Association of fluvoxamine with mortality and symptom resolution among inpatients with COVID-19 in Uganda: a prospective interventional open-label cohort study.

Prior research suggests that fluvoxamine, a selective serotonin reuptake inhibitor (SSRI) used for the treatment of obsessive-compulsive disorder and major depressive disorder, could be repurposed against COVID-19. We undertook a prospective interventional open-label cohort study to evaluate the efficacy and tolerability of fluvoxamine among inpatients with laboratory-confirmed COVID-19 in Uganda. The main outcome was all-cause mortality. Secondary outcomes were hospital discharge and complete symptom resolution. We included 316 patients, of whom 94 received fluvoxamine in addition to standard care [median age, 60 years (IQR = 37.0); women, 52.2%]. Fluvoxamine use was significantly associated with reduced mortality [AHR = 0.32; 95% CI = 0.19-0.53; p < 0.001, NNT = 4.46] and with increased complete symptom resolution [AOR = 2.56; 95% CI = 1.53-5.51; p < 0.001, NNT = 4.44]. Sensitivity analyses yielded similar results. These effects did not significantly differ by clinical characteristic, including vaccination status. Among the 161 survivors, fluvoxamine was not significantly associated with time to hospital discharge [AHR 0.81, 95% CI (0.54-1.23), p = 0.32]. There was a trend toward greater side effects with fluvoxamine (7.45% versus 3.15%; SMD = 0.21; χ2 = 3.46, p = 0.06), most of which were light or mild in severity and none of which were serious. One hundred mg of fluvoxamine prescribed twice daily for 10 days was well tolerated and significantly associated with reduced mortality and with increased complete symptom resolution, without a significant increase in time to hospital discharge, among inpatients with COVID-19. Large-scale randomized trials are urgently needed to confirm these findings, especially for low- and middle-income countries, where access to vaccines and approved treatments against COVID-19 is limited.

Factors associated with HIV self-testing among female university students in Uganda: a cross-sectional study.

BACKGROUND: Adolescent girls and young women (AGYW) at institutions of higher learning are at high risk of HIV, and conventional HIV testing services may not reach them sufficiently. HIV self-testing (HIVST) scalability can be informed by identifying AGYW who have used or are interested in using HIVST. We aimed to determine factors associated with use and willingness to use HIVST among female university students. METHODS: An online cross-sectional survey was conducted among 483 female students at Makerere University, Uganda. Proportions of students who have used or are willing to use HIVST and their associated factors were determined. Modified Poisson regression models were used to estimate prevalence ratios (PR) and their 95% confidence intervals (CI). RESULTS: The median age of the participants was 22 (Interquartile range [IQR] 21-23) years, and 21% had never tested for HIV. Over 93% were willing to utilize HIVST, and 19% had ever used HIV self-test kits. Increasing age (adjusted prevalence ratio [aPR] 1.23 per year, 95% CI 1.07-1.43) was significantly associated with HIVST use. Predictors of willingness to self-test for HIV were college type (arts vs. science-based, aPR 0.92, 95% CI 0.88-0.97), number of sexual partners (one, aPR 1.07, 95% CI 1.03-1.12 or ≥ 2, aPR 1.08, 95% CI 1.04-1.19, vs. none), alcohol (aPR 1.04, 95% CI: 1.00-1.09) or injection drug (aPR 1.04, 95% CI 1.00-1.09) use, a history of sexually transmitted infections in past 12 months (aPR 1.05, 95% CI 1.01-1.09), and HIV testing experience (tested in past 12 months, aPR 1.12, 95% CI 1.02-1.22 or over 12 months, aPR 1.13, 95% CI 1.03-1.24, vs. never tested). CONCLUSION: HIVST was highly acceptable despite its limited use. This study demonstrates female student characteristics that can be leveraged to scale up HIVST programs in higher institutions of learning.

