1 / 31

TRACK B RAPPORTEUR REPORT

TRACK B RAPPORTEUR REPORT. Jürgen Rockstroh on behalf of…. Sharon Walmsley. Jintanat Ananworanich. Mark Bloch. Jason Brophy. Jan van Lunzen. David Hardy. WHEN TO START WHAT TO START. When to start in adults: what is new in the 2013 Guidelines

zora
Download Presentation

TRACK B RAPPORTEUR REPORT

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. TRACK B RAPPORTEUR REPORT Jürgen Rockstroh on behalf of… Sharon Walmsley Jintanat Ananworanich

  2. Mark Bloch Jason Brophy Jan van Lunzen David Hardy

  3. WHEN TO STARTWHAT TO START

  4. When to start in adults: what is new in the 2013 Guidelines Considering both the individual and the Public Health benefit…. • Threshold moved to < 500 CD4 • Priority for reaching all HIV+ symptomatic persons and those with CD4 ≤ 350 • More CD4-independent situations for ART initiation (in addition to HIV/TB coinfection and HBV advanced liver disease): • HIV serodiscordant couples, • Pregnancy • Children less than 5 years of age GL are a “tool” for countries to produce their own guidelines: they will adapt the new threshold(s) with operational / programmatic local context Vella S IAS 2013

  5. 2013 WHO ART Guidelines in Adults: summary Earlier initiation Simpler treatment Less toxic, more robust regimens Better monitoring An important step towards the global alignment of the HIV standard of care HIV/AIDS Department

  6. New Recommendations in 2013 Guidelines for Pregnant Women All pregnant and breastfeeding women infected with HIV should initiate triple ARVs (ART), which should be maintained at least for the duration of mother-to-child transmission risk. Women meeting treatment eligibility criteria should continue lifelong ART . (strong recommendation, moderate-quality evidence) “Option B+” “Option B” For programmatic and operational reasons, particularly in generalized epidemics, all pregnant and breastfeeding women infected with HIV should initiate ART as lifelong treatment. (conditional recommendation, low-quality evidence) In some countries, for women who are not eligible for ART for their own health, consideration can be given to stopping the ARV regimen after the period of mother-to-child transmission risk has ceased. (conditional recommendation, low-quality evidence) • TDF + 3TC (or FTC) + EFV as a fixed-dose combination (FDC) is recommended as the preferred option to initiate ART (strong recommendation, moderate-quality evidence) • Pregnancy/Breast Feeding warrants ART initiation • Major issue now is not “when to start” but “whether to stop”

  7. New guidelines increase ART eligibility to up to 25.9 million people 9.7 million 16.2 million

  8. Is ART becoming more successful?

  9. Efficacy: all studies from 1994 to 2010 Frederick J. Lee, Janaki Amin, Andrew Carr, IAS 2013; WEAB0104

  10. Is there room for better ART (more efficacious, less toxic, easier to take)

  11. Encore1 study design • A randomized, double-blind, placebo-controlled, non-inferiority clinical trial to compare the safety and efficacy of reduced dose EFV with standard dose EFV plus 2N(t)RTI in ART-naïve HIV-infected individuals over 96 weeks • Patient population • ART-naïve HIV-infected adults with no prior AIDS, plasma HIV-1 RNA (pVL) >1,000 copies/mL, 50 <CD4+ T cells/µL <500, creatinine clearance ≥50 mL/min, no pregnancy or nursing mothers • Randomisation • I. TDF/FTC +400 mg EFV qd • (2 x 200 mg EFV + 1 x 200 mg matched placebo) • II. TDF/FTC + 600 mg EFV qd • (3 x 200 mg EFV) • 1:1 (400mg:600mg), stratified by clinical site and screening pVL Puls R for the ENCORE1 Study Group, AS 2013; WELBB01

  12. Primary endpoint: non inferiority at week 48 favours EFV600 favours EFV400 Difference in percentage of participants with pVL <200 copies/mL Puls R for the ENCORE1 Study Group, AS 2013; WELBB01

  13. Study design HIV-infected children age < 18 yrs with VL < 50 copies/ml (n=200) Randomize 1:1 Stratify by research sites and body weight Standard dose of LPV/r (FDA recommended dose) Low dose of LPV/r (70% of standard dose) Sample size calculation: Rate of failure in standard arm 12%, Non-inferiority 95% CI within -12%, power 80%, alpha 0.05, one-sided Puthanakit T et al., IAS 2013; MOAB0101

  14. Virological efficacy at week 48 • Intention to treat (ITT) analysis (missing = failure) • Per protocol (PP)analysis (missing = censored) At week 48; 8 patients had HIV HIV RNA > 400 copies/ml Factors related to virological failure Poor adherence (aOR =3.3) and Weight 35-50 kg (aOR 3.6) Puthanakit T et al., IAS 2013; MOAB0101

  15. New drugs

  16. SAILING (ING111762) Study Design DTG 50 mg QD + RAL PBO + BR HIV ART-experienced, INI-naive HIV-1 RNA >400 c/mLa 1:1 Randomization stratified by HIV-1 RNA (≤ or >50,000), DRV/r use and # of fully active drugs RAL 400 mg BID + DTG PBO + BR Week 24 Randomization Week 48primary analysis planned interim a At Screening and a second consecutive test >400 c/mL within 4 months prior to Screening (if Screening HIV-1 RNA >1000 c/mL, no additional HIV-1 RNA assessment was needed). PBO, placebo; BR, background regimen comprising at least 1 and no more than 2 active agents.

