presented by: dr mekala srirajalingam november 2016 · 2020. 3. 13. · ©ashm 2016 • every 2...

© ASHM 2016

Presented by: Dr Mekala Srirajalingam

November 2016

© ASHM 2016

• ASHM Scholarship to attend AIDS2060

• Previous: HIV Pharmaceutical companies funding to

attend conferences and meeting within Australia.

Disclosures

© ASHM 2016

• Every 2 years from 1985, a forum for intersection of

science and advocacy

• Focal point to intensify political and financial

commitments & Building partnerships

• Funding esp Middle income countries and sustainable

transition

• 18,000 delegates & 2000 posters displayed for one day.

• Dignitaries: Prince Harry, Prince of Lesotho, Charlize

Theron

• TB2016 - IAS organised a two day preconference

workshop for advancing global response to TB. More TB

deaths than deaths due to HIV.

THEME: Access, Equity, Rights Now

© ASHM 2016

• Engaging Youth – inferior outcomes on ART

• Prison Health

• PrEP/PEP access in a global setting: eg sex-workers in

Kenya

• Integrase inhibitors

• POC tests

• Hepatitis C

• Nurse’s role

• Vaccines/Antibody prophylaxis

• 2014: UN 90-90-90 by 2020

• Elimination goal by 2030

• Inspiring People

© ASHM 2016

• Opening was on Nelson Mandela Day.

• AIDS2000 was all about access to Rx and prohibition

and the current theme was more a push for lifting

prohibition and discriminatory laws and harm

minimisation.

• ~20 % HIV positive in SA ~25% in Lesotho.

•

© ASHM 2016

• US has the highest incarceration rate in the world, with

blacks over represented in the prisons

• Annually 30 million people are passing through some

form of detention

• Only eight countries have needle and syringe exchange

programmes in prison.

• The focus of incarceration should be rehabilitation.

• Reduce incarceration for key populations, especially

people who inject drugs

• Introduce and scale-up HIV prevention with Opioid

Agonist Therapy, Needle Syringe programmes and Anti

Retroviral therapy, including effective transitional

programs post-release

The Lancet Special Theme Issue: HIV, Viral Hepatitis,

and TB among Prisoners

© ASHM 2016

“It is said that no one truly knows a nation until one has been inside it jails. A nation should not be judged by how it treats it highest citizens, but its lowest ones.”…………Nelson Mandela

© ASHM 2016

DHAA & IAS updated guidelines

July 2016

July 2016 Updates on Recommended

Regimens for First-line ART

DHHS[1]

– Recommended regimens include 3 INSTIs and 1 boosted PI

– Primary change since Jan 2016 update is addition of TAF/FTC

IAS-USA[2]

– All recommended regimens include INSTI + TAF/FTC or ABC/3TC

– Major changes since 2014 update include removal of NNRTIs, boosted PIs, and TDF

Regimen DHHS[1] IAS-USA[2]

DTG/ABC/3TC

DTG + TAF/FTC

DTG + TDF/FTC

EVG/COBI/TAF/FTC

EVG/COBI/TDF/FTC

RAL + TAF/FTC

RAL + TDF/FTC

DRV + RTV +

TAF/FTC

DRV + RTV +

TDF/FTC

Preferred/recommended Alternative

1. DHHS Guidelines. July 2016.

2. Günthard HF, et al. JAMA. 2016;316:191-210. Slide credit: clinicaloptions.com

http://www.clinicaloptions.com/oncology

© ASHM 2016

Treatment studies

ARIA Multi National Open-label RCT in non pregnant Hep B

negative, ART naïve women

•Efficacy in treatment-naive patients previously evaluated in

the SINGLE trial DTG/ABC/3TC found to be superior to

EFV/TDF/FTC at Week 48 of therapy

•Trial population was only 16% women

ARIA: DTG/ABC/3TC vs ATV + RTV +

TDF/FTC in Treatment-Naive Women

Multinational, randomized, open-label phase IIIb trial

– Primary endpoint: Wk 48 HIV-1 RNA < 50 copies/mL

Orrell C, et al. AIDS 2016. Abstract THAB0205LB. Slide credit: clinicaloptions.com

DTG/ABC/3TC QD

(n = 248)

ATV + RTV + TDF/FTC QD

(n = 247)

ART-naive women*

with HIV-1 RNA

≥ 500 copies/mL,

HLA-B*5701 negative,

and CrCl ≥ 50 mL/min

(N = 495)

Wk 48

*Women enrolled in North America, European Union, Argentina, Puerto Rico, Russian Federation,

South Africa, and Thailand.

Dosing: ATV 300 mg, RTV 100 mg, TDF/FTC 300/200 mg, DTG/ABC/3TC 50/600/300 mg.

After 48 wks, pts in the DTG/ABC/3TC arm could enter the continuation phase.

Women

who became

pregnant offered

option to enter

DTG/ABC/3TC

pregnancy study

NCT02075593

Stratified by

HIV-1 RNA ≤ or > 100,000 copies/mL,

CD4+ cell count ≤ or > 350 cells/mm3


Primary virologic outcomes (ITT-E analysis)

ARIA: DTG/ABC/3TC Superior to ATV +

RTV + TDF/FTC at Wk 48

Slide credit: clinicaloptions.com Orrell C, et al. AIDS 2016. Abstract THAB0205LB.

HIV-1 RNA < 50 copies/mL, % DTG/ABC/3TC ATV + RTV + TDF/FTC

Baseline HIV-1 RNA, copies/mL

≤ 100,000 83 74

> 100,000 80 64

Baseline CD4+ cell count, cells/mm³

≤ 350 85 72

> 350 78 71

Outcome, % (n) DTG/ABC/3TC

(n = 248)

ATV + RTV + TDF/FTC (n = 247)

Treatment Difference (95% CI)

P Value

Virologic success (HIV-1 RNA < 50 copies/mL)

82 (203) 71 (176) 10.5

(3.1-17.8) .005

Virologic nonresponse 6 (16) 14 (35) -- --

No virologic data 12 (29) 15 (36) -- --

Virologic outcomes by baseline randomization strata (ITT-E analysis)


ARIA: Safety Outcomes

Slide credit: clinicaloptions.com Orrell C, et al. AIDS 2016. Abstract THAB0205LB.

AE, % DTG/ABC/3TC

(n = 248)

ATV + RTV + TDF/FTC

(n = 247)

Discontinuations due to AE 4 7

Serious AE 5 8

Fatal AE < 1* 0

Drug-related serious AE 0 1

Any AE 79 80

Grade 2-4 AE 46 55

Drug-related AE occurring

in ≥ 5% of pts in either arm 33 49

Nausea 13 14

Diarrhea 5 7

Dyspepsia 2 6

Ocular icterus 0 7

Headache 2 6

Jaundice 0 5 *1 death deemed unrelated to study drugs.


