id week 2016: hiv update - university of...
TRANSCRIPT
This presentation is intended for educational use only, and does not in any way constitute medical consultation or advice
related to any specific patient.
Mountain West AIDS Education and Training Center
ID Week 2016: HIV Update
Robert Harrington, M.D.
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
#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)
#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 < 200”
- 4-6 plasma samples from 4 patients with blips of 50-200
(after having been < 50)
- Retested the same sample with Cobas AmpliPrep/Cobas
Taqman v2.0 assay (Roche) at Covance Laboratories
#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
#949: DTG/ABC/3TC versus ATZ/r + TDF/FTC
in women (ARIA study) (Hagins, et al)
#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
#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
#951: RCT of Omega-3 fatty acids in HIV: Long
term effects on lipids and vascular function
(Volpe, et al)
#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
#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 0.041
Change in HDL No difference
Change in CRP -0.3 +0.6 0.008
Brachial artery
reactivity
No difference
Carotid-femoral
pulse wave
velocity
-46 ms-1 +18 ms-1 0.1
#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
#953: HIV Reservoir size and decay in 114
individuals with suppressed plasma HIV for at least
7 years (Golob, et al)
#953: HIV Reservoir size and decay in 114 individuals with
suppressed plasma HIV for at least 7 years
HIV
Acquired
Dx and Viral
Suppression
Reservoir
Size by
qPCR
At least
5 years
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?
Design of Study and Cohort
#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) Value
Age (median and range) 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 T0 8 years
CD4 T-cell count at T0 (median and range) 554 (83 – 1260)
Study details Value
Median follow-up period after T0 (range) 1.4 (0 – 8.5) years
Median number of reservoir measurements (range) 3 (1 - 23)
#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 0.144 0.693
Heterosexual Contact 0.295 0.352
MSM 0.378 0.264
IDU 0.124 0.272
ARV Exposure (Before)
nNRTI 0.074 0.472
Protease Inhibitor 0.187 0.092
Integrase Inhibitor 0.075 0.599
Demographics
Age (after 5 years of clinical suppression) 0.016 0.019
Male (Biological gender) 0.157 0.501
White Race -0.196 0.114
Model
Time (years) after 5 years of clinical
suppression -0.025 0.039
(Intercept) -1.408 0.002
#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
Estimate p
Time
(years) -0.025 0.040
Half-life = Log10 (2) / (Coefficient) *-1
Log10 (2) / (-0.025) *-1 = 12 years
(6.1 – 436.9)
Coefficient =
#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
1
10
100
1000
10000
100000
1000000
J-9
8
J-9
9
J-0
0
J-0
1
J-0
2
J-0
3
J-0
4
J-0
5
J-0
6
J-0
7
J-0
8
J-0
9
J-1
0
J-1
1
J-1
2
J-1
3
J-1
4
J-1
5
HIV Viral Load (Log10) for Patient 1028
Suppressed
Quantifiable
Detectable, not quant
Not detectable
#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 111 477 -0.025 -0.037 to -0.013 144 73 to 5243 0.040
Patients with:
Undetectable
21 59 -0.056 -0.093 to -0.020 64 39 to 182 0.123
Detectable 83 401 -0.025 -0.038 to -0.012 146 96 to 305 0.053
Quantifiable 4 14 -0.018 -0.046 to 0.01 204 79 to -348
(dt)
0.529
Siliciano et al. Nat Med. 2003 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)
#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
Honorable mention
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)
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% 0 11.6%
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
• 79/140 patients had post GA ARV changes: 85%
remained suppressed at 3 months
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
Thank you
Questions?