Early antiretroviral therapy not associated with higher cryptococcal meningitis mortality in people with HIV in high-income countries: an international collaborative cohort study. Clinical Infectious Disease
Ingle et al. aimed to investigate the impact of antiretroviral therapy (ART) timing on mortality rates associated with cryptococcal meningitis (CM) among people in high-income settings.
The authors used data from ART-naive people with HIV (PWH) with CM diagnosed from 1994 to 2012 from Europe/North America pooled from the COHERE, NA-ACCORD, and CNICS HIV cohort collaborations. The used marginal structural models to mimic a randomize controlled trial (RCT) comparing the effects of early (within 14 days of CM) and late (14–56 days after CM) ART on all-cause mortality, adjusting for potential confounders.
Of 190 participants identified, 33 (17%) died within 6 months. At CM diagnosis, their median age (interquartile range) was 38 (33–44) years; the median CD4+ T-cell count, 19/μL (10–56/μL); and median HIV viral load, 5.3 (4.9–5.6) log10 copies/mL. Most participants (n = 157 [83%]) were male, and 145 (76%) started ART. Mimicking an RCT, with 190 people in each group, there were 13 deaths among participants with an early ART regimen and 20 deaths among those with a late ART regimen. The crude and adjusted hazard ratios comparing late with early ART were 1.28 (95% confidence interval, .64–2.56) and 1.40 (.66–2.95), respectively.
In conclusion, the study found little evidence that early ART after CM was associated with higher mortality rates than late ART in ART-naive PWH living in high-income settings. Importantly, the present study used a selected sample of the total population, only representative of PWH in care in high-income settings, whereas current guidelines are based on low-income settings.