R. Steingrover, S. Jurriaans, J. Lange, J.M. Prins on behalf of the Primo-SHM study group
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Transcript of R. Steingrover, S. Jurriaans, J. Lange, J.M. Prins on behalf of the Primo-SHM study group
Transient HAART During PHI Prolongs the
Total Time Off HAART in Patients Presenting
with PHI: Data from the Dutch Primo-SHM
Cohort
R. Steingrover, S. Jurriaans, J. Lange, J.M. Prins
on behalf of the Primo-SHM study group
Introduction
• Is temporary HAART during PHI beneficial?
• To the individual:– lower plasma viral load set-point?– longer time off HAART?
Lower viral set-point: RCT
Steingrover et al, Temporary ART During PHI Lowers the Viral Set-point: the Prospective Randomized Trial Primo-SHM CROI 2008, poster 698b
Introduction
• Is temporary HAART during PHI beneficial?• To the individual:
– lower plasma HIV viral load?– longer time off HAART?
Introduction
• Is temporary HAART during PHI beneficial?• To the individual:
– lower plasma HIV viral load?– longer time off HAART?
• Objective of current analysis
Methods
• Patients with PHI– Negative/indeterminate WB– Detectable plasma HIV-1 RNA– or– Negative screening < 180 days
• Participating in Prospective Primo-SHM Trial or Cohort
Methods
• Primo-SHM Trial: randomization– No treatment– 24 weeks early HAART– 60 weeks early HAART
• Primo-SHM Cohort: physician/patient choice:– No treatment– early HAART
Methods
• Objectives, to analyze:
– the effect of transient HAART during PHI: the total time off antiretroviral therapy
– factors associated with a longer total time off HAART
Methods
Endpoint: restart of HAART• Two times CD4 < 350• Symptomatic HIV-1 disease• CDC-B or C
Statistical analysis:• Corrected KM• Corrected Cox’ proportional hazards analysis
Correction of KM analysis
Correction of KM analysis
Survival proportions
0 25 50 75 100 1250
50
100 UntreatedTreated
Time
Per
cen
t S
urv
ival
Correction of KM analysis
Results
• 141 Patients identified at Feb 1st 2008• 102 in the analysis
Flow of patients
141 Patients identified
5 Lost
136 Enrolled32 Still on early HAART
2 Protocol violation
47 Untreated 55 Transient HAART
102 In analysis
51 Primo-SHM Trial
51 Primo-SHM Cohort
Baseline and epidemiological data
Untreated early HAART P
N 47 55
Age 38 (36-41) 40 (37-42 0.4
Male 45 (96%) 53 (96%) 0.7
MSM 37 (79%) 46 (84%) 0.5
Caucasian 37 (79%) 52 (95%) 0.2
HIV-1 RNA 5.2 (4.9-5.5) 4.9 (4.6-5.2) 0.1
CD4 cells 516 (446-587) 565 (502-628) 0.3
Wks SC to HAART - 5 (3-7)
Duration of early HAART (wks, range)
- 28 (21-62)
Results (cont’d)
• 47 untreated– 23 started HAART for low CD4 count, 2 for symptomatic
HIV-1 disease
• 55 early HAART + interruption– 10 restarted HAART, all for low CD4 counts
Untreated Transient HAART p
CD4 at (re)start
222 (179-266) 254 (190-319) 0.4
Corrected Time off HAART (weeks)250.00200.00150.00100.0050.000.00
On
e M
inu
s C
um
Su
rviv
al1.0
0.8
0.6
0.4
0.2
0.0
Early HAARTUntreated
group
Time to (re)start HAART
Kaplan Meier plot of the time to (re)start HAART, corrected for the duration of early HAART
p = 0.001
Results corrected KM
• Total time off HAART:
– 126 (95%CI: 104-150) weeks for untreated patients
– 181 (161-201) weeks for treated patients
– p=0.001
The time to (re)start HAART in the Cox' proportional hazards modeladjusted for age and baseline CD4 count.
Corrected Time off HAART (weeks)200.00150.00100.0050.000.00
On
e M
inu
s C
um
Su
rviv
al1.0
0.8
0.6
0.4
0.2
0.0
Early HAARTUntreated
group
Time to (re)start HAART
p < 0.001
Conclusion
• Transient, early HAART during PHI prolongs the total time that patients can remain off HAART
• Other independent predictors:– Age– CD4 count at baseline
• Note: pVL at baseline is not an independent predictor
Discussion
• What is the effect of details of early treatment:– timing– duration
• Is treatment of PHI worth the effort?• Confirmed by randomized trials?
– Primo-SHM– SPARTAC
AcknowledgementsAMC
• Dpt Internal Medicine- Jan Prins- Marlous Grijsen- Joep Lange- Nicollette Hulshof, Marian Nievaard, Bonnie
Slegtenhorst Harold Doevelaar
• Dpt Experimental Immunology- Hanneke Schuitemaker
• Dpt Medical Microbiology- Suzanne Jurriaans, Nicole Back
- Dpt Experimental Virology- Georgios Pollakis
UMC Utrecht• Dpt Immunology
- Frank Miedema
HIV monitoring foundation- Frank de Wolf
- Rosalind Beard
Participating sites• Maastricht UMC• EMC, Rotterdam• HAGA, Den Haag• KGH, Haarlem• Leiden UMC• MC Leeuwarden• MST, Enschede• OLVG, Amsterdam• St. Elizabeth, Tilburg• UMC Nijmegen
All study participants