Anton Pozniak MD FRCP

Consultant Physician Chelsea and Westminster Hospital

Hon. Professor LSHTM

IAS President

Reduced Drug Regimens Data and Implementation

Disclosures

● Type of affiliation / financial interest

● Receipt of grants/research supports:

● Receipt of honoraria or consultation fees:

● Participation in a company sponsored speaker’s bureau:

● Stock shareholder:

● Spouse/partner:

● Name of commercial company

● To my unit from Janssen, Merck, Viiv and Gilead

● To me from Janssen, Merck, Viiv ,Gilead, Cipla

● None

● None

● None

Why Dual Therapy?Toxicities of Nukes CV risk, bone , renal disease

Smaller STRs

Cost

Keep drugs for later etc…….

Dual Therapy-Talking Points

• - What are the pros and cons of two drug combinations?

• In Naïve

• In Switch

• As Long acting therapy

What are the GUIDELINES saying?EACS 2019 First Guidelines to Recommend Dual therapy

Its not a new conceptEvolution of Dual Therapy:

1996 - 2000 2001-2005 2006 -2010 2011-2014 2015-2017

6

ACTG 3431 OLE7, SALT8

DUAL-GESIDA9

SWORD10

ACTG51423DMP-0062

NEAT0014

GARDEL5MODERN6

PADDLE11

Initial Therapy

Maintenance Therapy

1. Havir D et al. N Engl J Med. 1998: 1261-82. Staszewski S et al. N Engl J Med. 1999:1865-733. Riddler SA et al. N Engl J Med 2008;358:2095-1064. Raffi F et al. Lancet. 2014:1942-515. Cahn P et al. Lancet Infect Dis. 2014:572-806. Stellbrink HJ et al. AIDS 2016:1229–12387. Arribas J, et al. Lancet Infect Dis. 2015:785-92.

8. Perez-Molina JA, et al. Lancet Infect Dis. 2015:775-849. Pulido F et al. Clin Infect Dis. 201710. Liibre JM et al. Lancet 201811. Cahn P et al. J Int AIDS Soc 201712. Cahn P et al. Lancet 20113. Figueroa MI et al. CROI 2018

ANDES13

GEMINI 1 and 212

Which combinations have been tested?Analysing the efficacy of 2-drug versus 3-drug treatments

PI/r + raltegravirPI/r + maravirocPI/r + NRTI (mainly 3TC)DTG + 3TCDTG + RPVCTV + RPV

8

Dual therapy in ARV naïve?

Boosted PIs plus

PIs+ NNRTIs

· LPV/r - EFV

· ATV/r - EFV

· LPV/r - NVP

· Good virological response, but increased rate of

side effects

MODERN: MVC QD + DRV/RTVNot-Noninferior to TDF/FTC + DRV/RTV in naïve patients

100

80

86.8%

TDF/FTC + DRV/RTV (n = 401)

MVC + DRV/RTV (n = 396)

60

77.3%Similar rates of HIV-1 RNA suppression

at Wk 48 by screening assay type

40

20

Adjusted treatment difference:-9.5% (95%% CI: -14.8% to -4.2%)

Assay

Type

Phenotypic

Genotypic

MVC +

DRV/RTV

(n = 396)

74.4

80.7

TDF/FTC +

DRV/RTV

(n = 401)

87.0

86.5

0BL 4 8 12 16 20 24 36 48

Δ (95% CI) 6.9% (-1.3% to

15%)NR

Wk

‘IDMC, Sept 27th 2013 (Wk 48 preliminary review): Recommendation toterminate the trial, MVC has inferior efficacy compared to TDF/FTC’1. Stellbrink HJ, et al. AIDS 2014 Graphic used with permission. Abstract MOAB0101. 2. van Lunzen J, et

al. AIDS 2014. Abstract LBPE19.

