Back to Search
Start Over
Benefits of enhanced infection prophylaxis at antiretroviral therapy initiation by cryptococcal antigen status
- Source :
- AIDS
- Publication Year :
- 2020
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2020.
-
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 100 mg/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-ratio = 0.36 (95% confidence interval 0.13–0.98), incidence 19.5 vs. 56.5/100 person-years] and CrAg-negatives [hazard-ratio = 0.33 (0.03–3.14), incidence 0.3 vs. 0.9/100 person-years; Pheterogeneity = 0.95]; nor for all deaths, cryptococcal deaths or unknown deaths (Pheterogeneity > 0.3). Conclusions: 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 100 mg fluconazole in an enhanced-prophylaxis package at antiretroviral therapy initiation where CrAg screening is unavailable/impractical.
- Subjects :
- Adult
0301 basic medicine
medicine.medical_specialty
Antifungal Agents
Antigens, Fungal
Immunology
HIV Infections
Meningitis, Cryptococcal
Azithromycin
Article
law.invention
03 medical and health sciences
0302 clinical medicine
Randomized controlled trial
law
Internal medicine
medicine
Humans
Immunology and Allergy
030212 general & internal medicine
Child
Retrospective Studies
AIDS-Related Opportunistic Infections
Proportional hazards model
business.industry
Incidence (epidemiology)
Retrospective cohort study
medicine.disease
Confidence interval
CD4 Lymphocyte Count
030104 developmental biology
Infectious Diseases
business
Meningitis
Fluconazole
medicine.drug
Subjects
Details
- ISSN :
- 14735571 and 02699370
- Volume :
- 35
- Database :
- OpenAIRE
- Journal :
- AIDS
- Accession number :
- edsair.doi.dedup.....1e09006a75805852479e35a20b2d6f06