The first single once-daily tablet containing a protease inhibitor Viral suppression In almost all who switched therapy after plunging levels of undetectable HIV RNA into a multi-tablet regimen, according to a report in the 9 International AIDS Society's Conference on HIV Science (IAS 2017) last week in Paris , France.
Recommended antiretroviral therapy (ART) for first-line HIV treatment usually involves single-shot regimens, which are taken once daily.
Taking fewer pills may improve adherence, but there are fewer options for a single pill for second line therapy. Many treatment experienced individuals who have developed drug resistance may require a protease inhibitor, a class of drugs with potent and long-lasting antiviral activity and a great barrier to resistance.
Jean-Michel Molina of the University of Paris reported results from the EMERALD study, a 3 phase clinical trial to evaluate a tablet regime - dubbed D / C / F / TAF - containing the protease inhibitor darunavir (Prezista®), Cobicistat as an amplifier, and emtricitabine and tenofovir alaphaenamide (TAF) as a non-nucleoside reverse transcriptase inhibitor skeleton NRTI.
The single tablet regimen has been recommended for approval by the scientific committee of the European Medicines Agency and will be marketed as Symtuza In the European Union after formal marketing approval by the European Commission later this year.
The EMERALD Study enrolled 1141 participants in the UK, Europe and USA. More than 80% were men, 75% were white and the mean age was 46 years. They had HIV for an average of 9 years and the mean CD4 cell count was approximately 630 cells / Mm3. They had normal renal function at baseline, with an estimated rate of glomerular filtration (eGFR) with an average of about 107.
Participants should have maintained a viral load below 50 copies / ml for at least two months using a stronger protease inhibitor plus emtricitabine and older tenofovir disoproxil fumarate (TDF). For a little more 40%, this was his first therapeutic regimen (ART).
Most (about 70%) were treated with Darunavir boosted, 22% were in the retapiar that uses atazanavir as enhancer (Reyataz) And 8% was in lopinavir / ritonavir (Kaletra). About 15% already used cobicistat, instead of ritonavir, as their booster. About 15% had a history of prior virologic failure but could not have a previous failure of darunavir or evidence of darunavir resistance mutations.
Participants in this open study were randomly assigned to receive the new regimen of darunavir with a single tablet or remain in their current regimen for 48 weeks (Editor's note: THAT I consider sensible.I find it disgusting to use placebos in studies with humans, by no means, in any way the arguments in favor of the Placebo).
Molina presented interim results of 24 weeks:
After the primary endpoint of 48 weeks, all participants will continue with the tablet combination up to 96 weeks (Editor's note: This is also sensible).
D / C / F / TAF was highly effective: 96% of participants who switched maintained undetectable viral load, matching the proportion of what they did in their existing regimen.
Virologic recovery (reactivation of infection) was rare in both study arms (1,8 vs. 2,1%, respectively). Most rebounds regained viral suppression without altering therapy and there were no confirmed rebounds above 200 copies / ml or discontinuations of virologic failure treatment. Among the four people submitted to genotypic tests (two in each arm), no evidence of primary protease inhibitor or NRTI resistance mutations.
Treatment was generally safe and well tolerated. There were few drug-related 3 to 4 adverse events (1,2% in arm D / C / FF / TAF and 0,5% in continuity arm) or discontinuations anticipated by adverse events (1,3 vs 1,1%, respectively). The most common adverse events in both groups were nasopharyngitis (inflammation of the nose and throat), upper respiratory tract infections, and vitamin D deficiency.
Researchers have focused on the side effects of the kidneys and bones because TAF is less damaging to the kidneys and bones than TDF. The estimated GFR fell somewhat more in the D / C / F / TAF group than in the continuous therapy group.
However, Molina explained that cobicistat has a known inhibitory effect on creatinine secretion from the renal tubule, which leads to a decrease in estimated GFR, but has no effect on "real GFR." When GFR was measured using a different method, it increased slightly in the D / C / F / TAF arm while declining by about 1% in the continuous therapeutic arm.
The bone mineral density in the hip and spine increased slightly in the arm D / C / F / TAF (0,6 and 1,2%, respectively), while it fell by an even smaller amount in the continuation arm (-0,3% in both sites).
Based on these findings, the researchers concluded, "D / C / F / TAF combines the safety advantages of TAF and darunavir with the known efficacy and high genetic barrier to the resistance of darunavir in a single tablet regimen."