ATV 300 mg BID + RAL in NAIVE

SPARTAN

Week 24 Results

100 NC = F 100 NC = M

80

60

40

74.6%

63.3%

80

60

40

81%

70.4%

20

0

ATV + RAL (n=63)ATV/RTV + TDF/FTC (n=30)

20

0

J0 4 8 12 16 20 24 J0 4 8 12 16 20 24

WeeksHIV-1 RNA <50 c/mL (%), CVR

Weeks

The overall profile did not appear optimal for further clinical development given high rate ofresistance to RAL (4/6 VF) and higher rates of G4 hyperbilirubinemia with twice daily ATVcompared with ATV/RTV (21% vs. 0%)’

KozalMJ, et al. HIV Clin Trial 2012;13:119–30

HIV RNA < 50 c/mL

NEAT 001/ANRS 143 DRV/r + RAL vs DRV/r + TDF/FTC

• 805 ART naive patients

• CD4 : 345/mm3

• CV : 4.76 log

• > 105cp/ml : 35%

20

40

100

60

%

80

00 4 8 12 18 24 32 48 64 80 96

DRV/r + RAL, 89.4% (95% CI : 85.7-92.4)

DRV/r + TDF/FTC, 93.3% (95% CI : 90.3-95.6)

Raffi F. Lancet 2014;384:1942-51

PI/Ral

When CD4 are low or VL high prefer triple ART

Primary Endpoint – NEAT 001 RAL+DRV/r vs TDF/FTC DRV/r

By BL Characteristics

Raffi F et al. Lancet 2014

Overall analysis: RAL + DRV/r non-inferior to TDF/FTC + DRV/r

However, inferior in patients < 200 cells/µl

n = 805

n = 530

n = 275

n = 123

n = 682

Overall

< 100,000 copies/ml

> 100,000 copies/ml

< 200 cells/mm3

> 200 cells/mm3

Baseline HIV-1 RNA

Baseline CD4+

17.8 %

7.4 %

36.8 %

43.2 %

13.7 %

13.8 %

7.3 %

27.3 %

20.9 %

12.3 %

RAL +

DRV/r

TDF/FTC + DRV/r

100-10 20 30

9

Difference in estimated proportion (95% CI) RAL – TDF/FTC; adjusted * Interaction Test

p = 0.10*

p = 0.010*

-0.8 8.8

-3.8 4.0

-0.1 20.1

7.4 37.1

-3.5 6.3

40

No significant difference

Significant difference

Success!!-GARDELDual ART With LPV/RTV + 3TC vs Triple ART With LPV/RTV + 2 NRTIs

Noninferior to Triple ART at Wk 48 and Wk 96

● Safety and tolerability also similar between treatment arms

VirologicSuccess

VirologicNonresponse

D/C due to AE or Death

D/C for Other Reasons

Cahn P, et al. EACS 2015. Abstract 961.

Wk 48 difference: +4.6% (95% CI: -2.2 to 11.8; P = .171)

Wk 96 difference: +5.9% (95% CI: -2.3 to 14.1; P = .165)

100

80

60

40

20

0

Pts

(%

)

Dual ART N-=217

Triple ART N-= 209

4.7 5.90.9

4.9 6.1 5.42.4 2.1 0.62.8

6.610.6

88.383.7

90.384.4

Wk: 9648 9648 9648 9648

Success!!- ANDES

Dual DRV/r 800/100 +3TC vs TDF+FTC+DRV/r

Phase 4, randomized, multicentric, open label study , Wk 48 Primary endpoint

Dual therapy DRV/r 800/100mg QD

+ 3TC 300 mg QD

n= 75

Triple therapy :

DRV/r 800/100mg QD+

3TC /TDF 300/300mg QD

n=70

145 ARV- naive patients

5 sites in Argentina

• 18 years

• 4.5 log HIV copies/ml

• 24% >5 log

• CD4 : 383 /mm3

• No IAS-USA defined NRTI or PI resistance at screening*

• HB(s)Ag negative

Stratified at screening by HIV-1 RNA

(≤ or > 100,000 copies/mL)

% HIV RNA < 400 cp/mL Wk 24

Interim analysis

PI /3TC

ITT snapshot 95%On Treatment 100%Discontinuations 4Withdraw consent (1) ,SAE (1), LTFU (1) ,

RASH (1)

ITT snapshot 97%On Treatment 99 %Discontinuations 1

PDVF 1 P. Cahn IAS 2017 MoAB0106LB

Only Combinations with Reverse Transcriptase Inhibitors work!!

Less Drugs then Less ToxicitySo Should everyone be on a 2DR?

• Increasing concern about NRTI toxicities

• Unboosted high barrier agents

• Lower costs?

• Fewer drugs may be a good thing

– Ageing, multi-morbidity, polypharmacy….

