Track B Summary
Jeff Lennox
Emory University
Atlanta
Special thanks to my fellow Track B
Rapporteurs:
Annie Luetkemeyer
San Francisco
Trip Gulick
New York
Juergen Rockstroh
Bonn
And to the wonderful people of Rome for their hospitality!
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
When to Start ART
Most recent CD4
First new AIDS event Death from any cause
cell count (cells/µL) or death from any
(no. of events)
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 AfricaPatients who achieved a CD4 of 350-499 had 1.69 AHR for mortality compared to
those who achieved CD4 >500
WELB05 Heiner;
TUBDP0106 Maman
HPTN 052: Effects of early versus delayed initiation of
ART on HIV clinical outcomes
Death, WHO stage 4 clinical event, pulmonary TB or severe bacterial infection
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).
HR: 0.6 [ 0.4, 0.9 ], P=0.01
Delayed
Immediate
Number at risk
Delayed
Immediate
New Drugs and New Strategies
Efficacy and safety of lersivirine vs efavirenz in
antiretroviral treatment-naïve HIV-1-infected
patients: Week 48 primary analysis results
LRV 500 mg QD + TDF/FTC
Randomization
1:1:1
LRV 750 mg QD + TDF/FTC
EFV 600 mg QD + TDF/FTC
6 weeks
0
24 wk
• 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)
48 wk
96 wk
Primary endpoint: Patients
achieving
HIV-1 RNA <50 c/mL
TUAB0101, Pozniak
7
Lersivirine vs efavirenz- Efficacy results through
Week 48
% of subjects with plasma
HIV-1 RNA <50 c/mL through Week 48
(plasma HIV-1 RNA <50 c/mL, ITT, NC=F)
100
90
80
54/63 (86%)
51/65 (79%)
70
51/65 (79%)
60
50
40
30
LRV 500 mg
20
LRV 750 mg
10
EFV 600 mg
0
0 2 4
8
16
24
32
40
48
Time (weeks)
Number of Subjects with AE, n (%)
Nausea
Headache
Abnormal dreams
Dizziness
Rash
LRV 500 mg
N = 65
15 (23)
15 (23)
5 (8)
5 (8)
3 (5)
LRV 750 mg
N = 65
27 (42)
11 (17)
5 (8)
4 (6)
1 (2)
EFV 600 mg
N = 63
8 (13)
9 (14)
12 (19)
13 (21)
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)
DTG 10 mg
HIV-1 RNA >1000 c/mL
CD4 ≥200 cells/mm3
1:1:1:1
Randomization
Stratified by
• HIV RNA
>100,000
or ≤ 100,000
• Epzicom/Kivexa
or Truvada
DTG 25 mg
DTG 50 mg
EFV 600 mg
Wk 48 interim
Wk 96
analysis
*Post hoc analysis using bioMONTR HIV-1 EQ SuperLow Assay LLOD=2 c/mL at Weeks 16, 24 and 48
TUAB0102 Van Lunzen
DTG: Rapid and Sustained Antiviral Activity
Week 48 Efficacy Analysis (%<50 c/mL)
Proportion (%) <50 c/mL (TLOVR)
91%
90%
88%
82%
DTG 10mg
DTG 25mg
DTG 50mg
EFV 600mg
95% confidence intervals are derived using the normal approximation
TUAB0102 Van Lunzen
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 creatinine
See 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
FTC/TDF + ATV/r (300/100 mg QD)
Randomization
1:1
N=121
Screening
(6 weeks)
MVC (150 mg QD) + ATV/r (300/100 mg QD)
0
• 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
16 wk
24 wk
Interim analyses
48 wk
Primary analysis
– Study is not powered to show
a treatment difference and no
formal comparative statistics
will be performed
TUAB0103, Mills
Patients with HIV-1 RNA <50 copies/mL (%)
HIV-1 RNA <50 copies/mL at Week 24 and
Week 48 according to baseline viral load
100
94.9
37/39
90
80
35/43
34/39
76.7
33/43
70
FTC/TDF + ATV/r
87.2
81.4
MVC + ATV/r
81.3
13/16
77.3
17/22
77.3
68.8
17/22
11/16
60
50
40
30
20
10
0
Week 24
Week 48
<100,000 copies/mL
Week 24
Week 48
≥100,000 copies/mL
Baseline HIV-1 RNA
Intent-to-treat. Missing=failure
TUAB0103, Mills
Elvitegravir QD is non-inferior to raltegravir BID in
treatment experienced patients:48 week results
• 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%
WELBB05, Molina
2011- The Year of (val)Acyclovir?
MOAC0201- Valacyclovir suppression reduces breast milk and plasma HIV-1 RNA
postpartum: -results of a randomized clinical trial
TUAB0202- Peripartum valacyclovir improves markers of HIV-1 disease progression
in women co-infected with HSV-2: a randomized trial
TUAB0104- Impact of HSV-2 suppressive therapy with daily acyclovir on HIV-1
disease progression: a randomized placebo-controlled trial in Rakai, Uganda
WEPDB0106- High-dose valacyclovir suppressive therapy results in greater reduction in
plasma HIV-1 levels compared to standard dose acyclovir suppression among HIV1/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
1.3
Hazard Ratio
1.2
1.1
1.0
0.9
0.8
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.
MAOB0101, Bedimo
HIV-Related Predictors and Outcomes in 125 Liver
and 150 Kidney Transplant Recipients
Studied rates and predictors of
Patient survival
AIDS-related opportunistic infections (OI) and neoplasms
Other serious infections with hospitalization (SI)
•1 & 3 year patient survival
Kidney:
95% (90%, 98%) & 91% (84%, 95%)
Liver:
80% (72%, 86%) & 67% (56%, 75%)
•Predictors of Mortality
Liver:
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)
MOAB0105, Beatty
Infections
CARINEMO ANRS 12146
•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
ART + RMP
ART alone
Bhatt WELBX05
Risk factors for TB-IRIS
•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/µL
26% of patients developed TB IRIS a median of 2 weeks after ART
Early ART
Late ART
CD4 ≤100
CD4 101-200
Extra-pulmonary
Disseminated
Pulmonary
Adjusted HR
2.23
1
1.85
1
2.06
1.61
1
95% CI
1.51–3.27
p
<0.001
1.02–3.34
0.04
1.34–3.17
1.10–2.37
0.001
•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
21
WEAX0104 Laureillard, WEPDB0202 Marcy
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
Sensitivit y of LFA
100%
100%
98%
95% CI*
94-100%
94-100%
91-100%
*95% co nfidence interval