START Study Outcomes: Early ART Initiation
The START study demonstrated decreased risk of both AIDS-related events AND serious non-AIDS-related events with early ART initiation, making none of the provided options fully accurate, though option A comes closest by correctly identifying decreased AIDS-related events.
Primary Findings from START
The Strategic Timing of Antiretroviral Treatment (START) trial enrolled 4,684 ART-naive HIV-positive adults with CD4+ counts >500 cells/mm³ and compared immediate versus deferred treatment (initiated when CD4 dropped to <350 cells/mm³) 1.
Key Outcomes Demonstrated:
Early ART initiation reduced the composite primary endpoint of AIDS, serious non-AIDS events, or death by 57% (HR 0.47,95% CI 0.34-0.65; P<0.001) through 2015 1
Both AIDS-related AND serious non-AIDS-related events were reduced with immediate treatment, contradicting the premise of options A and B that suggest only one category benefited 1
Mortality reduction was significant: The study showed decreased overall mortality with early treatment, supporting benefits regardless of CD4 count 1
Long-term follow-up through 2021 revealed persistent excess risk among those who deferred treatment, even after eventually initiating ART (HR 0.79,95% CI 0.60-1.04 post-2016 versus HR 0.47 pre-2016) 1
Why Each Answer Option is Problematic:
Option A - Partially Correct but Incomplete
- Correctly identifies decreased AIDS-related events 1
- Incorrectly states increased non-AIDS-related events - START actually showed decreased serious non-AIDS events with early treatment 1
Option B - Incorrect
- Contradicts START findings - the study demonstrated reduced AIDS-related events, not similar risk 1
- Non-AIDS event reduction was present but not the distinguishing feature 1
Option C - Not the Primary Outcome
- While HIV transmission reduction was demonstrated in HPTN 052 (HR 0.11,95% CI 0.04-0.32) 2, this was not START's primary focus
- Treatment-related side effects were not reduced; this was not a measured outcome 1
Option D - Most Accurate Available
- Mortality reduction was demonstrated across CD4 strata in pooled analyses (RR 0.90,95% CI 0.82-0.99) 3
- Chinese cohort data confirmed 63% mortality reduction with immediate ART even at CD4 >500 cells/mm³ (adjusted HR 0.37,95% CI 0.23-0.58) 4
- START specifically enrolled patients with CD4 >500 cells/mm³, demonstrating benefit regardless of baseline CD4 count 1
Clinical Implications from START:
Current guidelines now recommend immediate ART initiation for all HIV-positive individuals regardless of CD4 count, based largely on START findings 5
The benefit of early treatment persists long-term, with those who deferred treatment showing continued excess risk even after eventually starting ART 1
Time-averaged CD4 difference of 199 cells/mm³ was maintained between immediate and deferred groups through 2015, translating to clinical benefit 1