番茄社区

BOSTON -- A novel version of a standard HIV treatment backbone performed as well as the original with fewer safety issues, a researcher said here.

For years, the fixed-dose single-pill combination of tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) -- sold as Truvada -- has been a favored backbone for many three-drug anti-HIV regimens, noted , of the Southwest Care Center in Santa Fe, N.M.

But a new prodrug of TDF -- tenofovir alafenamide, or TAF -- appears to have similar efficacy with fewer side effects, Gallant reported at the (CROI).

Indeed, randomized trials reported last year showed that when TAF was substituted for TDF in a four-drug combination pill, efficacy outcomes were similar but patients had better bone and renal health.

Gallant was reporting on a placebo-controlled investigation in which Truvada or its analogue with TAF was combined with another anti-HIV drug, either a boosted protease inhibitor or an unboosted third agent.

Patients whose HIV was under control on Truvada plus a third agent were randomly assigned to stay on their regimen (dubbed F/TDF for this study) or to switch to the Truvada analogue with TAF (F/TAF), while continuing their third agent, Gallant told 番茄社区.

"From an efficacy standpoint they were the same -- very high rates of virologic success, very minimal rates of virologic failure," Gallant said.

Indeed, after 48 weeks of treatment, 94.3% of the 333 patients started on F/TAF maintained HIV suppression, compared with 93% of the 330 who remained on F/TDF. The small difference established the non-inferiority of the novel regimen, Gallant said.

"The more interesting data, I think, are in the toxicity," he said.

TDF has long been known to lead to renal and bone side effects, owing to high plasma levels of the drug. In particular, it reduces bone mineral density, depresses creatinine clearance, and increases urinary protein to creatinine ratios.

But TAF has markedly lower levels in plasma -- some 91% lower than for TDF -- while maintaining similar levels in cells, he noted.

The analysis found that patients switched to F/TAF saw their estimated glomerular filtration rate rise significantly (at P<0.001) compared with those remaining on F/TDF. Urinary protein to creatinine ratios also improved significantly (at P<0.001 for all comparisons).

Bone mineral density, both at the spine and hip, improved for those on F/TAF, while remaining stable for those taking F/TDF and at the end of 48 weeks of treatment the differences at both sites were significant at P<0.001, Gallant reported.

As well, 30% of F/TAF patients had at least a 3% increase in spine bone density and 17% showed at least a 3% increase in bone density at the hip. In contrast, 14% and 9% of F/TDF patients had such increases -- differences between treatment groups that were significant at P<0.001 and P=0.003, respectively.

The differences in toxicity are statistically significant but might not play a major role in decisions to change therapy, commented , of University Hospital Geneva in Switzerland, who was not part of the study but who co-moderated the session at which it was presented.

"There was no difference in the rate of discontinuation," she told 番茄社区, "so is there really a need to switch?"

On the other hand, the study should serve to reassure clinicians concerned about how well the F/TAF pill will work with various third agents, commented co-moderator, of Johns Hopkins University in Baltimore.

For those people, she told 番茄社区, the study "fills in a gap."

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