One of the driving forces for 2DRChallenging the Standard 3 drugs

NRTI: tenofovir-DF vs abacavirConcerns re Toxicity

Dolutegravir-based 2DR

• SWORD: dolutegravir + rilpivirine– Non-inferior to continued 3DR (suppressed switch only)– Resistance common in small number of failures

• GEMINI: dolutegravir + lamivudine 1st line– Non-inferior to tenofovir-DF/emtricitabine + dolutegravir 1st line

at 96 weeks (including high VL & sensitive assays)– No resistance emergence

• TANGO: dolutegravir + lamivudine suppressed switch– Non-inferior to continued TAF-based 3DR at 48 weeks– No resistance emergence

GEMINI-1,-2 and TANGO: Virologic Outcomes With DTG + 3TC as Initial or Switch Therapy

• GEMINI-1,-2: Initial therapy with DTG + 3TC noninferior to DTG + TDF/FTC for primary endpoint of HIV-1 RNA < 50 c/mL[1]

– Adjusted Δ: -1.7% (95% CI: -4.4% to 1.1%)

• TANGO: Switch to DTG/3TC noninferior to continued TAF-based ART for primary endpoint of HIV-1 RNA ≥ 50 c/mL[3]

– Adjusted Δ : -0.3% (95% CI: -1.2% to 0.7%)

1. Cahn. Lancet. 2019;393:P143. 2. Cahn. IAS 2019. Abstr WEAB0404LB. 3. Van Wyk J. IAS 2019. Abstr WEAB0403LB. Slide credit: clinicaloptions.com

100

80

40

60

20

0 Virologic Nonresponse

Virologic Success

No Virologic Data

0.3 0.5

93.2 93.0

6.5 6.5

Switch to DTG/3TC(n = 369)

Continue TAF-based ART (n = 372)

DTG + 3TC (n = 716)DTG + TDF/FTC (n = 717)

Virologic Success

Virologic Nonresponse

No Virologic Data

Pat

ien

ts (

%)

100

80

60

40

20

0

91 93

3 2 6 5

Response sustained at Wk 96 (86.0% vs 89.5%) with no

emergent resistance at VF[2]

Naïve -GEMINI-1 and -2: Wk 48 Subgroup Analysis

Orkin. Glasgow 2018. Abstr P021.

HIV-1 RNA < 50 copies/mL, n/N (%)

DTG + 3TC (n = 716)

DTG + FTC/TDF (n = 717)

Age, yrs

▪ < 35 386/420 (92) 381/408 (93)

▪ 35 to < 50 211/231 (91) 216/229 (94)

▪ ≥ 50 58/65 (89) 72/80 (90)

Sex▪ Female 100/113 (88) 89/98 (91)

▪ Male 555/603 (92) 580/619 (94)

Race

▪ White 447/480 (93) 471/497 (95)

▪ Black 83/99 (84) 64/76 (84)

▪ Asian 67/71 (94) 68/72 (94)

HIV-1 RNA, copies/mL

▪ ≤ 100,000 526/576 (91) 531/564 (94)

▪ > 100,000 129/140 (92) 138/153 (90)

▪ > 250,000 45/51 (88) 41/46 (89)

▪ > 400,000 16/18 (89) 20/24 (83)

CD4+ count, cells/mm3

▪ ≤ 200 50/63 (79) 51/55 (93)

▪ > 200 605/653 (93) 618/662 (93)-30 30

% Treatment Difference (95% CI)

-20 0 10

-0.1

-10 20

-0.7

-13.4

5.6

-0.9

1.9

-2.8

-0.4

-1.6

-1.7

-2.3

-0.8

-3.0

-1.5Two-Drug Regimen

Three-Drug Regimen

GEMINI-1 and -2: Snapshot Nonresponse in Patients With Baseline CD4+ Cell Counts ≤ 200 cells/mm3

Slide credit: clinicaloptions.comvan Wyk. IDWeek 2019. Abstr 2842.

*CVW criteria met for 1 other patient at Wk 12, not reported in Wk 48 analysis due to lab error; participant permitted to continue on study with virologic suppression from Wk 24 to Wk 96. †Resuppressed, n = 1. ‡Worsening of fatigue, anxiety, irritability. §Tuberculosis, Chagas disease. ║Incorrect randomization, n = 2; pregnancy, n = 1. ¶Relocated, n = 3; due to non–treatment-related AE, n = 1. #Relocated, n = 1. **Incarcerated. ††Initiated HCV treatment.

