Initiation of Antiretroviral Therapy in Early Asymptomatic HIV

Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection The INSIGHT START Study Group Ben Andres Oct 15, 2015

Background • ART reduces morbidity and mortality in HIV infected individuals • There is clear data to show morbidity and mortality reduction in pts with CD 4 count <350, even stronger when CD 4 count <200

Background • The benefits of early initiation of ART are less clear in pts with CD 4 count of > 350 - most studies have focused on AIDS associated complications/mortality • The risks of these are less in those with higher CD 4 counts – however non AIDS related complications of untreated HIV infection as well as increased transmission should also be considered

Research question • Do the benefits outweigh the risks in starting ART in pts with CD 4 count > 500 vs deferring until CD 4 count declined to < 350?

Study design • Multi-center randomized controlled trial • Subjects randomized to either immediate initiation of ART or deferred initiation of ART – Deferred initiation started ART when CD 4 count declined to <350 or when another event occurred otherwise requiring initiation of ART (such as pregnancy) • Primary end point was a composite of any serious AIDS-related event plus any serious non-AIDS-related event • Secondary end points: above plus unscheduled hospitalizations and “grade 4 events” ART regimens used:

Study Subjects HIV+ pts > 18 yo in “generally good health” No hx of AIDS Not pregnant or breast-feeding No prior ART therapy CD 4+ counts > 500 twice at least two weeks apart within 60 d of enrollment • total of 4685 pts enrolled from 4/2009 to 12/2013 at 215 sites in 35 countries • • • – Median age 36, 27% female, median cd 4 count 651 – Mean follow up time of 3 years - 212 pts with unknown primary end point (lost to f/u for >10 mos)

Results • At the conclusion of the trial, 98% of pts in immediate initiation group and 48% in the deferred group had started on ART • Median CD 4 count at the time of initiation in the deferred group was 408

Conclusions • Results showed that there is a consistent benefit to initiating ART regardless of CD 4 count • The primary end point occurred in 42 patients in the immediate-initiation group (1. 8%) and 96 patients in the deferred group (4. 1%), HR of 0. 43, 95% CI 0. 30. 62, P<0. 001 • In 5/2015, study terminated on basis of interim analysis and pts in the deferred group offered ART • Main limitation is length of f/u – 3 yrs for pts who will presumably need to be on ART indefinitely