Benefits of enhanced infection prophylaxis at antiretroviral therapy initiation by cryptococcal antigen status
Autor: | K Magut Cornelius, Moira J. Spyer, Robert S. Heyderman, James Hakim, Laura A Benjamin, Cissy Kityo, Amin S. Hassan, Ruth Nhema, Juliet Kitabalwa, Godfrey Musoro, Reality trial team, George Selemani, Chrispus Katemba, Diana M. Gibb, Sarah Pett, Grace Najjuka, Lewis J. Haddow, Sithembile Bilima, AS Walker, J A Berkley, Ibrahim I. Daud, Salome Kandie |
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Rok vydání: | 2020 |
Předmět: |
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 |
Zdroj: | AIDS |
ISSN: | 1473-5571 0269-9370 |
Popis: | 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. |
Databáze: | OpenAIRE |
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