Renal outcomes in adults with HBV, HIV and HBV/HIV coinfection after 3 years of antiviral therapy in urban Tanzania.

BACKGROUND: An enhanced understanding of renal outcomes in persons with chronic HBV, HIV, and HBV/HIV coinfection is needed to mitigate chronic kidney disease in regions where HBV and HIV are endemic. OBJECTIVES: To investigate changes in estimated glomerular filtration rate (eGFR) in adults with HBV, HIV or HBV/HIV enrolled in a 3 year prospective cohort study of liver outcomes in Dar es Salaam, Tanzania and initiated on antiviral therapy. METHODS: We compared eGFR between and within groups over time using mixed-effects models. RESULTS: Four hundred and ninety-nine participants were included in the analysis (HBV: 164; HIV: 271; HBV/HIV: 64). Mean baseline eGFRs were 106.88, 106.03 and 107.18 mL/min/1.73 m2, respectively. From baseline to Year 3, mean eGFR declined by 4.3 mL/min/1.73 m2 (95% CI -9.3 to 0.7) and 3.7 (-7.8 to 0.5) in participants with HBV and HIV, respectively, and increased by 5.1 (-4.7 to 14.9) in those with HBV/HIV. In multivariable models, participants with HBV had lower eGFRs compared with those with HIV or HBV/HIV and, after adjusting for HBV DNA level and hepatitis B e antigen (HBeAg) status, significantly lower eGFRs than those with HBV/HIV at all follow-up visits. CONCLUSIONS: In this Tanzanian cohort, coinfection with HBV/HIV did not appear to exacerbate renal dysfunction compared with those with either infection alone. Although overall changes in eGFR were small, persons with HBV experienced lower eGFRs throughout follow-up despite their younger age and similar baseline values. Longer-term studies are needed to evaluate continuing changes in eGFR and contributions from infection duration and other comorbidities.

Hypertension and traditional risk factors for cardiovascular diseases among treatment naïve HIV- infected adults initiating antiretroviral therapy in Urban Tanzania.

BACKGROUND: Cardiovascular diseases (CVDs) have become an important cause of ill health and death among people living with HIV and/or AIDS (PLHIV) in the antiretroviral therapy (ART) era. There is scarce data on the burden of hypertension (HTN) and risk factors for CVDs among PLHIV in developing countries, including Tanzania during the ART era. OBJECTIVE(S): To determine the prevalence of HTN and risk factors for CVDs among ART naïve PLHIV initiating ART. METHODS: We analysed baseline data of 430 clinical trial participants on the effect of low-dose aspirin on HIV disease progression among HIV-infected individuals initiating ART. HTN was the outcome CVD. Traditional risk factors for CVDs studied were age, alcohol consumption, cigarette smoking, individual and family history of CVDs, diabetes mellitus (DM), obesity/overweight, and dyslipidaemia. A generalized linear model (robust Poisson regression) was used to determine the predictors for HTN. RESULTS: The median (IQR) age was 37 (28, 45) years. Females were the majority contributing 64.9% of all participants. The prevalence of HTN was 24.8%. The most prevalent risk factors for CVDs were dyslipidaemia (88.3%), alcohol consumption (49.3%), and overweight or obesity (29.1%). Being overweight or obese predicted the occurrence of HTN, aPR 1.60 (95% CI 1.16-2.21) while WHO HIV clinical stage 3 was protective against HTN, aPR 0.42(95% CI 0.18-0.97). CONCLUSION: The prevalence of HTN and traditional risk factors for CVDs in the treatment naïve PLHIV initiating ART are significant. Identifying these risk factors and managing them at the time of ART initiation may lower future CVDs among PLHIV.

Dietary Iron Intake and HIV-Related Outcomes Among Adults Initiating Antiretroviral Therapy in Tanzania.

OBJECTIVE: Anemia is highly prevalent among people living with HIV (PLWHIV) and is often due to iron deficiency. This study evaluated the relationship of dietary iron intake levels and sources with mortality and clinical outcomes among adults initiating HAART. DESIGN: We conducted a secondary analysis of a multivitamin supplementation trial among 2293 PLWHIV initiating HAART in Dar es Salaam, Tanzania. METHODS: Dietary iron intake was assessed with a food frequency questionnaire at HAART initiation, and participants followed until death or censoring. Total, animal-, and plant-sourced iron were categorized into quartiles. Intake of food groups was categorized into 0-1, 2-3, and ≥4 servings/wk. Cox proportional hazards models estimated hazard ratios for mortality and incident clinical outcomes. RESULTS: There were 175 deaths (8%). Red meat intake was associated with a lower risk of all-cause mortality (HR: 0.54; 95% CI: 0.35 to 0.83), AIDS-related mortality (HR: 0.49; 95% CI: 0.28 to 0.85), and severe anemia (HR: 0.57; 95% CI: 0.35 to 0.91), when intake ≥4 servings/wk, compared with 0-1 servings/wk. Legume intake was a lower risk of associated with all-cause mortality (HR: 0.49; 95% CI: 0.31 to 0.77) and AIDS-related mortality (HR: 0.37; 95% CI: 0.23 to 0.61), when intake ≥4 servings/wk, compared with 0-1 servings/wk. Although total dietary iron and overall plant-sourced iron intake were not associated with the risk of mortality or HIV-related outcomes, the highest quartile of animal-sourced iron intake was associated with a lower risk of all-cause mortality (HR: 0.56; 95% CI: 0.35 to 0.90) and a lower risk of AIDS-related mortality (HR: 0.50; 95% CI: 0.30 to 0.90), compared with the lowest quartile. CONCLUSION: Intake of iron-rich food groups may be associated with a lower risk of mortality and critical HIV-related outcomes among adults initiating HAART. TRIAL REGISTRATION: The parent trial was registered at Clinicaltrials.gov . Identifier: NCT00383669.

