Prevalence, patterns, and determinants of breastfeeding cessation among mothers of children under 24 months in Uganda.

BACKGROUND: Breastfeeding duration is a critical component of infant and child nutrition, providing immediate and long-term benefits to both children and their mothers. This study uses data from the lot quality assurance sampling (LQAS) survey to examine the prevalence, patterns, and determinants of breastfeeding cessation in Uganda. METHODS: This study was a secondary analysis of data collected by the cross-sectional LQAS surveys in 2021 and 2022 covering 77 districts in Uganda. The LQAS survey methodology employs a systematic sampling approach to assess whether predefined quality standards are met within specific subgroups of a population. The study employed spatial analysis, bivariate analysis and logistic regression, both with and without clustering, to explore associations between independent variables and breastfeeding cessation. Unadjusted and adjusted odds ratios with 95% confidence intervals were calculated. Statistical significance was set at 5%. RESULTS: Overall, the study analysed 26,377 records of mothers with children under 24 months old. The mothers' mean age was 27.9 years while that of their children was 11.0 months. While the general breastfeeding cessation rate was 17.7%, cessation was highest (49.7%) among mothers of children 18-23 months. Factors associated with increased odds of breastfeeding cessation included older child's age, older mother's age, using modern family planning, being pregnant and having an unknown pregnancy status. Lower odds of breastfeeding cessation were observed among mothers who; were married, lived in larger households, lived in rural residences, whose children received vitamin A supplementation and among all other regions compared to Kampala. CONCLUSION: One in five mothers cessed breastfeeding before their child reached 2 years, with a significant increase in cessation odds among mothers of older children. These findings underscore the importance of interventions to promote breastfeeding continuation and adequate nutrition for non-breastfed infants, particularly in regions with high cessation rates.

The impact of the parenting for respectability programme on violent parenting and intimate partner relationships in Uganda: A pre-post study.

BACKGROUND: There is a growing need for interventions that reduce both violence against children and intimate partner violence in low- and middle-income countries. However, few parenting interventions deliberately address this link. We tested the feasibility of a 16-session group-based parenting programme, Parenting for Respectability, in semi-rural Ugandan communities. METHODS: This was a pre-post study with parents and their children (N = 484 parents; 212 children). RESULTS: Pre-post comparisons found large effects for parent-reported reduced harsh parenting (Cohen's f2 = 0.41 overall; f2 = 0.47 (among session attendees); with an overall reduction of 26% for harsh parenting. Session attendees reported higher reductions than non-attendees (p = 0.014), and male caregivers reported higher reductions than female caregivers (p<0.001). Children also reported reduced harsh parenting by attending fathers (f2 = 0.64 overall; f2 = 0.60) and attending mothers (f2 = 0.56 overall; f2 = 0.51); with reduction in harsh parenting ranging between 27% to 29% in the various categories. Overall, spousal violence reduced by 27% (f2 = 0.19 overall; f2 = 0.26 (among session attendees). Both parents and children reported reduced dysfunctional parent relationships; parents: f2 = 0.19 overall; f2 = 0.26 (among session attendees); and children: f2 = 0.35 overall; f2 = 0.32 (for attending parents); with reductions ranging between 22% to 28%. Parents who attended more than 50% of the program reported greater effects on reduced dysfunctional relationships than those who attended less than half of the program (B = -0.74, p = 0.013). All secondary outcomes were improved with f2 ranging between 0.08 and 0.39; and improvements ranging between 6% and 28%. CONCLUSION: Results suggest the importance of more rigorous testing to determine program effectiveness.

Prevalence and determinants of minimum dietary diversity for women of reproductive age in Uganda.

