ID Week 2016: HIV Update

Transcription

1 Mountain West AIDS Education and Training Center ID Week 2016: HIV Update Robert Harrington, M.D. This presentation is intended for educational use only, and does not in any way constitute medical consultation or advice related to any specific patient.

2 ID Week 2016: HIV Update New management of low-level viral blips DTG/ABC/3TC versus ATZ/r + TDF/FTC in women (ARIA) Omega-3 fatty acids HIV reservoir decay and low-level plasma HIV RNA Honorable mention - TAF in older patients - GenoSure archive in clinical practice - DTG + RPV in experienced patients

3 #948: Retesting of suspected low-level HIV-1 viral load blips: A new paradigm to prevent extra clinic visits and unnecessary patient anxiety (Eron, et al)

4 #948: Retesting of suspected low-level HIV-1 viral load blips Testing the hypothesis that many low-level pvl values represent assay variability Methods: - 50 aliquots of diluted WHO standards with VL < plasma samples from 4 patients with blips of (after having been < 50) - Retested the same sample with Cobas AmpliPrep/Cobas Taqman v2.0 assay (Roche) at Covance Laboratories

5 #948: Retesting of suspected low-level HIV-1 viral load blips Results - WHO standards: 17 c/ml: 18% > 50 on retesting - WHO standards: 36 c/ml: 66% > 50 on retesting - Patient samples > 50: 94% (15/16) were < 50 on retesting Low level viremia likely be due to assay variability (coefficient of variation) rather than virologic failure. Retesting the same sample may obviate the need to bring patients in for retesting

6 #949: DTG/ABC/3TC versus ATZ/r + TDF/FTC in women (ARIA study) (Hagins, et al)

7 #949: DTG/ABC/3TC versus ATZ/r + TDF/FTC in women (ARIA study) International study of treatment naïve women - Stratified by HIV RNA and CD4 count - Randomized to DTG/ABC/3TC versus ATZ/r + TDF/FTC Patients: N=495 - Median age 37, 45% white, 42% African heritage Results - DTG/ABC/3TC superior to ATZ/r + TDF/FTC - Difference due to lower rates of discontinuation and fewer virologic failures in the DTG arm

8 #949: DTG/ABC/3TC versus ATZ/r + TDF/FTC in women (ARIA study) Proportion with HIV RNA < 50c/mL (Snapshot) DTG/ABC/3TC N=248 ATZ/r + TDF/FTC N=247 Difference Overall 82% 71% 10.5% (p=0.005) White 86% 80% African heritage 74% 67% Other 94% 56% US subjects 74% 67% DTG/ABC/3TC superior to ATZ/r + TDF/FTC in HIV+ women regardless of race

9 #951: RCT of Omega-3 fatty acids in HIV: Long term effects on lipids and vascular function (Volpe, et al)

10 #951: RCT of Omega-3 fatty acids in HIV: Long term effects on lipids and vascular function RCT of 4 grams per day of Omega-3 FA vs placebo Outcomes - Primary: effects on TG and HDL and CRP - Secondary: effects on brachial artery reactivity and arterial stiffness (measured by pulse wave velocity) Patients: N=117 (61 Omega-3 FA, 56 placebo) - Mean age 51, 21% female, 95% virologically suppressed, median CD4 648

11 #951: RCT of Omega-3 fatty acids in HIV: Long term effects on lipids and vascular function Results at 24 weeks Omega-3 FA Placebo P value Change in TG -68 mg/dl -22 mg/dl Change in HDL No difference Change in CRP Brachial artery reactivity Carotid-femoral pulse wave velocity No difference -46 ms ms

12 #951: RCT of Omega-3 fatty acids in HIV: Long term effects on lipids and vascular function Triglycerides CRP Omega-3FAs reduce TGs, may limit chronic inflammation and improve vascular function

13 #953: HIV Reservoir size and decay in 114 individuals with suppressed plasma HIV for at least 7 years (Golob, et al)

14 #953: HIV Reservoir size and decay in 114 individuals with suppressed plasma HIV for at least 7 years Design of Study and Cohort HIV Acquired Dx and Viral Suppression At least 5 years Reservoir Size by qpcr Reservoir Size by qpcr 111 Patients. 477 reservoir size measurements. PBMC total cellular DNA qpcr for gag or pol gene Normalized to total genomic DNA and CD4 count close to time of collection Questions: - Correlates with HIV reservoir size after five years of clinical suppression? - Correlates with HIV reservoir decay after five years of clinical suppression?

