Two Drug Regimens Pros and Cons - Virology...

Two Drug Regimens – Pros and Cons

Jürgen RockstrohDepartment of Medicine I

University Hospital Bonn, Bonn, Germany

HIV Clinical Forum, Moscow, Russia,

Friday 23rd November 2018

• Honoraria for lectures and/or consultancies from Abbott,

AbbVie, Gilead, Hexal, Janssen, Merck, and ViiV.

• Research grants from Dt. Leberstiftung, DZIF, NEAT ID.

Conflict of Interest: JKR

Is life-long Triple Therapy

Needed for Every Patient?

3

Goals of Antiretroviral Therapy

• Maintain viral suppression without jeopardizing future treatment options

• Enhance tolerability and decrease short- or long-term toxicity

• Simplify by reducing pill burden and dosing frequency

• Prevent or mitigate interactions

• Eliminate food or fluid requirements

Life-long antiretroviral therapy

1. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents

Living with HIV. Department of Health and Human Services. Available at

http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf Accessed 02/2018

2. Achhra AC et al. Lancet HIV 2016; 3: e351–60

Potential Benefits of Dual Therapy

• Avoid long-term toxicities

• Preserve long-term ART options

• Reduce costs

• May be easier for producing FDC and smaller tablet size

http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf Accessed 02/2018

Seite 4

Evolution of Dual Therapy: Major Clinical Studies Including

Dual Regimens

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

5

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: 1261-8

2. Staszewski S et al. N Engl J Med. 1999:1865-73

3. Riddler SA et al. N Engl J Med 2008;358:2095-106

4. Raffi F et al. Lancet. 2014:1942-51

5. Cahn P et al. Lancet Infect Dis. 2014:572-80

6. Stellbrink HJ et al. AIDS 2016:1229–1238

7. Arribas J, et al. Lancet Infect Dis. 2015:785-92.

8. Perez-Molina JA, et al. Lancet Infect Dis. 2015:775-84

9. Pulido F et al. Clin Infect Dis. 2017

10. Liibre JM et al. Lancet 2018

11. Cahn P et al. J Int AIDS Soc 2017

12. Cahn P et al. Lancet 201

13. Figueroa MI et al. CROI 2018

ANDES13

GEMINI 1 and 212

Two Drug Regimens –

Pros and Cons

Initial therapy

Seite 6

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

Evolution of Dual Therapy: Outcomes of Dual Regimens in Initial

Therapy

7

DMP-0061 ACTG51422 NEAT0013 GARDEL4 MODERN5

Comparators EFV+IDV vs. 2 NRTIs + EFV or IDV

EFV+LPV/r vs. 2 NRTIs + EFV or LPV/r

RAL+DRV/r vs.DRV/r+2 NRTIs

LPV/r+3TC vs.LPV/r + 2 NRTIs

MVC + DRV/r vs.DRV/r + 2 NRTIs

Efficacy Inferior Non-Inferior Non-Inferiorin CD4>200

Non-Inferior Inferior

Tolerability No differences Superior No differences

Development of Resistance

More resistance in DL 16% vs. 9% and 6%

Dual arm: M184V (n=2)

1. Staszewski S et al. N Engl J Med. 1999:1865-73

2. Riddler SA et al. N Engl J Med 2008;358:2095-106

3. Raffi F et al. Lancet. 2014:1942-51

4. Cahn P et al. Lancet Infect Dis. 2014:572-80

5. Stellbrink HJ et al. AIDS 2016:1229–1238

ACTG51422DMP-0061

NEAT0013

GARDEL4 MODERN5

ANDES Study - DRV/r + 3TC Vs DRV/r

+TDF/3TC for HIV-1 Treatment-Naïve

Patients: Week 48 Results

Figueroa M, et al. 25th CROI; Boston, MA; March 4-7, 2018. Abst. 489.Bacon O, et al. 25th CROI; Boston, MA; March 4-7, 2018. Abst. 93.