BACKGROUND: Globally, over a billion women of reproductive age (WRA) suffer from some kind of undernutrition micronutrient deficiencies, and/or anemia as a result of inadequate dietary diversity. This leads to poor maternal and child health outcomes, however, there is limited research on population level research on minimum dietary diversity for women (MDD-W). This study assessed the prevalence and predictors of MDD-W among WRA in Uganda. METHODS: This study was a secondary analysis of data from the lot quality assurance sampling (LQAS) survey conducted across 55 Ugandan districts between May and September 2022. Women of various ages were interviewed across 5 study subgroups that this study used to construct its study population (WRA). Descriptive analyses, tests for outcome differences, and multilevel mixed-effects logistic regression were conducted at a 5% statistical significance level using STATA version 17. The results were reported using Adjusted Odds Ratios (aOR) as the measure of the outcome. RESULTS: The study analyzed responses from 29,802 WRA with a mean age of 27.8 (± 6.8) years. Only 8.8% (95% CI 8.5-9.3) achieved the MDD-W, the least proportion was observed in the South-Central region (3.13%). In the adjusted analysis, WRA who were older than 25 years (aOR 1.1, 95% CI 1.1-1.3, p < 0.001), had secondary education (aOR = 1.4, 95% CI 1.1-1.7, p = 0.003) or above (aOR = 1.7, 95% CI 1.3-2.2, p < 0.001), and used modern contraceptives (aOR = 1.1, 95% CI 1.0-1.3, p = 0.01) were more likely to achieve the MDD-W. Conversely, WRA who travelled longer distances to the nearest household water source (aOR = 0.8, 95% CI 0.7-0.9, p = 0.002) and those residing in larger households (aOR = 0.9, 95% CI 0.8-1.0, p = 0.019) were less likely to achieve the MDD-W. CONCLUSION: A low proportion of WRA met the MDD-W. Age, education level, household sizes and use of modern contraception were predictors of MDD-W among WRA in Uganda. MDD-W-related program efforts in Uganda should strengthen multisectoral collaboration with prioritization of younger women, education, household sizes and access to safe water sources.

Sociodemographic and health-related factors associated with exclusive breastfeeding in 77 districts of Uganda.

BACKGROUND: Uganda surpasses many African nations and the global average in exclusive breastfeeding (EBF) rates. Yet, malnutrition is a critical issue, with stunting impacting roughly 29% of children under 5 years. Enhancing EBF could mitigate such nutritional challenges. This study focused on determining the current EBF prevalence and identifying associated factors across 77 surveyed districts. METHODS: Pooled data from the Lot Quality Assurance Sampling (LQAS) surveys conducted in 77 districts in Uganda during 2021 and 2022 were analyzed. The analysis involved 7,210 mothers of children under 6 months, EBF was considered as the proportion of infants who received breast milk only in the 24 hours before the survey. A mother practicing EBF was (1) currently breastfeeding (2) had not started giving foods other than breastmilk (3) had not given any other probed liquids or (4) semi-solid foods the previous day or night. Multivariable logistic regression was used to identify factors associated with EBF, presenting adjusted odds ratios (aOR) with corresponding 95% confidence intervals at a 5% significance level. RESULTS: The prevalence of EBF was 62.3%. In the adjusted analysis, EBF was more common among older mothers 20-24 years, 25-29 years and 30 + years (aOR 1.4; 95% CI 1.2,1.6), (aOR 1.4; 95% CI 1.1, 1.6) and (aOR 1.3; 95% CI 1.1, 1.5) respectively compared to teenage mothers. Also, EBF was more likely among mothers who lived in rural areas compared to urban areas (aOR 1.1; 95% CI 1.0, 1.3) and those who attended antenatal care (ANC) (aOR 2.2; 95% CI 1.5, 3.1). On the contrary, EBF was less common for children aged 3-5 months compared to younger (aOR 0.5; 95% CI 0.5, 0.6) and children who had received Vitamin A supplementation (aOR 0.7; 95% 0.6, 0.8). CONCLUSION: The study suggests that most districts in Uganda might not have made significant strides in improving EBF rates over the last twenty years, pointing to possible ongoing hurdles that need urgent attention. Particularly, there's a pressing need to focus on teenage mothers. Maintaining and strengthening programs that advocate EBF, such as ANC, is crucial to bridge the gaps and bring about more equitable rates among different groups.

Level of minimum acceptable diet and its associated factors among children aged 12-23 months in Ugandan districts.

