Factors affecting mortality among HIV positive patients two years after completing recommended therapy for Cryptococcal meningitis in Uganda

Abstract

BackgroundCryptococcal meningitis (CCM) remains a leading cause of mortality amongst HIV infected patients in sub-Saharan Africa. When patients receive recommended therapy, mortality at 10 weeks has been reported to vary between 20 to 36%. However, mortality rate and factors affecting mortality after completing recommended therapy are not well known. We investigated mortality rate, and factors affecting mortality at 2 years among CCM patients following completion of recommended CCM therapy in Uganda.MethodsA retrospective cohort study was conducted among HIV infected patients that had completed 10 weeks of recommended therapy for CCM (2 weeks of intravenous amphotericin B 1mg/kg and 10 weeks of oral Fluconazole 800mg daily) in the CryptoDex trial (ISRCTN59144167) between 2013 and 2015. Survival analysis applying Cox regression was used to determine the mortality rate and factors affecting mortality at 2 years.ResultsThis study followed up 112 participants for 2 years. Mean age (±SD) was 34.9 ± 8, 48 (57.1%) were female and 80 (74.8%) had been on ART for less than 1 year. At 2 years, overall mortality was 30.9% (20 deaths per 100 person-years). Majority of deaths (61.8%) occurred during the first 6 months. In multivariable analysis, mortality was associated with ever being re-admitted since discharge after hospital-based management of CCM (aHR = 13.33, 95% CI: 5.92–30.03), p<0.001; and self-perceived quality of life, with quality of life 50–75% having reduced risk compared to <50% (aHR = 0.21, 95% CI: 0.09–0.5), p<0.001, as well as >75% compared to <50% (HR = 0.29, 95% CI: 0.11–0.81), p = 0.018.ConclusionThere remains a considerable risk of mortality in the first two years after completion of standard therapy for CCM in resource-limited settings with risk highest during the first 6 months. Maintenance of patient follow up during this period may reduce mortality.

Determinants of loss to follow-up among HIV positive patients receiving antiretroviral therapy in a test and treat setting: A retrospective cohort study in Masaka, Uganda

“…Similarly, our median (IQR) baseline CD4 cell count was high (327 (180-485)) compared to the best group in the study by Mberi et al of 87 [26]. Besides, patients with low CD4 cell counts are likely to be in WHO stage 3 or 4, a group prone to opportunistic infections and an elevated risk of mortality [36,37]. It is therefore possible that patients with lower CD4 cell counts in our study were bed ridden or died shortly after initiation of ART and were never reported to the HIV clinic.…”

“…This is likely to make their continued engagement with the HIV clinic difficult. Such patients also have an increased risk of death especially in the first 6 months of ART due to severe immune reconstitution inflammatory syndrome and Cryptococcal meningitis [36,37]. It is therefore possible that they died shortly after starting ART and never reported to the ART clinic again.…”

The Burden of Fungal Infections in Ethiopia

“…CM is among the leading causes of mortality among adult HIV/AIDS patients in sub-Saharan Africa [42,43]. Early screening with cryptococcal antigen (CrAg) among the target population or advanced HIV-infected patients and giving pre-emptive treatment can prevent the development of CM and associated mortality.…”

Starting antiretroviral therapy within seven days of a positive HIV test increased the risk of loss to follow up in a primary healthcare clinic: a retrospective cohort study in Masaka, Uganda

“…This might make their continued engagement with the HIV clinic hard. Such patients are further at an increased risk of death especially in the first 6 months of ART due to severe immune reconstitution inflammatory syndrome and Cryptococcal meningitis [34,35]. It is therefore possible that they could have died shortly after starting ART and were never reported to the ART clinic.…”