Conference on Retroviruses and Opportunistic Infections 2015

113LB [26] aimed at establishing the virologicalnon-inferiority of the TAF formulation compared to the TDFformulation. The primary endpoint was the proportion of peoplewith a viral load (VL) ≤50 copies/mL at 48 weeks using the FDAsnapshot endpoint. Median ages of the two groups were 33 and35 years, 85% in both groups were men, about 25% black and19% Hispanic/Latino. Median pre-ART CD4 cell count was404 cells/mm3 in the TAF arm and 406 cells/mm3 in the TDF arm.Pre-ART viral load was 4.58 log10 copies/mL in both arms. Thetwo arms seemed balanced for all measured characteristics. By 48 weeks from enrolment, 5% stopped treatment in the TAFarm and 8% stopped in the TDF arm. At 48 weeks 92% in theTAF arm and 90% in the TDF arm had a VL ≤50 copies/mL. Thedifference between arms (2.0%, 95% CI: -0.7%–4.7%) andtherefore virological non-inferiority of TAF to TDF in thissingle-tablet combination given to previously untreated peoplewas established. Resistance profiles for people whose treatmentfailed also appeared to be similar. Virological response rates didnot differ between study arms after stratifying participants bypre-treatment viral load above or below 100,000 copies/mL,baseline CD4 cell count above or below 200cells/mm3, age aboveor below 50 years, gender or race (no significant interactionsdetected). Treatment was generally safe and well tolerated, withno statistical differences in overall drug safety profiles betweenarms. There were few serious adverse events (8% for TAF vs 7%for TDF) or drug discontinuation for this reason (0.9% for TAF vs1.5% for TDF) in either group. The most common side effectswere diarrhoea (18%), nausea (16%) and headache, all occurringwith similar frequency in both groups. Although it was reassuring to see that virological non-inferiorityand general safety was established it remained unclear from thisfirst presentation whether TAF was indeed inducing less renaltoxicity than TDF, which was the main objective for conducting anon-inferiority trial. These potential concerns were partially addressed in the followingAbstract 143LB [27] by Paul Sax and colleagues. In this analysis,pre-specified safety endpoints were serum creatinine, proteinuria,and hip and spine bone mineral density (BMD). Tenofovir levelsin plasma were 91% lower with TAF than TDF. But tenofovir levelsin cells were four times higher with TAF. At week 48 serumcreatinine increased on average by 0.11 mg/dL with TDF versus0.08 mg/dL with TAF (P<0.001), consequently eGFR fell by anaverage of 11.2 mL/min with TDF versus 6.6 mL/min with TAF(P<0.001). None of the participants who received TAF and fourpeople receiving TDF (0.5%) left the study because of renaladverse events (two renal failures, one decreased eGFR, onenephropathy). Three people in the TAF arm (0.3%) and four inthe TDF arm (0.5%) had hypophosphataemia, and two people ineach arm (0.2%) had a grade 2 or greater increase in proteinuria.Nobody in the trial developed proximal tubulopathy. Healthiervalues of urine protein, albumin and β2-microglobulin through48 weeks were observed in the TAF compared to the TDF arm(P<0.001). Overall, there was a general sense that TAF mightcause less toxicity than TDF. However, despite highly statisticalsignificant differences for some of the parameters the clinicaldifference appeared to be small and it remains unclear whetherthe small improvement in safety profile justifies the much highercost of the new compound (TDF is likely to become generic inthe near future). Maturation inhibitor BMS-955176 Max Lataillade from Bristol-Myers Squibb presented findingsfrom a Phase IIa proof-of-concept study evaluatingBMS-955176, a second-generation maturation inhibitor(Abstract 114LB) [28]. Maturation inhibitors interfere withprotease cleavage of the Gag polyprotein, leading to the releaseof immature virus particles that cannot complete their lifecycle