Didactic Series. CROI 2014 Update. March 27, 2014

Transcription

1 Didactic Series CROI 2014 Update Christian Ramers, MD, MPH Family Health Centers of San Diego Ciaccio Memorial Clinic Jacqueline Peterson Tulsky, MD UCSF Positive Health Program at SFGH Medical Director, SF and North Coast AETC March 27, 2014 ACCREDITATION STATEMENT: University of California, San Diego School of Medicine is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The University of California, San Diego School of Medicine designates this educational activity for a maximum of one credit per hour AMA PRA Category 1 Credits. Physicians should only claim credit commensurate with the extent of their participation in the activity. 1

2 Learning Objectives Discuss findings from CROI 2014 Apply new ART information to patients with HIV Discuss prevention interventions Review additional information about complications 2

3 Discordant Partners PARTNER Study (Rodger) ZERO linked transmission events among serodiscordant couples when the HIV+ partner was on ART 3

4 Details of Partner Study Observational, multi-site serodiscordant couples with HIV+ partner on suppressive ART (<200 in last year) 727 couples (282 or 36% MSM couples) HIV negative MSM partners 16% diagnosed with STI 34% reported outside partners 70% reported condomless receptive anal sex *ZERO transmissions over 894 years of f/u Rodger A, #153LB 4

5 Poll 1: How it Applies to Your Practice Tom (HIV+) and Sam (HIV-) are a devoted couple. They heard that a study at CROI said they do not need to use condoms. What do you think? 1. It seems reasonable given the data 2. There are no guarantees so I can t recommend 3. I agree to the choice of no condoms, but we should test Sam more often 4. Other 5

6 Pre-Exposure Prophylaxis Follow-up from PrEP RCTs Self-reported adherence measures = not useful Efficacy of tenofovir (TDF) alone not significantly different than Truvada (TDF/FTC) in Partners PrEP Testing identified low level resistance in 4/51 (7.8%) of those who became infected after enrollment in Partners PrEP and were in TDF or TDF/FTC arm New and alternate agents (injectables, vaginal ring, expanded PrEP combos) Implementation of daily oral TDF/FTC Van der Straten #44, Baeten #43, Lehman #590LB 6

7 What about Blips? Blip study Viral loads that were detectable, but below 200 copies, did not predict subsequent treatment failure, but above 200 copies did. 7

8 Detectable viral loads Patients with virologic suppression on ART-CC analysis who in follow up had subsequent low level viremia (2 consecutive VLs of copies ) Viremia was associated with virologic failure (HR 4.15; CI ) Viremia NOT associated with AIDS or death **Low level viremia (50-199) was not associated with virologic failure, AIDS or death* (Abstract #1014)

9 Poll 2: How it Applies to Your Practice JT reports taking her meds with 95% adherence, but in the last 2 years she has had VL under 100 twice. You talk to her about what it means. Which of the following would be your approach? 1. She will become resistant if this continues 2. She cannot be taking her meds as reported 3. You review her adherence and plan to check VL more often 4. You plan to check for resistance now and change her ART 9

10 HPV and Anal Cancer 2,800 patients getting anal PAPs at UCSD, progression from HGAIN to invasive cancer occurred at 1-2.2% over 2 years, whereas regression of HGAIN occurred in 27-62%, depending on assumptions on accuracy of cytology (#753) Suggest that observation of HGAIN may be reasonable 103 HIV-infected men, age 22-61, who got quadravalent HPV vaccine, titers dropped over 2 years, but there was a brisk response to a booster shot, suggesting strong anamnestic response (#102) Routine HPV vaccination for all women, all MSM and HIV+ men up to age 26??

11 What it all means? Suppress VL, for lots of reasons PrEP evolving, but important for prevention Monitor, but don t change ART for blips Watchful waiting may have a role in anal dysplasia Watch and intervene for bone and kidney health

12 DHHS Antiretroviral Therapy Guidelines: October 2013 UPDATED Preferred Regimens for ARV-Naïve Patients: Pill Burden Class Therapy Pill Burden NNRTI-Based Efavirenz-Tenofovir-Emtricitabine PI-Based Ritonavir + Atazanavir + Tenofovir-Emtricitabine Darunavir + Ritonavir + Tenofovir-Emtricitabine INSTI-Based Raltegravir + Tenofovir-Emtricitabine INSTI-Based* Elvitegravir-Cobicistat-Tenofovir-Emtricitabine* INSTI-Based Dolutegravir + Tenofovir-Emtricitabine OR Abacavir-Lamivudine or * only of egfr > 70 ml/min

