ID Week 2016: HIV Update - University of...

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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)


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


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



• 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



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



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)



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



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 =



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



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)



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

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ID Week 2016: HIV Update - University of...

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