HAART Initiation Within 2 Weeks of Seroconversion Associated With Virologic and Immunologic Benefits Slideset on: Hecht FM, Wang L, Collier A, et al. A multicenter observational study of the potential benefits of initiating combination antiretroviral therapy during acute HIV infection. J Infect Dis. 2006;194:

clinicaloptions.com/hiv HAART Initiation Within 2 Weeks of Seroconversion Associated With Virologic and Immunologic Benefits Hecht FM, et al. J Infect Dis. 2006;194: Background and Rationale  HIV-1 RNA set point after seroconversion predictive of subsequent disease progression –Suggests early events in HIV pathogenesis could influence long-term outcomes  Previous clinical trials suggested possible benefit of HAART when initiated during primary infection, then discontinued  Current study evaluated whether HAART initiation within 2-24 weeks after HIV seroconversion associated with improvements in viral load or CD4+ cell count following treatment discontinuation

clinicaloptions.com/hiv HAART Initiation Within 2 Weeks of Seroconversion Associated With Virologic and Immunologic Benefits Hecht FM, et al. J Infect Dis. 2006;194:  Patient data from AIEDRP cohort (n = 395)  Participants self-selected whether to initiate HAART  Inclusion criteria for current analysis –Treatment commenced within 6 months of negative or indeterminate antibody test –Treatment consisted of ≥ 3 antiretroviral drugs –Treatment maintained for ≥ 12 weeks, stopped for ≥ 4 weeks –Acute treatment group: HAART initiation 0-2 weeks after seroconversion –Early treatment group: HAART initiation 2-24 weeks after seroconversion –Untreated patients –Same study entry criteria except no HAART and monitored for ≥ 6 months  Primary endpoints –HIV-1 RNA level, CD4+ cell counts at 24, 48, 72 weeks of untreated observation Summary of Study Design

clinicaloptions.com/hiv HAART Initiation Within 2 Weeks of Seroconversion Associated With Virologic and Immunologic Benefits Hecht FM, et al. J Infect Dis. 2006;194:  HAART initiation within 2 weeks of seroconversion associated with significant HIV-1 RNA level decreases, CD4+ cell count increases –Benefit continued to Week 72 following treatment discontinuation –Difference vs untreated group significant only in analyses adjusted for baseline HIV-1 RNA and CD4+ cell counts  Compared with no treatment, limited benefit to HAART initiation ≥ 2 weeks after seroconversion Main Findings CI, confidence interval; NS, not significant. *Adjusted for baseline HIV-1 RNA and CD4+ cell counts. Follow-up Time Point Acute Treatment Minus Untreated* P Value Early Treatment Minus Untreated* P Value Week 24, HIV-1 RNA log 10 copies/mL (95% CI) (-1.01 to -0.38)< (-0.68 to -0.35)<.05 Week 48, HIV-1 RNA log 10 copies/mL (95% CI) (-1.02 to -0.16)< (-0.35 to 0.15)NS Week 72, HIV-1 RNA log 10 copies/mL (95% CI) (-1.30 to -0.07)< (-0.27 to 0.47)NS

clinicaloptions.com/hiv HAART Initiation Within 2 Weeks of Seroconversion Associated With Virologic and Immunologic Benefits Hecht FM, et al. J Infect Dis. 2006;194:  Mean CD4+ cell counts (adjusted data) in acute treatment group consistently > 120 cells/mm 3 higher than untreated groups –CD4+ cell count benefit remained significant through Week 72  Mean CD4+ cell count in early treatment group ≥ 100 cells/mm 3 higher than untreated group at 24, 48 weeks only –CD4+ cell count benefit remained significant through Week 72 Patient Outcomes Follow-up Time Point Acute Treatment Minus Untreated* P Value Early Treatment Minus Untreated* P Value Week 24, CD4+ cells/mm 3 (95% CI) 132 (51-213)< (88-163)<.05 Week 48, CD4+ cells/mm 3 (95% CI) 120 (24-217)< (68-169)<.05 Week 72, CD4+ cells/mm 3 (95% CI) 125 (3-247)<.0579 (11-146)<.05 CI, confidence interval; NS, not significant. *Adjusted for baseline HIV-1 RNA and CD4+ cell counts.

clinicaloptions.com/hiv HAART Initiation Within 2 Weeks of Seroconversion Associated With Virologic and Immunologic Benefits Hecht FM, et al. J Infect Dis. 2006;194: Other Outcomes  Adjusted analyses may overstate therapeutic benefit –Differences in unadjusted analyses not significant for viral load and CD4+ cell counts in acute treatment group after Week 24 –Differences in unadjusted analyses not significant for viral load in early treatment group after Week 24  Study limitations: nonrandom treatment assignation, heterogeneous regimens, varied treatment duration, no assessment of reasons for treatment discontinuation, small acute treatment group

clinicaloptions.com/hiv HAART Initiation Within 2 Weeks of Seroconversion Associated With Virologic and Immunologic Benefits Hecht FM, et al. J Infect Dis. 2006;194:  HAART initiation within 2 weeks of seroconversion associated with decreased viral load, increased CD4+ cell count to 72 weeks after treatment discontinuation –Trend toward long-term benefit  HAART initiation ≥ 2 weeks after seroconversion associated with smaller CD4+ cell count benefit, loss of viral load benefit by Week 72 –Magnitude of benefit decreased with time Key Conclusions