13 Poll 3 What is your approach to discussing DHHSrecommended regimens with your patients? (EFV, ATZ/r, DRV/r, RAL, ELV, DTG) 1) I present them all as equal options 2) I explain differences and let patient decide 3) I try to steer my patients to best match 4) I strongly favor the few with which I m most comfortable 13

14 ACTG Background Many large trials are PhRMA-supported, so involve unfair comparisons Rarely are 1 st -line recommended regimens pitted against each other Clinicians and patients need information on relative efficacy and tolerability of different ART choices 14

15 ACTG Design Week HIV+ > 18 yr, Rx naïve, VL > 1000 c/ml Randomized Open Label 1:1:1 N=605 N=603 ATV 300 QD + RTV 100 QD + FTC/TDF QD RAL 400 BID + FTC/TDF QD N=556 N=560 Stratified by VL N=601 DRV 800 QD + RTV 100 QD + FTC/TDF QD N=546 Primary Endpoint: Time to VL > 200 copies/ml - Virologic failure (VF), Time to discontinuation due to toxicity Toxicity Failure (TF) Composite Endpoint: VF or TF, whichever first Landovitz RJ et al CROI 2014

16 ACTG 5257 Results Landovitz RJ et al CROI

17 ACTG 5257 Results Landovitz RJ et al CROI

18 ACTG 5257 Implications First line RAL, ATZ/r, and DRV/r regimens were virologically equivalent ATZ/r was less well tolerated than DRV/r or RAL RAL was superior to both PI-based regimens for combined tolerability/efficacy endpoint Both PI-based regimens caused greater increases in LDL and TG s than RAL INSTI-based regimens may offer advantages to PI-based regimens in tolerability/metabolic changes Ofotokun et al CROI 2014 #746 18

19 SINGLE Study 96 week results Phase III randomized double-blind, double-dummy study of DTG+ABC/3TC vs. FTC/TDF/EFV in Rx-naïve patients N = 414 and 419 DTG+ABC/3TC superior at 48 weeks NO INSTI or NRTI resistance in patients on DTG (n=414) Discontinuations: 3% DTG vs. 11% EFV Walmsley et al CROI

20 ART Switch Studies STRATEGY PI/NNRTI Week 0 96 STRATEGY - PI VL < 50 x 6 mos 1 st or 2 nd ART No resistance egfr > 70 ml/m 2:1 N=140 N=293 PI + RTV + FTC/TDF QD FTC/TDF/ELV/COBI QD Primary Endpoint: 48 week virologic suppression STRATEGY-NNRTI VL < 50 x 6 mos 1 st or 2 nd ART No resistance egfr > 70 ml/m 2:1 N=143 N=291 NNRTI + FTC/TDF QD FTC/TDF/ELV/COBI QD Secondary Endpoints: QOL indicators, CD4 change, safety, tolerability through 96 weeks Pozniak A et al CROI 2014 Arribas J et al CROI 2014

21 STRATEGY NNRTI Results Conclusions FTC/TDF/ELV/CO BI switch from NNRTI regimen was non-inferior Discontinuations were rare in all groups Decreases in egfr consistent with known COBI effect Less neuropsychiatric effects in FTC/TDF/ELV/CO BI switches Pozniak A et al CROI

22 STRATEGY PI Results Conclusions FTC/TDF/ELV/COBI switch from PI/r regimen was noninferior and met superiority criteria Discontinuations were rare in all groups Decreases in egfr consistent with known COBI effect No renal tubulopathy Less diarrhea and bloating in FTC/TDF/ELV/COBI switches Arribas J et al CROI

23 Summary ART regimens continue to improve with tolerability, metabolic impact being important long-term considerations Growing body of switch data, but still largely off-label DHHS guidelines now have three INSTIs on first line recommendation 23

24 Additional Slides 24

25 Vitamin D and Bone Density - ACTG 5280 Starting Atripla with Vitamin D levels ng/ml Vit D3 (4000 IU/d) + Calcium (1000mg/d) vs placebo #133

26 A5257: BMD analysis Brown 779LB

27 CKD Risk Score Derived from >21,000 HIV + male Veterans on ART Risk of developing egfr <60 ml/min Abstract#798

28 #798 CKD Risk Score

29 Resources 29