The effect of sertraline on depression and associations with persistent depression in survivors of HIV-related cryptococcal meningitis

Background: Depression is a risk factor for worse outcomes in persons living with HIV/AIDS and has a prevalence more than three times as high as in the general population. Despite this, there are few randomized studies of antidepressants in HIV-infected Africans. Methods: We enrolled 460 HIV-infected Africans with cryptococcal meningitis into a randomized clinical trial of adjunctive sertraline vs placebo (2015-2017). We defined depression using depression using a Center for Epidemiologic Studies Depression Scale (CES-D) score of >15, and severe depression as >26 at one and three months after meningitis diagnosis and initiation of treatment.We evaluated the relationship between sertraline and depression, as well as associations with persistent depression, at three months. Results: At one- and three-months post meningitis diagnosis, 62% (108/174) and 44% (74/169) of all subjects had depression (CES>15), respectively. At three months, sertraline-treated subjects had consistent risk for depression as placebo-treated subjects but were significantly less likely to have severe depression (CES>26) (OR 0.335; 95%CI, 0.130-0.865). Of those with depression at one month, sertraline-treated subjects were less likely than placebo-treated subjects to be depressed at three months (p=0.05). Sertraline was the only factor we found significant in predicting persistent depression at three months among those who had depression at one month. Conclusions: Depression is highly prevalent in HIV-infected persons who have survived cryptococcal meningitis. We found that sertraline is associated with a modest reduction in depression in those with depression at baseline and a significant decrease in severe depression

A secondary analysis of depression outcomes from a randomized controlled trial of adjunctive sertraline for HIV-associated cryptococcal meningitis.

Background: Depression is a risk factor for worse HIV outcomes in persons living with HIV/AIDS, including engagement-in-care, HIV medication adherence, and retention-in-care. Depression has a prevalence of more than three times as high as in the general population. Despite this, there are few randomized studies of antidepressants in HIV-infected Africans, including those with opportunistic infections. Methods: We enrolled 460 HIV-infected Ugandans with cryptococcal meningitis into a randomized clinical trial of adjunctive sertraline vs placebo (2015-2017). We defined depression using the Center for Epidemiologic Studies Depression Scale (CES-D) score of >15, and severe depression as >26 at one and three months after meningitis diagnosis and initiation of treatment. We evaluated the relationship between sertraline and depression, as well as associations with persistent depression, at three months. Results: At one- and three-months post meningitis diagnosis, 62% (108/174) and 44% (74/169) of all subjects had depression (CES>15), respectively. At three months, sertraline-treated subjects had consistent risk for depression as placebo-treated subjects but were significantly less likely to have severe depression (CES>26) (OR 0.335; 95%CI, 0.130-0.865). Of those with depression at one month, sertraline-treated subjects were less likely than placebo-treated subjects to be depressed at three months (p=0.05). Sertraline was the only factor we found significant in predicting persistent depression at three months among those with depression at one month. Conclusions: Depression is highly prevalent in HIV-infected persons who have survived cryptococcal meningitis. We found that sertraline is associated with a modest reduction in depression in those with depression at baseline and a significant decrease in severe depression

Single-Dose Liposomal Amphotericin B Treatment for Cryptococcal Meningitis.

BACKGROUND: Cryptococcal meningitis is a leading cause of human immunodeficiency virus (HIV)-related death in sub-Saharan Africa. Whether a treatment regimen that includes a single high dose of liposomal amphotericin B would be efficacious is not known. METHODS: In this phase 3 randomized, controlled, noninferiority trial conducted in five African countries, we assigned HIV-positive adults with cryptococcal meningitis in a 1:1 ratio to receive either a single high dose of liposomal amphotericin B (10 mg per kilogram of body weight) on day 1 plus 14 days of flucytosine (100 mg per kilogram per day) and fluconazole (1200 mg per day) or the current World Health Organization-recommended treatment, which includes amphotericin B deoxycholate (1 mg per kilogram per day) plus flucytosine (100 mg per kilogram per day) for 7 days, followed by fluconazole (1200 mg per day) for 7 days (control). The primary end point was death from any cause at 10 weeks; the trial was powered to show noninferiority at a 10-percentage-point margin. RESULTS: A total of 844 participants underwent randomization; 814 were included in the intention-to-treat population. At 10 weeks, deaths were reported in 101 participants (24.8%; 95% confidence interval [CI], 20.7 to 29.3) in the liposomal amphotericin B group and 117 (28.7%; 95% CI, 24.4 to 33.4) in the control group (difference, -3.9 percentage points); the upper boundary of the one-sided 95% confidence interval was 1.2 percentage points (within the noninferiority margin; P<0.001 for noninferiority). Fungal clearance from cerebrospinal fluid was -0.40 log10 colony-forming units (CFU) per milliliter per day in the liposomal amphotericin B group and -0.42 log10 CFU per milliliter per day in the control group. Fewer participants had grade 3 or 4 adverse events in the liposomal amphotericin B group than in the control group (50.0% vs. 62.3%). CONCLUSIONS: Single-dose liposomal amphotericin B combined with flucytosine and fluconazole was noninferior to the WHO-recommended treatment for HIV-associated cryptococcal meningitis and was associated with fewer adverse events. (Funded by the European and Developing Countries Clinical Trials Partnership and others; Ambition ISRCTN number, ISRCTN72509687.)

Single-Dose Liposomal Amphotericin B Treatment for Cryptococcal Meningitis.

BackgroundCryptococcal meningitis is a leading cause of human immunodeficiency virus (HIV)-related death in sub-Saharan Africa. Whether a treatment regimen that includes a single high dose of liposomal amphotericin B would be efficacious is not known.MethodsIn this phase 3 randomized, controlled, noninferiority trial conducted in five African countries, we assigned HIV-positive adults with cryptococcal meningitis in a 1:1 ratio to receive either a single high dose of liposomal amphotericin B (10 mg per kilogram of body weight) on day 1 plus 14 days of flucytosine (100 mg per kilogram per day) and fluconazole (1200 mg per day) or the current World Health Organization-recommended treatment, which includes amphotericin B deoxycholate (1 mg per kilogram per day) plus flucytosine (100 mg per kilogram per day) for 7 days, followed by fluconazole (1200 mg per day) for 7 days (control). The primary end point was death from any cause at 10 weeks; the trial was powered to show noninferiority at a 10-percentage-point margin.ResultsA total of 844 participants underwent randomization; 814 were included in the intention-to-treat population. At 10 weeks, deaths were reported in 101 participants (24.8%; 95% confidence interval [CI], 20.7 to 29.3) in the liposomal amphotericin B group and 117 (28.7%; 95% CI, 24.4 to 33.4) in the control group (difference, -3.9 percentage points); the upper boundary of the one-sided 95% confidence interval was 1.2 percentage points (within the noninferiority margin; P10 colony-forming units (CFU) per milliliter per day in the liposomal amphotericin B group and -0.42 log10 CFU per milliliter per day in the control group. Fewer participants had grade 3 or 4 adverse events in the liposomal amphotericin B group than in the control group (50.0% vs. 62.3%).ConclusionsSingle-dose liposomal amphotericin B combined with flucytosine and fluconazole was noninferior to the WHO-recommended treatment for HIV-associated cryptococcal meningitis and was associated with fewer adverse events. (Funded by the European and Developing Countries Clinical Trials Partnership and others; Ambition ISRCTN number, ISRCTN72509687.)