1. 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

2. Introduction Is temporary HAART during PHI beneficial? To the individual: –lower plasma viral load set-point? –longer time off HAART?

3. Yes: –Girard, AIDS 2001 –Hecht, JID 2006 –Fidler, AIDS 2007 –Steingrover, CROI 2007 No: –Markowitz, JID 2002 –Fidler, AIDS 2002 –Desquilbet, AIDS 2004 –Streeck, JID 2006 Lower viral set-point in cohort studies?

4. 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

5. Introduction Is temporary HAART during PHI beneficial? To the individual: –lower plasma HIV viral load? –longer time off HAART?

6. Introduction Is temporary HAART during PHI beneficial? To the individual: –lower plasma HIV viral load? –longer time off HAART? Objective of current analysis

7. 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

8. 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

9. 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

10. 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

11. Correction of KM analysis

14. Results 141 Patients identified at Feb 1 st 2008 102 in the analysis

15. Flow of patients

16. Baseline and epidemiological data Untreatedearly HAARTP N4755 Age38 (36-41)40 (37-420.4 Male45 (96%)53 (96%)0.7 MSM37 (79%)46 (84%)0.5 Caucasian37 (79%)52 (95%)0.2 HIV-1 RNA5.2 (4.9-5.5)4.9 (4.6-5.2)0.1 CD4 cells516 (446-587)565 (502-628)0.3 Wks SC to HAART-5 (3-7) Duration of early HAART (wks, range) -28 (21-62)

17. Results (contd) 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 UntreatedTransient HAARTp CD4 at (re)start 222 (179-266)254 (190-319)0.4

19. Kaplan Meier plot of the time to (re)start HAART, corrected for the duration of early HAART p = 0.001

20. 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

22. The time to (re)start HAART in the Cox' proportional hazards model adjusted for age and baseline CD4 count. p < 0.001

23. 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

24. 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

25. Acknowledgements AMC 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