Uganda has made notable progress in improving child nutrition indicators, albeit not fast enough to meet global targets. Navigating the landscape of child nutrition in Uganda demands attention, particularly in light of the necessity for a minimum acceptable diet (MAD) for children aged 12-23 months. While the focus on local nutritional planning is crucial, the absence of routine-specific nutritional status data creates a significant information gap. To bridge this void, this study used datasets from the 2021 Lot Quality Assurance Sampling (LQAS) survey. Data were analysed using multilevel mixed-effects logistic regression (clustering districts based on regional boundaries) at a 5% statistical significance level using STATA version 17. Of the 7,111 children surveyed, 3,256 (49.20%) received the minimum meal frequency, 695 (9.80%) received the minimum dietary diversity, and only 380 (5.34%) received the MAD. There was a notable variation in the proportion of children that received the MAD across regions and districts. Children living in urban areas, children whose mothers had a higher education, and children whose mothers had a diverse diet were more likely to receive the MAD. Children were less likely to receive the MAD if they lived in a household that did not receive a health worker visit within the year. These findings suggest a need to prioritize initiatives aimed at increasing dietary diversity among children in Uganda. This could be done through a variety of approaches, such as leveraging the use of home gardens to boost nutrition through diverse crop cultivation, demonstration gardens, and offering nutrition counselling through village health teams.

Postpartum family planning uptake in Uganda: findings from the lot quality assurance sampling survey.

BACKGROUND: The initiation and use of family planning (FP) services within the first 12 months following childbirth, postpartum family planning (PPFP), promotes safe motherhood by reducing unintended pregnancies and ensuring appropriate pregnancy spacing. However, there is a paucity of information on PPFP uptake from community surveys. This study aimed to quantify the reported use of PPFP and identify predictors and barriers to PPFP uptake from a large community survey. METHODS: We analysed data collected from the 2021 Lot Quality Assurance Sampling (LQAS) survey, a cross-sectional community and household survey that covered 68 districts in Uganda. The survey uses small sample sizes to designate health or administrative geographical areas which are assessed to determine whether they achieved the pre-determined target for defined indicators of interest. We abstracted and analysed data collected from mothers of children aged 12 months or younger on reproductive health and FP. PPFP use was defined as the reported use of modern FP by the mother or their partner. Associations were measured using Pearson's chi-square test at 5% significance. Multivariate logistic regression was performed for variables that were significantly associated with PPFP use to identify the predictors of PPFP. RESULTS: Overall, 8103 mothers of children aged less than 12 years were included in the analysis; the majority of mothers, 55.8% (4521/8103) were above 24 years while 11.7% (950/8103) were 19 years and under. 98% (7942/8103) of the mothers attended at least one antenatal care (ANC) visit and 86.3% (6997/8103) delivered at a health facility. Only 10% (814/8103) of mothers who participated in the survey reported PPFP use at the time of the survey. Reporting of PPFP use was 5 times higher among mothers of children aged 7-12 months (AOR 4.9; 95%CI 4.1-5.8), 50% higher among mothers with secondary education (AOR 1.5; 95%CI 1.0-2.3), 80% higher among breastfeeding mothers (AOR 1.8; 95%CI 1.3-2.4) and 30% lower among those that didn't receive a health worker visit within 3 months preceding the survey (AOR 0.7; 95% CI 0.5-0.8). Among 4.6% (372/8103) who stated a reason for non-use of PPFP, the most cited reasons for not using were breastfeeding 43% (161/372), fear of side effects 26.9% (100/372), respondent/partner opposition 17.6% (48/372) and infrequent sex 12.1% (48/372). CONCLUSION: The analysis showed a low proportion of PPFP uptake among mothers of children under 12 years. Possible barriers included child age, education, a health worker visit, and side effects and perceived benefits of possibly improperly implementing lactation amenorrhea method. Integration of social, community and health services could provide a more holistic approach to improving PPFP uptake.

Modelling the impact of combining HIV prevention interventions on HIV dynamics in fishing communities in Uganda.

