TY - JOUR

T1 - Early Antiretroviral Therapy Not Associated With Higher Cryptococcal Meningitis Mortality in People With Human Immunodeficiency Virus in High-Income Countries

T2 - An International Collaborative Cohort Study

AU - Ingle, Suzanne M.

AU - Miro, Jose M.

AU - May, Margaret T.

AU - Cain, Lauren E.

AU - Schwimmer, Christine

AU - Zangerle, Robert

AU - Sambatakou, Helen

AU - Cazanave, Charles

AU - Reiss, Peter

AU - Brandes, Vanessa

AU - Bucher, Heiner C.

AU - Sabin, Caroline

AU - Vidal, Francesc

AU - Obel, Niels

AU - Mocroft, Amanda

AU - Wittkop, Linda

AU - Monforte, Antonella D.Arminio

AU - Torti, Carlo

AU - Mussini, Cristina

AU - Furrer, Hansjakob

AU - Konopnicki, Deborah

AU - Teira, Ramon

AU - Saag, Michael S.

AU - Crane, Heidi M.

AU - Moore, Richard D.

AU - Jacobson, Jeffrey M.

AU - Mathews, W. Chris

AU - Geng, Elvin

AU - Eron, Joseph J.

AU - Althoff, Keri N.

AU - Kroch, Abigail

AU - Lang, Raynell

AU - Gill, M. John

AU - Sterne, Jonathan A.C.

AU - ART-CC, COHERE in EuroCoord, CNICS, and NA-ACCORD

N1 - Publisher Copyright: © 2023 The Author(s).

PY - 2023

Y1 - 2023

N2 - Background: Randomized controlled trials (RCTs) from low- and middle-income settings suggested that early initiation of antiretroviral therapy (ART) leads to higher mortality rates among people with HIV (PWH) who present with cryptococcal meningitis (CM). There is limited information about the impact of ART timing on mortality rates in similar people in high-income settings. Methods: Data on ART-naive PWH with CM diagnosed from 1994 to 2012 from Europe/North America were pooled from the COHERE, NA-ACCORD, and CNICS HIV cohort collaborations. Follow-up was considered to span from the date of CM diagnosis to earliest of the following: death, last follow-up, or 6 months. We used marginal structural models to mimic an 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. Results: 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. Conclusions: We found little evidence that early ART was associated with higher mortality rates among PWH presenting with CM in high-income settings, although confidence intervals were wide.

AB - Background: Randomized controlled trials (RCTs) from low- and middle-income settings suggested that early initiation of antiretroviral therapy (ART) leads to higher mortality rates among people with HIV (PWH) who present with cryptococcal meningitis (CM). There is limited information about the impact of ART timing on mortality rates in similar people in high-income settings. Methods: Data on ART-naive PWH with CM diagnosed from 1994 to 2012 from Europe/North America were pooled from the COHERE, NA-ACCORD, and CNICS HIV cohort collaborations. Follow-up was considered to span from the date of CM diagnosis to earliest of the following: death, last follow-up, or 6 months. We used marginal structural models to mimic an 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. Results: 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. Conclusions: We found little evidence that early ART was associated with higher mortality rates among PWH presenting with CM in high-income settings, although confidence intervals were wide.

KW - ART

KW - causal inference

KW - cryptococcal meningitis

KW - HIV

U2 - 10.1093/cid/ciad122

DO - 10.1093/cid/ciad122

M3 - Journal article

C2 - 36883578

AN - SCOPUS:85164240108

VL - 77

SP - 64

EP - 73

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

SN - 1058-4838

IS - 1

ER -