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Background: Cryptococcal meningitis (CCM) remains one of the leading causes of mortality among HIV infected patients. Due to factors such as the severity of CCM pathology, the quality of life (QOL) of patients post-treatment is likely to be poor. Few studies have reported on QOL of CCM patients post treatment completion. We used data collected among patients in the CryptoDex trial (ISRCTN59144167) to determine QOL and associated factors at week 10 and six months from treatment initiation. Methodology: CryptoDex was a double-blind placebo-controlled trial of adjunctive dexamethasone in HIV infected adults with CCM, conducted between 2013 and 2015 in six countries in Asia and Africa. QOL was determined using the descriptive and Visual Analog Scales (VAS) of the EuroQol Five-Dimension-Three-Level (EQ-5D-3L) tool. We derived index scores, and described these and the VAS scores at 10 weeks and 6 months; and used linear regression to determine the relationship between various characteristics and VAS scores at both time points. VAS scores were interpreted as very good (81–100), good (51–80), normal (31–50) and bad/very bad (0–30). Results: Of 451 patients enrolled in the trial, 238 had QOL evaluations at week 10. At baseline, their mean age (SD) was 35.2(8.5) years. The mean index scores (SD) were 0.785(0.2) and 0.619(0.4) among African and Asian patients respectively at week 10, and 0.879(0.2) and 0.731(0.4) among African and Asian patients respectively at month six. The overall mean VAS score (SD) at 10 weeks was 57.2 (29.7), increasing significantly to 72(27.4) at month six (p<0.001). At week 10, higher VAS score was associated with greater weight (p = 0.007) and being African (p<0.001), while lower VAS score was associated with positive yeast culture at day 14 (p = 0.026). At month six, higher VAS score remained associated with African origin (p = 0.006) while lower VAS score was associated with positive yeast culture (p = 0.006). Lower VAS scores were associated with higher number of inpatient days at 10 weeks and 6 months (p = 0.003 and 0.002 respectively). Conclusion: QOL was good among patients that had completed therapy for CCM, but below perfect. Strategies to improve QOL among CCM survivors are required. Author summary: In spite of the remarkable reduction in Cryptococcal meningitis (CCM) related morbidity and mortality with increased use of antiretroviral therapy, incidence remains unacceptably high especially in sub-Saharan Africa and Asia where more than 90% of the cases and deaths occur. Due to factors such as the severity of CCM pathology, the quality of life (QOL) of patients post-treatment is also likely to be poor. Few studies have reported on QOL of CCM patients post treatment completion. We used data collected among patients in the CryptoDex trial (ISRCTN59144167) to determine self-perceived QOL and associated factors among 238 survivors at week 10 and 203 survivors at six months from treatment initiation. We determined QOL using the descriptive and Visual Analog Scales (VAS) of the EuroQol Five-Dimension-Three-Level (EQ-5D-3L) tool. We found that while self-perceived QOL was only relatively good among this cohort of patients who had survived through treatment for CCM, it continued to improve over the 6 months following diagnosis. Low weight at diagnosis, prolonged hospital admission, positive yeast culture at day 14/treatment completion, and being Asian were associated with lower QOL. QOL is an important outcome that should be considered among HIV infected patients treated for serious infections such as CCM. [ABSTRACT FROM AUTHOR]

Globally, early initiation of antiretroviral therapy for HIV led to a reduction in the estimated mortality from cryptococcal meningitis (CCM) from 624,700 in 2009 to 181,100 in 2014. However, CCM remains one of the leading causes of mortality among HIV infected patients especially in sub-Saharan Africa where 75% of the deaths occur. Most of the studies evaluating mortality have reported short-term mortality (at or before 10 weeks of therapy). We determined mortality and associated factors among patients treated for CCM in the CryptoDex trial (ISRCTN59144167) in Uganda, and the effect of dexamethasone adjunctive therapy on mortality at two years. We conducted a retrospective cohort study between May 2017 and July 2017 to determine the long term survival (up to 2 years post-randomization) of all patients who had been enrolled into the CryptoDex trial in Uganda. The CryptoDex trial recruited between April 2013 and February 2015. We estimated mortality rates and determined factors affecting mortality at two years using Cox regression. The study followed up 211 participants, 127 (60.2%) of whom were male. Sixteen participants (7.58%) were diagnosed with HIV at the same admission when CCM was diagnosed. By two years following randomization 127 (60%) participants had died, a mortality rate of 67 deaths per 100 person-years. Mortality was associated with Glasgow coma score (GCS) below 15 (adjusted Hazard ratio (aHR) 1.77, 95% CI: 1.02–2.44), p = 0.040; weight (aHR 0.97, per 1 Kg increase; 95% CI: 0.94–0.99), p = 0.003; and presence of convulsions (aHR 2.31, 95% CI: 1.32–4.04), p = 0.004, while dexamethasone use and fungal burden had no effect. Long-term mortality in CCM patients remains high even among patients receiving recommended therapy. Strategies to improve long-term survival in CCM patients are urgently needed, especially targeting those with reduced GCS, low weight, and convulsions. Author summary: With early initiation of ART among HIV infected patients, mortality from CCM has significantly gone down. CCM however remains the second highest cause of mortality in HIV, the highest burden being in sub-Saharan Africa where 75% of all deaths occur. Most of the studies evaluating mortality have reported short-term mortality. We determined mortality and associated factors among patients treated for CCM using recommended therapy in the CryptoDex trial (ISRCTN59144167) in Uganda, and the effect of dexamethasone adjunctive therapy on mortality at two years. This was done by looking back at all 211 patients who had previously been enrolled into a trial of treatment for CCM (the CryptoDex trial, which recruited patients between April 2013 and February 2015) and determining their survival up to 2 years after they entered the study. This retrospective cohort study was done between May 2017 and July 2017. 127 (60%) of the patients had died by two years. Those with Glasgow coma score (GCS) below 15, those with lower weight, and those that had convulsions were more likely to die, while dexamethasone use and fungal burden did not affect mortality. Long-term mortality in CCM patients remains high even among patients receiving recommended therapy. Strategies to improve long-term survival in CCM patients are urgently needed, especially targeting those with reduced GCS, low weight, and convulsions. [ABSTRACT FROM AUTHOR]