BACKGROUND: In countries with mature generalized HIV epidemics such as Uganda, there are still groups of individuals that are disproportionately affected. Among the key populations in Uganda are fishing communities, which make up about 10% of the population. Compared to the general population, HIV prevalence and incidence among individuals living in these communities is high. This high HIV burden has been attributed to several factors including limited access to prevention and treatment services as well as ongoing high-risk sexual behaviour. METHODS: We investigated the impact of combined HIV prevention interventions on HIV transmission dynamics in high-risk fishing communities in Uganda using a deterministic compartmental model. The model was calibrated to seroprevalence data from a census performed in 2014. To account for remaining uncertainty in the calibrated model parameters, 50 000 simulated scenarios were modelled to investigate the impact of combined prevention interventions. RESULTS: The projected HIV incidence decreased from 1.87 per 100 PY without intervention scale-up to 0.25 per 100 PY after 15 years (2014-2029) of intervention scale-up. A potential combination achieving this 87% reduction in incidence over 15 years in Ugandan FCs included condom use in about 60% of sexual acts, 23% of susceptible men circumcised, 87% of people living with HIV aware of their status, 75% of those on ART, and about 3% of susceptible individuals on oral PrEP. Uncertainty analysis revealed relative reductions in incidence ranging from 30.9 to 86.8%. Sensitivity analyses suggested that condom use and early ART were the most important interventions. CONCLUSION: Reducing HIV incidence, as well as prevalence and AIDS-related mortality, in these high-risk fishing communities in Uganda is attainable over 15 years with a combination prevention package. Our projected intervention coverage levels are well within the national targets set by the Uganda government and enable coming close to reaching the UNAIDS 95-95-95 targets to end AIDS as a public health threat by 2030.

Feasibility of using a mobile App to monitor and report COVID-19 related symptoms and people's movements in Uganda.

BACKGROUND: Feasibility of mobile Apps to monitor diseases has not been well documented particularly in developing countries. We developed and studied the feasibility of using a mobile App to collect daily data on COVID-19 symptoms and people's movements. METHODS: We used an open source software "KoBo Toolbox" to develop the App and installed it on low cost smart mobile phones. We named this App "Wetaase" ("protect yourself"). The App was tested on 30 selected households from 3 densely populated areas of Kampala, Uganda, and followed them for 3 months. One trained member per household captured the data in the App for each enrolled member and uploaded it to a virtual server on a daily basis. The App is embedded with an algorithm that flags participants who report fever and any other COVID-19 related symptom. RESULTS: A total of 101 participants were enrolled; 61% female; median age 23 (interquartile range (IQR): 17-36) years. Usage of the App was 78% (95% confidence interval (CI): 77.0%-78.8%). It increased from 40% on day 1 to a peak of 81% on day 45 and then declined to 59% on day 90. Usage of the App did not significantly vary by site, sex or age. Only 57/6617 (0.86%) records included a report of at least one of the 17 listed COVID-19 related symptoms. The most reported symptom was flu/runny nose (21%) followed by sneezing (15%), with the rest ranging between 2% and 7%. Reports on movements away from home were 45% with 74% going to markets or shops. The participants liked the "Wetaase" App and recommended it for use as an alert system for COVID-19. CONCLUSION: Usage of the "Wetaase" App was high (78%) and it was similar across the three study sites, sex and age groups. Reporting of symptoms related to COVID-19 was low. Movements were mainly to markets and shops. Users reported that the App was easy to use and recommended its scale up. We recommend that this App be assessed at a large scale for feasibility, usability and acceptability as an additional tool for increasing alerts on COVID-19 in Uganda and similar settings.

Phylogenetic Networks and Parameters Inferred from HIV Nucleotide Sequences of High-Risk and General Population Groups in Uganda: Implications for Epidemic Control.

Phylogenetic inference is useful in characterising HIV transmission networks and assessing where prevention is likely to have the greatest impact. However, estimating parameters that influence the network structure is still scarce, but important in evaluating determinants of HIV spread. We analyzed 2017 HIV pol sequences (728 Lake Victoria fisherfolk communities (FFCs), 592 female sex workers (FSWs) and 697 general population (GP)) to identify transmission networks on Maximum Likelihood (ML) phylogenetic trees and refined them using time-resolved phylogenies. Network generative models were fitted to the observed degree distributions and network parameters, and corrected Akaike Information Criteria and Bayesian Information Criteria values were estimated. 347 (17.2%) HIV sequences were linked on ML trees (maximum genetic distance ≤4.5%, ≥95% bootstrap support) and, of these, 303 (86.7%) that consisted of pure A1 (n = 168) and D (n = 135) subtypes were analyzed in BEAST v1.8.4. The majority of networks (at least 40%) were found at a time depth of ≤5 years. The waring and yule models fitted best networks of FFCs and FSWs respectively while the negative binomial model fitted best networks in the GP. The network structure in the HIV-hyperendemic FFCs is likely to be scale-free and shaped by preferential attachment, in contrast to the GP. The findings support the targeting of interventions for FFCs in a timely manner for effective epidemic control. Interventions ought to be tailored according to the dynamics of the HIV epidemic in the target population and understanding the network structure is critical in ensuring the success of HIV prevention programs.