Global(n=145)

Triple Therapy (n=70)Double Therapy

(n=75)

33.1±9.930 (25.5-39.5)

32.5±8.430 (26-38)

33.7±11.130 (24-92)

Males 131 (91%) 61 (88%) 70 (93%)

Hispanic/Latino102 (71%) 49 (71%) 53 (71%)

MSM/Bisexual 101 (73%) 48 (71%) 53 (76%)

CDC Stage B 11 (8%) 5 (7%) 6 (8%)

Viral Load (log) 4.5 (4.0-5.0) 4.5 (3.9-5.0) 4.6 (4.1-5.1)

CD4 Count 383 (286-562) 366.5 (275-544) 419 (290-564)

CD4 % 19 (14-25) 19 (14-25) 19 (14-25)

VL > 100000 c/mL (Baseline) 35 (24%) 15 (22%) 20 (27%)

Demographics at Screening

ANDES Study: Proportion with

HIV-RNA < 50 Copies/mL and

Safety

Figueroa M, et al. 25th CROI; Boston, MA; March 4-7, 2018. Abst. 489.

GlobalTriple

TherapyDouble Therapy Difference

Primary Outcome: VL<50 c/mL at Week 48

ITT Snapshot, (n=145) 136 (94%) 66 (94%) 70 (93%) -1.0% (-7.5; 5.6%)

ITT Snapshot, Baseline VL>100,00 c/ml (n=35)

32 (91%) 12 (92%)20 (91%)

-1.4% (-17.2; 14.4%)

Observed (n=140) 136 (99%) 66 (99%) 70 (100%) -1.5% (-0.9; 3.9%)

Adverse Events

Rash 7% 8%

Gastrointestinal 14% 7%

Total Cholesterol(Change from BSL)

4% 19%; p:0.01

LDL-Cholesterol 6% 14%

Triglycerides 14% 25%

GEMINI-1 & 2:

study design

Orkin et al. HIV Glasgow 2018; Glasgow, UK. Poster P021.

DTG + 3TC (N=716)

D1

Screening

(~28 days)

Identically designed, randomized, double-blind, parallel-group,

multicenter, noninferiority studies

DTG + TDF/FTC (N=717)

DTG + 3TC

W48

Primary endpoint

at Week 48:

participants with

HIV-1 RNA <50 c/mL

(ITT–E snapshot)a

Double-blind

phase

Open-label

phase

Continuation

phase

CountriesArgentina Australia

Belgium

Canada France

Germany

Italy Republic of Korea

Mexico

Netherlands Peru

Poland

Portugal Romania

Russian Federation

South Africa Spain

Switzerland

Taiwan United Kingdom

United States

W144W24 W96

• ART-naive adults

• VL 1000-500,000 c/mL

1:1

Eligibility criteria• ≤10 days of prior ART

• No evidence of pre-existing viral resistance

based on presence of any major

resistance-associated mutation

• No HBV infection or need for HCV therapy

Baseline stratification factors: plasma HIV-1 RNA (≤100,000 vs >100,000 c/mL) CD4+ cell count (≤200 vs >200 cells/mm3)a−10% noninferiority margin for individual studies.

Demographics and Baseline

Characteristics: Pooled ITT–E Population


Characteristic

DTG + 3TC

(N=716)

DTG +

TDF/FTC

(N=717)

Age, median (range), y 32.0 (18-72) 33.0 (18-70)

Female, n (%) 113 (16) 98 (14)

Race, n (%)

African heritage

Asian

White

Other

99 (14)

71 (10)

480 (67)

66 (9)

76 (11)

72 (10)

497 (69)

72 (10)

HIV-1 RNA, median (range), log10

c/mL

>100,000, n (%)

4.43 (1.59-

6.27)

140 (20)

4.46 (2.11-

6.37)

153 (21)

CD4+ cell count, median (range),

cells/mm3

≤200, n (%)

427.0 (19-

1399)

63 (9)

438.0 (19-

1497)

55 (8)

GEMINI 1 and 2: Snapshot

Outcomes at Week 48

Virologic outcome Adjusted treatment difference (95% CI)a

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

Percentage-point difference

DTG + TDF/FTC

-6.7 1.5

-4.3 2.9

GEMINI-1

GEMINI-2 -0.7

-2.6

DTG + TDF/FTC DTG + 3TC90

4 6

93

26

93

25

94

2 4

0

20

40

60

80

100

Virologicsuccess

Virologicnonresponse

No virologicdata

HIV

-1 R

NA

<50

c/m

L, %

GEMINI-1 DTG + 3TC (N=356) DTG + TDF/FTC (N=358)GEMINI-2 DTG + 3TC (N=360) DTG + TDF/FTC (N=359)

Cahn P, et al. AIDS 2018; Amsterdam, the Netherlands; July 23-27, 2018; Abst. TUAB0106LB.

