update on current and near future antiretroviral …...update on current and near future...

Update on Current and Near Future Antiretroviral Therapy

Jihad Slim, MD

Assistant Professor of Medicine

NYMC, Valhalla, N.Y.

Chief of Infectious Disease

SMMC, Newark, N.J.

HIV+ Patients are living longer

ART, antiretroviral therapy; PY, person years. 1 Palella FJ, et al. J Acquir Immune Defic Syndr. 2006;43:27-34; 2 Centers for Disease Control and Prevention (CDC). HIV/AIDS

Surveillance Report: Cases of HIV Infection and AIDS in the United States and Dependent Areas. 2005; 3 CDC. Diagnoses of HIV

Infection in the United States and Dependent Areas. 2011; 4 Effros RB, et al. Clin Infect Dis. 2008;47:542-553; 5 Samji H, et al.

PLoS ONE 2013; 8e81355.

Estimated Percentage of Persons Living

With HIV/AIDS Who Are Aged ≥50 Years2-4

• In the United States, a 20-year-old HIV-positive patient can now expect to live into his/her early 70s5

COMORBIDITIES ARE MORE PREVALENT IN HIV-POSITIVE PATIENTS

• Similarities between aging and the courses of HIV and AIDS suggest that HIV infection may compress certain aging processes, thereby accelerating comorbidities and frailty1

• Duration of ART use (OR 1.24 per 5 additional years of ART use) and lower nadir CD4 cell count (OR 1.12 per 100 fewer cells) were associated with an increased risk of a higher number of comorbidities

CLD, chronic liver disease; HTN, hypertension; MI, myocardial infarction; OR, odds ratio; PAD, peripheral artery disease. 1 Effros RB, et al. Clin Infect Dis. 2008;47:542-553; 2 Schouten J, et al. IAC 2012. Washington, DC. THAB0205.

Subjects ≥45 Years With Age-Associated Noncommunicable

Comorbidities, by HIV Serostatus (AGEhIV Study, 2010-2012)2

Age-Associated Noncommunicable Comorbidity

P <.0001

HTN Non-AIDS Cancer

Angina Pectoris

MI PAD CLD Cerebrovascular Disease

Pa

rtic

ipa

nts

, %

0

20

30

40

50

10

P <.0001

P <.05

P <.05 P <.05

P <.05 P <.05

HIV-Positive Patients (n=381) HIV-Uninfected Individuals (n=349)

Current Antiretroviral Medications NRTI

•Abacavir

•Didanosine

•Emtricitabine

•Lamivudine

•Stavudine

•Tenofovir

•Zidovudine

NNRTI

•Delavirdine

•Efavirenz

•Rilpivirine

•Etravirine

•Nevirapine

PI

•Atazanavir

•Darunavir

•Fosamprenavir

•Indinavir

•Lopinavir

•Nelfinavir

•Ritonavir

•Saquinavir

•Tipranavir

Fusion Inhibitor

• Enfuvirtide

CCR5 Antagonist

• Maraviroc

Integrase Inhibitor

• Raltegravir

• Elvitegravir

• Dolutegravir

Combined Drugs

NRTI

•Lamivudine

•Zidovudine

NNRTI

PI

Fusion Inhibitor

CCR5 Antagonist

Integrase Inhibitor

COMBIVIR

Combined Drugs

NRTI

•Abacavir

•Lamivudine

NNRTI

PI Fusion Inhibitor

CCR5 Antagonist

Integrase Inhibitor

EPZICOM

Combined Drugs

NRTI

•Abacavir

•Lamivudine

•Zidovudine

NNRTI

PI

Fusion Inhibitor

CCR5 Antagonist

Integrase Inhibitor

TRIZIVIR

Combined Drugs

NRTI

•Emtricitabine

•Tenofovir (TDF)

NNRTI

PI

Fusion Inhibitor

CCR5 Antagonist

Integrase Inhibitor

TRUVADA

Combined Drugs

NRTI

•Emtricitabine

•Tenofovir (TAF)

NNRTI

PI

Fusion Inhibitor

CCR5 Antagonist

Integrase Inhibitor

DESCOVY

Combined Drugs

NRTI

NNRTI

PI

•Atazanavir

+Cobicistat

Fusion Inhibitor

CCR5 Antagonist

Integrase Inhibitor

EVOTAZ

Combined Drugs

NRTI

NNRTI

PI

•Darunavir

+ Cobicistat

Fusion Inhibitor

CCR5 Antagonist

Integrase Inhibitor

PREZCOBIX

Combined Drugs (STR)