The 5-HTTLPR-rs25531 S-A-S-A Haplotype and Chronic Stress Moderate the Association Between Acute Stress and Internalizing Mental Disorders Among HIV+ Children and Adolescents in Uganda.

Background: Internalizing mental disorders (IMDs) among HIV-positive (HIV+) children and adolescents are associated with poor disease outcomes, such as faster HIV disease progression. Although it has been suggested that the development of IMDs is moderated by interaction of stressful life events and vulnerability factors, the underlying etiology is largely unknown. Serotonin transporter gene [solute carrier family 6 member A4 (SLC6A4)] and human tryptophan hydroxylase 2 gene (TPH2) polymorphisms have been implicated in the development of IMDs. This study investigated the association between acute stress and IMDs, and moderation by chronic stress and genetic variants in SLC6A4 and TPH2. Hypothesis: Acute stress acts through genetic and environmental vulnerability factors to increase the risk of developing IMDs. Methods: Polymorphisms in SLC6A4 (5-HTTLPR, rs25531, 5-HTTLPR-rs25531, and STin2 VNTR) and TPH2 (rs1843809, rs1386494, rs4570625, and rs34517220) were genotyped in 368 HIV+ children and adolescents (aged 5-17 years) with any internalizing mental disorder (depression, anxiety disorders, or posttraumatic stress disorder), and 368 age- and sex-matched controls, who were also HIV+. Chronic and acute stress categories were derived by hierarchical cluster analysis. Logistic regression analysis was used to assess the independent moderating effect of chronic stress and each selected polymorphism on the association between acute stress and IMDs. Results: We observed a statistically significant association between severe acute stress and IMDs (p = 0.001). Children and adolescents who experienced severe acute stress were twice as likely to develop IMDs, compared to children and adolescents who experienced mild acute stress (p = 0.001). Chronic stress interacted with severe acute stress to increase the risk of IMDs (p = 0.033). Acute stress was found to interact with 5-HTTLPR-rs25531 S-A-S-A haplotype to increase the risk for IMDs among Ugandan HIV+ children and adolescents (p = 0.049). We found no evidence for a combined interaction of acute stress, chronic stress, and 5-HTTLPR-rs25531 on IMDs. Conclusion: The odds of having an internalizing mental disorder (IMD) were higher among HIV+ children and adolescents who experienced severe acute stress compared to HIV+ children and adolescents who experienced mild acute stress. Chronic stress and 5-HTTLPR-rs25531 independently moderated the association between acute stress and IMDs.

Discovery and fine-mapping of kidney function loci in first genome-wide association study in Africans.

Genome-wide association studies (GWAS) of kidney function have uncovered hundreds of loci, primarily in populations of European ancestry. We have undertaken the first continental African GWAS of estimated glomerular filtration rate (eGFR), a measure of kidney function used to define chronic kidney disease (CKD). We conducted GWAS of eGFR in 3288 East Africans from the Uganda General Population Cohort (GPC) and replicated in 8224 African Americans from the Women's Health Initiative. Loci attaining genome-wide significant evidence for association (P < 5 × 10-8) were followed up with Bayesian fine-mapping to localize potential causal variants. The predictive power of a genetic risk score (GRS) constructed from previously reported trans-ancestry eGFR lead single nucleotide polymorphism (SNPs) was evaluated in the Uganda GPC. We identified and validated two eGFR loci. At the glycine amidinotransferase (GATM) locus, the association signal (lead SNP rs2433603, P = 1.0 × 10-8) in the Uganda GPC GWAS was distinct from previously reported signals at this locus. At the haemoglobin beta (HBB) locus, the association signal (lead SNP rs141845179, P = 3.0 × 10-8) has been previously reported. The lead SNP at the HBB locus accounted for 88% of the posterior probability of causality after fine-mapping, but did not colocalise with kidney expression quantitative trait loci. The trans-ancestry GRS of eGFR was not significantly predictive into the Ugandan population. In the first GWAS of eGFR in continental Africa, we validated two previously reported loci at GATM and HBB. At the GATM locus, the association signal was distinct from that previously reported. These results demonstrate the value of performing GWAS in continental Africans, providing a rich genomic resource to larger consortia for further discovery and fine-mapping. The study emphasizes that additional large-scale efforts in Africa are warranted to gain further insight into the genetic architecture of CKD.