© ASHM 2016

ARIA: Summary of Key Conclusions

•In treatment-naive women (n=495) DTG/ABC/3TC was

superior to ATV/r/TDF/FTC at 48 weeks by US (FDA)

snapshot analysis

• ITT-E analysis: 10.5% (95% CI: 3.1% to 17.8%; P =

.005)

• PP analysis : 9.7% (95% CI: 2.6% to 16.8%)

• Efficacy difference driven by lower rate of virologic

nonresponse and fewer discontinuations due to adverse

events (AEs) in the DTG/ABC/3TC arm

•Favourable safety profile for DTG/ABC/3TC

•No treatment-emergent mutations in the DTG/ABC/3TC

group

•The study provides important additional information on

DTG/ABC/3TC efficacy and tolerability in women

© ASHM 2016

Treatment studies

PROMISE

(n=1653)

Current study evaluated risks and benefits of continuous vs

interrupted ART in non–breast-feeding women with CD4 ≥ 400 at

entry following delivery

Multicentre, RCT, Open-label, phase IV

Analyses reflect follow-up until July 7, 2015, at which point all

participants were offered ART based on the results of the START

trial

Randomized trial in women receiving ART or stopping ART following pregnancy

Slide credit: clinicaloptions.com

PROMISE: Continuing vs Stopping ART in

Postpartum, Non–Breast-feeding Women

Currier J, et al. AIDS 2016. Abstract THAB0103LB.

Continue ART

(n = 827)

Stop ART*

(n = 825)

HIV-infected, ART-naive (except PMTCT)

postpartum women without guideline-

specified indication for ART, CD4+ cell

count ≥ 400 cells/mm3, not breastfeeding

(N = 1652)

Randomized within

42 days of delivery

*Restarted ART if CD4+ cell count fell below 350 cells/mm3 or was clinically indicated.

Pts seen 4 wks post enrollment,

then every 12 wks through 84 wks

after last enrollment

Study sites: Argentina, Botswana, Brazil, China, Haiti, Peru, Thailand, and United States

Median follow-up: Continue ART arm, 2.31 yrs; Stop arm, 2.35 yrs

ART during study (Continue ART arm): 74% LPV/RTV based, 19% ATV/RTV based


© ASHM 2016

CD4 ≥400cells/cmm before ART and at

delivery.

ART not indicated based on local

guidelines.

Preferred Regimen: Lop/r + TDF/FTC

Received ≥4 wks ART fro PMTCT

ART restarted in Stop ART arm – if CD4

<350 or clinically indicated.

PROMISE


PROMISE: Efficacy and Safety

Between treatment arms, no significant difference in primary safety or efficacy endpoints; continuing ART associated with lower HIV event rate

Currier J, et al. AIDS 2016. Abstract THAB0103LB.

Outcome, n (Rate/100 PY) Continue ART (n = 827) Stop ART (n = 825) HR (95% CI)

Primary efficacy composite

endpoint events 4 (0.21) 6 (0.31) 0.68 (0.19-2.40)*

AIDS-defining events 2 (0.10) 3 (0.15) 0.67 (0.11-4.02)

Serious non-AIDS event 0 0 --

Death 2 (0.10) 4 (0.20) 0.52 (0.09-2.81)

Primary safety composite

endpoint events† 260 (18.4) 232 (15.4)‡ --

Composite of HIV/AIDS-related

or WHO stage 2/3 events 57 (3.09) 99 (5.49) 0.56 (0.41-0.78)

WHO stage 2/3 events 39 (2.02) 80 (4.36) 0.47 (0.32-0.68)§

189 (23%) pts in Continue ART arm experienced virologic failure; in pts with virologic failure who had resistance testing, 52/155 (34%) had evidence of resistance

*P = .54. †Time to first grade 3/4 sign or symptom or grade 2-4 chemistry or hematology result. ‡P = .08. §P < .001.


© ASHM 2016

• Continuation arm: CD4 increased from median of 696

cells/mm3 at Week 0 to ~ 850 cells/mm3 at Week 204

• Discontinuation arm: CD4 decreased from 695 cells/mm3

at baseline to 580 cells/mm3 at Week 204

• 31% of women who had stopped ART at delivery

restarted ART following CD4+ cell count declines – Median CD4+ cell count upon restarting: 372 cells/mm3

CD4

PROMISE

© ASHM 2016

Treatment studies

ONCEMRK Multinational Double Blind RCT – Phase III

QDMRK trial failed to show noninferiority of 2 tablets of 400-mg

RAL taken every 24 hours to 1 tablet of 400-mg RAL taken every

12 hours, both with TDF/FTC, in treatment-naive patients

RAL 1200 mg (600mg x2) designed to bring exposure-response

curve closer to BID dosing

Multinational, randomized, double-blind phase III trial

– Primary endpoint: Wk 48 HIV-1 RNA < 40 copies/mL

– Reformulated RAL 600 mg tablets allow 1200 mg QD dosing


ONCEMRK: RAL 1200 mg QD vs

400 mg BID + TDF/FTC in ART-Naive Pts

Cahn P, et al. AIDS 2016. Abstract FRAB0103LB.

RAL 1200 mg* QD +

TDF/FTC

(n = 533)

RAL 400 mg BID +

TDF/FTC

(n = 269)

ART-naive adults

with HIV-1 RNA

≥ 1000 copies/mL

(N = 802)

Pts followed

for 14 days

96 wks Randomized 2:1 48 wks

Baseline HIV-1 RNA > 100,000 copies/mL: 28.1% to 28.6%

*Two 600-mg tablets.



ONCEMRK: RAL 1200 mg QD Noninferior

to RAL 400 mg BID at Wk 48

Cahn P, et al. AIDS 2016. Abstract FRAB0103LB.

Reproduced with permission.

Wk 48 HIV-1 RNA < 40 copies/mL in pts with BL HIV-1 RNA > 100,000 copies/mL: RAL QD, 86.7%; RAL BID, 83.8% (∆ 2.9; 95% CI: -6.5-14.1)

RAL QD associated with overall safety profile similar to RAL BID

100

80

60

40

20

0

Pts

With H

IV-1

RN

A

< 4

0 c

opie

s/m

L (

%)

0 4 8 12 16 20 24 28 32 36 40 44 48

Treatment Wk

RAL 1200 mg QD + TDF/FTC

RAL 400 mg BID + TDF/FTC

88.3 88.7 86.5 83.5 78.2

51.9

53.5

76.3 82.1 87.4 87.2 88.9


© ASHM 2016

• RAL 1200mg od non-inferior to 400mg bd in ART

naïve patients

• CD4 changes similar

• More AE related discontinuations in bd arm.