NRTI

•Emtricitabine

•Tenofovir (TDF)

NNRTI

•Efavirenz

PI

Fusion Inhibitor

CCR5 Antagonist

Integrase Inhibitor

ATRIPLA


NRTI

•Emtricitabine

•Tenofovir (TDF)

NNRTI

•Rilpivirine

PI Fusion Inhibitor

CCR5 Antagonist

Integrase Inhibitor

COMPLERA


NRTI

•Abacavir

•Lamivudine

NNRTI

PI

Fusion Inhibitor

CCR5 Antagonist

Integrase Inhibitor

•Dolutegravir

TRIUMEQ


NRTI

•Emtricitabine

•Tenofovir (TDF)

NNRTI

PI Fusion Inhibitor

CCR5 Antagonist

Integrase Inhibitor

Elvitegravir

STRIBILD

Cobicistat


NRTI

•Emtricitabine

•Tenofovir (TAF)

NNRTI

•Rilpivirine

PI Fusion Inhibitor

CCR5 Antagonist

Integrase Inhibitor

ODEFSEY


NRTI

•Emtricitabine

•Tenofovir (TAF)

NNRTI

PI Fusion Inhibitor

CCR5 Antagonist

Integrase Inhibitor

Elvitegravir

GENVOYA

Cobicistat

Studies 104/111: TAF vs TDF in Treatment-Naive Pts

• Parallel, randomized, double-blind, active-controlled phase

III studies

– Primary endpoint: HIV-1 RNA < 50 c/mL at Wk 48 (FDA

Snapshot)

Arribas JR, et al. CROI 2017. Abstract 453. Sax PE, et al. Lancet. 2015;385:2606-2615.

EVG/COBI/FTC/TAF* single-tablet regimen

(n = 866)

EVG/COBI/FTC/TDF†

single-tablet regimen (n = 867)

Treatment-naive HIV-infected pts with

HIV-1 RNA ≥ 1000 copies/mL, eGFR ≥ 50 mL/min

(N = 1733)

Stratified by HIV-1 RNA, CD4+ cell count, geographic region

Wk 48:

Primary Endpoint Wk

144

*150/150/200/10 mg once daily. †150/150/200/300 mg once daily.

Initial ART With E/C/F/TAF Superior to E/C/F/TDF

at Wk 144

• Efficacy similar across pt

subgroups, trending

toward or significantly

better with TAF in each

group

– By baseline HIV-1 RNA,

baseline CD4+ cell count,

adherence, age, sex,

race, region

• Virologic failure with

resistance by Wk 144:

1.4% in each arm

Arribas JR, et al. CROI 2017. Abstract 453. Sax PE, et al. Lancet. 2015;385:2606-2615.

0

20

60

40

80

100

48 96 144 48 96 144 48 96 144 Wk:

Virologic

Success

Virologic

Failure

No Data

E/C/F/TAF (n = 866)

E/C/F/TDF (n = 867)

92 90 87 85 84 80

4 4 5 4 5 4 4 6 9 11 11

16

Pts

(%

)

Treatment Difference Wk 48: 2.0% (95% CI: -0.7% to

4.7%) Wk 144: 4.2% (95% CI: 0.6% to

7.8%; P = .02)

Initial ART With E/C/F/TAF vs E/C/F/TDF: Wk 144

Safety Outcomes

• Rate of discontinuation for AEs

higher with TDF vs TAF regimen

– 3.3% vs 1.3% (P = .01)

• Spine and hip BMD loss greater

with TDF vs TAF regimen

– 6 discontinuations for bone AEs in

TDF arm vs 0 in TAF arm

• TC, LDL, and HDL increases

greater with TAF vs TDF regimen,

but no difference in TC:HDL ratio

– Rates of lipid-modifying therapy

initiation similar: 5.5% vs 5.8%

Renal Events Leading to Discontinuation, n

E/C/F/TAF (n = 866)

E/C/F/TDF (n = 867)

Proximal renal tubulopathy

0 4

Cr elevation or eGFR decrease

0 3

Renal failure 0 2

Nephropathy 0 1

Proteinuria 0 1

Bladder spasm 0 1

Total 0 12

Arribas JR, et al. CROI 2017. Abstract 453.

Future Combined Drugs (STR)

NRTI

•Lamivudine

NNRTI

PI

Fusion Inhibitor

CCR5 Antagonist

Integrase Inhibitor

•Dolutegravir

?

