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Benefits of enhanced infection prophylaxis at antiretroviral therapy initiation by cryptococcal antigen status

Title: Benefits of enhanced infection prophylaxis at antiretroviral therapy initiation by cryptococcal antigen status
Authors: Petta, Sarah L; Spyerb, Moira; Haddowa, Lewis J; Nhema, Ruth; Benjamine, Laura A; Najjukag, Grace; Bilima, Sithembile; Daudi, Ibrahim; Musorod, Godfrey; Kitabalwag, Juliet; Selemani, George; Kandiei, Salome; Corneliusi, K Magut; Katemba, Chrispus; Berkley, Jay A; Hassan, Amin S; Kityog, Cissy; Hakim, James; Heyderman, Robert S; Gibbb, Diana M; Walker, Ann S
Publisher Information: Wolter Klower
Publication Year: 2020
Collection: Moi University Repository
Subject Terms: Cryptococcus; HIV; Late presentation; Prophylaxis
Description: 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 CD4þ cell count less than 100 cells/ml starting antiretrovi ral therapy who were randomized to receive 12-week enhanced-prophylaxis (flucona zole 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 ¼ 0.36 (95% confidence interval 0.13–0.98), incidence 19.5 vs. 56.5/100 person-years] and CrAg-negatives [hazard ratio ¼ 0.33 (0.03–3.14), incidence 0.3 vs. 0.9/100 person-years; Pheterogeneity¼ 0.95]; nor for all deaths, cryptococcal deaths or unknown deaths.
Document Type: article in journal/newspaper
File Description: application/pdf
Language: English
Relation: http://ir.mu.ac.ke:8080/jspui/handle/123456789/6258
Availability: http://ir.mu.ac.ke:8080/jspui/handle/123456789/6258
Accession Number: edsbas.E588BBA1
Database: BASE