• 14/18 Qd arm with PDV Failure had GRA. Four

had RAL associated resistance mutations; Five had

FTC mutations.

• 3/9 in Bd arm with PDV failure had GRA. One test

failed. No resistance mutations.

© ASHM 2016

Treatment studies

STRIVING

n=553

Multicenter, randomized, open-label phase IIIb study,

in North America

Switching suppressed patients on NNRI/PI/INI to

ABC/DTG/3TC

© ASHM 2016

Primary endpoint - was non-inferiority (-10% margin) of

ABC/DTG/3TC relative to cART in maintaining plasma HIV-

1 RNA < 50 c/mL at W24 by FDA snapshot.

Secondary endpoint - Plasma HIV-RNA < 50 c/mL at W48

after all subjects switched to the DTG-based FDC.

STRIIVING: Switch From Suppressive ART

to Fixed-Dose DTG/ABC/3TC

Multicenter, randomized, open-label phase IIIb study

– Conducted in US, Canada, and Puerto Rico

– Primary endpoint: HIV-1 RNA < 50 copies/mL at Wk 24

Pts with HIV-1 RNA

< 50 copies/mL

on stable ART ≥ 6 mos,

no previous virologic failure,

HLA-B*5701 negative

(N = 553)

DTG/ABC/3TC (n = 275)

Wk 48 Wk 24

*Containing 2 NRTIs plus NNRTI, PI, or INSTI.

Baseline ART* (n = 278)

DTG/ABC/3TC

(n = 244)

Slide credit: clinicaloptions.com Lake J, et al. AIDS 2016. Abstract THAB0203.


STRIIVING: Virologic Outcomes at Wks 24

and 48

Similar virologic response rates with switch to DTG/ABC/3TC vs continued baseline ART at Wk 24 primary endpoint

In pts switched to DTG/ABC/3TC at randomization, 83% maintained virologic suppression through Wk 48

In pts switched from baseline ART to DTG/ABC/3TC at Wk 24 (n = 244), 92% maintained virologic suppression from Wk 24 to Wk 48

No cases of protocol-defined virologic failure

– 1 pt in early switch arm (< 1%) and 3 pts in post-switch BL ART arm (1%) had HIV-1 RNA ≥ 50 c/mL at Wk 48 but all resuppressed to < 50 c/mL

Slide credit: clinicaloptions.com Lake J, et al. AIDS 2016. Abstract THAB0203.

Wk 24 Outcome, % DTG/ABC/3TC

(n = 275)

Baseline ART

(n = 278)

Virologic success (HIV-1 RNA < 50 c/mL) 85 88

Virologic nonresponse 1 1

No virologic data 14 10


© ASHM 2016

In virologically suppressed patients, switching to once daily

ABC/DTG/3TC FDC was non-inferior to continuing cART with

no evidence of virologic failure or treatment emergent resistance

through 24 weeks.

Early switch subjects also maintained virologic suppression from

W24 through W48.

There were fewer withdrawals due to AEs in the LS vs. ES arm.

The safety profile of ABC/DTG/3TC in STRIIVING is consistent

with current labeling for ABC/DTG/3TC.

© ASHM 2016

Treatment studies

LATTE-2 (n=309)

Cabotegravir (CAB) and rilpivirine (RPV) are under

development as long-acting (LA) injectable

nanosuspensions.

LATTE-2 was designed to select an intramuscular (IM)

regimen of CAB LA + RPV LA and to evaluate safety and

efficacy of 2-drug IM ART, relative to 3-drug oral ART (CAB

+ ABC/3TC) to maintain viral suppression of HIV-1.

Phase 2b, international, multicentre, parallel group, open-label

study – 48 wk

LATTE-2: Cabotegravir IM + Rilpivirine IM

for Long-Acting Maintenance ART

Multicenter, open-label, randomized phase IIb study

– Primary endpoints: HIV-1 RNA < 50 copies/mL at maintenance Wk 32, PDVF, and safety

Slide credit: clinicaloptions.com Margolis DA, et al. AIDS 2016. Abstract THAB0206LB.

CAB 400 mg + RPV 600 mg IM Q4W (n = 115)

CAB 600 mg + RPV 900 mg IM Q8W (n = 115)

*Pts with HIV-1 RNA < 50 copies/mL from Wk 16-20 continued to maintenance phase. †Pts eligible for Q4W or Q8W LA extension past Wk 96.

ART-naive HIV-

infected pts older

than 18 yrs of age

with CD4+ cell

count > 200

cells/mm3

(N = 309) CAB 30 mg + ABC/3TC 600/300 mg PO QD

(n = 56)

CAB 30 mg + ABC/3TC 600/ 300 mg PO QD

Wk 32

Wk 20

Induction Phase* Maintenance Phase

Day 1 Wk 96† Wk 16: RPV 25 mg

PO QD added Wk 48


LATTE-2: Efficacy and Safety Through

Maintenance Wk 48

Virologic efficacy of Q4W/Q8W IM therapy similar to oral therapy

99% of ISRs for pts receiving injectable therapy grade 1 (82%) or 2 (17%); none grade 4

– Most frequent ISRs: pain (67%), nodules (7%), swelling (6%)

– Reported ISRs decreased over time (86% Day 1, 29% Wk 48)

– 2/230 pts (< 1%) withdrew for ISRs (both in Q8W arm)

AEs leading to withdrawal

– Pooled Q4W/Q8W IM arms, 4%

– Oral arm, 2%

Slide credit: clinicaloptions.com Margolis DA, et al. AIDS 2016. Abstract THAB0206LB

Outcome, % (n)

IM CAB +

RPV Q4W

(n = 115)

IM CAB

+ RPV

Q8W

(n = 115)

Oral CAB

+ ABC/3TC

(n = 56)

Virologic success

(HIV-1 RNA

< 50 copies/mL)

91 (105) 92 (106) 89 (50)

Virologic

nonresponse < 1 (1) 7 (8) 2 (1)

No virologic data 8 (9) < 1 (1) 9 (5)


LATTE-2: Wk 48 Pt Satisfaction With IM

and PO Regimens

Slide credit: clinicaloptions.com Margolis DA, et al. AIDS 2016. Abstract THAB0206LB.

Wk 48 Pt-Reported Outcomes, %

IM CAB + RPV Q4W

(n = 103)

IM CAB + RPV Q8W

(n = 109)

PO CAB + ABC/3TC (n = 49)

How satisfied are you with your current treatment?

