Liens d Intérêt Evalutation de Nouveaux Antirétroviraux : 13 Millions (61% des personnes éligibles) - PDF

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5/3/216 Liens d Intérêt Evalutation de Nouveaux Antirétroviraux L exemple de la Rilpivirine Jean-Michel Molina Université de Paris Diderot, Sorbonne Paris Cité Hopital Saint-Louis, Paris Participation

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5/3/216 Liens d Intérêt Evalutation de Nouveaux Antirétroviraux L exemple de la Rilpivirine Jean-Michel Molina Université de Paris Diderot, Sorbonne Paris Cité Hopital Saint-Louis, Paris Participation à des réunions de conseils pour les laboratoires Gilead, BMS, ViiV, Merck, Janssen, et Tobira Subventions de recherche: Laboratoires Merck et Gilead 1 2 Situation de l Epidémie de VIH/SIDA Rapport ONUSIDA 214 (1) Nombre de personnes vivant avec le VIH - 21: 2,6 Millions - 213: 35,2 Millions Décès liés au SIDA - 21: 1, Millions - 213: 1,5 Millions (-35% par rapport à 25) Personnes nouvellement infectées par le VIH - 21: 3,4 Millions - 213: 2,1 Millions (diminution de 3%) Situation de l Epidémie de VIH/SIDA Rapport ONUSIDA 214 (2) Nombre de personnes traitées - 213: 13 Millions (61% des personnes éligibles) Les 3 objectifs de l ONUSIDA pour 22-9% des personnes infectées connaissent leur statut - 9% des personnes infectées ont accès au traitement - 9% des personnes traitées ont une charge virale indétectable Situation en France Données de la FHDH (114 personnes : % des diagnostics) Amélioration continue de l efficacité des traitements 9% des patients traités ont ARN VIH 2 cp/ml Médiane des CD4 à 43/mm 3 (59% 5 CD4) Evolution des recommendations de mise sous traitement 9% des patients infectés par le VIH reçoivent un traitement Très faible proportion de patients sans alternative thérapeutique: 1-2% (avec une disparité régionale) Molécules antirétrovirales disponibles 216 Inhibiteurs nucléosidiques de RT (NRTIs) Abacavir (ABC) Emtricitabine (FTC) Lamivudine (3TC) Tenofovir (TDF) Zidovudine (ZDV) 3TC/ABC 3TC/ZDV FTC/TDF Inhibiteurs non nucléosidiques de RT (NNRTIs) Efavirenz () Nevirapine (NVP) Efavirenz/TDF/FTC Etravirine Rilpivirine Rilpivirine/TDF/FTC Inhibiteurs d entrée (EIs) Maraviroc (MVC) Inhibiteurs de protéase (IPs) Atazanavir (ATV) Fosamprenavir (FPV) Lopinavir/ritonavir (LPV/RTV) Ritonavir (RTV) Saquinavir (SQV hgc) Tipranavir (TPV) Darunavir (DRV) Inhibiteurs d intégrase (IIs) Raltegravir (RTG) Elvitegravir/cobicistat Elvitegravir/cobicistat/TDF/FTC Dolutegravir Dolutegravir/ABC/3TC Inhibiteurs de fusion (FIs) Enfuvirtide (ENF) 1 5/3/216 Recommendations Françaises 215 Efavirenz + TDF/FTC : Atripla (9 Euros/an) Efavirenz générique + TDF/FTC (Truvada) (7 Euros) Efavirenz + ABC/3TC: Sustiva + Kivexa ( Euros) Rilpivirine + TDF/FTC : Eviplera (9 Euros) ATV/r + TDF/FTC : Reyataz / Norvir /Truvada (12 Euros) ATV/r + ABC/3TC : Reyataz / Norvir /Kivexa (11 Euros) DRV/r + TDF/FTC : Prezista / Norvir /Truvada (12 Euros) Raltegravir + TDF/FTC : Isentress /Truvada (135 Euros) Elvitegravir/c + TDF/FTC: Stribild (12 Euros) Dolutegravir + ABC/3TC: Triumeq (12 Euros) Dolutegravir + TDF/FTC: Tivicay + Truvada (135 Euros) Background Overview of Rilpivirine Trials in ARV naïve patients Phase 3 Pooled ECHO/THRIVE Week 96 Phase 3 Star Trial Trials in ARV experienced patients (switch) Switch from PIs (Spirit) Switch from Cohort study in