One-a-day regimens mean better adherence for patients starting HIV treatment

A meta-analysis of eleven different randomised studies has found that once-daily HIV treatment combinations result in better adherence, most notably amongst patients starting HIV treatment for the first time. The study is published in the February 15^th edition of Clinical Infectious Diseases.

There was no improvement, however, in adherence rates amongst treatment-experienced patients who switched to once-daily regimens. What’s more there was a slight worsening of treatment outcomes amongst this group of patients.

Investigators identified eleven randomised, open-label studies that compared adherence rates between drugs that were taken once daily and ones taken twice daily.

Six of the studies compared the effect of once- versus twice-daily dosing of one drug or pill in regimes that were otherwise taken once daily. Half of the patients in these studies were therefore taking true once-a-day regimens.

These studies included two comparing once- with twice-daily lopinavir/ritonavir (Kaletra) plus once-daily tenofovir/FTC (Truvada), and three others where the comparison was, respectively, between Truvada and abacavir/3TC (Kivexa), plus a third once-daily drug; between d4T and the XR longer-lasting version of the drug, plus once-daily 3TC and efavirenz; between once- versus twice-daily abacavir/3TC/AZT (Trizivir); and between d4T (stavudine, Zerit)/3TC (lamivudine, Epivir)/efavirenz (Sustiva), and any other regimen.

The other five studies also compared once- versus twice-daily dosing of one drug in a regimen, but the other regimen components could be taken twice daily. Four compared, respectively, once- versus twice-daily dosing of Kaletra, AZT/3TC (Combivir), nevirapine (Viramune) and Kivexa ,while the fifth compared the near-equivalent drugs 3TC (twice daily) and FTC (once daily).

A total of 3029 patients took part in the eleven studies. Of these 55% were in studies of entirely once-daily regimens and 64% were treatment-naïve. About 30% of patients (22% drug-naïve) actually took entirely once-daily regimens after randomisation.

The meta-analysis found an overall improvement of 2.3% in adherence for once-daily drugs, which was statistically significant (p

However it found an improvement of 4.4% in adherence in treatment-naïve patients (p

The authors suggest that the reason adherence and virological outcome did not improve in treatment-experienced patients who switched, may have been because it was an entry requirement to the switch studies that patients already had an undetectable viral load. They must therefore already have had good adherence and there was little scope for improvement in viral load. They also speculate that in switch studies there are also higher chances of the new once-daily regimen proving to be less tolerable than the old regimen, and so the number of patients having to switch back to their old twice-daily regimen, or to a new one, are higher.

The authors conclude that once-daily dosing does improve adherence as long as all regimen components are to be taken once a day, and that they also produce better results in people new to HIV therapy.

However they also add that “the objective impact of once-daily versus twice-daily dosing on adherence is modest,” and urge that other factors such as tolerability, potency and the potential for resistance must be taken into consideration.