Initiation of AntiretroviralTherapy in Early AsymptomaticHIV InfectionThe INSIGHT START Study Group
Ben Andres
Oct 15, 2015
Background
• ART reduces morbidity and mortality in HIVinfected individuals
•There is clear data to show morbidity andmortality reduction in pts with CD4 count<350, even stronger when CD4 count <200
Background
•The benefits of early initiation of ART are lessclear in pts with CD4 count of > 350 - moststudies have focused on AIDS associatedcomplications/mortality
•The risks of these are less in those with higherCD4 counts – however non AIDS relatedcomplications of untreated HIV infection aswell as increased transmission should also beconsidered
Research question
•Do the benefits outweigh the risks in startingART in pts with CD4 count > 500 vs deferringuntil CD4 count declined to < 350?
Study design
•Multi-center randomized controlled trial
•Subjects randomized to either immediate initiation of ART or deferredinitiation of ART
–Deferred initiation started ART when CD4 count declined to <350 or when another eventoccurred otherwise requiring initiation of ART (such as pregnancy)
•Primary end point was a composite of any serious AIDS-related event plusany serious non-AIDS-related event
•Secondary end points: above plus unscheduled hospitalizations and“grade 4 events”
ART regimens used:
Study Subjects
•HIV+ pts > 18yo in “generally good health”
•No hx of AIDS
•Not pregnant or breast-feeding
•No prior ART therapy
•CD4+ counts > 500 twice at least two weeks apartwithin 60d of enrollment
•total of 4685 pts enrolled from 4/2009 to 12/2013 at215 sites in 35 countries
–Median age 36, 27% female, median cd4 count 651
–Mean follow up time of 3 years - 212 pts with unknownprimary end point (lost to f/u for >10 mos)
Results
•At the conclusion of the trial, 98% of pts inimmediate initiation group and 48% in thedeferred group had started on ART
•Median CD4 count at the time of initiation inthe deferred group was 408
Conclusions
•Results showed that there is a consistent benefit toinitiating ART regardless of CD4 count
•The primary end point occurred in 42 patients in theimmediate-initiation group (1.8%) and 96 patients inthe deferred group (4.1%), HR of 0.43, 95% CI 0.3-0.62, P<0.001
•In 5/2015, study terminated on basis of interimanalysis and pts in the deferred group offered ART
•Main limitation is length of f/u – 3 yrs for pts whowill presumably need to be on ART indefinitely