Anton Pozniak MD FRCP Consultant Physician Chelsea and Westminster Hospital Hon. Professor LSHTM IAS President Reduced Drug Regimens Data and Implementation
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