Cryptococcal Meningitis May Be Linked With Higher Mortality in PLWHIV

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Investigators find that immune reconstitution inflammatory syndrome has been implicated as the reason for higher mortality in those who initiate ART early.
Investigators find that immune reconstitution inflammatory syndrome has been implicated as the reason for higher mortality in those who initiate ART early.

Antiretroviral therapy (ART) initiation in individuals who are positive for HIV infection, and are within 4 weeks of a cryptococcal meningitis diagnosis appears to be associated with a higher mortality risk, according to the results of a new Cochrane Review.

The optimum timing of ART initiation in people with HIV and cryptococcal meningitis is unclear, primarily because of conflicting data on the mortality risk and occurrence of immune reconstitution inflammatory syndrome. In this review, the study authors evaluated outcomes of early ART initiation compared with delayed initiation of ART in individuals with HIV and concurrent cryptococcal meningitis. A total of 4 trials with a cohort of 294 participants were identified, comprised primarily of patients from low- and middle-income countries. Two trials used amphotericin B and fluconazole to treat the infection, one used fluconazole monotherapy, and one did not specify the treatment.

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Results suggested that early ART initiation may increase all-cause mortality vs delayed initiation (relative risk [RR] 1.42; 95% CI, 1.02-1.97; 294 participants, 4 trials; low-certainty evidence), but early ART initiation may reduce the occurrence of relapse of cryptococcal meningitis vs delayed treatment (RR .27; 95% CI, .07-1.04; 205 participants, 2 trials, low-certainty evidence). There was uncertainty whether early ART therapy increased or decreased cryptococcal immune reconstitution inflammatory syndrome events vs delayed treatment (RR 3.56; 95% CI, .51-25.02; 205 participants, 2 trials; I2 = 54%; very low-certainty evidence).

The study authors concluded that there appears to be a higher mortality risk with earlier ART initiation, but that “it is unclear if this higher mortality risk is related to cryptococcal meningitis-[immune reconstitution inflammatory syndrome].”

Reference

Eshun-Wilson I, Okwen MP, Richardson M, Bicanic T. Early versus delayed antiretroviral treatment in HIV-positive people with cryptococcal meningitis. Cochrane Database Syst Rev. 2018;7:CD009012

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