Switch to DTG + 3TC From Virologically

Suppressive Triple ART

• Noncomparative, open-label, single-arm multicenter trial

– Primary endpoint: therapeutic success at Wk 56 (ie, after

48 wks of dual therapy)

• Therapeutic failure: HIV-1 RNA > 50 copies/mL, interruption,

lost to f/u, death

Joly V, et al. CROI 2017. Abstract 458.

DTG 50 mg QD + 2 NRTI†

HIV-infected pts with HIV-1 RNA ≤ 50 copies/mL for ≥ 2 yrs on first-line ART;

≤ 2 ART modifications allowed, except within 6 mos of study start; CD4+ cell count

> 200 cells/mm3

(N = 110)

Wk 8* Wk 56

*Pts with HIV-1 RNA ≤ 50 copies/mL proceeded to phase II. †In phase I, third agent in regimen replaced with DTG; baseline

NRTI backbone maintained.

DTG 50 mg QD +

3TC 300 mg QD

(n = 104)

Phase I Phase II

Switch to DTG + 3TC Maintains Viral Suppression

• 97% (101/104) pts maintained

therapeutic success through 40

wks of dual therapy (study Wk 48)[1]

– No INSTI resistance in 3 pts with

virologic failure

– 7 pts with serious AEs, only 2

related to dual therapy

• DTG + 3TC dual therapy currently

under phase III evaluation as both

initial ART[2,3] and as a switch

strategy for virologically

suppressed pts[4]

1. Joly V, et al. CROI 2017. Abstract 458. 2. ClinicalTrials.gov. NCT02831673. 3.

ClinicalTrials.gov. NCT02831764 4. ClinicalTrials.gov. NCT02263326.

Therapeutic Success, n/N* (%) DTG + 3TC

Wk 0 (entry; on BL triple therapy) 110/110 (100)

Wk 8 (end of phase I, start of phase II) 104/104 (100)

Wk 12 104/104 (100)

Wk 16 103/104 (99)

Wk 24 103/104 (99)

Wk 32 103/104 (99)

Wk 40 102/104 (98)

Wk 48 101/104 (97)

*Pts enrolled in phase I, N = 110; pts enrolled in

phase II, N = 104.


NRTI

NNRTI

•Rilpivirine

PI

Fusion Inhibitor

CCR5 Antagonist

Integrase Inhibitor

•Dolutegravir

?

SWORD 1 & 2: Switch From Suppressive ART to

DTG + RPV Dual Therapy

• Randomized, open-label, multicenter phase III trials

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

(ITT-E snapshot)

• 70% to 73% of pts receiving TDF at baseline

Llibre JM, et al. CROI 2017. Abstract 44LB.

Switch to DTG + RPV (n = 513)

Continue Baseline ART

(n = 511)

HIV-infected pts with HIV-1 RNA < 50 c/mL for

≥ 12 mos while receiving first or second ART regimen with 2 NRTIs + INSTI, NNRTI, or PI; no previous VF; HBV negative

(N = 1024)

Wk 52 Wk 148

Switch to DTG + RPV

Continue DTG + RPV

DTG + RPV

Switch From Suppressive ART to DTG + RPV

Noninferior to Cont. BL ART at Wk 48

• 1 pt with confirmed criteria

for virologic withdrawal at

Wk 36 in DTG + RPV arm

had K101K/E

– Documented

nonadherence at VF

– Resuppressed with

continued DTG + RPV

– No INSTI resistance


Virologic

Nonresponse

Wk 48

HIV-1 RNA

< 50 c/mL

No Data

100

80

60

40

20

0

Pts

(%

)

95 95

< 1 1 5 4

Treatment difference: -0.2% (95% CI: -3.0% to 2.5%)

DTG + RPV (n = 513) Baseline ART (n = 511)

Switch From Suppressive ART to DTG + RPV:

Safety Outcomes

• AE rates generally similar

between treatment arms

through Wk 52

– Numerically higher rate of

drug-related grade 1/2 AEs

with switch: 17% vs 2%

– Numerically higher rate of

withdrawal for AEs with

switch: 4% vs < 1%

• No notable change in serum

lipid values from baseline to

Wk 48 in either treatment

arm


Bone-specific

alkaline

phosphatase

Osteocalcin Procollagen 1

N-terminal

propeptide

Bone Turnover Marker

DTG + RPV Baseline ART

0

20

60

40

80

Me

an

(µ

g/L

)

Baseline

Wk 48

15.9 12.9

100 Baseline

Wk 48

16.2 17.1 23.8

19.0 24.0 23.1

53.0 45.6

55.3 54.7

P < .001 P < .001

P < .001


NRTI

•Emtricitabine

•Tenofovir (TAF)

NNRTI

PI

•Darunavir

+ Cobicistat

Fusion Inhibitor

CCR5 Antagonist

Integrase Inhibitor

?

Future New Drugs in Existing Classes

• NNRTI: Doravirine.

• INSTI : Bictegravir

Doravirine or Darunavir + RTV Both With 2 NRTIs

in Treatment-Naive Pts

• Doravirine: next-gen NNRTI, unique resistance profile, low DDI

potential, no food or PPI effects

• Multicenter, randomized, double-blind phase III trial


14-day follow-up

Molina JM, et al. CROI 2017. Abstract 45LB.

Wk 96

DOR 100 mg QD + FTC/TDF or ABC/3TC QD +

Placebo for DRV + RTV (n = 385)

DRV 800 mg + RTV 100 mg QD + FTC/TDF or ABC/3TC QD +

Placebo for DOR (n = 384)

HIV-infected pts with HIV-1 RNA

≥ 1000 copies/mL within 45 days of Day 1;

no previous ART; no resistance to study drugs

(N = 769)

Stratified by HIV-1 RNA > 100,000 c/mL, baseline NRTI

Wk 48

Doravirine Is Noninferior to DRV + RTV at Wk 48

• Efficacy similar in both

arms regardless of

baseline HIV-1 RNA or

CD4+ cell count

• No drug resistance

detected in pts with PDVF

through Wk 48 in either

arm

– n = 1 pt with

noncompliance

discontinued at Wk 24,

developed DOR and FTC

resistance


Virologic

Nonresponse

Wk 48

HIV-1 RNA

< 50 c/mL

No Data

100

80

60

40

20

0

Pts

(%

)

84 80

11 13 5 7

Treatment difference: 3.9% (95% CI: -1.6% to 9.4%)

DOR + 2 NRTIs (n = 383)

DRV + RTV + 2 NRTIs (n = 383)

Doravirine vs DRV + RTV: Safety


AE, % DOR

(n = 383)

DRV +

RTV

(n = 383)

≥ 1 AE 80 78

Treatment-related

AE 31 32

Serious AE 5 6

Discontinuation for

AE 2 3

AEs of clinical

interest

Rash*

Neuropsychiatric†

7

11

8

13

Fasting Lipid Δ From

BL to Wk 48, mg/dL

DOR

(n = 383)

DRV +

RTV

(n = 383)

LDL-c* -4.51 9.92

Non-HDL-c* -5.3 13.75

Cholesterol -1.37 17.9

Triglyceride -3.14 21.97

HDL-c 3.94 4.15

*Discontinued due to rash: n = 2 in DOR arm; n =

1 in DRV + RTV arm. †No discontinuation for neuropsychiatric

conditions.

*P < .0001 for DOR vs DRV + RTV.

Bictegravir + FTC/TAF vs DTG + FTC/TAF in

Treatment-Naive Pts

• Bictegravir: investigational QD INSTI, active against most INSTI RAVs,

low DDI potential, half-life ~ 18 hrs, no food requirement with dosing,

primarily metabolized by CYP3A4 and UGT1A1

• Randomized, double-blind, active-controlled phase II trial


Open-label extension

Sax PE, et al. CROI 2017. Abstract 41. Sax PE, et al. Lancet HIV. 2017;[Epub ahead

of print]. Zhang H, et al. CROI 2017. Abstract 40.

Wk 48

BIC + FTC/TAF QD + Placebo for DTG QD

(n = 65)

DTG + FTC/TAF QD + Placebo for BIC QD

(n = 33)

Wk 24

HIV-infected pts with HIV-1 RNA

≥ 1000 copies/mL; CD4+ ≥ 200 cells/mm3;

no previous ART; HBV and HCV negative

(N = 98)

Bictegravir + FTC/TAF vs DTG + FTC/TAF: Wk 24

and Wk 48 Efficacy (FDA Snapshot)

• No drug resistance detected in either arm through Wk 48

Sax PE, et al. CROI 2017. Abstract 41.

