The renal effects of tenofovir were associated with blood levels (abstract 603) at the conference. Another presentation (abstract 103) examined a prodrug of tenofovir, GS-7340, in a 10 day monotherapy study. This produg was associated with 88% lower plasma levels of tenofovir than when the currently prescribed prodrug TDF (tenofovir disproxil fumarate) was administered. It was highly potent and is likely to be studied further as an alternative to TDF.
ASHM Report Back
Clinical posts from members and guests of the Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine (ASHM) from various international medical and scientific conferences on HIV, AIDS, viral hepatitis, and sexual health.
The new "booster" drug, COBISTAT, is part of the "QUAD" single pill (see QUAD post) and a number of studies are in planning and in progress looking at the use of this agent. It may allow new regimens such as a once daily combination pill with a protease inhibitor for the first time.
The once daily dosed integrase inhibitor DOLUTEGRAVIR was the subject of a handful of presentations at the conference. Week 96 results from the SPRING-1 study were reported. This was a phase 2 study of 205 people comparing different doses of Dolutegravir (10, 24 and 50mg) with efavirenz, both in combination with a TDF/FTC or ABC/3TC backbone. At week 96 the proportion with a HIV viral load less than 50 copies per ml was 88% in the 50mg dolutegravr arm and 72% in the efavrenz arm (a non signficant difference). The treatment appeared well tolerated, although there was a mild elevation in serum creatinine, thought to be due to effects on renal secretion of creatinine and not real impairment of GFR. Phase 3 studies of this agent, which could provide a once daily integrase inhibitor regimen, are underway.
Session 26 on Wednesday was " State of ART and drug resistance” did not launch any new blockbuster antiretroviral – unlike some previous World AIDS or CROIs. However there was the first phase 3 results presented for QUAD.
Paper 101 is a 48 week phase 3 data on QUAD – Elvitegravir/Cobicistat/Emtricitabine/Tenofovir (trying saying that after 3 Seattle micro-brewery Pale Ales) versus Atripla involving 700 treatment naive patients. Quad was non-inferior to EFV/FTC/TDF with 88% and 84%, respectively, having viral suppression at week 48. Virologic failure rates at week 48 were 7% in both arms. Of AE occurring in ≥10% of subjects nausea was significantly more frequent in Quad than EFV/FTC/TDF, while dizziness, abnormal dreams, insomnia and rash were significantly less common in Quad than EFV/FTC/TDF. Of note creatinine clearance decrease was significantly greater than with EFV/FTC/TDF (–14.3 vs –3.0 mL/min by week 48).
A parallel phase 3 study is to be presented on Thursday (627) with the comparator arm being booster atavanavir /FTC/TDF in 708 treatment naive patients. Quad was non-inferior to EFV/FTC/TDF with 90% and 87% respectively, having viral suppression at week 48. Virologic failure rates at week 48 were 5% in both arms. Of AE occurring in ≥10% of subjects elevated bilirubin was significantly more frequent in the atavanavir arm. Of note creatinine clearance decrease was significantly greater than with the atavanavir arm (–12.7 vs –9.5 mL/min by week 48).
So in summary QUAD is a highly effective new STR (single tablet regimen) for HIV therapy. A concern is the decline in renal function with QUAD found in both studies which remains to be fully explained.