Benefits of enhanced infection prophylaxis at antiretroviral therapy initiation by cryptococcal antigen status
<p><strong>Objectives:</strong> 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.</p> <p>&l...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Wolters Kluwer Health
2020
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| _version_ | 1797078874747568128 |
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| author | Pett, SL Spyer, M Haddow, L Nhema, R Benjamin, L Najjuka, G Bilima, S Daud, I Musoro, G Kitabalwa, J Selemani, G Kandie, S Cornelius, KM Katemba, C Berkley, J Hassan, A Kityo, C Hakim, J Heyderman, R Gibb, DM Walker, AS |
| author_facet | Pett, SL Spyer, M Haddow, L Nhema, R Benjamin, L Najjuka, G Bilima, S Daud, I Musoro, G Kitabalwa, J Selemani, G Kandie, S Cornelius, KM Katemba, C Berkley, J Hassan, A Kityo, C Hakim, J Heyderman, R Gibb, DM Walker, AS |
| author_sort | Pett, SL |
| collection | OXFORD |
| description | <p><strong>Objectives:</strong> 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.</p>
<p><strong>Design:</strong> 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).</p>
<p><strong>Methods:</strong> 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.</p>
<p><strong>Results:</strong> 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).</p>
<p><strong>Conclusions:</strong> 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.</p> |
| first_indexed | 2024-03-07T00:37:47Z |
| format | Journal article |
| id | oxford-uuid:82020064-af62-444b-a66e-146a7b7e4cb9 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:37:47Z |
| publishDate | 2020 |
| publisher | Wolters Kluwer Health |
| record_format | dspace |
| spelling | oxford-uuid:82020064-af62-444b-a66e-146a7b7e4cb92022-03-26T21:34:26ZBenefits of enhanced infection prophylaxis at antiretroviral therapy initiation by cryptococcal antigen statusJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:82020064-af62-444b-a66e-146a7b7e4cb9EnglishSymplectic ElementsWolters Kluwer Health2020Pett, SLSpyer, MHaddow, LNhema, RBenjamin, LNajjuka, GBilima, SDaud, IMusoro, GKitabalwa, JSelemani, GKandie, SCornelius, KMKatemba, CBerkley, JHassan, AKityo, CHakim, JHeyderman, RGibb, DMWalker, AS<p><strong>Objectives:</strong> 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.</p> <p><strong>Design:</strong> 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).</p> <p><strong>Methods:</strong> 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.</p> <p><strong>Results:</strong> 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).</p> <p><strong>Conclusions:</strong> 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.</p> |
| spellingShingle | Pett, SL Spyer, M Haddow, L Nhema, R Benjamin, L Najjuka, G Bilima, S Daud, I Musoro, G Kitabalwa, J Selemani, G Kandie, S Cornelius, KM Katemba, C Berkley, J Hassan, A Kityo, C Hakim, J Heyderman, R Gibb, DM Walker, AS 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 |
| title_full | Benefits of enhanced infection prophylaxis at antiretroviral therapy initiation by cryptococcal antigen status |
| title_fullStr | Benefits of enhanced infection prophylaxis at antiretroviral therapy initiation by cryptococcal antigen status |
| title_full_unstemmed | Benefits of enhanced infection prophylaxis at antiretroviral therapy initiation by cryptococcal antigen status |
| title_short | Benefits of enhanced infection prophylaxis at antiretroviral therapy initiation by cryptococcal antigen status |
| title_sort | benefits of enhanced infection prophylaxis at antiretroviral therapy initiation by cryptococcal antigen status |
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