real life Background Effect of Food Type on Mean PK Profile Rilpivirine () is an NNRTI with the following attributes: Anti-HIV-1 activity, EC 5 =.3ng/mL 1 No teratogenicity in preclinical studies 2 Half-life of ~ 5 hours 3 Food increases s bioavailability by approximately 6% should be taken with a meal 4 No significant drug interaction with TDF 5 or FTC 6 99.7% protein-bound in vitro 7 Metabolised primarily via the CYP3A pathway Eviplera ( + TDF/FTC) or Edurant () 1. Azijn H, et al. AAC 21;54: Hoetelmans R, et al. IAS 25. Rio de Janeiro, Brazil. #WePe3.3C15 2. Desmidt M, et al. EACS 29. Cologne, Germany. #PE7.1/4 6. Mathias A, et al. IAC 21. Vienna, Italy. #LBPE17 3. Eviplera (emtricitabine/rilpivirine/tenofovir disoproxil fumarate). 7. Janssen PA, et al. J Med Chem 25;4:191 9 Summary of Proeuct Characteristics. November 211. Lachau-Durand S, et al. EACS 29. Cologne, Germany. #PE7.1/3 4. Crauwels H, et al. IWCPHT 2. New Orleans, LA. #P32 9 Mean plasma concentration (ng/ml) Time (hours) Crauwels HM, et al. IWCPHT 2. New Orleans, LA. #P32 Standard breakfast (533 kcal) High-fat breakfast (92 kcal) Fasting conditions ( kcal) Nutritional drink (3 kcal) Taking with food increases exposure by 57% compared to fasting. AUC was similar when administered after a high-fat or standard breakfast. 1 Drug Interactions: Contra-indications Drug that may decrease plasma concentrations 1. Drugs that increase gastric ph PPIs (esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole) Alternative #1: H 2 blocker given at least 12h before or 4h after Alternative #2: Antacids given 2h before or 4h after 2. CYP3A4 inducers Anticonvulsants (carbamazepine, oxcarbazepine, phenobarbital, phenytoin) Antimycobacterials (rifabutin, rifampin, rifapentine) St. John s Wort (Hypericum perforatum) System glucocorticoid dexamethasone (more than a single dose) Teratogenicity Preclinical Safety Objectives: to assess the potential effects of oral on embryo-foetal development in rats and rabbits did not show teratogenic potential in rat and rabbit models at exposures 13- to -times higher than those seen in HIV-1-infected patients receiving 25mg qd at steadystate These animal data suggest that further studies of in women of child bearing potential are warranted Desmidt M, et al. EACS 29. Cologne, Germany. #PE7.1/4 12 2 5/3/216 : high and sustained virologic response rate in combination with 2 NRTIs over 96 weeks in Phase II study ECHO and THRIVE Phase 3 Studies Study Designs Randomized, double-blind, double-dummy, multicenter, 96-week study 1 25mg qd (n=93) 15mg qd (n=91) 75mg qd (n=95) 6mg qd (n=9) ECHO (TMC27-C29) 69 patients 25mg qd + TDF/FTC qd + placebo qd (n=346) Virologic responders (%, 95% CI) % 72% 71% 71% Viral load 5 copies/ml to Week 96 (ITT-TLOVR algorithm) ARV-naïve HIV RNA 5, c/ml No NNRTI RAMs Sensitivity to the NRTIs 67 patients THRIVE (TMC27-C215) 6mg qd + TDF/FTC qd + placebo qd (n=344) 25mg qd + 2 NRTIs + placebo qd (n=34) 6mg qd + 2 NRTIs + placebo qd (n=33) Time (weeks) = rilpivirine ; = efavirenz; ITT-TLOVR = intent-to-treat time-to-loss-of-virologic-response ; CI = confidence interval Primary objective: to demonstrate non-inferiority (12% margin) vs. in confirmed virologic response (viral load [VL] 5 copies/ml, ITT-TLOVR) at Week 4 From 39 NNRTI RAMs based on list of 44 1 ; Based on Virco TYPE HIV-1 test; Tambuyzer L et al. Antivir Ther 29;14:13 