6 79 83 67

5 20 14 29

< 5 1 3 4

How satisfied would you be to continue with your present form of treatment?

6 85 88 55

5 13 11 33

< 5 2 1 12

Pt satisfaction assessed using 0 to 6 scoring (0 = very dissatisfied, 6 = very satisfied)


© ASHM 2016

Latte-2

Both Q8W and Q4W IM dosing demonstrated good

virologic response rates and were generally well tolerated

through 48 weeks.

Q4W dosing resulted in modestly lower rates of virologic

non-response than Q8W.

Q4W dosing was chosen for progression into phase 3

studies while Q8W and Q4W remain under evaluation

within LATTE-2.

© ASHM 2016

DUAL THERAPY STUDIES

Switch to DTG + RPV in

Suppressed Pts With

Multiple Previous

Treatment Failures (n=38)

© ASHM 2016

Heavily pretreated patients with multiple regimen failures

may require treatment with complex therapy

– Simplification of regimens in this setting has potential

to reduce drug–drug interactions, adverse events

DTG plus RPV currently being evaluated as NRTI- and PI-

sparing maintenance therapy in phase III trials

Current study assessed safety and efficacy of switch to

once-daily DTG plus RPV in virologically suppressed,

heavily pre-treated patients with no demonstrated

resistance to the study agents.

Background

© ASHM 2016

Characteristic Switch to DTG + RPV

(N = 38)

Male, % 66

Median age, yrs 53.4

AIDS, % 34

Previous injection drug use,

%

68

Previous HCV coinfection, % 70

Median nadir CD4+ cell

count, cells/mm3

179

Median baseline CD4+ cell

count, cells/mm3

592

Median time on ART, yrs 19.4

Duration of HIV-1 RNA < 50

copies/mL, yrs

6.7

Median pills in current

regimen, n

4.3

© ASHM 2016

Previous Treatment

Characteristics NRTI NNRTI PI INSTI

Previous exposure,* n

(%) 38 (100) 34 (90) 37 (97) 24 (62)

Previous failure, n (%) 38 (100) 28 (68) 27 (71) 3 (8)

Primary resistance

mutations, n (%) 25 (65) 14 (37) 12 (32) NA

Median number of

resistance mutations, n 3.8 2.0 4.2 NA

•Majority of patients had been exposed to ≥ 3 drug classes

before current switch

•55% (n = 21) of patients had experienced treatment

failure to drugs from ≥ 3 drug classes

•45% (n = 17) of patients had major resistance mutations

to ≥ 2 drug classes

Switch to DTG + RPV in Suppressed Pts

With Multiple Previous Treatment Failures

Open-label cohort study based in clinical practice setting (N = 38)

– DTG 50 mg/day + RPV 25 mg/day for pts with long-term virologic suppression but virologic failure on > 1 previous ART regimens

HIV-1 RNA suppressed to < 35 copies/mL in 92% (35/38) at Wk 48

– No virologic failures; 3 pts d/c (GI toxicity, DDI, physician decision, n = 1)

DTG + RPV associated with improved liver function tests, improved lipid profile, and stable kidney function at Wk 48

Slide credit: clinicaloptions.com Díaz A, et al. AIDS 2016. Abstract TUPDB0106.

Baseline Characteristic , % Switch to DTG + RPV (N = 38)

Regimen at time of switch NRTI + NNRTI + PI

NRTI + NNRTI + PI + INSTI

85

53

Reasons for switch to DTG + RPV Drug–drug interaction

Toxicity

Simplification

38

33

25

Pre-existing resistance mutations NRTI: 65; NNRTI: 37; PI: 32; INSTI: NA


© ASHM 2016


Summary of Key Conclusions

•Switching virologically suppressed HIV-infected patients

with multiple previous treatment failures to once-daily

dolutegravir (DTG) plus rilpivirine (RPV) found to be safe

and effective through Week 48

• No virologic failures to date after switch to DTG plus

RPV

• CD4+ cell count remained stable after switch

•Switch associated with improved safety profile at Week 48

vs baseline, including improved liver function tests,

improved lipid profile, and stable kidney function

© ASHM 2016


PADDLE: DOL & 3TC

(n=20)

Dolutegravir + Lamivudine for Treatment-Naive Pts

PADDLE: open-label, single-arm phase IV exploratory trial

in Argentina

PADDLE: Dolutegravir + Lamivudine for

Treatment-Naive Pts

Open-label, single-arm phase IV exploratory trial

18/20 pts achieved HIV-1 RNA < 50 c/mL at Wk 48 (& Wk8)

– 1 pt committed suicide (deemed unrelated to study drugs)

– 1 pt experienced PDVF at Wk 36 (BL HIV-1 RNA > 100,000 c/mL); resuppressed HIV-1 RNA without ART change by discontinuation visit (Wk 52)

– 3 other pts with BL HIV-1 RNA > 100,000 c/mL suppressed at Wk 48

Slide credit: clinicaloptions.com Cahn P, et al. AIDS 2016. Abstract FRAB0104LB.

Treatment-naive pts

with HIV-1 RNA

> 5000-100,000 c/mL,

CD4+ cell count ≥ 200

cells/mm3, HBsAg negative

(N = 20)

DTG 50 mg QD + 3TC 300 mg QD (N = 20*)

*10 pts enrolled initially; additional 10 pts enrolled after confirming virologic success of first cohort at Wk 8. †Primary endpoint.

Wk 48†


© ASHM 2016


•Current study has been extended to Week 96

•Phase III GEMINI noninferiority study planned –

• 700 patients

• DOL/3TC vs DOL/TDF/FTC as initial therapy

© ASHM 2016

PREVENTION & VACCINE

STUDIES

© ASHM 2016

MTN-020/ASPIRE


MTN-020/ASPIRE: Dapivirine Vaginal Ring

for HIV Prevention in Women

Multicenter, double-blind, placebo-controlled, randomized phase III trial in Malawi, South Africa, Uganda, and Zimbabwe

Silicone elastomer vaginal matrix ring containing NNRTI dapivirine 25 mg; ring replaced every 4 wks

Primary endpoints: efficacy and safety

HIV protection efficacy vs placebo: 27% (P = .046)

Brown E, et al. AIDS 2016. Abstract TUAC0105LB.

Baeten JM, et al. N Engl J Med. 2016;[Epub ahead of print].

