Robert Harrington MD ID Week 2016 HIV Update New management of lowlevel viral blips DTGABC3TC versus ATZr TDFFTC in women ARIA Omega3 fatty acids HIV reservoir decay and lowlevel plasma HIV RNA ID: 528594
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Slide1
ID Week 2016: HIV Update
Robert Harrington, M.D.Slide2
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 patientsSlide3
#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) Slide4
#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 LaboratoriesSlide5
#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 retestingSlide6
#949: DTG/ABC/3TC versus ATZ/r + TDF/FTC in women (ARIA study
) (
Hagins
, et al) Slide7
#949: DTG/ABC/3TC versus ATZ/r + TDF/FTC in women (ARIA study)
International study of treatment naïve women
S
tratified by HIV RNA and CD4 count
R
andomized 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 armSlide8
#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)
White86%80%African heritage74%67%Other94%56%US subjects74%67%
DTG/ABC/3TC
superior to
ATZ/r +
TDF/FTC in
HIV+ women regardless of raceSlide9
#951: RCT of Omega-3 fatty acids in HIV: Long term effects on lipids and vascular function
(Volpe, et al) Slide10
#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 648Slide11
#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 HDLNo differenceChange in CRP-0.3+0.60.008Brachial artery reactivityNo differenceCarotid-femoral pulse wave velocity-46 ms-1+18 ms-10.1Slide12
#951: RCT of Omega-3 fatty acids in HIV: Long term effects on lipids and vascular function
Triglycerides
CRP
Omega-3FAs reduce
TGs,
m
ay limit chronic
i
nflammation and improve
v
ascular function Slide13
#953: HIV Reservoir size and decay in 114 individuals with suppressed plasma HIV for at least 7 years (
Golob
, et al) Slide14
#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
CohortSlide15
#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/
F
emale / Male
-> Female
93
/ 15 / 3Race (Caucasian / Black / Asian or Pacific Islander / multiple)82 / 17 / 11 / 1Antiretroviral exposure (all exposed to nRTI) Protease inhibitors96 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 (83 – 1260)
Study details
Value
Median
follow-up period after T
0
(range)
1.4 (0 – 8.5) years
Median
number of reservoir measurements (range)
3 (1
- 23
)Slide16
#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
0.002Slide17
#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 = Slide18
#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
Suppressed
Quantifiable
Detectable, not quant
Not detectableSlide19
#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
Mean95% 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)Slide20
#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 monthsSlide21
Honorable mentionSlide22
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)Slide23
Overall
concordance
NRTI
NNRTI
PI
All
Any
On
GA only
24.6%
21.7%
17.4%
8.7%
36.2%Concordance72.5%72.5%76.8%53.6%91.3%Not detected on GA2.9%5.8%5.8%011.6%
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 monthsSlide24
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) + 2NRTIAt 48 weeks: data from 32 patients:VL <50: 93%, CD4 change: + 94, AEs: noneSlide25
Thank you
Questions?