9 Pozniak A, et al. AIDS 21;24: Cohen et al AIDS 212, Molina Lancet 211, Cohen Lancet Pooled ECHO and THRIVE Demographics and Baseline Characteristics Baseline parameter N=66 N=62 Female, % Median age, years Race, % Caucasian Black Asian Other races/not stated Efficacy results Median log 1 VL, copies/ml (min max) 5 (2 7) 5 (3 7) % viral load 1K copies/ml 54 4 Median CD4 cell count, cells/mm3 (min max) 249 (1 ) 26 (1 1,137) Hepatitis B or C co-infection, % 7 9 Background regimen (THRIVE) was balanced between treatment groups TDF/FTC 6%; AZT/3TC 3%; ABC/3TC 1% Adapted from Cohen C et al. IAS 211. Rome. Poster TULBPE Pooled ECHO & THRIVE (wk 96 FTC/TDF Dataset) HIV RNA 5 copies/ml ITT-TLOVR Responders (%, 95% CI) Time (weeks) +FTC/TDF was non-inferior to +FTC/TDF at weeks 4 & 96 Mean change in CD4 cell count from baseline (NC=F) 4 weeks : +193 vs. : +12 cells/mm 3 96 weeks : +226 vs. : +222 cells/mm 3 Favours Favours Difference (95% CI) in response rates ( ) 77% 77% Adapted from Nelson M et al. EACS 211. Belgrade. Poster LBPE7.3/7 Eviplera SPC. November % 2% Patients (%) Pooled ECHO and THRIVE: ITT-TLOVR outcome at Week 96 by baseline VL 4. ( 1.7, 9.7) 4 N =36 1K N =329 Patients (%) 1K Responders 7 75 Non responders N = (-12, 1.5) N =353 Discontinued due to other reasons Discontinued due to AE/death Responses by baseline CD4 cell count were ( 2 cells/mm 3 ): 2% vs 79%, ( 5 2 cells/mm 3 ): 71% vs 75% and ( 5 cells/mm 3 ): 56% vs 69% VF eff 3 5/3/216 Pooled ECHO and THRIVE: ITT-TLOVR outcome at Week 96 by self-reported M-MASRI adherence Patients (%) ( 6., 2.4) 1 4 N =552 N =499 Adherent ( 95%) Patients (%) (-22.7, 5.3) Responders* Non responders N =7 N =1 Suboptimally adherent ( 95%) Discontinued due to other reasons Discontinued due to AE/death VF eff Resistance *Responders = patients with viral load 5 copies/ml, ITT-TLOVR algorithm; Lost to follow-up, non-compliance, withdrew consent, ineligible to continue, sponsor's decision; VF eff determined by TLOVR in the ITT population: confirmed response before Week 96 and confirmed rebound (rebounders) at or before Week 96, or no response before Week 96 (never suppressed) Difference (95% CI) in response rates (-) M-MASRI = Modified Medication Adherence Self-Report Inventory Pooled ECHO/THRIVE: Week 4 Full Dataset Incidence of Treatment-emergent a NNRTI and N(t)RTI RAM in Virologic Failures by Baseline Viral Load Category Incidence, n (%) (N = 66) (N = 62) All virologic failure with genotypic data b n = 62 n = 2 NNRTI RAM 39 (63) 15 (54) N(t)RTI RAM 42 (6) 9 (32) NNRTI and N(t)RTI RAM 37 (6) (29) Baseline viral load 1K c/ml ( n=36), (, n =33) n = 16 n =12 NNRTI RAM 61.6% (3) 51.5% (42) N(t)RTI RAM 71.9% (44) 2.6% (17) NNRTI and N(t)RTI RAM 51.4% (31).3% 1 () Baseline viral load 1K c/ml c/ml (, n=31), (, n=352) n = 46 n = 16 NNRTI RAM % (72) 1 2.% (63) N(t)RTI RAM 3511% (76) 72% (44) NNRTI and N(t)RTI RAM 321% (7) 72% (44) Virologic failures with NNRTI RAMs (%) Pooled ECHO & THRIVE (wk 4 Full Dataset) Treatment-emergent* NNRTI RAMs Any mg qd (n=62) 6mg qd (n=2) 1 E13K K11E H221Y V19I Y11C V9I K13N V16M Y1C Among VFs with emerging NNRTI RAMs, 46%, 31% and 23% had 1, 2, or 3 NNRTI RAMs, respectively, at failure Non-clade B VFs (n=13, including clade C) did not exhibit any distinctive pattern of NNRTI RAMs *Not present at screening or baseline and present at time of failure while on treatment