Dapivirine 25 mg Vaginal Ring Q4W + HIV Prevention Service Package

(n = 1313)

Placebo Vaginal Ring Q4W + HIV Prevention Service Package

(n = 1316)

Sexually active HIV-

uninfected adult

women

(N = 2629)

≥ 1 yr; endpoint-

driven duration


Schedule of sample collection

Monthly follow-up w/ HIV-1 testing (min 12 / max 33 months)

• Monthly follow-up included HIV testing and provision of a new ring containing 25 mg of dapivirine

• Plasma was archived quarterly (for dapivirine and HIV RNA testing) • Starting one year after study initiation, returned rings were archived and sent to a

central lab for testing of remaining dapivirine levels (thus, nearly all participants have rings for visits at Month 12+ but some do not have prior to Month 12)


MTN-020/ASPIRE Subcohort: Adherence

by Residual DAP Levels in Vaginal Ring

Brown E, et al. AIDS 2016. Abstract TUAC0105LB. Reproduced with permission.

Outcome Placebo Nonadherent

(≥ 23.5 mg*)

Low-High Adherence

(< 23.5 mg*)

Med-High Adherence

(< 22 mg*)

Infections, n 50 13 14 7

HIV incidence/100 PY 4.6 3.6 1.9 1.5

Risk reduction vs PBO,

% (95% CI; P value) --

31

(-28 to 63; .24)

56

(20 to 76; .007)

65

(22 to 84; .01)

*Residual levels of DAP remaining in returned rings.

A lower level of residual DAP in the returned ring is indicative of higher adherence

16 18 20 22 24 26 28

DAP Remaining (mg)

Expected level of ring

used for 28 days: 20-21 mg

Expected level of

unused ring: 24-25 mg


Sustained adherence associated with 92% reduction in risk of HIV infection

MTN-020/ASPIRE Subcohort: Adherence

vs HIV Protection 3 Mos Before Detection

No use Bottom third Top third Middle third

HIV

Infe

ction R

isk R

eduction (

%)


Adherence*

*For seroconversions, adherence level taken from visit with lowest adherence of 3 months (3 visits)

before HIV detection.

100

50

0

-50

Risk reduction

92% (95% CI: 38 to 99)

Risk reduction

58% (95% CI: -7 to 83)

Risk reduction

29% (95% CI: -52 to 66) Risk reduction

11% (95% CI: -78 to 55)

Brown E, et al. AIDS 2016. Abstract TUAC0105LB.



Summary

• Across multiple analyses, there is a statistically significant relationship between ring use and HIV protection

• These analyses provide evidence suggesting a dose-response relationship between ring use and HIV acquisition

• Results suggest ring use is associated with at least 56% and potentially >75% protection when used consistently

© ASHM 2016

ATN 113:

Daily Oral TDF/FTC as PrEP for Adolescent

MSM in US

n=79

Observational, open-label, single-arm feasibility study

© ASHM 2016

– HIV-negative US MSM aged 15-17 yrs who demonstrated

high-risk behavior for acquiring HIV

– 2864 adolescent MSM individuals approached, 260 eligible

for prescreening, N = 79 enrolled, 32 (40%) prematurely

discontinued.

– daily oral TDF/FTC, with personalized counselling pre Rx

and full treatment package included integrated next step

counselling

– Follow-up visits at Wks 4, 8, 12, 24, 36, 48

ATN113

© ASHM 2016

•Endpoints

• Safety

• Adherence, assessed by TFV-DP levels in

dried blood spots (DBS)

• HIV acquisition

• Acceptability

• Sexual behavior

•Dual-energy x-ray absorptiometry data not available for

current analysis

© ASHM 2016

Wk 48 outcomes

– 3 seroconversions

• All 3 had low TFV-DP drug levels at time of seroconversion

at wk 32, 36 and 48 wks. Last case undetectable at all times.

• Marked drop in levels between wk12 and wk24 with drop in

clinic visits and progressive decline.

– HIV incidence: 6.41/100 PY (95% CI: 4.9-25.8)

– Reasons: convenience issues and fear that others would

think HIV positive.

– Weight loss 10-19% in two cases deemed due to drugs.

Hosek S, et al. AIDS 2016. Abstract TUAX0104LB.

ATN 113: Adherence

Drop off in TFV-DP levels between Wk 12 and Wk 24 corresponded to reduced frequency of scheduled study visits (from every 4 wks to every 12 wks)


Hosek S, et al. AIDS 2016. Abstract TUAX0104LB.


1200

1000

800

600

400

200

0

TF

V-D

P (

fmol/punch)

via

DB

S

0 12 24 36 48

Overall

White

Latino

Mixed

Black

Wk

4 8


© ASHM 2016

Efficacy of on demand PrEP with TDF-FTC in the ANRS

IPERGAY open-label extension study

J.-M. Molina et al.

ANRS IPERGAY, on demand PrEP with TDF-FTC reduced by

86% the incidence of HIV-1 infection in high risk MSM

(n=400)

336 (84%) were eligible for the open-label phase, study

retention was good with 23 discontinuations.

November 2014 to June 2016, 2 monthly f/u on TDF/FTC

Pts used a mean of 18 pills/month and 39% acquired a new

STI.

Single discontinuation due to increase in Serum creatinine.

© ASHM 2016

There was no significant changes between the double-blinded

phase and the open-label phase in the median number of sexual

intercourses or sexual partners, but there was a significant

decrease in condom use for receptive anal Intercourse (p=0.0004)

IPERGAY phase Person-years of follow-

up

Incidence of HIV

Infection per 100 person-

years [95% confidence

interval]

IPERGAY double-blinded

(Placebo Arm) 212 6.60 [3.61-11.07]

IPERGAY double-blinded

(TDF-FTC Arm) 219 0.91 [0.11-3.30]

IPERGAY open-label

extension (open-label

TDF-FTC)

334 0.30 [0.00-1.67]

© ASHM 2016

Hormonal Contraception and HIV: A

Review of the Science and Research, and

their implications for Research,

Programme and Policy.

© ASHM 2016

DMPA has activity like cortisol.

Collectively, clinical, animal, and ex vivo studies are broadly

consistent and show that DMPA increases permeability of

the female genital tract and compromises select FGT and

systemic immune responses. This most likely leads to

increases in HIV acquisition via multiple mechanisms more

so in some individuals than others.

• However, pregnancy per se increases HIV acquisition by

2-fold

Janet Hapgood, SA,

Biological/immunological mechanisms

for an association between HC and HIV.

© ASHM 2016

This review was to update the evidence on which the WHO

guidance and local policy is bases.

ART and HC effectiveness

Efavirenz – most clinically significant interactions were

with Efavirenz.

Implant users: pregnancy rates from 5-15 per 100 w-

y. (c.f 0-2 per 100 w-y)

Combined oral contraceptive pill: 13-15 per 100 w-

y.