  17. Primary Endpoint: HIV-1 RNA <50 c/mL at Week 48 95% CI for difference FavorsRAL FavorsDTG 0.7 7.4 14.2 -20% -12% 0 20%

  18. First study of repeat dose co-administration of GSK1265744 and TMC278 long-acting parenteral nanosuspensions • GSK744 LAP and TMC278 LA formulations were generally safe and well tolerated • Mild-moderate injection site reactions occurred in a majority of study participants; the overall tolerability profile supports evaluation in longer-term clinical studies • GSK744 LAP pharmacokinetics indicate q 4 weekly or less frequent injections will maintain plasma drug levels well above 4x PA-IC90 • TMC278 LA pharmacokinetics suggest q 4 weekly injections give plasma levels comparable to approved oral dose of rilpivirine 25mg/daily • These results, along with an ongoing study of GSK744 + rilpivirine as an oral two-drug maintenance regimen in HIV-infected patients, will enable a similar study using the two-drug, long-acting injectable regimen Spreen W et al., IAS 2013; WEAB0103 18

  19. What to learn about second-line therapy?

  20. EARNEST Trial design HIV positive adolescents / adults (n=1200)1st line NNRTI-based regimen >12m; > 90% adherence last 1mFailure by WHO (2010) clinical, CD4 (VL-confirmed) or VL criteria RANDOMIZE PI + RAL (12 wk induction) PI + 2-3 NRTIs (NRTIs according to local standard of care) PI + RAL PI (Monotherapy) FOLLOW-UP FOR 144 WEEKS • Primary outcome at week 96: • Good HIV disease control –defined as all of: • Alive and no new WHO4 events from 0-96 weeks AND • CD4 cell count > 250 cells/mm3 at 96 weeks AND • VL<10,000 c/ml OR >10,000 c/ml without PI res. mutations at 96 weeks Paton N et al., IAS 2013; WELBB02

  21. Primary endpoint at 96 weeks Note: using multiple imputation for missing CD4 (10%), VL (10%) and resistance (11% with VL >1000 c/ml ) at week 96 • Good disease control: PI/NRTI: 60% PI/RAL: 64% PI mono+: 56% • Risk diff (95% CI): PI/RAL – PI/NRTI: +4.2% (-2.4%,+10.8%; P=0.21) • Risk diff (95% CI): PImono+ – PI/NRTI: -4.1% (-10.8%, +2.6%; P=0.23) P<0.0001 P=0.08 Paton N et al., IAS 2013; WELBB02

  22. Mean % change in BMD -2.0% -2.9% -4.2% -5.2% All analyses are adjusted for baseline imbalances in sex, BMI and smoking status Hoy J et al., IAS 2013; WELBB05

  23. Long-term complications

  24. HazardRatio (HR) for hip, andall clinical fractures for HIV infected VS uninfectedpatients. IR = incidencerate; py = person-years at risk; CI = confidenceinterval. aFurtheradjustedforbodymassindex, smoking, alcohol use, oral corticosteroid use, and thefollowingcomorbidconditions (as listed in theCharlsoncomorbidityindex): type 2 diabetes, chronicobstructivepulmonarydisease, heartfailure, myocardialinfarction, rheumatoidarthritis, cardiovascular disease, peripheral vascular disease, renal failure, liverdisease, malignancy, paraplegia, ulcer, and dementia. Knobel H et al., IAS 2013; WEABO205

  25. Hepatitis

  26. New HCV /HIV epidemiological data. Center for Disease Analysis 2013 Andrieux-Meyer I, IAS 2013

  27. Study to compare the prognostic performance of liver biopsy with that of liver stiffness measurement to predict survival and liver decompensations Median (IQR) follow-up: 5 (4.2-5.4) years. Lost to follow-up: 26 (8.8%) patients. • Decompensations: 21 (7.1%, 95%CI: 4.1%-10%). • Ascites: 12 (57%) • Portal hypertensive gastrointestinal bleeding: 4 (19%). • Hepatic encephalopathy: 2 (9.5%). According to fibrosis stage (LB) According to LSM category LSM ≤6 KPa F0 LSM 6.1-8.9 KPa F1 LSM 9-14.6 KPa F2 LSM 14.6-21 KPa F3 LSM ≥21 KPa F4 Probability of remaining free of decompensation Probability of remaining free of decompensation p<0.0001 p<0.0001 Macias J et al., IAS 2013, Kula Lumpur, Malaysia, TUABO1

  28. Early virological response (n=80) 70% previous non-responders, 30% cirrhotics Telaprevir Boceprevir W4 W24 W4 W24 W12 W12 Salmon D et al., IAS 2013, Kula Lumpur, Malaysia, TUABO1

  29. Overcoming the cost barrier http://www.medicinespatentpool.org Lacombe K, IAS 2013, plenary 48

  30. Patient B (2.6 years post-HSCT) PBMC DNA CD4+ T Cell Count Minimum 3.5 - 4 log10 reduction of PBMC DNA after alloHSCT, CCR5 wildtype No RNA and/or DNA detectable after 15 weeks off ART Henrich T et al. WELBA05

  31. Track B Team

More Related