Study on Switching to TDF/FTC/RPV SPIRIT Study
Explore the SPIRIT study focusing on switching from PI/r + 2 NRTIs to TDF/FTC/RPV in HIV-positive adults. The study aims to assess non-inferiority in achieving HIV-1 RNA
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Switch to TDF/FTC/RPV SPIRIT Study
SPIRIT study: Switch PI/r + 2 NRTI to TDF/FTC/RPV Design Randomisation 2 : 1 Open-label W24 W48 476 HIV+ adults Stable PI + RTV + 2 NRTI 6 months with HIV RNA < 50 c/mL On 1stor 2ndregimen No prior NNRTI use No known resistance to study agents N = 317 TDF/FTC/RPV STR TDF/FTC/RPV STR TDF/FTC/RPV STR PI/r + 2 NRTIs N = 159 24 weeks 48 weeks 48 weeks 24 weeks Primary Endpoint Primary Endpoint Secondary Endpoint Secondary Endpoint Objective Primary Endpoint : Non-inferiority in the proportion of patients with HIV-1 RNA < 50 c/mL at W24 (FDA snapshot analysis) ; upper limit of the 95% CI for the difference = 12% Secondary Endpoints: Proportion of HIV1 RNA < 50 copies/mL at W48 ; Change in fasting lipid and CD4 cell count at W24 and W48 ; Safety and tolerability Palella F, AIDS 2014;28:335-44 SPIRIT
SPIRIT study: Switch PI/r + 2 NRTI to TDF/FTC/RPV Baseline characteristics and disposition TDF/FTC/RPV N = 159 14% 576 2.9 N = 20 7 / 1 N = 7 0 / 1 2 NRTI + PI/r N = 317 9% 600 2.6 N = 7 0 / 0 N = 9 5 / 1 Female Baseline CD4/mm3(mean) Time since first ART, years (median) Discontinued before W24 Adverse event / Lack of efficacy Discontinued between W24 and W48 Adverse event / Lack of efficacy ART at screening NRTI PI/r 81% 37% TDF/FTC ATV/r 13% 20% ABC/3TC DRV/r 3.4% 33% ZDV/3TC FPV/r 33% LPV/r Palella F, AIDS 2014;28:335-44 SPIRIT
SPIRIT study: Switch PI/r + 2 NRTI to TDF/FTC/RPV HIV RNA < 50 c/mL at W24 according to pre-ART HIV RNA HIV RNA < 50 c/mL at W24 and W48 (ITT, snapshot) TDF/FTC/RPV (D1 to W24) 2 NRTI + PI/r (D1 to W24) TDF/FTC/RPV (delayed switch, W24 to W48) % 95 100 95.5 TDF/FTC/RPV (immediate switch, D1 to W48) 92.3 89.2 % 80 100 93.7 92.1 89.3 89.9 60 80 60 40 40 20 152/ 160 83/ 93 128/ 134 48/ 52 20 0 > 100 000 c/ml < 100 000 c/ml Virologic failure HIV RNA, pre-ART (23 patients TDF/FTC/RPV and 14 PI/r excluded from analysis [data not avalaible]) % 0 (95%CI) 5 3.8 (- 1.6 ; 9.1) : non inferiority 2.5 1.3 (95%CI) : 5.8 (- 1.4 ; 12.9) (95%CI) : 3.2 (- 4.8 ; 11.3) 0.9 HIV RNA < 50 c/mL, ITT, M = excluded RPV = 99.7% vs PI/r = 94.7% 8/317 3/317 8/159 2/152 Non inferiority Palella F, AIDS 2014;28:335-44 SPIRIT
SPIRIT study: Switch PI/r + 2 NRTI to TDF/FTC/RPV Among the 24 patients with the K103N mutation on historical genotype 18 in the immediate switch arm All maintain HIV RNA < 50 c/mL at W24 1 virologic failure at W48 (pre-existing mutations : K103N + V179I, emergence : M184V, E138K and V108V/I) 6 in the delayed switch arm 5 maintain HIV RNA < 50 c/mL at W48 (24 weeks after switch) 1 without data at W48 (HIV RNA < 50 c/mL at last study visit) Virologic failure on TDF/FTC/RPV, N = 7 (1.5%) 3 without emergence of resistance mutations 4 with emergence of resistance mutations K103N + L100I + M184I M184I E138E/K + M184M/V E138K + V108V/I + M184V Palella F, AIDS 2014;28:335-44 SPIRIT
SPIRIT study: Switch PI/r + 2 NRTI to TDF/FTC/RPV Mean change from baseline at W24 Discontinuation for adverse event (W24) TDF/FTC/RPV, N = 6 tubulopathy, N = 1 neuro-psychiatric events, N = 4 (depression, headache, insomnia, psychiatric event) 2 NRTI + PI/r, N = 0 Total-chol (mg/dl) LDL-c (mg/dl) TG HDL-c (mg/dl) Ratio total-c HDL-c dL (mg/dl) 10 0.08 3 0 0 - 1 - 4 - 1 -10 GFR decrease significantly more important with RPV -20 -16 - 0.27 - 25 -30 -40 Grade 3-4 Adverse events and laboratoratory abnormalities to W48 P < 0.001 for all comparisons -50 - 53 RPV RPV Delayed switch (at W24) -60 Immediate switch (at W48) PI/r (at W24) TDF/FTC/RPV 2 NRTI + PI/r Adverse events 5.7 % 6.9 % 7.9% Laboratory abnormalities 8.8 % 11.3 % 15.2% Palella F, AIDS 2014;28:335-44 SPIRIT
SPIRIT study: Switch PI/r + 2 NRTI to TDF/FTC/RPV Conclusion Switching to the STR TDF/FTC/RPV from a PI/r regimen in virologically suppressed, HIV-1-infected participants maintained virologic suppression with a low risk of virologic failure, while improving total cholesterol, LDL-cholesterol, and triglycerides Participants had been virologically suppressed on a PI/r regimen for at least 6 months prior to study entry and had no previous ART failure Pretreatment HIV-1 RNA levels (while still ARV-naive) did not affect maintenance of viral suppression after switch to TDF/FTC/RPV Historical K103 resistance mutation (probably transmitted) did not affect efficacy of switch to TDF/FTC/RPV in participants of the study Palella F, AIDS 2014;28:335-44 SPIRIT
