Does optimal timing of HAART initiation differ with newer treatment regimens that include efavirenz or ritonavir-boosted protease Inhibitors?
Background: Observational studies with early-generation (unboosted protease inhibitor) regimens demonstrated that HAART should be initiated before CD4<200. Newer regimens utilizing efavirenz (EFV) or ritonavir-boosted protease inhibitors (bPI) are more effective and easier to administer, which could influence HAART initiation.
Methods: Observational cohort study at the Johns Hopkins HIV Clinic and Comprehensive Care Center (Nashville) from June 1998-April 2005. Inclusion criteria: in care >90 days and >30 days of first HAART regimen that included EFV or bPI. Disease progression = new AIDS-defining event (ADE) or death after starting therapy. X2 and ranksum tests compared categorical and continuous variables; Cox proportional hazards models assessed time to event. Durable virologic suppression (marker of adherence) =more undetectable (<400 c/ml) than detectable HIV-1 RNA measurements.
Results: 942 persons (658 EFV, 284 bPI) met inclusion criteria: 27% female, 61% black, 28% injection drug user (IDU);median age=40 years. Persons receiving EFV had higher median baseline CD4(166 vs. 128;P=0.01), lower median HIV-1 RNA (50,100 vs. 72,391 c/ml;P=0.01), longer median treatment duration (78 vs. 48 weeks;P<0.001) and longer median follow-up (102 vs. 54 weeks;P<0.001). There were 205 events: 116 deaths, 89 ADE. In a Cox model adjusting for CD4, HIV-1 RNA, treatment duration, virologic suppression, IDU, and study site, there was no difference in disease progression by treatment regimen (HR=0.75;P=0.12). There was no interaction between CD4 and regimen, so the 2 treatment groups were combined. In a Cox model with the same variables as above, compared to CD4>350, CD4<200 (HR=2.4;P=0.002) but not 200-349(HR=1.4;P=0.33) was associated with an increased risk of disease progression. CD4%<13 independently predicted disease progression, particularly if CD4 >350(HR=6.7;P=0.03).
Conclusions: This is the first assessment of HAART initiation using only newer regimens. Similar to early-generation HAART, disease progression is increased when CD4<200. HAART should be started when CD4>200; persons with CD4>350 and low CD4% may particularly benefit from HAART.
AIDS 2006 - XVI International AIDS Conference
"T.Sterling, et al.
Does optimal timing of HAART initiation differ with newer treatment regimens that include efavirenz or ritonavir-boosted protease Inhibitors?.
AIDS 2006 - XVI International AIDS Conference: