Does Optimal Timing of HAART Initiation Differ with Newer Treatment Regimens That Include Efavirenz or Ritonavir-boosted Protease Inhibitors?

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.

This was an 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.

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 but not 200-349 was associated with an increased risk of disease progression.

Based on these results, the authors conclude, "CD4% <13 independently predicted disease progression, particularly if CD4 >350.

"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."

Vanderbilt University, Infectious Diseases, Nashville, United States, Comprehensive Care Center, Nashville, United States, Johns Hopkins University, Medicine, Baltimore, United States.

08/18/06

Reference
T Sterling, G Barkanic, S Raffanti, and others. Does optimal timing of HAART initiation differ with newer treatment regimens that include efavirenz or ritonavir-boosted protease Inhibitors? 16th International AIDS Conference. August 13-18, 2006, Toronto, Canada. Abstract TUPE0205.