Virologic

Failure

Wk 48

Virologic

Success

No Data

100

80

60

40

20

0

97 91

2 6 2 3

Treatment difference: 6.4% (95% CI: -6% to 18.8%)

Virologic

Failure

Wk 24

Virologic

Success

No Data

100

80

60

40

20

0

Pts

(%

)

97 94

3 6 0 0

Treatment difference: 2.9% (95% CI: -8.5% to 14.2%)

BIC + FTC/TAF (n = 65) DTG + FTC/TAF (n = 33)

• Difficult to conclude on safety from

small study, but 4 fully enrolled

phase III trials now evaluating

efficacy, safety, tolerability of

coformulated BIC/FTC/TAF

Bictegravir + FTC/TAF vs DTG + FTC/TAF: Safety

Sax PE, et al. CROI 2017. Abstract 41.

Any Grade AE

Occurring in ≥ 5% in

Either Arm, %

BIC +

FTC/TAF

(n = 65)

DTG +

FTC/TAF

(n = 33)

Diarrhea 12 12

Nausea 8 12

Headache 8 3

URTI 8 0

Fatigue 6 6

Arthralgia 6 6

Chlamydial infection 6 3

Back pain 6 0

Furuncle 5 6

Flatulence 2 6

Gastroenteritis 2 6

Costochondritis 0 6

Hemorrhoids 0 6

Pruritus 0 6

Grade 2-4 Lab

Abnormality ≥ 5% in

Either Arm, %

BIC +

FTC/TAF

(n = 64*)

DTG +

FTC/TAF

(n = 32*)

Creatine kinase 13 9

AST 9 3

Hyperglycemia 8 13

ALT 6 0

LDL 6 9

Amylase 5 6

Hematuria 3 6

Glycosuria 2 6

*Pts with ≥ 1 post-BL laboratory assessment,

excluding those not specified for all pts.

Emerging Investigational Agents for Pts With MDR HIV

1. Lalezari JP, et al. Lancet HIV. 2015;2:e427-437. 2. Granados-Reyes ER, et

al. HIV Glasgow 2016. Abstract O335A. 3. ClinicalTrials.gov. NCT02362503. 4.

Lewis S, et al. CROI 2017. Abstract 449LB.

5. Lin H-H, et al. CROI 2017. Abstract 438.

Investigational

Agent Phase MoA

Fostemsavir[1-3] III

Prodrug; when metabolized

binds gp120 to prevent CD4+

cell attachment, entry

Ibalizumab[4,5] III Humanized anti-CD4 receptor

mAb

AI438011: Fostemsavir + RAL + TDF in Treatment-Experienced Pts

• Fostemsavir: prodrug; proposed MoA: binding HIV-1 gp120 prevents viral attachment and entry into host CD4+ cells

• Randomized, active-controlled phase IIb study, blinded to dose

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

Granados-Reyes ER, et al. HIV Glasgow 2016. Abstract O335A.

Llamoso C, et al. HIV Glasgow 2016. Abstract O335B.

Fostemsavir 600 mg QD* PO + RAL + TDF

(n = 51)

HIV-infected pts with exposure

to ≥ 1 ARV for ≥ 1 wk;

HIV-1 RNA ≥ 1000 c/mL;

CD4+ ≥ 50 cells/mm3; virus

susceptible to RAL, TDF, ATV,

and fostemsavir IC50 < 100 nM

(N = 254)

Wk 48 Wk 24: 1̊ endpoint

ATV/RTV 300/100 mg QD + RAL + TDF

(n = 51)

Fostemsavir 1200 mg QD PO + RAL + TDF

(n = 50)

Fostemsavir 400 mg BID* PO + RAL + TDF

(n = 50)

Fostemsavir 800 mg BID* PO + RAL + TDF

(n = 49)

Wk

96

*Fostemsavir dose changed to 1200 mg QD from

Wk 48 to Wk 96.

Efficacy, Safety of Fostemsavir + RAL + TDF

At Wk 96, 90% of pts had HIV-1 RNA < 50 copies/mL in both fostemsavir and ATV/RTV arms in observed analysis[1]

– No significant differences in virologic efficacy regardless of race, sex, age, BL HIV-1 RNA, BL CD4+ cell count, or IC50 subgroups[1]

– Fostemsavir generally well tolerated, with higher rates of grade 2-4 treatment-emergent AEs (37% vs 9%) and d/c for AEs (10% vs 3%) for ATV/RTV arm vs fostemsavir arm[2]

1. Granados-Reyes ER, et al. HIV Glasgow 2016. Abstract O335A.

2. Llamoso C, et al. HIV Glasgow 2016. Abstract O335B.

TMB-301: Ibalizumab in Pretreated Pts Infected With Multidrug-Resistant HIV

• Ibalizumab: humanized mAb to CD4 receptor that blocks HIV entry into CD4+ T-cells