15 #953: HIV Reservoir size and decay in 114 individuals with suppressed plasma HIV for at least 7 years Patient characteristics and study details Patient characteristics (n = 111) Age (median and range) Value 48 (31-66) years Male/ Female / Male -> Female 93 / 15 / 3 Race (Caucasian / Black / Asian or Pacific Islander / multiple) 82 / 17 / 11 / 1 Antiretroviral exposure (all exposed to nrti) Protease inhibitors 96 Non-nucleoside RTI 89 Integrase inhibitors 47 Median Years Clinically Suppressed at T 0 8 years CD4 T-cell count at T 0 (median and range) 554 ( ) Study details Median follow-up period after T 0 (range) Value 1.4 (0 8.5) years Median number of reservoir measurements (range) 3 (1-23)

16 #953: HIV Reservoir size and decay in 114 individuals with suppressed plasma HIV for at least 7 years Reservoir size correlates with age only Estimate p HIV Risk Factor Transfusion / Transplant Heterosexual Contact MSM IDU ARV Exposure (Before) nnrti Protease Inhibitor Integrase Inhibitor Demographics Age (after 5 years of clinical suppression) Male (Biological gender) White Race Model Time (years) after 5 years of clinical suppression (Intercept)

17 #953: HIV Reservoir size and decay in 114 individuals with suppressed plasma HIV for at least 7 years Reservoir half-life estimated to be 12 years Half-life = Log10 (2) / (Coefficient) *-1 Coefficient = Estimate p Time (years) Log10 (2) / (-0.025) *-1 = 12 years ( )

18 J-98 J-99 J-00 J-01 J-02 J-03 J-04 J-05 J-06 J-07 J-08 J-09 J-10 J-11 J-12 J-13 J-14 J-15 #953: HIV Reservoir size and decay in 114 individuals with suppressed plasma HIV for at least 7 years Clinical Suppression: Undetectable, Detectable-not-Quantifiable, and Blips HIV Viral Load (Log10) for Patient 1028 Suppressed Quantifiable Detectable, not quant Not detectable

19 #953: HIV Reservoir size and decay in 114 individuals with suppressed plasma HIV for at least 7 years Decay rate of the latent reservoir Category # Pts # Reservoir assays Decay rate (slope) Half-life (mo) P value Mean 95% CI Mean 95% CI Entire cohort to to Patients with: Undetectable to to Detectable to to Quantifiable to to -348 (dt) Siliciano et al. Nat Med Jun;9(6):727-8: Reservoir t1/2 in cohort of 62 patients: 44.2 months (entire cohort), 30.8 months (no blips), 57.7 months (+ viral blips)

20 #953: HIV Reservoir size and decay in 114 individuals with suppressed plasma HIV for at least 7 years Conclusions Antiretroviral regimen, gender, race and HIV risk factor did not correlate to HIV reservoir size but age did. The half-life of the HIV reservoir in this cohort of 111 clinically suppressed patients contributing 477 measurements was 12 years The subgroup of patients with undetectable plasma virus throughout the follow-up period had a reservoir half-life of 64 months

21 Honorable mention

22 Honorable mention #952: TAF in older adults (>50): Subgroup analysis of a randomized switch study (Daar et al) 48 wk data, >50 yo from a R,DB,C study in suppressed patients changing to TAF/FTC from TDF/FTC % VL <50: 96% (TAF) vs 94.4% (TDF) Bone and renal effects better with TAF Discontinued due to AEs: 3.3% (TAF) vs 1.4% (TDF)

23 Honorable mention #1507: GenoSure Archive in clinical practice (Singh, et al) 140 patients with suppressed virus (<200), 21% had blips, 39% no historical R assays Reasons for getting GenoSure Archive: regimen simplification, regimen verification, AEs, DDI s Overall concordance NRTI NNRTI PI All Any On GA only 24.6% 21.7% 17.4% 8.7% 36.2% Concordance 72.5% 72.5% 76.8% 53.6% 91.3% Not detected on GA 2.9% 5.8% 5.8% % 79/140 patients had post GA ARV changes: 85% remained suppressed at 3 months

24 Honorable mention #1519: DTG + RPV in treatment experienced patients (Saling, et al) Retrospective study of 14 pts switched to DTG+RPV after failure Prior ART: NNRTI based (4), PI based (5), contained II (6), 2 nrti (11) 50% R to prior regimen: nrti resistant (3), 2 class resistance (4) Short follow-up (<6 months) all VL <20 #1522: Switch to once daily MVC (Degazon, et al) 34 patients suppressed on standard ART: switched to MVC (600 mg QD) + 2NRTI At 48 weeks: data from 32 patients: VL <50: 93%, CD4 change: + 94, AEs: none

25 Thank you Questions?