Track B Summary

Jeff LennoxEmory University

Atlanta

Special thanks to my fellow Track B Rapporteurs:

Annie Luetkemeyer San Francisco

Trip GulickNew York

Juergen RockstrohBonn

And to the wonderful people of Rome for their hospitality!

When to Start ART

When to Start ART

Risk of progression to AIDS or death in relation to CD4 cell levels in patients with sustained viral response to ART: COHERE cohort

Results - event rates per 1000 years suppressed

Most recent CD4 cell count (cells/µL)

First new AIDS eventor death from any cause (no. of events)

Death from any cause(no. of events)

<50 94.9 (54) 64.8 (38)

50-<200 30.5 (489) 20.0 (325)

200-<350 12.0 (548) 6.9 (318)

350-<500 7.9 (487) 3.8 (240)

500 5.2 (679) 2.4 (315)

•Similar results in an analysis of 27,108 patients in 4 M.S.F. programs in Africa- Patients who achieved a CD4 of 350-499 had 1.69 AHR for mortality compared to those who achieved CD4 >500

WELB05 Heiner; TUBDP0106 Maman

Delayed

Immediate

DelayedImmediate

HR: 0.6 [ 0.4, 0.9 ], P=0.01

Number at risk

HPTN 052: Effects of early versus delayed initiation ofART on HIV clinical outcomes

1763 HIV-infected individuals were randomized to receive ART at a CD4 count of 350-550 (immediate arm) or after two consecutive CD4 counts< 250/μL>200 (delayed arm).

Death, WHO stage 4 clinical event, pulmonary TB or severe bacterial infection

New Drugs and New Strategies

7

Efficacy and safety of lersivirine vs efavirenz in antiretroviral treatment-naïve HIV-1-infected patients: Week 48 primary analysis results

• Randomized, double-blind • Selection criteria

– ARV naïve, HIV-1 RNA ≥1000 c/mL, CD4+ >200 cells/mm3

– No RT mutations by standard genotyping• Stratified by viral load (<100,000 or ≥100,000

c/mL) & geographic region (A & B)

Randomization 1:1:1

EFV 600 mg QD + TDF/FTC

LRV 750 mg QD + TDF/FTC

0 48 wk 96 wk6 weeks 24 wk

Primary endpoint: Patients achieving

HIV-1 RNA <50 c/mL

LRV 500 mg QD + TDF/FTC

TUAB0101, Pozniak

0 2 4 8 16 24 32 40 48

0

10

20

30

40

50

60

70

80

90

100

Time (weeks)

% o

f subje

cts

with p

lasm

a

HIV

-1 R

NA

<50

c/m

L th

rough W

eek 4

8

LRV 500 mg

LRV 750 mg

EFV 600 mg

54/63 (86%)51/65 (79%)

51/65 (79%)

Lersivirine vs efavirenz- Efficacy results through Week 48(plasma HIV-1 RNA <50 c/mL, ITT, NC=F)

Number of Subjects with AE, n (%)

LRV 500 mgN = 65

LRV 750 mg N = 65

EFV 600 mg N = 63

Nausea 15 (23) 27 (42) 8 (13) Headache 15 (23) 11 (17) 9 (14) Abnormal dreams 5 (8) 5 (8) 12 (19) Dizziness 5 (8) 4 (6) 13 (21) Rash 3 (5) 1 (2) 7 (11)

TUAB0101, Pozniak

Once-daily Dolutegravir, a Next Generation Integrase Inhibitor in in Antiretroviral-naïve Adults 48 Week Results from SPRING-1 (ING112276)

● Phase IIb dose-ranging, partially-blinded, N~200 ART-naïve patients

● All arms include 2 NRTI backbone given once daily

● Primary endpoint: % <50 c/mL at 16 weeks (TLOVR)

● Planned interim analysis: % <50 c/mL at 48 weeks (TLOVR)

HIV-1 RNA >1000 c/mL

CD4 ≥200 cells/mm3

1:1:1:1 Randomization

EFV 600 mg

DTG 50 mg

DTG 25 mg

DTG 10 mg

Wk 48 interim

analysis

Stratified by•HIV RNA >100,000

or ≤ 100,000•Epzicom/Kivexa or Truvada

*Post hoc analysis using bioMONTR HIV-1 EQ SuperLow Assay LLOD=2 c/mL at Weeks 16, 24 and 48

Wk 96

TUAB0102 Van Lunzen

TUAB0102 Van Lunzen

DTG: Rapid and Sustained Antiviral ActivityWeek 48 Efficacy Analysis (%<50 c/mL)

Pro

po

rtio

n (

%)

<5

0 c

/mL

(T

LO

VR

)

91%

88%90%

82%

DTG 10mgDTG 25mg

DTG 50mgEFV 600mg

95% confidence intervals are derived using the normal approximation

Laboratory Findings

● > Grade 3 lab abnormalities were rare (DTG 12% vs. EFV 14%)● No Grade 3 or 4 ALT elevations in any subject● Changes (+/- SD) in serum creatinine over time

Note: no clinically relevant events nor discontinuations related to creatinineSee also abstract TUPE238 (Min et. al.)