Relationship between maternal and/or newborn cholesterol levels and neonatal septicemia: protocol for a Ugandan cohort of mother-newborn pairs.

BACKGROUND: Many aspects of microbial dissemination appear to vary with host cholesterol levels. Since neonatal septicemia remains a leading cause of newborn admissions and mortality in resource-limited settings, the contribution of abnormal cholesterol levels in maternal and/or newborn blood to the risk of neonatal septicemia and outcome requires elucidation. We aim to determine a relationship between maternal serum and neonatal cord blood cholesterol levels and neonatal septicemia. METHODS: This will be a mother-newborn pair cohort study. Approximately 353 pregnant women who are eligible and consent to participate in the study will have blood drawn for a lipid profile. Upon delivery, we will analyse the cord blood cholesterol of their newborns and follow them for 28 days to determine whether the infants develop clinical signs and symptoms suggestive of neonatal septicemia. Relative risk will be used to determine the association between cholesterol and newborn septicemia. Poisson regression will be used to estimate the relative risk (with 95% confidence intervals) of developing septicemia. DISCUSSION: Findings from our study will contribute evidence to support the inclusion of lipid profile screening for pregnant women and newborns. Our study will determine whether newborns with abnormal cholesterol or those born to mothers with abnormal cholesterol will require rigorous follow-up in neonatal clinics.

HIV prevalence among children admitted with severe acute malnutrition and associated factors with mother-to-child HIV transmission at Mulago Hospital, Uganda: A mixed methods study.

BACKGROUND: Despite global efforts to eliminate mother-to-child-transmission of HIV (MTCT), many children continue to become infected. We determined the prevalence of HIV among children with severe acute malnutrition (SAM) and that of their mothers, at admission to Mwanamugimu Nutrition Unit, Mulago Hospital, Uganda. We also assessed child factors associated with HIV-infection, and explored factors leading to HIV-infection among a subset of the mother-child dyads that tested positive. METHODOLOGY: We conducted a cross-sectional evaluation within the REDMOTHIV (Reduce mortality in HIV) clinical trial that investigated strategies to reduce mortality among HIV-infected and HIV-exposed children admitted with SAM at the Nutrition Unit. From June 2021 to December 2022, we consecutively tested children aged 1 month to 5 years with SAM for HIV, and the mothers who were available, using rapid antibody testing upon admission to the unit. HIV-antibody positive children under 18 months of age had a confirmatory HIV-DNA PCR test done. In-depth interviews (IDIs) were conducted with mothers of HIV positive dyads, to explore the individual, relationship, social and structural factors associated with MTCT, until data saturation. Quantitative data was analyzed using descriptive statistics and logistic regression in STATAv14, while a content thematic approach was used to analyze qualitative data. RESULTS: Of 797 children tested, 463(58.1%) were male and 630(79.1%) were ≤18months of age; 76 (9.5%) tested positive. Of 709 mothers, median (IQR) age 26 (22, 30) years, 188(26.5%) were HIV positive. Sixty six of the 188 mother-infant pairs with HIV exposure tested positive for HIV, an MTCT rate of 35.1% (66/188). Child age >18 months was marginally associated with HIV-infection (crude OR = 1.87,95% CI: 1.11-3.12, p-value = 0.02; adjusted OR = 1.72, 95% CI: 0.96, 3.09, p-value = 0.068). The IDIs from 16 mothers revealed associated factors with HIV transmission at multiple levels. Individual level factors: inadequate information regarding prevention of MTCT(PMTCT), limited perception of HIV risk, and fear of antiretroviral drugs (ARVs). Relationship level factors: lack of family support and unfaithfulness (infidelity) among sexual partners. Health facility level factors: negative attitude of health workers and missed opportunities for HIV testing. Community level factors: poverty and health service disruptions due to the COVID-19 pandemic. CONCLUSION: In this era of universal antiretroviral therapy for PMTCT, a 10% HIV prevalence among severely malnourished children is substantially high. To eliminate vertical HIV transmission, more efforts are needed to address challenges mothers living with HIV face intrinsically and within their families, communities and at health facilities.