Snapshot Nonresponse at Wk 96, n DTG + 3TC (n = 63) DTG + FTC/TDF (n = 55)

Overall 20 7

▪ Confirmed virologic withdrawal 3 1*

▪ HIV-1 RNA ≥ 50 copies/mL in window 2† 0

▪ Discontinuation due to treatment-related AEs 1‡ 0

▪ Discontinuation due to nontreatment-related AEs 2§ 0

▪ Protocol violation 3║ 0

▪ Lost to follow-up 3 3

▪ Withdrew consent 4¶ 2#

▪ Change in ART 1** 0

▪ Investigator discretion 1†† 1**

GEMINI-1 and -2: Snapshot Outcomes at Wk 96 in Patients With BL HIV-1 RNA > 500,000 copies/mL

Slide credit: clinicaloptions.comvan Wyk. IDWeek 2019. Abstr 2842.

DTG + 3TC

BL HIV-1 RNA, c/mLBL CD4+ Cell Count,

cells/mm3

HIV-1 RNA < 50 c/mL at Wk 96

502,915 147 80 c/mL

510,168 229 ✓

523,934 305 ✓

558,856 337 No virologic data*

577,561 314 ✓

579,350 437 ✓

582,666 454 ✓

586,886 168 ✓

833,905 219 No virologic data*

902,151 316 ✓

934,790 255 ✓

1,341,981 262 ✓

1,848,435 22 No virologic data†

*D/c before Wk 96 for reasons other than efficacy or AEs with HIV-1 RNA < 40 c/mL at last on-study evaluation. †D/c soon after BL for not meeting entry criteria (ie, screening HIV-1 RNA > 500,000 c/mL).

DTG + FTC/TDF

BL HIV-1 RNA, c/mLBL CD4+ Cell Count,

cells/mm3

HIV-1 RNA < 50 c/mL at Wk 96

500,265 268 ✓

503,837 279 ✓

524,883 38 No virologic data*

593,008 428 ✓

630,132 19 ✓

633,199 445 ✓

675,028 131 ✓

690,490 112 No virologic data*

707,457 226 ✓

750,721 335 ✓

764,540 520 ✓

877,058 276 ✓

953,600 544 No virologic data*

987,059 245 ✓

2,317,510 27 ✓

Comparative Efficacy and Safety of Dolutegravir andLamivudine

in Treatment-Naïve HIV Patients

Virologic Suppression and change from baseline in CD4+ cell count at Week 48

Seite 24Radford et al BHIVA 2019 P007

Comparative Efficacy and Safety of Dolutegravir andLamivudine

in Treatment-Naïve HIV Patients

Safety outcomes by Week 48

Seite 25Radford et al BHIVA 2019 P007

Emergent Resistance With Two-Drug Regimens?

SWORD (switch to DTG + RPV)[2]

▪ Treatment-emergent NNRTI mutations(n = 4) and INSTI mutations (n = 3)in 8 patients with VF

ATLAS, FLAIR (switch to LA CAB + RPV)[3,4]

▪ Treatment-emergent NNRTI mutations(n = 6) and INSTI mutations (n = 4)in the 6 patients with VF

1. Cahn. Lancet. 2019;393:P143. 2. Aboud. Lancet HIV. 2019. Epub.3. Swindells. CROI 2019. Abstr 139. 4. Orkin. CROI 2019. Abstr 140LB

GEMINI (initial DTG + 3TC)[1]

▪ No treatment-emergent resistance mutations in patients with VF

Advantages -Cost

Vittoria JIAS 2016;19:20504

Other Data on Key Issues Related to DTG + 3TC

Issues Main Findings

Cost-effectiveness[1]

▪ Compared with standard 3DR, if 50% of ART-naive patients in US . . . – Initiated DTG + 3TC, cost savings would be $800 million within 5 yrs*– Initiated DTG/ABC/3TC → DTG + 3TC maintenance, cost savings would be $550 million

within 5 yrs

Genital shedding of HIV[2]

▪ Rates of genital HIV-1 RNA shedding while virologically suppressed in blood comparable with DTG + 3TC vs standard 3DR– Both rates within lower end of range reported for studies of 3DR (2% to 20%)

Viral reservoir[3]

▪ In virologically suppressed patients, switching from standard 3DR to DTG + 3TC did not increase residual viremia

Dynamics of viral decay[4]

▪ Viral decay rates comparable with DTG + 3TC vs DTG-based 3DR, including patients with BL HIV-1 RNA up to 500,000 copies/mL

Safety profile[5]

▪ Tolerability comparable with first-line DTG + 3TC vs DTG/FTC/TDF– Numerically fewer drug-related AEs with DTG + 3TC

*Assuming virologic suppression rate > 90% with DTG + 3TC.1. Girouard. Clin Infect Dis. 2016;62.784. 2. Gianella. JAIDS. 2018;79:e112. 3. Li. Open Forum Infect Dis. 2019;[Epub]. 4. Gillman. HIV Glasgow 2018. Abstr O213. 5. Cahn. Lancet. 2019;393:P143.