No resistance development in both study arms up to weeek 48

-3,8

-1,6

-0,1

-0,4

-1,7

-2,3

-1,5-3,0

-0,8

-13,4

-0,7

5,6-0,9

-2,8

1,9

-1,7

-30 -20 -10 0 10 20 30

Treatment difference, % (95% CI)

GEMINI studies subgroup analyses:

Baseline characteristics

Orkin C, et al. HIV Glasgow; 28-31 October 2018; Glasgow, UK; Abst. P021.

SubgroupDTG + 3TC

n/N (%)DTG + TDF/FTC

n/N (%)

Variable Overall 655/716 (91) 669/717 (93)

Age, y <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, n (%) White 447/480 (93) 471/497(95)

African heritage 83/99 (84) 64/76 (84)

Asian 67/71 (94) 68/72 (94)

Other 58/66 (88) 66/72 (92)

Baseline HIV-1 RNA, c/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)

Baseline CD4+cell ≤200 50/63 (79) 51/55 (93)

count, cells/mm3 >200 605/653 (93) 618/662 (93)

2-Drug regimen

3-Drug regimen

Snapshot non-response: participants

with Baseline CD4+ ≤200

DC, discontinuation; NA, not applicable; PV, protocol violation, aVL results from Week 60 shown for participants who continued the study beyond Week 48. bValue not provided due to potential for unblinding. cEnrolled with HBV coinfection. dParticipant had discontinued study treatment prior to study DC. eEnrolled

with Screening VL of >500,000 c/mL. fVL result available from Day 1 only.

Participant

Snapshot outcome

(Week 48) Clinical Reason for study DC

Study day of

DC

Last study VL,

c/mL

DTG + 3TC

1 VL ≥50 c/mL NA: continued in study NA ≥50a,b

2 VL ≥50 c/mL NA: continued in study NA <50a


4 VL ≥50 c/mLProtocol-defined virologic

withdrawal205 362

9 VL ≥50 c/mL NA: Unplanned change in ART NA ≥50a,b

10 VL ≥50 c/mL PV: randomized in errorc 15 102

12 VL ≥50 c/mL Lost to follow-up 356 64366

5 No virologic data AE: pulmonary TB 206 <50

6 No virologic data AE: cerebral chagoma 164 507,564d

7 No virologic data Treatment for HCV infection 165 <50

8 No virologic data Withdrew consent 115 <50

11 No virologic data PV: randomized in errore 28 1,848,435f

13 No virologic data Lost to follow-up 100 <50

DTG + TDF/FTC


16 VL ≥50 c/mLInvestigator discretion:

incarceration76 384

15 No virologic data Withdrew consent 342 <50

17 No virologic data Lost to follow-up 175 <50


Primary Endpoint – NEAT 001

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

DHHS GUIDELINES

UPDATE - October 2018

Most People with HIV

BIC/TAF/FTC

DTG/ABC/3TC

DTG-TFV/FTC

RAL-TFV/FTC

Certain Clinical Situations

EVG/c/TFV/FTC

RAL-ABC/3TC

DRV/c(r)/TFV/FTC

ATV/c(r)/TFV/FTC

DRV/c(r)-ABC/3TC

DOR/TDF/3TC or DOR-TAF/FTC

EFV/TDF/FTC(3TC), EFV-TAF/FTC

RPV/TFV/FTC

When ABC, TAF, and TDF Cannot be Used or Are Not Optimal

– DTG+3TC

– DRV/r + RAL BID

– DRV/r + 3TC

https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv/0

EACS GUIDELINES

UPDATE 9.1 - OCTOBER

2018

Recommended regimens (preferred)

DTG/ABC/3TC

DTG-TFV/FTC

BIC/TAF/FTC

RALqd/bid-TFV/FTC

Recommended regimens

RPV/TFV/FTC

DRV/c(r)/TFV/FTC

EFV/TDF/FTC(3TC), EFV-TAF/FTC

Alternative

– RAL-ABC/3TC

– EVG/c/TFV/FTC

– ABC/3TC-EFV

– TDF/FTC/EFV

– ABC/3TC-ATV/c(r)

– ABC/3TC-DRV/c(r)

– TFV/FTC-ATV/c(r)