DMPA: not impactecd.

Nevirapine – No significant impact.

Andy Gray, South Africa, presented on Interactions

between HC methods and ART- updated systematic

review.

© ASHM 2016

HC and ART effectiveness – No significant effect noted.

DMPA and PrEP – no significant effect.

Conclusions include:

Current published data do not support limiting access to

any HC.

Full range of HC options should be made available

© ASHM 2016

Jared Baeten, US, Update on ECHO Multi Centre, Open

Label, Randomised trial on HIV acquisition among users of

different hormonal contraception methods [DMPA, LNG

implant, Cu IUCD].

N=7800 f/u , 12 sites in Kenya, South Africa (9), Swaziland

and Zambia. 18 mths per women. Quarterly follow up with

usual standard of care.

Started in 2015 and will go on for ~36 mths.

© ASHM 2016

Status

Ongoing

Phase

I/II

DB RCT: South African adults (N = 252) randomized to

vaccination for clade C (n = 210) or placebo (n = 42)

Objective

Safety, Tolerability, Immune response

Are people able to take the study vaccines without

becoming too uncomfortable?

*Interim results from HVTN 100, presented July, 2016 at

the AIDS 2016 in Durban, provided the green light for a

Phase III efficacy trial (HVTN 702) on the modified RV144

regimen*


HVTN100: Investigational HIV-1 Vaccine

for HIV-Uninfected South African Adults

Double-blind, randomized, placebo-controlled phase I/II trial

– South African adults (N = 252) randomized to vaccination (n = 210) or placebo (n = 42)

– Vaccine: clade C ALVAC-HIV (vCP2438) and bivalent subtype C gp120/MF59

– Vaccination schedule: ALVAC-HIV at mos 0 and 1; ALVAC-HIV + gp120/MF59 at mos 3, 6, and 12 (booster)

Goal: after 6.5 mos, meet 4 prespecified immunogenic criteria required to move into phase IIb efficacy studies

1. Develop IgG-binding Abs to ≥ 2 of 3 gp120 vaccine antigens (LL of 95% CI ≥ 75%)

2. Exhibit noninferior IgG-binding Ab magnitude to 2 of 3 gp120 vaccine antigens vs RV144 (previous vaccine trial)

3. Exhibit noninferior response rate of Env-specific CD4+ T cells expressing IL-2, IFN-gamma, or CD40L vs RV144 (difference within 30%)

4. Develop IgG-binding Abs to ≥ 1 clade C V1V2 Ags/tags (LL of 95% CI ≥ 56%)

All criteria met; vaccine will move into phase IIb efficacy studies

Bekker LG, et al. AIDS 2016. Abstract TUAX0102LB.


ASTRAL-5: multicenter, open-label, single-arm phase III study[1]

– 12 wks of SOF/VEL in HIV/HCV-coinfected, GT 1-6 HCV , tx naive or experienced, stably suppressed on ART (N = 106)

Sofosbuvir/Velpatasvir in HIV/HCV-

Coinfected Pts


1. Bräu N, et al. AIDS 2016. Abstract WEAB0301. Reproduced with permission.

2. Mogalian E,et al. AIDS 2016. Abstract WEAB0302.

Drug-drug interaction study in healthy volunteers (N = 228)[2]

– 50% reduction in VEL exposure when EFV/TDF/FTC and SOF/VEL coadministered; EFV not recommended with SOF/VEL

– FTC, EFV, RPV, DTG, RAL, EVG, ATV, RTV, DRV, LPV, not affected by SOF/VEL; TDF exposure increased ~20% to 81%

100

80

60

40

20

0

SV

R1

2 (

%)

Total 1a 1b 2 3 4

Genotype

101/

106 63/

66

11/

12 11/

11

11/

12 5/

5

2 relapse

1 LTFU 1 LTFU

1 withdrew

consent

12/

12 n/N =

BL NS5A

RAVs


Additional Studies Assessing HCV

Therapy in Pts With HIV/HCV Coinfection

TURQUOISE-I, Part 2: multicenter phase III trial in which HIV/HCV-coinfected pts with GT1 or GT4 HCV treated with OBV/PTV/RTV ± DSV ± RBV (N = 228)[1]

– SVR12 (ITT): GT1, 97% (n/N = 190/195); GT4, 96% (n/N = 27/28)

– Intermittent HIV viremia in 10/228 (4%) pts; HIV-1 RNA < 200 copies/mL

– 4% of pts in each arm had BL HIV-1 RNA ≥ 40 copies/mL

6 wks of SOF/LDV for HIV-infected pts with acute GT1/4 HCV infection[2]

– SVR12: 77% (n/N = 20/26); 4 virologic failures (1 reinfection), 2 LTFU

– 3 relapsed pts had BL HCV RNA ≥ 7.0 log10 IU/mL


1. Rockstroh JK, et al. AIDS 2016. Abstract WEAB0304LB.

2. Nelson M, et al. AIDS 2016. Abstract WEPEB059.


© ASHM 2016

REALITY: Enhanced Prophylaxis for

Opportunistic Infections at ART Initiation

in Severely Immunocompromised

Individuals Associated With Reduced

Early Mortality

© ASHM 2016

•In sub-Saharan Africa, HIV-infected adults and children with advanced

disease and severe immunosuppression who initiate ART exhibit high

mortality[2-4]

• Causes of death include TB and other bacterial, fungal, and

protozoal opportunistic infections

•Current standard prophylaxis given at ART initiation for opportunistic

infections in patients with low CD4+ cell counts can include

cotrimoxazole (sulfamethoxazole/trimethoprim) with isoniazid

prophylactic therapy (IPT) added after 12 weeks for patients without TB

infection[5]

•REALITY investigated whether enhanced prophylaxis for opportunistic

infections given at ART initiation would reduce mortality in patients with

advanced HIV disease[1]

• Enhanced prophylaxis regimen included cotrimoxazole, IPT,

fluconazole, azithromycin, and albendazole

Background

Prospective, randomized trial conducted in Zimbabwe, Malawi, Uganda, and Kenya

– Primary endpoint: mortality at 24 wks


REALITY: Enhanced OI Prophylaxis at

ART Initiation in Immunocompromised Pts

Hakim J, et al. AIDS 2016. Abstract FRAB0101LB.

