| Title: |
Benefits of enhanced infection prophylaxis at antiretroviral therapy initiation by cryptococcal antigen status |
| Authors: |
Pett, Sarah L.; Spyer, Moira; Haddow, Lewis J.; Nhema, Ruth; Benjamin, Laura A.; Najjuka, Grace; Bilima, Sithembile; Daud, Ibrahim; Musoro, Godfrey; Kitabalwa, Juliet; Selemani, George; Kandie, Salome; Cornelius, K. Magut; Katemba, Chrispus; Berkley, Jay A.; Hassan, Amin S.; Kityo, Cissy; Hakim, James; Heyderman, Robert S.; Gibb, Diana M.; Walker, Ann S. |
| Source: |
AIDS ; volume 35, issue 4, page 585-594 ; ISSN 0269-9370 1473-5571 |
| Publisher Information: |
Ovid Technologies (Wolters Kluwer Health) |
| Publication Year: |
2020 |
| 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 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; P heterogeneity = 0.95]; nor for all deaths, cryptococcal deaths or unknown deaths ( P heterogeneity > 0.3). 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 ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1097/qad.0000000000002781 |
| DOI: |
10.1097/QAD.0000000000002781 |
| Availability: |
https://doi.org/10.1097/qad.0000000000002781; https://journals.lww.com/10.1097/QAD.0000000000002781 |
| Accession Number: |
edsbas.662AD11B |
| Database: |
BASE |