– FDA breakthrough and orphan drug designations

• Single-arm, open-label phase III trial

– Primary endpoint: ≥ 0.5 log10 HIV-1 RNA decrease at Day 14


Pts with HIV-1 RNA

> 1000 copies/mL;

on ART ≥ 6 mos, on

stable ART ≥ 8 wks;

resistant to

≥ 1 ARV from 3

classes, sensitive to ≥

1 ARV for OBR

(N = 40)

Wk 25

Ibalizumab

2000 mg IV Day 7

(loading dose)

Continue Failing ART

Days 0-14

Ibalizumab

800 mg IV Day 21, Q2W

(maintenance dose)

Switch to OBR

Day 14

Primary Endpoint:

Day 14 Control Period:

Day 0-7

TMB-301: Efficacy


Virologic Outcome Ibalizumab + OBR

Day 14

≥ 0.5 log10 HIV-1 RNA decrease, % 83*

≥ 1.0 log10 HIV-1 RNA decrease, % 60

Mean HIV-1 RNA decrease, log10 1.1

Wk 24



HIV-1 RNA < 50 copies/mL, % 43

HIV-1 RNA < 200 copies/mL, % 50

Mean HIV-1 RNA decrease from BL, log10 1.6

*Primary endpoint; P < .0001 vs 3% at end of control period.

TMB-301: Safety

• 9 pts reported 17 serious AEs[1]

– 1 drug-related serious AE (IRIS) resulted in discontinuation

• 9 other pts discontinued

– Death (n = 4; liver failure, Kaposi sarcoma; end-stage AIDS, lymphoma)

– Consent withdrawal (n = 3)

– Lost to follow-up (n = 2)

• No cases of anti-ibalizumab antibodies

• Phase III TMB-311 study ongoing; extension for pts from TMB-301; accepting new pts[2]

• IM dosing may be viable as administration route as compared with IV dosing[3]

1. Lewis S, et al. CROI 2017. Abstract 449LB. 2. ClinicalTrials.gov. NCT02707861. 3. Lin

H, et al. CROI 2017. Abstract 438.

Agent MoA or Formulation Phase Dosing/

Administration Implications

GS-CA1[1] HIV capsid inhibitor Pre-

clinical

Extended release, suitable for SC of solid

depot formulation

Potent ART with orthoganol resistance profile to existing ART; potential for long-acting formulation due to low aqueous solubility, high stability

GS-9131[2] NRTI Pre-

clinical Potential for once daily

dosing

Potent ART active against NRTI RAMs K65R, L74V, M184V alone or in combination; minimal loss of susceptibility with 4 or more TAMs

MK-8591[3]

Nucleoside Reverse Transcriptase Translocation

Inhibitor (NRTTI)

I 10 mg QW PO; potential

for extended duration

Comparable MK-8591 levels in animal rectal, vaginal tissue to TDF levels in tissues of human subjects highlights potential prophylaxis utility

GS-PI1[4] PI Pre-

clinical Potential for unboosted,

QD dosing

Potent ART with high barrier to resistance, including < 2-fold loss in potency against major PI RAMs, and 10-fold to 40-fold longer in vivo half life vs ATV or DRV

Additional Investigational Agents Reported

at CROI 2017: Preclinical and Phase I

1. Tse WC, et al. CROI 2017. Abstract 38. 2. White KL, et al. CROI 2017. Abstract 436. 3. Grobler J, et al. CROI 2017.

Abstract 435. 4. Link JO, et al. CROI 2017. Abstract 433.

Additional Investigational Agents

Reported at CROI 2017: Phase II

1. Bekker L-G, et al. CROI 2017. Abstract 421LB. 2. Murphy R, et al. CROI 2017.

Abstract 452LB. 3. Wang C-Y, et al. CROI 2017. Abstract 450LB.

Agent MoA or

Formulation Phase

Dosing/ Administration

Implications

TMC278 LA[1] LA injectable

RPV (IM) II 1200 mg IM Q8W Potential as injectable, long-acting PrEP

Elsulfavirine[2] Prodrug of new NNRTI VM1500A

IIb Combined therapy: 20 mg elsulfavirine + FTC/TDF PO QD

Less toxic alternative to EFV for initial ART

UB-421[3] Anti-CD4

receptor mAb II

10 mg/kg QW IV or 25 mg/kg Q2W IV

Possible ART alternative for maintenance therapy in virologically suppressed pts

update on current and near future antiretroviral …...update on current and near future...

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