Occurring in 5% of VF with available resistance data Most frequent NNRTI RAMS a Not present at screening or baseline and present at time of failure while on treatment. b At time of failure. Rimsky L, et al. IWHHC 211; Los Cabos, Mexico. Abstract Adapted from Eron J et al. ICAAC 21. Boston. Abstract H Pooled ECHO & THRIVE (wk 4 Full Dataset) Treatment-emergent IAS-USA N(t)RTI RAMs 1 Virologic failures with N(t)RTI RAM (%) mg (n=62) 6mg qd (n=2) Any M14V M14I M14I/V K65R Most frequent N(t)RTI RAMs* 5 7 Safety and tolerability 1/62 VFs and 12/2 VFs failed with wild-type virus 37/62 VFs and 6/2 VFs had both treatment-emergent NNRTI and N(t)RTI RAMs Adapted from Eron J et al. ICAAC 21. Boston. Abstract H 5/3/216 Pooled ECHO & THRIVE (wk 96 FTC/TDF Dataset) Adverse Events Pooled ECHO and THRIVE: Wk 96 FTC/TDF Dataset Lipid Changes Over 96 Weeks % N=55 N=546 P-value Any serious AEs ND Grade 2-4 treatment-related AEs .1 Any treatment-related neurologic AE* .1 Somnolence Dizziness 26 .1 Disturbance in attention Any treatment-related psychiatric AE* .1 Abnormal dreams/nightmares Any treatment-related rash 5 16 .1 Discontinued due to AEs Rash Depression Pregnancy FTC/TDF demonstrated a more favourable overall safety profile, with significantly less discontinuations due to AEs Fewer discontinuations for rash with +FTC/TDF (p=.3) Majority of AEs occurred in the first year In Year 2, the incidence of treatment-related grade 2-4 AEs was 2.5% (+FTC/TDF) and 3.7% (+FTC/TDF) Adapted from Nelson M et al. EACS 211. Belgrade. Poster LBPE7.3/7 25 mmol/l +FTC/TDF +FTC/TDF TC* LDL* HDL* TG* *P .1 for all comparisons ( vs. ) using Wilcoxon rank-sum test +FTC/TDF +FTC/TDF +FTC/TDF +FTC/TDF Subjects receiving +FTC/TDF had significantly less treatment-emergent lipid abnormalities compared with subjects receiving +FTC/TDF over 96 weeks +FTC/TDF produced minimal changes in TC, LDL, and TG levels from baseline through 96 weeks of treatment 43% 49% Total Cholesterol 72% 73% LDL 36% 33% 21% 19% 19% 14% 7%.2% 7% % of Subjects P .2 for all comparisons by individual grades ( vs. ) using Fisher s exact test Total Cholesterol mmol/l Grade : 5.2 Grade 1: Grade 2: Grade 3: 7.7 LDL Grade : Grade 1: Grade 2: Grade 3: mmol/l 3.4 4.9 Adapted from Nelson M, et al. EACS 211. Belgrade, Serbia. #LBPE7.3/7 26 2% 1% 5% Pooled ECHO and THRIVE: Conclusions at Week 96 showed sustained overall efficacy that was similar to over 96 weeks (7% overall response in each group) Suboptimal adherence was associated with reduced responses in both groups Response was numerically higher in the group with baseline VL 1K The effect of suboptimal adherence and higher baseline viral load on VF eff was more apparent with than with At Week 4 the overall VF res rate was higher with than, however, beyond Week 4 there were similar increases in VF res for both groups showed lower incidences than of Grade 2 4 overall AEs Dizziness, abnormal dreams/nightmares and rash (any grade) Discontinuations due to AEs (mainly rash and dizziness) Grade 2 to 4 lipid abnormalities From Week 4 to 96, there were no new safety concerns with either NNRTI was efficacious and well tolerated in a large and diverse group of treatment-naïve patients + TDF/FTC approved in Europe in naïve patients with 1. cp/ml STaR Study: Single-Tablet Regimen Emtricitabine/Rilpivirine/Tenofovir DF is Non-Inferior to Efavirenz/Emtricitabine/Tenofovir