,000 participants.
Efficacy -- defined as the proportion of patients able to suppress HIV to undetectable levels -- was about 47% in trials conducted before 2000, according to Frederick Lee, MD, of the St. Vincent's Centre for Applied Medical Research, Sydney, in Australia.
In studies after 2008, efficacy was about 82%, Lee reported at the 7th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention.
Interestingly, the so-called "preferred" regimens of the U.S. Department of Health and Human Services (DHHS) guidelines panel outperformed the "alternative" regimens, which in turn did better than other combinations, Lee reported.
Lee noted that guidelines are based on serial assessments of individual trials, so a meta-analysis of all available trials should increase the ability to evaluate outcomes in subpopulations of patients and identify predictors of treatment success.
He and colleagues looked at all reported prospective drug trials in treatment-naive HIV patients with at least 48 weeks of follow-up and an intent-to-treat efficacy analysis.
All told, they found 144 phase II, III, and IV studies with 216 treatment groups, starting with 10 trials from the pre-1996 era through to 17 in 2009 and 2010.
On average, follow-up was 82 weeks and efficacy on treatment was 60%, Lee reported. About 25% of participants stopped treatment during their trial, usually because of adverse events and less commonly because the drugs weren't working to suppress the virus.
The nucleoside reverse transcriptase inhibitor backbone of tenofovir and emtricitabine was significantly more efficacious than most other backbones, with the exception of emtricitabine and didanosine, which was equally good, Lee and colleagues found.
The third drug in triple-drug therapy until recently has usually been either a non-nucleoside reverse transcriptase inhibitor or a protease inhibitor, and analysis suggested they were equally efficacious at 61% and 67%, respectively.
Considered as a group the new integrase inhibitors yield efficacy of about 81%, Lee and colleagues found, which was significantly better (at P
=0.002) than either of the other two classes.
Finally, an analysis of preferred DHHS regimens over time showed efficacy of 75%, compared with 65% for alternative regimens, and 55% for other treatment options.
The difference between the preferred and alternative regimens was significant (P
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The study finding delivers good news in one sense, commented Dan Kuritzkes, MD, of Brigham and Women's Hospital in Boston -- it shows that guidelines committees are doing a good job.
As a member of the DHHS guidelines panel, Kuritzkes said he was gratified to find that "it turns out that a bunch of experts sitting around and looking at data actually get it right."
The study "is confirmatory that we are having better drugs, more friendly drugs, and easier (drugs) to use," commented Pedro Cahn, MD, of Fundación Huesped in Buenos Aires and a former president of the IAS.
Those improvements are "the reason we are seeing increasing efficacy over time," he told MedPage Today.
The study was supported by the National Health and Medical Reserach Council of Australia. Lee made no disclosures.
Cahn has reported financial links with Abbott, Pfizer, GlaxoSmithKline, Pharmacia, and Roche.
Primary source: International AIDS Society
Source reference:
Lee FJ, et al "Efficacy of initial antiretroviral therapy: a meta-analysis of 40,124 adults with up to 144 weeks' follow-up" IAS
2013; Abstract WEAB0104.