TERT rs2736100 and TERC rs16847897 genotypes moderate the association between internalizing mental disorders and accelerated telomere length attrition among HIV+ children and adolescents in Uganda.

BACKGROUND: Internalizing mental disorders (IMDs) (depression, anxiety and post-traumatic stress disorder) have been associated with accelerated telomere length (TL) attrition; however, this association has not been investigated in the context of genetic variation that has been found to influence TL. We have previously reported an association between IMDs and accelerated TL attrition among Ugandan HIV+ children and adolescents. This study investigated the moderating effects of selected single nucleotide polymorphisms in the telomerase reverse transcriptase gene (TERT) (rs2736100, rs7726159, rs10069690 and rs2853669) and the telomerase RNA component gene (TERC) (rs12696304, rs16847897 and rs10936599) on the association between IMDs and TL, among Ugandan HIV+ children (aged 5-11 years) and adolescents (aged 12-17 years). RESULTS: We found no significant interaction between IMDs as a group and any of the selected SNPs on TL at baseline. We observed significant interactions of IMDs with TERT rs2736100 (p = 0.007) and TERC rs16847897 (p = 0.012), respectively, on TL at 12 months. CONCLUSIONS: TERT rs2736100 and TERC rs16847897 moderate the association between IMDs and TL among Ugandan HIV+ children and adolescents at 12 months. Understanding the nature of this association may shed light on the pathophysiological mechanisms underlying advanced cellular aging in IMDs.

The Molecular Epidemiology and Transmission Dynamics of HIV Type 1 in a General Population Cohort in Uganda.

The General Population Cohort (GPC) in south-western Uganda has a low HIV-1 incidence rate (<1%). However, new infections continue to emerge. In this research, 3796 HIV-1 pol sequences (GPC: n = 1418, non-GPC sites: n = 1223, Central Uganda: n = 1010 and Eastern Uganda: n = 145) generated between 2003-2015 were analysed using phylogenetic methods with demographic data to understand HIV-1 transmission in this cohort and inform the epidemic response. HIV-1 subtype A1 was the most prevalent strain in the GPC area (GPC and non-GPC sites) (39.8%), central (45.9%) and eastern (52.4%) Uganda. However, in the GPC alone, subtype D was the predominant subtype (39.1%). Of the 524 transmission clusters identified by Cluster Picker, all large clusters (≥5 individuals, n = 8) involved individuals from the GPC. In a multivariate analysis, clustering was strongly associated with being female (adjusted Odds Ratio, aOR = 1.28; 95% CI, 1.06-1.54), being >25 years (aOR = 1.52; 95% CI, 1.16-2.0) and being a resident in the GPC (aOR = 6.90; 95% CI, 5.22-9.21). Phylogeographic analysis showed significant viral dissemination (Bayes Factor test, BF > 3) from the GPC without significant viral introductions (BF < 3) into the GPC. The findings suggest localized HIV-1 transmission in the GPC. Intensifying geographically focused combination interventions in the GPC would contribute towards controlling HIV-1 infections.

Determinants of two-year mortality among HIV positive patients with Cryptococcal meningitis initiating standard antifungal treatment with or without adjunctive dexamethasone in Uganda.

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.

Mathematical Modelling of HIV-HCV Coinfection Dynamics in Absence of Therapy.

Globally, it is estimated that of the 36.7 million people infected with human immunodeficiency virus (HIV), 6.3% are coinfected with hepatitis C virus (HCV). Coinfection with HIV reduces the chance of HCV spontaneous clearance. In this work, we formulated and analysed a deterministic model to study the HIV and HCV coinfection dynamics in absence of therapy. Due to chronic stage of HCV infection being long, asymptomatic, and infectious, our model formulation was based on the splitting of the chronic stage into the following: before onset of cirrhosis and its complications and after onset of cirrhosis. We computed the basic reproduction numbers using the next generation matrix method. We performed numerical simulations to support the analytical results. We carried out sensitivity analysis to determine the relative importance of the different parameters influencing the HIV-HCV coinfection dynamics. The findings reveal that, in the long run, there is a substantial number of individuals coinfected with HIV and latent HCV. Therefore, HIV and latently HCV-infected individuals need to seek early treatment so as to slow down the progression of HIV to AIDS and latent HCV to advanced HCV.