DF in ART-Naïve Adults Week 4 Results Calvin Cohen, David Wohl, Jose Arribas, Keith Henry, Jan van Lunzen, Mark Bloch, William Towner, Edmund Wilkins, Hui Wang, Kirsten White, Danielle Porter, Bill Guyer, Todd Fralich Eleventh International Congress on Drug Therapy in HIV Infection Glasgow, Scotland 15 November 212 Published in AIDS, 214 At least possibly related to treatment 2 STAR Study Design Baseline Demographics and Characteristics /FTC/TDF ARV-naive HIV-1 RNA 25 c/ml Sensitivity to, FTC,, TDF (N=76) Stratified by HIV RNA ( or 1, c/ml) Primary endpoint: Secondary endpoints: Cohen 212 Glasgow n=394 n=392 /FTC/TDF 4 Weeks Primary Endpoint 96 Weeks Efficacy of the 2 s by proportion with HIV-1 RNA 5 c/ml at Week 4 (FDA Snapshot analysis); non-inferiority margin of 12% Safety and efficacy of the 2 s by proportion with HIV-1 RNA 5 c/ml at Week 96 (FDA Snapshot analysis) Change in CD4 cell count at Weeks 4 and 96 Genotype/phenotype resistance at time of virologic failure Median age, years (IQR) 37 (29, 45) 35 (2, 45) Male % 93% 93% White % 6% 67% Black % 25% 24% Latino ethnicity % 15% 19% Mean CD4 cell count, cells/mm 3 (SD) 396 (1) 35 (17) HIV-1 RNA, log 1 c/ml, (SD) 4. (.7) 4. (.6) 1, c/ml, n (%) 26 (66%) 25 (64%) 1, to 5, c/ml, n (%) 9 (25%) 117 (3%) 5, c/ml, n (%) 36 (9%) 25 (6%) 5 5/3/216 Proportion of Participants, % Virologic Suppression and CD4 Change at Week 4 FDA Snapshot Analysis ITT Population FTC//TDF is non-inferior to /FTC/TDF 6 6 Virologic Virologic Failure Suppression (HIV-1 RNA 5 copies/ml) /FTC/TDF 13 No W4 Data 95% CI for Difference Favors /FTC/TDF Favors % 12% CD4 count change (cells/mm 3 ): +2 vs /FTC/TDF +191 (p=.34) Virologic Suppression by FDA Snapshot Analysis Stratified by Baseline HIV-1 RNA 1, c/ml HIV-1 RNA 5 c/ml (%) /FTC/TDF /26 24/25 17/ /142 1K 1K Baseline HIV-1 RNA copies/ml 95% CI for Difference Favors /FTC/TDF Favors 1K 1K compared to /FTC/TDF Superior for subjects with baseline HIV-1 RNA 1, c/ml Non-inferior for subjects with baseline HIV-1 RNA 1, c/ml Virologic Suppression at Week 4 FDA Snapshot Analysis by Baseline HIV-1 RNA HIV-1 RNA 5 c/ml (%) / 26 /FTC/TDF / 25 1/ 9 96/ / 36 2/ 25 1K 1-5K * * 5K Baseline HIV-1 RNA copies/ml * Post hoc analyses; analyses for non-inferiority only pre-specified for 1, c/ml and 1, c/ml Virologic Failure at Week 4 FDA Snapshot Analysis by Baseline HIV-1 RNA Virologic Failure (%) Baseline HIV-1 RNAcopies/mL Virologic failure: Week 4 HIV-1 RNA 5 copies/ml, or discontinued study drug due to lack of efficacy, or discontinued study drug due to other reasons and last available HIV-1 RNA 5 copies/ml *ECHO/THRIVE: Two Phase III double-blinded, double dummy, mulitcenter 96 week studies in treatment-naïve HIV-1 infected subjects randomized to receive either (25mg) or (6mg) in combination with 2 NRTIs (ECHO, FTC/TDF; THRIVE, Investigator s choice [FTC/TDF, n=46; 3TC/AZT, n=24; 3TC/ABC, n=6]). In the pooled TVD subset analysis (N=196), +TVD was non-inferior to +TVD (HIV-1 RNA 5 c/ml [3%, 1%]) STaR ECHO/THRIVE TVD Subsets* /FTC/TDF +FTC/TDF +FTC/TDF Overall 1K 1-5K 5K Resistance Analysis Through Week 4 All Grades Treatment-Emergent Adverse Events * of Importance STaR* ECHO/THRIVE TVD Subset /FTC/TDF +FTC/TDF +FTC/TDF (n=394) (n=392) (n=55) (n=546) Subjects with Resistance Data 5% 2% 11% 3% Subjects with Resistance to ARVs 4% 1% 7% 2% Any Primary NNRTI-R 4% 1% 6% 2% Key