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



Pett, Sarah L, Spyer, Moira, Haddow, Lewis J, Nhema, Ruth, Benjamin, Laura A ORCID: 0000-0002-9685-1664, Najjuka, Grace, Bilima, Sithembile, Daud, Ibrahim, Musoro, Godfrey, Kitabalwa, Juliet
et al (show 11 more authors) (2021) Benefits of enhanced infection prophylaxis at antiretroviral therapy initiation by cryptococcal antigen status. AIDS, 35 (4). pp. 585-594.

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Abstract

<h4>Objectives</h4>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.<h4>Design</h4>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).<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusion</h4>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.

Item Type: Article
Uncontrolled Keywords: Africa, cryptococcus, HIV, late presentation, prophylaxis
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences
Depositing User: Symplectic Admin
Date Deposited: 14 May 2021 15:31
Last Modified: 18 Jan 2023 22:47
DOI: 10.1097/QAD.0000000000002781
Open Access URL: https://discovery.ucl.ac.uk/id/eprint/10096689/
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3122731