Enhanced Prophylaxis

initiated at time of ART†

(n = 906)

Standard Prophylaxis

initiated at time of ART‡

(n = 899)

ART-naive HIV-infected adults

and children older than 5 yrs

of age with CD4+ cell counts

< 100 cells/mm3

(N = 1805)

Additional randomizations

conducted in factorial fashion*

*Raltegravir added to ART for 12 wks; food supplementation for 12 wks. †Cotrimoxazole, isoniazid/vitamin B6 300/25 mg/day for 12 wks (IPT), fluconazole 100 mg/day for

12 wks, azithromycin 500 mg/day for 5 days, albendazole 400 mg (single dose). ‡Cotrimoxazole, IPT added after 12 wks (except in Malawi).

In both prophylaxis regimens, cotrimoxazole and IPT given at half doses if younger than 12 yrs of age.



REALITY: Mortality Benefit With Enhanced

OI Prophylaxis for Pts Initiating ART

1. Hakim J, et al. AIDS 2016. Abstract FRAB0101LB.

2. Kityo C, et al. AIDS 2016. Abstract FRAB0102LB.

3.3 lives saved for every 100 treated with enhanced prophylaxis[1]

Additional REALITY factorial randomization assessed mortality for ART initiation with 2 NRTIs + NNRTI + RAL vs 2 NRTIs + NNRTI[2]

– Addition of RAL to standard 3-drug ART did not affect all-cause mortality at 24 or 48 wks

Deaths, %[1]

Enhanced

Prophylaxis

(n = 906)

Standard

Prophylaxis

(n = 899)

HR

(95% CI) P Value

Wk 24* 8.9 12.2 0.73

(0.54-0.97) .03

Wk 48 11.0 14.4 0.75

(0.58-0.98) .04

*Primary endpoint.



REALITY: Additional Outcomes Favor

Enhanced OI Prophylaxis

Hakim J, et al. AIDS 2016. Abstract FRAB0101LB.


WHO stage 4 disease or death

WHO stage 3/4 disease or death

New TB disease

AE causing OI drug modification

Hospitalizations

New cryptococcal disease

New candida disease

Presumptive severe bacterial infection

Grade 4 AE

Serious AE

Grade 3/4 AE

Grade 4 AE definitely/probably related to prophylaxis

Grade 4 AE definitely/probably/possibly related to prophylaxis

Favors Enhanced Prophylaxis Favors Standard Prophylaxis

.006

.007

.01

.01

.02

.04

.06

.07

.35

.21

.60

.21

.97

0.3 0.5 0.7 1.0 1.5 2.0

HR (Enhanced Prophylaxis:Standard Prophylaxis)

P Value


© ASHM 2016

The reduced mortality was not attributable to

CD4 reconstitution or

drop in HIV viral load.

Cost of this enhanced regimen varied

significantly between countries.

Multicenter, open-label, randomized phase III trial

– Pts in Benin, Guinea, and Senegal

– Primary outcome: mortality at 12 mos post-randomization


RAFA: ART With Standard- vs High-Dose

Rifampicin in HIV/TB-Coinfected Pts

Merle CS, et al. AIDS 2016. Abstract WEAB0205LB.

Pactr.org. PACTR201105000291300. EDCTP Project Portfolio.

Standard-Dose Rifampicin,† Start ART at Wk 8 (n = 258)

Standard-Dose Rifampicin,† Start ART at Wk 2 (n = 262)

ART-naive

HIV/TB-coinfected

adults with CD4+

cell count ≥ 50

cells/mm3

(N = 778)

High-Dose Rifampicin,* Start ART at Wk 8 (n = 258)

*Rifampicin 15 mg/kg plus ethambutol, isoniazid, pyrazinamide. †Rifampicin 10 mg/kg plus ethambutol, isoniazid, pyrazinamide.

ART regimen: EFV 600 mg + 2 NRTIs.

All pts received

rifampicin 10 mg/kg

+ isoniazid

Intensive Phase Continuation Phase Wk 8



RAFA: Survival Outcomes With High- vs

Standard-Dose Rifampicin

Overall survival not improved, but high-dose rifampicin may benefit severely immunocompromised pts

Merle CS, et al. AIDS 2016. Abstract WEAB0205LB.


Overall Survival, % HD RIF, ART Wk 8

(n = 249)

SD RIF, ART Wk 8

(n = 247)

SD RIF, ART Wk 2

(n = 251)

12 mos 90 86 89

18 mos 90 85 88

Mortality for Pts With CD4+ Cell Count < 100 cells/mm3 (n = 159)

SD RIF, ART Wk 8 (n = 47)

SD RIF, ART Wk 2 (n = 60)

HD RIF, ART Wk 8 (n = 52)

HD RIF vs SD RIF, ART Wk 2:

HR: 0.20 (95% CI: 0.04-0.90)

HD RIF vs SD RIF, ART Wk 8:

HR: 0.12 (95% CI: 0.03-0.55)

1.00

0.75

0.50

0.25

0 0 2 4 6 8 10 12 14 16 18

Mos Since Randomization

Surv

ival


© ASHM 2016

AUSTRALIA : Access to HIV self-

testing doubles the frequency of HIV

testing among gay and bisexual men at

higher risk of infection: a randomised

controlled trial

Authors

M.S. Jamil1, G. Prestage1,2, C.K. Fairley3,4, A.E. Grulich1, K.S.

Smith1, M. Chen3,4, M. Holt5, A.M. McNulty6, B.R. Bavinton1, D.P.

Conway1, H. Wand1, P. Keen1, J. Bradley1, J. Kolstee7, C.

Batrouney8, D. Russell9,10, M. Law1, J.M. Kaldor1, R.J. Guy1

© ASHM 2016

Methods: In this wait-list control randomised trial, HIV-negative

higher-risk GBM reporting condomless anal intercourse or >5 male

sexual partners in the past 3 months were recruited at three clinical

and two community-based sites in Australia.

Enrolled participants were randomly assigned (1:1) via computer-

generated randomisation codes to have free access to HIV self-

testing (intervention) or not (standard-care).

Participants completed 3-monthly online questionnaires.

The primary outcome was the number of HIV tests over 12

months, analysed by intention-to-treat. The study was designed

to evaluate the primary outcome overall and in two strata: frequent

(last HIV test ≤2 years ago) and infrequent (>2 years ago or never

tested) testers.

© ASHM 2016

• Dec-2013, and Nov-2014,

• 180 men were randomised to self-testing and 179 to standard-

care.

• The intention-to-treat analysis included men who completed

any follow-up questionnaire: 179 (98%) in self-testing; and

164 (92%) in standard-care.

• The mean number of HIV tests over 12 months in the self-

testing and standard-care arms was 3.9 and 1.6 per-person

overall (rate ratio (RR):2.39, 95% CI: 2.08-2.76,p< 0.001),

• 4.0 and 1.8 among frequent testers (RR:2.23, 1.93-2.59,p<

0.001), and

• 3.2 and 0.6 among infrequent testers (RR:5.54, 3.15-9.74,p<

0.001), respectively.