Other

– DTG+3TC

– DRV/r(c)+ RAL BID

http://www.eacsociety.org/guidelines/eacs-guidelines/eacs-guidelines.html


Pros and Cons: initial

therapy

PROS

Cost

Avoid toxicities

Smaller tablet potentially

CONS

Not enough data in advanced patients

No data in patients with viral load > 500.000 copies/ml

Not recommendable in test and treat strategy

Toxicity of modern integrase and TAF based therapies is very low

No effective HBV therapy or HBV prevention

No FDC of Dolutegravir/3TC available yet

No FDC of Darunavir/r/3TC available

Not yet recommended as initial treatment by guidelines

Seite 18


Pros and Cons

Maintenance

therapy

Seite 19

Evolution of Dual Therapy:

Outcomes of Dual Regimens in

Maintenance Therapy

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

20

ACTG 343 OLE, SALT

DUAL-GESIDA

SWORD

ACTG3431 OLE2 SALT3 DUAL-GESIDA4 SWORD5

Comparators IDV + AZT/3TC vs. IDV vs. AZT/3TC

LPV/r + 3TC vs. LPV/r + 2 NRTIs

ATV/r + 3TC vs.ATV/r + 2 NRTIs

DRV/r + 3TC vs.DRV/r + 2 NRTIs

DTG + RPV vs.Triple ART

Efficacy Inferior Non-Inferior Non-Inferior Non-Inferior Non-Inferior

Tolerability No differences Less discontinuations2% vs. 7% (p=0.047)

No differences No differences

Development of Resistance

No differences No differences No differences No differences

1. Havir D et al. N Engl J Med. 1998: 1261-8

2. Arribasl J, et al. Lancet Infect Dis. 2015:785-92

3. Perez-Molina JA, et al. Lancet Infect Dis. 2015:775-84

4. Pulido F et al. Clin Infect Dis. 2017

5. Liibre JM et al. Lancet 2018

SWORD study: Dolutegravir +

Rilpivirine for Maintenance of

Suppression

Phase III, Randomized, Multicenter, Open-label, Parallel-Group, Non-Inferiority Studies

a. DTG + RPV once daily or 2 NRTIs + INI/PI/NNRTI (CAR). b. 90% power based on 10% non-inferiority margin (estimated response rate =87%).

VL <50 c/mLon INI, NNRTI,or PI + 2 NRTIs

1:1

Screening Early Switch Phasea Late Switch Phase Continuation Phase

DTG + RPV (N=513)

CAR (N=511)

DTG + RPV DTG + RPV

Day 1 Week 52 Week 148

CountriesArgentina

France

Russia

United States

Australia

Germany

Spain

Belgium

Italy

Taiwan

Canada

Netherlands

United Kingdom

Primary endpoints at 48 weeks:subjects with VL <50 c/mL

(ITT-E snapshot)b

Aboud M, et al. AIDS 2018; Amsterdam, the Netherlands; July 23-27, 2018; Abst. THPEB047

Inclusion Criteria

▪ On stable CAR ≥6 months before screening

▪ 1st or 2nd ART with no change in prior regimen due to VF

▪ Confirmed HIV-1RNA <50 c/mL during the 12 months before screening

SWORD 1&2: Week 48

and Week 100 Snapshot

Outcomes

AE, adverse event; DTG, dolutegravir; RPV, rilpivirine.

1. Llibre et al. Lancet. 2018;391:839-849. and Aboud et al. IAS 2018 Poster THPEB047

Early-switch group Late-switch group

DTG+ RPVN=513n (%)

Week 481

DTG + RPVN=513n (%)

Week 100

DTG + RPVN=477n (%)

Week 100

Virologic success 486 (95) 456 (89) 444 (93)

Virologic nonresponse 3 (<1) 13 (3) 10 (2)

Data in window, not <50 copies/mL 0 5 (<1) 3 (<1)

Discontinued for lack of efficacy 2 (<1) 7 (1) 3 (<1)

Discontinued while not <50 copies per mL 1 (<1) 1 (<1) 0

Change in ART 0 0 4 (<1)

No virologic data 24 (5) 44 (9) 23 (5)

Discontinued because of AE or death 17 (3) 27 (5) 11 (2)

Discontinued for other reasons 7 (1) 17 (3) 9 (2)

Missing data during window but on study 0 0 3 (<1)