QD maraviroc 150 mg in combination with ATV/r vs. FTC/TDF + ATV/r in treatment-naïve patients infected with R5 HIV-1 (Study A4001078): 48 week results

• Patient eligibility criteria – R5 HIV at screening– HIV-1 RNA ≥1000

copies/mL– CD4 ≥100 cells/mm3

– No evidence of resistance to ATV/r, TDF, or FTC

– Study is not powered to show a treatment difference and no formal comparative statistics will be performed

Randomization 1:1

N=121 MVC (150 mg QD) + ATV/r (300/100 mg QD)

FTC/TDF + ATV/r (300/100 mg QD)

0 24 wk 48 wkScreening(6 weeks) 16 wk

Interim analyses Primary analysis

TUAB0103, Mills

HIV-1 RNA <50 copies/mL at Week 24 and Week 48 according to baseline viral load

Week 24 Week 48 Week 24 Week 48

Pat

ien

ts w

ith

HIV

-1 R

NA

<50

co

pie

s/m

L (

%)

0

10

60

70

80

90

100

50

40

30

20

<100,000 copies/mL ≥100,000 copies/mL

Baseline HIV-1 RNA

34/39

33/43 17/22

11/16

76.7

87.2

68.8

77.3

37/39

35/43 13/1617/22

81.4

94.9

81.377.3

Intent-to-treat. Missing=failure

MVC + ATV/r

FTC/TDF + ATV/r

TUAB0103, Mills

Elvitegravir QD is non-inferior to raltegravir BID in treatment experienced patients:48 week results

WELBB05, Molina

• 702 Treatment-experienced patients, double blind, randomized • Background regimen (BR) based on resistance testing:

2nd Agent: fully active PI/r 3rd Agent: NRTI, ETR, MVC, T-20; If M184V/I, may add 3TC or FTC

• Non Inferiority Study with lower limit 95% CI at -10%

2011- The Year of (val)Acyclovir?

MOAC0201- Valacyclovir suppression reduces breast milk and plasma HIV-1 RNA postpartum: -results of a randomized clinical trial

TUAB0104- Impact of HSV-2 suppressive therapy with daily acyclovir on HIV-1 disease progression: a randomized placebo-controlled trial in Rakai, Uganda

TUAB0202- Peripartum valacyclovir improves markers of HIV-1 disease progression in women co-infected with HSV-2: a randomized trial

WEPDB0106- High-dose valacyclovir suppressive therapy results in greater reduction in plasma HIV-1 levels compared to standard dose acyclovir suppression among HIV-1/HSV-2 co-infected persons: a randomized, open-label, crossover trial

Complications

US VA Database- ARV Exposure and Risk of Osteoporotic Fractures 1984-2009: >900 fractures in >56,000 patients

MV Model 1: Controlling for CKD, age, race, tobacco use, diabetes and BMI; MV Model 2: Controlling for Model 1 variables + concomitant exposure to other ARVs.

TDFTD

F1TD

F2AB

CAB

C1AB

C2

AZT/

D4T

AZT/

D4T1

AZT/

D4T2

NNRTI

NNRTI1

NNRTI2 rP

IrP

I1rP

I20.8

0.9

1.0

1.1

1.2

1.3

Haz

ard

Rat

io

MAOB0101, Bedimo

HIV-Related Predictors and Outcomes in 125 Liver and 150 Kidney Transplant Recipients

MOAB0105, Beatty

Studied rates and predictors ofPatient survivalAIDS-related opportunistic infections (OI) and neoplasmsOther serious infections with hospitalization (SI)

•1 & 3 year patient survivalKidney: 95% (90%, 98%) & 91% (84%, 95%)Liver: 80% (72%, 86%) & 67% (56%, 75%)

•Predictors of MortalityLiver:

Dual organ HR 4.86 (1.93, 12.2) Pre-TX BMI<21 HR 2.74 (1.25, 5.98)

Age >40 HR 2.23 (1.07, 4.64)Kidney:

HCV HR 3.17 (1.10, 9.09) Age HR 1.06 (1.01,1.11)

Infections

CARINEMO ANRS 12146

ART + RMP ART alone

•2NRTI + NVP 200mg BID vs EFV begun at 4-6 weeks of Rifampin containing therapy for TB•No difference in incidence of hepatitis or grade >2 rash between arms

Bhatt WELBX05

21

Risk factors for TB-IRIS

Adjusted HR 95% CI pEarly ARTLate ART

2.231

1.51–3.27 <0.001

CD4 ≤100CD4 101-200

1.851

1.02–3.34 0.04

Extra-pulmonary DisseminatedPulmonary

2.061.61

1

1.34–3.171.10–2.37

0.001

•CAMELIA- ART initiation ‘‘early’’ (at 2 weeks) vs. ‘‘late’’ (at 8 weeks) after TB treatment onset in 661 naïve HIV-infected adults with CD4 cell count ≤200/µL26% of patients developed TB IRIS a median of 2 weeks after ART

WEAX0104 Laureillard, WEPDB0202 Marcy

•CAMELIA Causes of Death- 149/661 (22%) patients died, mortality was highest in the first 6 months. -TB was the most common cause of death, occurring early in therapy.- Drug Toxicity was the second most common cause of death, with a majority being due to D4T and occurring after 50 weeks

Evaluation of a Point of Care Cryptococcal Antigen Test on Serum, Plasma and Urine from Patients with HIV-associated Cryptococcal Meningitis

Serum Plasma Urine

CRAG LFA+ 61 61 61

CRAG LFA +/- 1 1 0

CRAG LFA - 0 0 1

Sensitivity of LFA 100% 100% 98%

95% CI* 94-100% 94-100% 91-100%

*95% confidence interval