2DR DTG/3TC or DTG/RPVLimitations

• Hepatitis B co-infection• Access to resistance testing

– ?outcome DTG + 3TC if 3TC resistance

• TB treatment– Need for twice daily DTG?

• Pregnancy-efficacy

• Worse lipids if not on TDF• Women, adolescents need more data• High VL and Low CD4

– Not studied well in patients with HIV-1 RNA > 500,000 copies/mL or CD4<200

• Rapid Start-can you use • Will we see bictegravir-based 2DR at some stage….?

Other StrategiesWill patients only take their drugs 4 days a week?

ANRS 170 QUATUOR: Study Design

Multicenter, randomized, open-label phase III noninferiority study

Landman. IAS 2019. Abstr WEAB0406LB.

HIV-infected adults with HIV-1 RNA < 50 c/mL for ≥ 12 mos on ART,* no genotypic

resistance, CD4+ cell count > 250 cells/mm3

(N = 640)

ART on 4 Days Out of 7 (4D/7)(n = 320)

ART on 7 Days Out of 7 (7D/7)(n = 320)

Primary EndpointWk 48

Stratified by 3rd agent

*ART regimen based on either PI, NNRTI, or INSTI with 2 NRTIs.

All participants receive open-label 4D/7 through Wk

96

Primary endpoint: HIV-1 RNA < 50 copies/mL and no strategy interruption (except for pregnancy and within-class switches)

Noninferiority margin: -5%

ANRS 170 QUATUOR: Treatment Failure by Third AgentMaybe only useful in high resistance barrier regimens

Landman. IAS 2019. Abstr WEAB0406LB. Reproduced with permission.

Virologic FailureDifference (95% CI) of Proportion

4D/77D/7

0.0

1.4

-5 -4 -3 -2 -1 0 1 2 3 4 5

0.0INSTI

NNRTI

PI

Third Agent

4 D /7 (n = 318) 7 D /7 (n = 318)

Virological

non-response

Confirmed VL > 50 c/mL

INI group (n = 304)

R emergence

NNRTI group (n = 296)

R emergence

6

3

1 (on RAL)

3

2 (on RPV)

4

1

0

3

1 (on RPV)

LONG ACTING ARVS

Forget Pills !

In the next ten years

Is this where HIV treatment is really going ?

Dual therapy in ARV naïveHow does it compare with triple?

Long Acting – What’s the attraction?

▪ Prevents poor adherence▪ Infrequent dosing▪ Use in patients with pill fatigue /aversion?▪ Better protects health privacy▪ Lower overall drug dose

Less Drug Less Toxicity Yearly intake of ARV by regimen

Regimen Daily Dose (mg) Yearly dose (g)

3-Drug Regimens:

DRV/r + FTC/TDF

RAL + F/TAF

DTG/ABC/3TC

EVG/c/FTC/TAF

800/100 + 200/300

800 + 200/10

50/600/300

150/150/200/10

511.0

368.7

346.8

186.2

2-Drug Regimens:

DTG + 3TC

DTG + RPV

CABoral + RPVoral

CABim + RPVim

50 + 300

50 + 25

30 + 25

400 + 600 (every 2 mo)

127.8

27.4

20.1

6g

50 years of tx

Injectable drugs:

Cabotegravir and

Rilpivirine

Yearly intake of ARV by regimen

Regimen Daily Dose (mg) Yearly dose (g)

3-Drug Regimens:

DRV/r + FTC/TDF

RAL + F/TAF

DTG/ABC/3TC

EVG/c/FTC/TAF

800/100 + 200/300

800 + 200/10

50/600/300

150/150/200/10

511.0

368.7

346.8

186.2

2-Drug Regimens:

DTG + 3TC

DTG + RPV

CABoral + RPVoral

CABim + RPVim

50 + 300

50 + 25

30 + 25

400 + 600 (every 2 mo)

127.8

27.4

20.1

6g

50 years of tx

Outcome, n (%)

All CAB + RPV

Wk 96*(n = 160)

Wk 312(n = 160)

Virologic success (HIV-1 RNA < 50 c/mL) 137 (86) 105 (66)