HIV pre-exposure prophylaxis uptake, retention and adherence among female sex workers in sub-Saharan Africa: a systematic review.

OBJECTIVE: To evaluate oral pre-exposure prophylaxis (PrEP) uptake, retention and adherence among female sex workers (FSWs) receiving care through community and facility delivery models in sub-Saharan Africa (SSA). DESIGN: Systematic review and meta-analysis. DATA SOURCES: We searched online databases (PubMed, MEDLINE, SCOPUS, EMBASE, Google Scholar, Cochrane Database of Systematic Reviews and Web of Science) between January 2012 and 3 April 2022. ELIGIBILITY CRITERIA FOR STUDIES: Randomised controlled trials, cohort studies, cross-sectional studies and quasi-experimental studies with PrEP uptake, adherence and retention outcomes among FSWs in SSA. DATA EXTRACTION AND SYNTHESIS: Seven coders extracted data. The framework of the Cochrane Consumers and Communication Review Group guided data synthesis. The Risk of Bias In Non-Randomized Studies of Interventions tool was used to evaluate the risk of bias. Meta-analysis was conducted using a random-effects model. A narrative synthesis was performed to analyse the primary outcomes of PrEP uptake, adherence and retention. RESULTS: Of 8538 records evaluated, 23 studies with 40 669 FSWs were included in this analysis. The pooled proportion of FSWs initiating PrEP was 70% (95% CI: 56% to 85%) in studies that reported on facility-based models and 49% (95% CI: 10% to 87%) in community-based models. At 6 months, the pooled proportion of FSWs retained was 66% (95% CI: 15% to 100%) for facility-based models and 83% (95% CI: 75% to 91%) for community-based models. Factors associated with increased PrEP uptake were visiting a sex worker programme (adjusted OR (aOR) 2.92; 95% CI: 1.91 to 4.46), having ≥10 clients per day (aOR 1.71; 95% CI: 1.06 to 2.76) and lack of access to free healthcare in government-run health clinics (relative risk: 1.16; 95% CI: 1.06 to 1.26). CONCLUSIONS: A hybrid approach incorporating both facility-based strategies for increasing uptake and community-based strategies for improving retention and adherence may effectively improve PrEP coverage among FSWs. PROSPERO REGISTRATION NUMBER: CRD42020219363.

Socio-demographic and clinical characteristics associated with retention in care among adults living with HIV and severe mental illness and reasons for loss to follow-up in Uganda: a mixed-methods study.

OBJECTIVE: This study aimed to determine the socio-demographic and clinical characteristics associated with retention in care and reasons for loss to follow-up (LTFU) among people living with HIV (PLWH) with a known diagnosis of severe mental illness (SMI). DESIGN: We conducted a parallel convergent mixed-methods study. The quantitative study was used to determine the proportion and factors associated with retention in care among PLWH and SMI. The qualitative study explored reasons for LTFU. SETTING: This study was conducted at two the HIV clinics of two tertiary hospitals in Uganda. PARTICIPANTS: We reviewed records of 608 PLWH who started antiretroviral therapy (ART) and included participants who had a documented diagnosis of SMI. OUTCOMES: The primary outcome was retention in care. Age, gender, religion, tuberculosis (TB) status, WHO clinical stage, functional status, cluster of differentiation 4 (CD4) cell count, viral load and SMI diagnosis were among the predictor variables. RESULTS: We collected data from 328 participants. Retention at 6 months was 43.3% compared with 35.7% at 12 months. Having an unsuppressed viral load (≥1000 copies/mL) (adjusted incidence risk ratio (IRR)=1.54, 95% CI: 1.17 to 2.03), being 36 years and below (adjusted IRR=0.94, 95% CI: 0.94 to 0.95), initial presentation at outpatient department (adjusted IRR=0.74, 95% CI: 0.57 to 0.96), having TB signs and symptoms (adjusted IRR=0.98 95% CI: 0.97 to 0.99) and being in lower WHO stages (I and II) (adjusted IRR=1.08, 95% CI: 1.02 to 1.14) at ART initiation were significantly associated with retention in care at 6 and 12 months. Inadequate social support, long waiting hours at the clinic, perceived stigma and discrimination, competing life activities, low socioeconomic status and poor adherence to psychiatric medication were barriers to retention in care. CONCLUSION: Twelve-month retention in care remains low at 35.7% far below the 90% WHO target. There is a need to design and implement targeted interventions to address barriers to retention in care among PLWH and SMI.