• Through 100 weeks of treatment, DTG + RPV continued to be efficacious in the early-switch

group

• Virologic efficacy in the late-switch group at Week 100 was comparable to that of the early-

switch group at Week 48

DTG + RPV: Low Rates of

CVW Through Week 100

aShading represents participants with treatment-emergent NNRTI resistance–associated mutations. bUnderlined value

denotes viral load when participant met virologic withdrawal. cHIV-1 baseline resistance testing was performed on

integrated HIV-1 proviral DNA using GenoSure Archive® assay (Monogram Biosciences, South San Francisco, CA). On-

study resistance testing used standard plasma-based genotypic and phenotypic resistance testing. dParticipants in the

late-switch group. eResistance testing not performed because of low viral load.

CAR, current antiretroviral regimen; CVW, confirmed virologic withdrawal; INSTI, integrase strand transfer inhibitor; NNRTI, non-

nucleoside reverse transcriptase inhibitor.

Aboud et al. IAS 2018 Poster THPEB047

No significant changes to

residual viremia after switch

to DTG and 3TC

» Baseline Characteristics:» Male: 88%

» Age: 47 years

» White/black/Hispanic: 60%/38%/15%

» CD4: 680 cells/µL

» Time on ART: 5.7 years

» Current ART:NNRTI (30%), PI/r (33%), INSTI (37%)

FTC/TDF (86%), ABC/3TC (14%)

Switch to DTG 50 mg + 3TC 300 mg qd (n=44)

Randomization1:1

Continue Triple Therapy(n=45)

Week 0 24 48

Primary Endpoint

Li J, et al. HIV Glasgow; 28-31 October 2018; Glasgow, UK; Abst. O145.

0

20

40

60

80

100

Virologic Outcomes (FDA

Snapshot)

Dolutegravir + lamivudine (n=44) Continue triple therapy (n=45)

Pati

ents

(%

)

93% 91%

2%

Difference (%):2.1 (-11.2, 15.3)

91% 89%

Week 24 Week 48

Virologic Failure

Week 24 Week 48

HIV RNA <50 Copies/mL

0% 2% 2%

Difference (%):2.0 (-12.6, 16.5)


» Integrase Single Copy Assay (iSCA) with a 0.5 HIV-1 RNA copies/mL

limit of detection

» At baseline, mean residual viremia did not differ between arms

4.9 c/ml (DTG+3TC) vs. 5.3 c/ml (cART) diff = -0.5 c/ml, 95% CI [-3.8, 2.8], p=0.78

0

25

50

75

100

0 24 48

study week

Study Results


HIV viral load by iSCA by Treatment Arm at Baseline, 24 and 48 Weeks

Treatment

DTG+3TC

ART

cop

ies/

ml


Pros and Cons:

Maintenanace therapy

PROS

Cost (for some combinations)

Avoid toxicities

Smaller tablet potentially

May allow simplification in historicpatients with prior NRTI and efavirenz or PI/r failure

Seite 27

CONS

Cost (for some combinations)

Toxicity of modern integrase and TAF based therapies is very low

Risk for resistance development overtime?

Change in genetic barrier?

No effective HBV therapy or HBV prevention

Not all dual regimens available as FDC yet


Pros and Cons

General

considerations

Seite 28

EACS 9.1: Indications for

ART Switch in

Suppressed Patients

1. Documented toxicity caused by one or more of the antiretrovirals included in

the regimen. Examples of these reactive switches: lipoatrophy (d4T, AZT),

central nervous system adverse events (EFV), diarrhoea (PI/r) and jaundice

(ATV), proximal renal tubulopathy and low bone mineral density (TDF), see

Adverse Effects of ARVs and Drug Classes.

2. Prevention of long-term toxicity. Example of this proactive switch: prevention of

lipoatrophy in persons receiving d4T or AZT and prevention of proximal renal

tubulopathy with TDF, see Adverse Effects of ARVs and Drug Classes.

3. Avoid serious drug-drug interactions

4. Planned pregnancy

5. Ageing and/or co-morbidity with a possible negative impact of drug(s) in current

regimen, e.g. on CVD risk, metabolic parameters.

6. Simplification: to reduce pill burden, adjust food restrictions and improve

adherence.