High Levels of Acquired HIV Drug Resistance Following Virological Nonsuppression in HIV-Infected Women from a High-Risk Cohort in Uganda.

HIV drug resistance (HIVDR) is of increasing health concern, especially among key populations. We investigated the prevalence of virological suppression (VS), prevalence and correlates of HIVDR in HIV-infected women, enrolled in a high-risk cohort. We enrolled 267 women initiated on first-line antiretroviral therapy (ART) between 2015 and 2018. Participants' plasma samples were analyzed for HIV RNA viral load (VL) and genotypic resistance testing was performed on those with VL nonsuppression (defined as VL ≥1,000 copies/mL). We used the Stanford HIVDR database-algorithm to assess HIVDR mutations and logistic regression to assess risk factors for VL nonsuppression and HIVDR. We observed an overall VS prevalence of 76.0% (203/267) and detected respective acquired drug resistance prevalence to non-nucleoside reverse transcriptase inhibitors (NNRTIs) and nucleoside reverse transcriptase inhibitors (NRTIs) of 81.3% [confidence interval (CI) 67.4-91.1] and 45.8% (CI 31.4-60.8) among the 48 successfully genotyped VL nonsuppressors. NNRTI mutations were observed in 81.3% (39/48) of the genotyped participants and 45.8% (22/48) had both NRTI and NNRTI mutations. The mutation K103N was detected in 62.5% (30/48) of participants, 41.7% (20/48) had M184V/I, 14.6% had K65R, and 12.5% (6/48) had thymidine analog mutations (TAMs). None of the analyzed potential risk factors, including age and duration on ART, was significantly correlated with VL nonsuppression or HIVDR. Although high levels of NNRTI mutations support the transition to dolutegravir, the presence of NRTI mutations, especially TAMs, may compromise dolutegravir-based regimens or other second-line ART options. The moderate VS prevalence and high HIVDR prevalence therefore call for timely ART switching and intensive adherence counseling.

Pervasive and non-random recombination in near full-length HIV genomes from Uganda.

Recombination is an important feature of HIV evolution, occurring both within and between the major branches of diversity (subtypes). The Ugandan epidemic is primarily composed of two subtypes, A1 and D, that have been co-circulating for 50 years, frequently recombining in dually infected patients. Here, we investigate the frequency of recombinants in this population and the location of breakpoints along the genome. As part of the PANGEA-HIV consortium, 1,472 consensus genome sequences over 5 kb have been obtained from 1,857 samples collected by the MRC/UVRI & LSHTM Research unit in Uganda, 465 (31.6 per cent) of which were near full-length sequences (>8 kb). Using the subtyping tool SCUEAL, we find that of the near full-length dataset, 233 (50.1 per cent) genomes contained only one subtype, 30.8 per cent A1 (n = 143), 17.6 per cent D (n = 82), and 1.7 per cent C (n = 8), while 49.9 per cent (n = 232) contained more than one subtype (including A1/D (n = 164), A1/C (n = 13), C/D (n = 9); A1/C/D (n = 13), and 33 complex types). K-means clustering of the recombinant A1/D genomes revealed a section of envelope (C2gp120-TMgp41) is often inherited intact, whilst a generalized linear model was used to demonstrate significantly fewer breakpoints in the gag-pol and envelope C2-TM regions compared with accessory gene regions. Despite similar recombination patterns in many recombinants, no clearly supported circulating recombinant form (CRF) was found, there was limited evidence of the transmission of breakpoints, and the vast majority (153/164; 93 per cent) of the A1/D recombinants appear to be unique recombinant forms. Thus, recombination is pervasive with clear biases in breakpoint location, but CRFs are not a significant feature, characteristic of a complex, and diverse epidemic.

Uganda Genome Resource Enables Insights into Population History and Genomic Discovery in Africa.

