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