Gilead Sciences presents latest findings from DISCOVER trial in a subset of patients and on the impact of HIV pre-exposure prophylaxis in the US.

Gilead Sciences, Inc. announced important findings from the DISCOVER trial evaluating Descovy (emtricitabine 200 mg and tenofovir alafenamide 25 mg tablets; F/TAF) for HIV pre-exposure prophylaxis (PrEP) , showing significant improvements in key measures of bone and renal safety parameters in a subset of study participants who switched from Truvada (emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg tablets; F/TDF) for PrEP to Descovy for PrEP. The company also released the latest data demonstrating that major metropolitan areas in the United States with the highest use of HIV PrEP experienced the greatest decreases in new diagnoses. The data will be presented at the IDWeek 2019 conference being held in Washington, D.C. from October 2-6.

DISCOVER Trial: Renal and Bone Safety Profile Data Among Participants Switching from Truvada to Descovy for HIV Pre-exposure Prophylaxis : Two sub-analyses of data from the DISCOVER trial, a multi-year global Phase III clinical study of HIV prevention in 5,387 men and transgender women who have sex with men (MSM, TGW) will be presented. These findings provide new bone and renal safety profile data from a subgroup of 905 study participants (17 percent) who were using Truvada for PrEP at baseline and were randomized 1:1 to either continue Truvada or to switch to Descovy for PrEP.

The first study (oral abstract 1962) reports 48-week renal safety parameters among 465 participants who switched from Truvada for PrEP to Descovy for PrEP after enrolling in the DISCOVER trial, finding statistically significant improvements in key prespecified laboratory measures of kidney function, including urine protein:creatinine (CR) ratio (UPCR), estimated glomerular filtration rate (eGFRCG) and markers of proximal tubular function ( beta2-microglobulin:Cr ratio [beta2M:Cr] and retinol binding protein:Cr ratio [RBP Cr]). Improvements were statistically significant as early as Week 4 of the trial. At Week 48, eGFRCG increased by 3.9 mL/min from baseline for those randomized to F/TAF and decreased by 0.6 mL/min in those who continued to receive F/TDF (p<0.001). greater declines in rbp:cr and beta2m:cr were observed among participants randomized to f taf compared with those who received f tdf. additional renal outcomes data from the 5,387 discover trial participants through 48 weeks will also be presented, including that study participants randomized to f taf for prep had fewer study drug-related renal adverse effects (aes) and fewer discontinuations due to renal aes compared with study participants randomized to f tdf. common adverse reactions ( greater than 2 percent; all grades) in the discover trial included diarrhea, nausea, headache, fatigue, and abdominal pain.>

A second presentation (abstract 1288 reports 48-week data on bone mineral density (BMD) outcomes among a subgroup of DISCOVER trial participants who received additional bone strength evaluations. Of these individuals (n=383), 53 participants were on baseline F/TDF PrEP at enrollment, 26 of whom were randomized to F/TAF. Participants who were randomized to switch to F/TAF experienced statistically significant improvements in BMD of the hip and spine compared with those randomized to continue F/TDF. In addition, participants taking F/TAF for PrEP were significantly less likely to develop osteopenia of the spine. The prevalence of osteopenia among the 2,694 study participants who took F/TAF for PrEP was 0.4 percent. The prevalence of osteopenia among the 2,693 study participants who took F/TDF for PrEP was 0.6 percent. Rates of fracture incidence were similar across the F/TAF and F/TDF groups. Among the subset of participants who were taking F/TDF for PrEP prior to randomization to F/TAF, significant improvements in hip BMD compared with baseline were observed, while spine BMD was unchanged.

Increased PrEP Use associated with significant reductions in New HIV diagnoses in major U.S. metropolitan areas : A new analysis (abstract 1963) demonstrates the significant impact of PrEP for reducing new HIV diagnoses since the approval of the biomedical intervention, finding that between 2012 and 2017 metropolitan statistical areas (MSAs) in the United States with the highest rates of PrEP use experienced the greatest decreases in HIV diagnoses. Importantly, this effect was independent of the impact of treatment as prevention (TasP). The analysis evaluates U.S. Centers for Disease Control and Prevention (CDC) HIV surveillance data collected between 2012 and 2017 from 105 MSAs, national pharmacy and medical claims databases and proxy data for TasP from HIV-suppressed individuals in 38 states and Washington, D.C. Between 2012 and 2017, the rate of PrEP use among at-risk individuals increased by greater than nine-fold, at an average rate of 2.95 percent per year, and HIV viral suppression increased by 1.34 percent per year during the same period. Overall, from 2012 to 2017, there was a 15.2 percent decline in the total rate of new HIV diagnoses. In MSAs with the highest rates of PrEP use, HIV diagnoses decreased by as much as 4.24 percent per year, whereas in MSAs with the lowest rates of PrEP use, HIV diagnoses decreased by 0.23 percent per year; these declines were statistically significant and independent of TasP. Comparatively, TasP independent of PrEP contributed to a 2.87 percent decline in HIV diagnoses for each percent increase in the proportion of HIV-infected people achieving viral suppression. Projecting out five years, the analysis suggests that if PrEP utilization among individuals at high risk of HIV could reach 50 percent by 2022 in the MSAs analyzed, a 40.7 percent decline in the rate of new HIV diagnoses is possible.