Phase 2 -LATTE Cabotegravir and Rilpivirine As Two-Drug Oral Maintenance Therapy

6-Yr Follow-up: Virologic Efficacy Through Wk 312

▪ PDVF occurred in 8 of 160 (5%) patients receiving CAB + RPV during 5.5 yrs of follow-up

‒ n = 6 through Wk 144

‒ Treatment-emergent mutations: INSTI in 1/6, NNRTI in 3/6

‒ 4/6 occurred in CAB 10 mg arm and 2/6 in CAB 30 mg arm

‒ n = 2 between Wk 144 and Wk 312

‒ Treatment-emergent INSTI and NNRTI mutations detected in both patients

Margolis. IDWeek 2019. Abstr 2840.

Evidence for Injectable Long-Acting Therapy in Virologically Suppressed Patients

Phase 3 results: in a Nutshell

• Two large RCTs of injectable cabotegravir + rilpvirine vsoral therapy– ATLAS: suppressed switch– FLAIR: naïve with a lead-in phase

• Very high rates of viral suppression– Injectables non-inferior to oral treatment– Injectables preferred by patients– Small failure/resistance signal in subtype A

IAS Conference 2019

Injectable Long-Acting Therapy ATLAS and FLAIR Pooled Analysis:

Efficacy at Wk 48 in ITT-E Population

Overton. IAS 2019. Abstr MOPEB257.

Par

tici

pan

ts (

%)

100

80

40

60

20

0Virologic

Nonresponse (≥ 50 c/mL)

Virologic Success

(< 50 c/mL)

No Virologic Data

1.9 1.7

93.1 94.4

5.1 3.9

LA CAB + RPV(n = 591)

Continue oral ART(n = 591)

-10

Oral ARTLA CAB + RPV

-1.4 1.7

0.2

-8 -6 -4 -2 0 2 4 6 8 10

4% NImargin

Primary Endpoint(HIV-1 RNA ≥ 50

copies/mL)LA CAB + RPV noninferior to

continued BL ART

Challenges• Pregnancy safety• Hep B not covered• Cold chain • IM injections

– Long-term acceptability of injection site reactions– Impact of: BMI, other IM injections

• Drug-drug interactions e.g. rifampicin• Resistance • Delayed/missed doses

– Adherence VERY high in trials to date….real life?

• Drug tails: long half-lives in PrEP trials– Cabotegravir: 17% detectable 52 weeks post-injection– Rilpivirine: detected for a mean of 541 days post-dose

David Back, CROI 2019; Ford et al. HIVR4P 2016; Chicago, IL. Abstract OA12.06LB.

ATLAS and FLAIR:

Remaining questions

‒ What proportion of people receiving treatment will want this treatment?

‒ How to choose the right candidates?

‒ How to implement?

‒ Role for less adherent under investigation

1. Swindells. CROI 2019. Abstr 139. 2. Orkin. CROI 2019. Abstr 140LB.

Injectables -We will have to change the way we workService capacity

The Care Paradox

1000 ‘stable’ patients30-minute clinic visits

ORAL: 2 visits/year= 1000 clinic hours

INJECTABLE: 6 visits/year= 3000 clinic hours

Staff

BookingPrescribing

AdministeringChasing DNA

Patients

TimeConvenience

ConfidentialityTolerability

TAF Thin FilmPolycaprolactoneDevice Prototypes:

(A) 2.5mm diameter,40mm longprototypes loadedwith 230mg 1:1TAF:PEG300 (w/w)

(B) 0.6mm diameter,20mm long prototypeloaded with 26mg 1:1TAF:PEG300 (w/w)

TDF-FTC combination implants• Potential for refillable implants?

• Administration demonstrate adequateintracellular TFV-DP and FTC-TB exposureover 83 days.

Chuaa et al. Journal of controlled delivery. 2018.

Conclusions- 2DR

• Immediate start ART-not certain• What ART to Start-

– 2Drug or 3 Drug- still areas of 2DR to be resolved– Role of new drugs moving away from conventional drugs

• What ART to switch to-– 2DR if undetectable – role in 2nd line?

• Knowledge gaps – TB co-infection, Hepatitis B, Pregnancy adolescents, and children?

• Injectables-Implantables– The way to go ?????

Thank you

• Laura Waters

• Marta Boffito

• Pedro Cahn

• Charles Flexner

• Marco Vitoria

• Andrew Hill

• David Back