NNRTI-R E13K/Q (2%) K13N (.3%) E13K/Q (4%) K13N (1%) Y11C/I (2%) Y11C/I (1%) K11E (1%) K11E (1%) Any Primary NRTI-R 4%.3% 7% 1% Key NRTI-R M14V/I (4%) M14I (.3%) M14V/I(6%) M14V/I (1%) K65R/N (1%) K65R/N (1%) K65R/N (.4%) Within Baseline (BL) HIV-1 RNA 1, copies/ml at BL 2% 1% 2% 1% 1, 5, copies/ml at BL 5% 9% 2% 5, copies/ml at BL 19% 4% 21% 7% The s used in STaR, compared to the components of the regimens used in ECHO and THRIVE, demonstrated less emergent resistance (n=394) Psychiatric Events, n (%) 62 (16%) 147 (3%) p .1 Events 5% of subjects, either arm Abnormal Dreams 23 (6%) 96 (25%) Depression 26 (7%) 35 (9%) Anxiety, nervousness 2 (5%) 34 (9%) *prespecified evaluation for common adverse events, US Efavirenz Prescribing Information 1 (.3%) suicide occurred in the /FTC/TDF arm, day 36 of study /FTC/TDF (n=392) Nervous System Events, n (%) 117 (3%) 19 (51%) p .1 Events 5% of subjects, either arm Dizziness, vertigo, balance disorder 3 (%) 1 (26%) Insomnia 3 (1%) 55 (14%) Somnolence 1 (3%) 27 (7%) Headache 49 (12%) 53 (14%) 6 5/3/216 Adverse Events Leading to Discontinuation of Study Drug Discontinuations* Due to Adverse Event (AE), n (%) AE leading to discontinuation in 1 subject in either arm Nervous System Events *per safety population (n=394) Dizziness Abnormal Dreams or Nightmare Insomnia 1 (.3%) Psychiatric Disorders Depression, Anxiety or Depressed Mood Suicidal Ideation GI, General, Skin Disorders Diarrhea Fatigue Pyrexia Toxic Skin Eruption /FTC/TDF (n=392) 1 (2.5%) 34 (.7%) P .1 23 (6%) 96 (25%) 5 (1.3%) 6 (1.5%) 3 (.%) 9 (2.3%) 2 (.5%) 2 (.5%) 2 (.5%) 2 (.5%) 2 (.5%) Star Conclusions Overall, /TDF/FTC was non-inferior to /FTC/TDF through 4 weeks for the primary endpoint of virologic suppression Superior when baseline HIV-1 RNA 1, copies/ml Non-inferior when baseline HIV-1 RNA 1, copies/ml Overall, low and similar rates of virologic failure occurred for (%) and /FTC/TDF (6%) Similar rates observed for virologic failure with baseline HIV-1 RNA 1, c/ml ( 5%, /FTC/TDF 3%) and for 1, to 5, c/ml ( 1%, /FTC/TDF 9%); low rates of resistance Higher rates of virologic failures for baseline HIV-1 RNA 5, c/ml ( 25%, /FTC/TDF 16%); resistance rate higher for (19% vs /FTC/TDF 4%) is well-tolerated compared to /FTC/TDF Significantly fewer nervous system and rash adverse events Significantly fewer discontinuations due to adverse events Significant differences for change in lipids TC, LDL, and TG favoring HDL favoring /FTC/TDF Similar change to TC:HDL ratio for both arms Switch Studies Switch d vers (GS 111) Phase 2b, open-label, multicentre, 4-week study of immediate switch from /FTC/TDF to FTC//TDF in stable, virologically controlled subjects Stable on /FTC/TDF x 3 months -Desire to switch due to tolerability issues -VL 5 c/ml wks -No genotypic resistance -egfr 5mL/min N=5 FTC//TDF Week Primary endpoint: % of subjects with HIV-1 RNA 5 c/ml at Week 12 post-switch - ITT population FDA Snapshot Analysis Secondary endpoints: Safety of FTC//TDF over 24 & 4 wks HIV-1 RNA 5 c/ml at Week 24 and Week 4 Pharmacokinetics of after switching ITT = intent to treat Mills et al. AIDS HIV Clin Trials Primary Endpoint: HIV-1 RNA 5 copies/ml at Wk 12 (FDA Snapshot Analysis ITT Population) % HIV-1 RNA 5c/mL Mills et al. AIDS HIV Clin Trials 213 1% % 6% 4% 2% % 1% 49/49 FTC//TDF 1 subject wit
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