Benefits of enhanced infection prophylaxis at antiretroviral therapy initiation by cryptococcal antigen status.
AIDS
; 35(4): 585-594, 2021 03 15.
Article
en En
| MEDLINE
| ID: mdl-33306556
ABSTRACT
OBJECTIVES:
To assess baseline prevalence of cryptococcal antigen (CrAg) positivity; and its contribution to reductions in all-cause mortality, deaths from cryptococcus and unknown causes, and new cryptococcal disease in the REALITY trial.DESIGN:
Retrospective CrAg testing of baseline and week-4 plasma samples in all 1805 African adults/children with CD4+ cell count less than 100 cells/µl starting antiretroviral therapy who were randomized to receive 12-week enhanced-prophylaxis (fluconazole 100âmg/day, azithromycin, isoniazid, cotrimoxazole) vs. standard-prophylaxis (cotrimoxazole).METHODS:
Proportional hazards models were used to estimate the relative impact of enhanced-prophylaxis vs. standard-cotrimoxazole on all, cryptococcal and unknown deaths, and new cryptococcal disease, through 24 weeks, by baseline CrAg positivity.RESULTS:
Excluding 24 (1.4%) participants with active/prior cryptococcal disease at enrolment (all treated for cryptococcal disease), 133/1781 (7.5%) participants were CrAg-positive. By 24 weeks, 105 standard-cotrimoxazole vs. 78 enhanced-prophylaxis participants died. Of nine standard-cotrimoxazole and three enhanced-prophylaxis cryptococcal deaths, seven and two, respectively, were CrAg-positive at baseline. Among deaths of unknown cause, only 1/46 standard-cotrimoxazole and 1/28 enhanced-prophylaxis were CrAg-positive at baseline. There was no evidence that relative reductions in new cryptococcal disease associated with enhanced-prophylaxis varied between baseline CrAg-positives [hazard-ratioâ=â0.36 (95% confidence interval 0.13-0.98), incidence 19.5 vs. 56.5/100 person-years] and CrAg-negatives [hazard-ratioâ=â0.33 (0.03-3.14), incidence 0.3 vs. 0.9/100 person-years; Pheterogeneityâ=â0.95]; nor for all deaths, cryptococcal deaths or unknown deaths (Pheterogeneityâ>â0.3).CONCLUSION:
Relative reductions in cryptococcal disease/death did not depend on CrAg status. Deaths of unknown cause were unlikely to be cryptococcus-related; plausibly azithromycin contributed to their reduction. Findings support including 100âmg fluconazole in an enhanced-prophylaxis package at antiretroviral therapy initiation where CrAg screening is unavailable/impractical.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Infecciones por VIH
/
Meningitis Criptocócica
/
Infecciones Oportunistas Relacionadas con el SIDA
Tipo de estudio:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Adult
/
Child
/
Humans
Idioma:
En
Revista:
AIDS
Asunto de la revista:
SINDROME DA IMUNODEFICIENCIA ADQUIRIDA (AIDS)
Año:
2021
Tipo del documento:
Article