Strategies to Reduce Mortality Among Children Living With HIV and Children Exposed to HIV but Are Uninfected, Admitted With Severe Acute Malnutrition at Mulago Hospital, Uganda (REDMOTHIV): A Mixed Methods Study.

Background: Children living with HIV (CLHIV) and children who are exposed to HIV but uninfected (CHEU) are at increased risk of developing malnutrition. Severely malnourished children have high mortality rates, but mortality is higher in CLHIV/CHEU. This study aims to investigate whether empiric use of an antibiotic with greater antimicrobial sensitivity (ceftriaxone) than standard-of-care (ampicillin plus gentamicin) will reduce mortality among CLHIV/CHEU admitted with severe acute malnutrition. Methods: This is an open label randomized controlled trial involving 300 children; 76 CLHIV and 224 CHEU. The participants are being randomized to receive 1 week of ceftriaxone (n = 150) or standard-of-care (ampicillin/gentamicin) (n = 150), in addition to other routine care. The trial's primary outcome is in-hospital mortality. Secondary outcomes are: length of hospitalization; weight-for-height, weight-for-age and height-for-age z-scores; and pattern/antimicrobial sensitivity of pathogens. In addition, 280 severely malnourished children of unknown serostatus will be tested for HIV at admission to determine the prevalence and factors associated with HIV-infection. Furthermore, all the CLHIV on LPV/r will each provide sparse pharmacokinetic (PK) samples to evaluate the PK of LPV/r among malnourished children. In this PK sub-study, geometric means of steady-state LPV PK parameters [Area Under the Curve (AUC) 0-12h , maximum concentration (Cmax) and concentration at 12 h after dose (C12h)] will be determined. They will then be put in pharmacokinetic-pharmacodynamic (PK-PD) models to determine optimal doses for the study population. Discussion: This study will ascertain whether antibiotics with higher sensitivity patterns to common organisms in Uganda and similar settings, will produce better treatment outcomes. The study will also provide insights into the current pattern of organisms isolated from blood cultures and their antimicrobial sensitivities, in this population. In addition, the study will ascertain whether there has been a significant change in the prevalence of HIV-infection among children presenting with severe malnutrition in the WHO recommended option B plus era, while determining the social/structural factors associated with HIV-infection. There will also be an opportunity to study PK parameters of antiretroviral drugs among severely malnourished children which is rarely done, and yet it is very important to understand the dosing requirements of this population. Trial Registration: ClinicalTrials.gov, identifier: NCT05051163.

Erratum: Symptomatic cerebrospinal fluid HIV-1 escape in two patients on second-line antiretroviral therapy in Uganda.

[This corrects the article DOI: 10.1093/omcr/omy132.].

Symptomatic cerebrospinal fluid HIV-1 escape in two patients on second-line antiretroviral therapy in Uganda.

Two HIV-infected individuals on second-line atazanavir-based antiretroviral therapy presented with neuropsychiatric symptoms. Cerebrospinal fluid HIV RNA was higher than plasma HIV RNA and antiretroviral regimens' optimization led to prompt resolution of symptoms in one. Patients on second-line atazanavir-based antiretroviral therapy with documented previous treatment failure may be at risk of symptomatic cerebrospinal fluid escape.