7. Starting of HCV treatment in case of drug-drug interaction

29EACS Guidelines 9.0 October 2017

Principles in switching:

EACS guidelines 9.1

» Clinicians should always review possible adverse events or tolerability

issues with current antiretroviral regimens. Just because the HIV-VL is

suppressed it should not be assumed that the HIV-positive person is well

adapted and tolerating the current regimen.

1. The objectives of treatment modification should be to eliminate or improve adverse

events, facilitate adequate treatment of co-morbid conditions, and improve quality of life.

2. The primary concern when switching should be to sustain and not to jeopardize

virological suppression. In persons without prior virological failures and no archived

resistance, switching regimens entail a low risk of subsequent failure if clinicians select

one of the recommended combinations for first-line therapy. The majority of clinical trials

showing non-inferiority of the new regimen after the switch have actively excluded

persons with prior virological failures.

3. A complete ARV history with HIV-VL, tolerability issues and cumulative genotypic

resistance history should be analysed prior to any drug switch.

4. A PI/r or PI/c may be switched to unboosted ATV, an NNRTI, or an INSTI only if full

activity of the 2 NRTIs remaining in the regimen can be guaranteed. Switches have to be

planned especially carefully when they result in a decrease in the genetic barrier of the

regimen in case of prior virologic failures. Clinicians should review the complete ARV

history and available resistance test and HIV-VL results before switching, and ensure no

drug-drug interactions may lead to suboptimal drug levels (e.g. unboosted ATV and TDF).

Principles in switching:

EACS guidelines 9.1

5. Before switching, remaining treatment options in case of potential virological

failure of the new regimen should be taken into consideration. For example, the

development of the M184V RT mutation in HIV-positive persons who fail a 3TC-

containing regimen might preclude the future useof all currently available single-

tablet regimens.

6. Switches of single drugs with the same genetic barrier (for example EFV to RAL)

is usually virologically safe in the absence of resistance to the new compound.

7. When selecting a new regimen, clinicians should carefully review the possibility

of new drug-drug interactions with antiretroviral and concomitant medication, as

well as the lag time for hepatic enzyme nduction or blockade following

discontinuation of the offending drug.

8. If the switch implies discontinuing TDF and not starting TAF, clinicians should

check the HBV status (avoid discontinuation of TDF in persons with chronic HBV

and assess HBV vaccination status).

9. HIV-positive persons should be seen soon (e.g. 4 weeks) after treatment

switches to check for maintenance of suppression and possible toxicity of the new

regimen.

10. If a HIV-positive person receives and tolerates a regimen that is no longer a

preferred option, there is no need to change. Example: persons tolerating EFV-

containing regimens.


Pros and Cons

Future

Seite 32

» Cabotegravir: InSTIs formulated as PO tablet and for long-acting IM injection

» LATTE-2: phase IIb study in which pts randomized to CAB 400 mg + RPV 600 mg IM Q4W, CAB

600 mg + RPV 900 mg IM Q8W, or CAB 30 mg + ABC/3TC 600/300 mg PO QD after

induction/virologic suppression with oral CAB + ABC/3TC (N = 309)

Dual therapy with Cabotegravir IM + Rilpivirine IM as Long-Acting Maintenance ART: 96-Wk Results (LATTE-2)

Eron J, et al. IAS 2017. Abstract MOAX0205LB. Margolis DA, et al. Lancet. 2017;[Epub ahead of print].

*HIV-1 RNA < 50 copies/mL.

Few drug-related AEs. At 96 wks, ~ 30% pts receiving IM injection experienced ISR 99% of ISRs mild/moderate /

AEs leading to withdrawal: Pooled Q4W/Q8W IM arms, 4%. PO arm, 2%

~ 88% of pts receiving IM CAB very satisfied to continue present treatment vs 43% receiving PO CAB

VirologicSuccess*

9487

84

40 2 2

13 14

VirologicNon-response

No VirologicData

Pts

, Wk

96

(%

)

100

80

60

40

20

0

IM CAB + RPV Q4W (n = 115)IM CAB + RPV Q8W (n = 115)PO CAB + ABC/3TC (n = 56)

10.0%

-12 -9 -6 -3 0 3 6 9 12 15

20.5-0.6

Q8W IM

Treatment Differences (95% CI)

3.0%

-12 -9 -6 -3 0 3 6 9 12 15

14.4-8.4

Q4W IM

InjectableRilpivirinerequires

cold chain

Long-Acting InSTIss

Two Drug Regimens Pros and Cons - Virology...

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