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Mortality After Cryptococcal Infection in the Modern Antiretroviral Therapy Era.

ABSTRACT: BACKGROUND:The prevalence of cryptococcosis in people living with HIV (PLWH) in the developed world has decreased considerably in the modern antiretroviral therapy (ART) era. Although early mortality of PLWH with opportunistic infections is well understood, overall mortality has not been previously evaluated. METHODS:We conducted a retrospective cohort study of cryptococcosis in PLWH from January 1, 2002, to July 1, 2017. Data were also evaluated before and after 2008 to evaluate the possible effect of modern ART on outcomes. Death date was obtained from the hospital's medical informatics database and the Social Security Death Index. Participants were grouped as survivors, early-mortality (death <90 days), and late-mortality (death ?90 days) individuals. RESULTS:We reviewed 105 PLWH with cryptococcosis, with 55 survivors (52.4%), 17 early-mortality (16.2%), and 33 late-mortality individuals (31.4%). Overall, mortality was 47.6% (n = 50) with a median follow-up of 3.7 years (interquartile range 1.1, 8.1 years). Late-mortality individuals were less likely to be virally suppressed at the last observation compared with survivors (24% vs 62%, P < 0.001). Individuals diagnosed in the modern ART era had significantly lower mortality (hazard ratio 0.5, confidence interval: 0.2 to 0.8) and were more likely to be virally suppressed at the last observation (57% vs 29%, P = 0.003). Individuals with government-provided insurance had a higher mortality compared to those with private insurance (hazard ratio 2.8, confidence interval: 1.1 to 7.2, P = 0.013). CONCLUSIONS:Despite improvements in ART, PLWH have high mortality after cryptococcal infection that persists beyond their initial hospitalization. Lower mortality was associated with increased HIV viral suppression and private insurance in the modern ART era.

SUBMITTER: Hevey MA

PROVIDER: S-EPMC6693647 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Mortality After Cryptococcal Infection in the Modern Antiretroviral Therapy Era.

Hevey Matthew A MA Presti Rachel M RM OʼHalloran Jane A JA Larson Lindsey L Raval Krunal K Powderly William G WG Spec Andrej A

Journal of acquired immune deficiency syndromes (1999) 20190901 1

<h4>Background</h4>The prevalence of cryptococcosis in people living with HIV (PLWH) in the developed world has decreased considerably in the modern antiretroviral therapy (ART) era. Although early mortality of PLWH with opportunistic infections is well understood, overall mortality has not been previously evaluated.<h4>Methods</h4>We conducted a retrospective cohort study of cryptococcosis in PLWH from January 1, 2002, to July 1, 2017. Data were also evaluated before and after 2008 to evaluate ...[more]

PMID: 31408451

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Project description:ObjectivesTo 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.DesignRetrospective 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).MethodsProportional 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.ResultsExcluding 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).ConclusionRelative 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.

Project description:BACKGROUND:Cryptococcal meningitis accounts for 20 to 25% of acquired immunodeficiency syndrome-related deaths in Africa. Antiretroviral therapy (ART) is essential for survival; however, the question of when ART should be initiated after diagnosis of cryptococcal meningitis remains unanswered. METHODS:We assessed survival at 26 weeks among 177 human immunodeficiency virus-infected adults in Uganda and South Africa who had cryptococcal meningitis and had not previously received ART. We randomly assigned study participants to undergo either earlier ART initiation (1 to 2 weeks after diagnosis) or deferred ART initiation (5 weeks after diagnosis). Participants received amphotericin B (0.7 to 1.0 mg per kilogram of body weight per day) and fluconazole (800 mg per day) for 14 days, followed by consolidation therapy with fluconazole. RESULTS:The 26-week mortality with earlier ART initiation was significantly higher than with deferred ART initiation (45% [40 of 88 patients] vs. 30% [27 of 89 patients]; hazard ratio for death, 1.73; 95% confidence interval [CI], 1.06 to 2.82; P=0.03). The excess deaths associated with earlier ART initiation occurred 2 to 5 weeks after diagnosis (P=0.007 for the comparison between groups); mortality was similar in the two groups thereafter. Among patients with few white cells in their cerebrospinal fluid (<5 per cubic millimeter) at randomization, mortality was particularly elevated with earlier ART as compared with deferred ART (hazard ratio, 3.87; 95% CI, 1.41 to 10.58; P=0.008). The incidence of recognized cryptococcal immune reconstitution inflammatory syndrome did not differ significantly between the earlier-ART group and the deferred-ART group (20% and 13%, respectively; P=0.32). All other clinical, immunologic, virologic, and microbiologic outcomes, as well as adverse events, were similar between the groups. CONCLUSIONS:Deferring ART for 5 weeks after the diagnosis of cryptococcal meningitis was associated with significantly improved survival, as compared with initiating ART at 1 to 2 weeks, especially among patients with a paucity of white cells in cerebrospinal fluid. (Funded by the National Institute of Allergy and Infectious Diseases and others; COAT ClinicalTrials.gov number, NCT01075152.).

Dataset Information

Mortality After Cryptococcal Infection in the Modern Antiretroviral Therapy Era.

Publications

Mortality After Cryptococcal Infection in the Modern Antiretroviral Therapy Era.

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