• There was no statistical difference between the two arms in

the mean number of facility-based HIV tests (1.4 vs 1.6,

RR:0.89, 0.75-1.06) and any STI test (1.6 vs 1.7, RR:0.93,

0.79-1.10).

FORTH: HIV Self-Testing in Australian

MSM

HIV-uninfected Australian MSM who had > 5 male partners or condomless anal intercourse in past 3 mos (N = 362) randomized to free access to HIV self-testing (n = 182) or standard care (n = 180)

Slide credit: clinicaloptions.com Jamil MS, et al. AIDS 2016. Abstract FRAC0102. Reproduced with permission.

5.0

1.0

0

Mean H

IV T

ests

/Yr

3.0

2.0

4.0

Self-testing

(n = 178)

Standard care

(n = 165)

Self-testing

(n = 148)

Standard care

(n = 141)

Self-testing

(n = 30)

Standard care

(n = 24)

Overall Recent HIV Test at BL

(≤ Last 2 Yrs)

Nonrecent HIV Test at BL

(> Last 2 Yrs)

Self tests

Facility-based testing RR: 2.1 (P < .001)

RR: 2.0 (P < .001)

RR: 3.95 (P < .001)

1.7 1.9 1.8 2.1

0.8 0.7

2.4 2.4

2.1

No decline in STI testing for self-testing group vs standard care group


ANRS 12249: Test and Treat Strategies in

Rural South Africa (KwaZulu-Natal)

Test and treat trial; treatment cluster-randomized by site

– Rapid HIV testing during home visits every 6 mos; if HIV infected, pts moved to randomized treatment

Similar HIV incidence between randomized groups

Slide credit: clinicaloptions.com Iwuji C, et al. AIDS 2016. Abstract FRAC0105LB.

Intervention Arm

Immediate ART

(n = 13,236)

Control Arm (Guideline-Based ART)

ART if CD4+ cell count ≤ 350/500 cells/mm3* or stage WHO 3/4

(n = 14,917)

HIV-infected adults

(N = 28,153)

Outcome Intervention Control Adjusted RR P Value

Mean HIV prevalence, % 30 31 -- --

12-mo linkage to care for HIV-

infected pts,† % 47 47 -- --

HIV incidence/100 PY 2.13 2.27 0.95 .5821

*Guidelines for ART initiation cutoff changed during study. †Pts not previously receiving care.


Accessing Male Partners of Pregnant

Women for HIV Testing

Pregnant or postpartum women in Kenya with male HIV-uninfected or HIV-unknown partners randomized to groups in which they gave partner an HIV self-test (HIVST group, n = 284) or HIV clinic referral voucher (comparison group, n = 286)

Slide credit: clinicaloptions.com Thirumurthy H, et al. AIDS 2016. Abstract FRAC0104.

Outcome, n (%) HIVST Comparison Difference, % (95% CI)

Male partner testing 258 (90.8) 148 (51.7) 39.1 (32.4 to 45.8)

Discuss HIV testing 271 (95.4) 276 (96.5) -1.1 (-4.3 to 2.2)

Couples testing 214 (75.4) 95 (33.2) 42.1 (34.7 to 49.6)

Learned partner’s HIV

status 255 (89.8) 145 (50.7) 39.1 (32.3 to 45.9)

Partner violence due to

testing 1 (0.4) 1 (0.3) 0 (-1.0 to 1.0)


CHALO: E-Messaging Reminders for HIV

Testing and Condom Use for MSM in India

HIV-uninfected, sexually active MSM in Mumbai, India recruited via social websites and sent e-messages regarding condom use and HIV testing

– N = 130 completed 12-wk follow-up

– Messages included either “avoidance” language emphasizing negative outcomes (n = 62) or “approach” language highlighting a benefit (n = 68)

E-messaging increased recent HIV testing* vs baseline (44% vs 32%; P < .05)

“Avoidance” messaging language was associated with higher rate of testing or intention to test vs “approach” messaging language (82% vs 65%, P =.03)

Slide credit: clinicaloptions.com Patel VV, et al. AIDS 2016. Abstract FRAC0101.

*HIV testing in the past 6 mos.


© ASHM 2016

Xpert® HIV-1 Viral Load*

• Hands On-Time: < 1 minute

• Results Turnaround time: ~ 90 minutes

• Sample extraction, amplification, detection performed in self-

contained cartridge

• Modular system enables on-demand testing

• Test throughput of up to 400 results/8H

• Bi-directional LIS connectivity

• Dynamic Range from 40 – 10,000,000 copies/mL

• Primer and probes target highly conserved 5’ LTR region

• Quantitates HIV-1 across a broad range of subtypes, including

Group O

Built-in Controls Ensure Results Integrity

Validation of Cepheid GeneXpert HIV-1 Quant for monitoring HIV-1 RNA in pts on ART[1]

– Point-of-care, PCR-based testing system

– Compared with Abbott Real Time HIV-1 assay,

LAg-Avidity for detecting viral breakthrough for pts on ART[2]

Studies Assessing Tools for Monitoring

ART Efficacy and Failure

Slide credit: clinicaloptions.com 1. Kulkarni S, et al. AIDS 2016. Abstract THPDB0205. 2. Nicholas S, et al. AIDS 2016.

Abstract THPEB046. 3. Wendel SK, et al. AIDS 2016. Abstract THPEB039.

Study Findings

Validation of GeneXpert HIV-1 Quant for

monitoring HIV-1 RNA in pts on ART[1]

Point-of-care, PCR-based testing system

Assessed samples from Indian pts with varying

HIV-1 RNA levels (N = 219) and controls

Similar detection with GeneXpert

vs standard Real Time assay:

R2 = 0.784

Sensitivity/specificity for detecting

HIV-1 RNA > 200 c/mL: 97%/100%

Assessment of SAMBA-1 for routine

monitoring of HIV-1 RNA in pts on ART[2]

Nearly point-of-care, PCR-based testing system

Assessed pts on first-line ART at hospital/health

centers in Malawi from Aug 2013 to Dec 2015

13675/19036 (72%) received ≥ 1 test

> 80% of tests reviewed the same

day at health centers

LAg-Avidity for detecting viral breakthrough

for pts on ART[3]

Antigen avidity enzyme immunoassay

Assessed samples from US pts pre/post ART

(n = 72) and suppressed pts who had

breakthrough (n = 179)

Sensitivity/specificity for detecting

viral breakthrough: 65%/86%


presented by: dr mekala srirajalingam november 2016 · 2020. 3. 13. · ©ashm 2016 • every 2...

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