Genomic studies in African populations provide unique opportunities to understand disease etiology, human diversity, and population history. In the largest study of its kind, comprising genome-wide data from 6,400 individuals and whole-genome sequences from 1,978 individuals from rural Uganda, we find evidence of geographically correlated fine-scale population substructure. Historically, the ancestry of modern Ugandans was best represented by a mixture of ancient East African pastoralists. We demonstrate the value of the largest sequence panel from Africa to date as an imputation resource. Examining 34 cardiometabolic traits, we show systematic differences in trait heritability between European and African populations, probably reflecting the differential impact of genes and environment. In a multi-trait pan-African GWAS of up to 14,126 individuals, we identify novel loci associated with anthropometric, hematological, lipid, and glycemic traits. We find that several functionally important signals are driven by Africa-specific variants, highlighting the value of studying diverse populations across the region.

Internalizing Mental Disorders and Accelerated Cellular Aging Among Perinatally HIV-Infected Youth in Uganda.

Introduction: Internalizing mental disorders (IMDs) in HIV+ children and adolescents are associated with impaired quality of life and non-adherence to anti-retroviral treatment. Telomere length is a biomarker of cellular aging, and shorter telomere length has been associated with IMDs. However, the nature of this association has yet to be elucidated. Objective: We determined the longitudinal association between IMDs and relative telomere length (rTL) and the influence of chronic stress among Ugandan perinatally HIV-infected youth (PHIY). Methods: IMDs (depressive disorders, anxiety disorders, and post-traumatic stress disorder) and IMDs were assessed using the locally adapted Child and Adolescent Symptom Inventory-5. In 368 PHIY with any IMD and 368 age- and sex-matched PHIY controls without any psychiatric disorder, rTL was assessed using quantitative polymerase chain reaction. Hierarchical cluster analysis was used to generate the three chronic stress classes (mild, moderate, and severe). t-tests were used to assess the difference between baseline and 12 month rTL and the mean difference in rTL between cases and controls both at baseline and at 12 months. Linear regression analysis was used to model the effects of chronic stress on the association between IMDs and rTL, controlling for age and sex. Results: We observed longer rTL among cases of IMDs compared with controls (p < 0.001). We also observed a statistically significant reduction in rTL between baseline and 12 months in the combined sample of cases and controls (p < 0.001). The same statistical difference was observed when cases and controls were individually analyzed (p < 0.001). We found no significant difference in rTL between cases and controls at 12 months (p = 0.117). We found no significant influence of chronic stress on the association between IMDs and rTL at both baseline and 12 months. Conclusion: rTL is longer among cases of IMDs compared with age- and sex-matched controls. We observed a significant attrition in rTL over 12 months, which seems to be driven by the presence of any IMDs. There is a need for future longitudinal and experimental studies to understand the mechanisms driving our findings.

Rates of HIV-1 virological suppression and patterns of acquired drug resistance among fisherfolk on first-line antiretroviral therapy in Uganda.

OBJECTIVES: We examined virological outcomes, patterns of acquired HIV drug resistance (ADR), correlates of virological failure (VF) and acquired drug resistance among fisherfolk on first-line ART. METHODS: We enrolled 1169 adults on ART for a median duration of 6, 12, 24, 36 and ≥48 months and used a pooled VL testing approach to identify VF (VL ≥1000 copies/mL). We performed genotyping among VF cases and determined correlates of VF and ADR by logistic regression. RESULTS: The overall virological suppression rate was 91.7% and ADR was detected in 71/97 (73.2%) VF cases. The most prevalent mutations were M184V/I (53.6%) for NRTIs and K103N (39.2%) for NNRTIs. Thymidine analogue mutations were detected in 21.6% of VF cases while PI mutations were absent. A zidovudine-based ART regimen, duration on ART (≥24 months) and secondary/higher education level were significantly associated with VF. A nevirapine-based regimen [adjusted OR (aOR): 1.87; 95% CI: 0.03-0.54)] and VL ≥10000 copies/mL (aOR: 3.48; 95% CI: 1.37-8.85) were ADR correlates. The pooling strategies for VL testing with a negative predictive value (NPV) of ≥95.2% saved US $20320 (43.5%) in VL testing costs. CONCLUSIONS: We observed high virological suppression rates among these highly mobile fisherfolk; however, there was widespread ADR among those with VF at the first VL testing prior to intensive adherence counselling. Timely treatment switching and adherence support is recommended for better treatment outcomes. Adoption of pooled VL testing could be cost effective, particularly in resource-limited settings.