Iron status among HIV-infected adults during the first year of antiretroviral therapy in Tanzania.

BACKGROUND: The influence of inflammation on iron status among people living with HIV (PLWHIV) has not been well explored. We evaluated the trajectory of iron status among PLWHIV during the first year of highly active antiretroviral therapy (HAART), compared alternative approaches for inflammation correction, and assessed the associations of iron status with HIV-1 viral load and anthropometric outcomes. METHODS: We conducted a secondary analysis of data from a randomized trial among 400 adults initiating HAART in Tanzania. Ferritin and C-reactive protein (CRP) were measured at baseline, 1, 6 or 12 months. Ferritin was considered in four ways: unadjusted, and adjusted for inflammation using higher cut-off (HC), Thurnham-corrected (TC) and regression-corrected (RC) approaches. For unadjusted, TC and RC ferritin, iron deficiency (ID) was defined using ferritin < 15 µg/L and elevated iron status was defined using ferritin > 150 µg/L among females and > 200 µg/L among males. For HC ferritin, elevated iron status was defined based on serum ferritin > 500 µg/L, while ID was defined using ferritin < 70 µg/L in the presence of inflammation and < 15 µg/L in the absence of inflammation. Regression models evaluated the trajectory of ferritin concentration across categories of baseline characteristics, and assessed the association of iron status with viral and anthropometric outcomes. RESULTS: The prevalence of iron deficiency at HAART initiation was 9% for unadjusted, 17% for HC, 12% for TC and 22% for RC ferritin. The prevalence of elevated iron status was 42% for unadjusted, 18% for HC, 31% for TC, and 15% for RC ferritin. The prevalence of iron deficiency for all three methods increased during the first year of HAART, while the prevalence of elevated iron status decreased. Baseline elevated iron status defined using HC ferritin was associated with a greater risk of HIV-1 viral load > 1000 copies/mL [relative risk (RR) = 4.29, 95% CI: 1.38-13.3] and incidence of being underweight [body mass index (BMI) < 18.5 kg/m2 , hazard ratio (HR) = 3.65, 95% confidence interval (CI): 1.38-9.67]. Neither baseline-elevated iron status defined using TC or RC ferritin nor baseline iron deficiency defined using any of the three methods was associated with HIV-1 viral load or anthropometric outcomes. CONCLUSIONS: Whether and how inflammation correction is done influences findings of studies of iron status among PLWHIV.

Inhaler Non-Adherence, Associated Factors and Asthma Control among Asthma Patients in a Tertiary Level Hospital in Tanzania.

Background: Inhaled medications including corticosteroids are the most effective long-term controller medicines for asthma-related chronic airway inflammation. Despite this fact, 30% to 70% of the uncontrolled asthma patients report non-adherence to their inhalers. This study investigated factors affecting inhaler non-adherence among outpatient asthma patients in Muhimbili National Hospital, Dar es Salaam Tanzania and related the level of inhaler adherence to the extent of asthma control. Methods: A cross-sectional hospital-based study was conducted among patients with bronchial asthma in the pulmonology clinic of Muhimbili National Hospital in Dar-es-salaam, Tanzania. Patients' demographic, clinical and socio-economic factors were collected using a structured questionnaire. Medication adherence was self-reported using a 10-item Test of Adherence to Inhalers (TAI) questionnaire. Adherence was gauged as good when the score was 50, intermediate (score 46-49) or poor (score ≤ 45). Asthma control was assessed using a 5-question Asthma Control Test (ACT). A score of ≥20 meant well controlled asthma while a score of ≤19 meant poorly controlled asthma. Patients' inhaler use technique was assessed using a 10-step checklist. Patient's technique was regarded correct when all the steps were performed correctly. Categorical data were summarised as proportions. Binary logistic regression was performed to identify factors associated with inhaler non-adherence. Significance level was set at p-value less than .05. Results: A total of 385 asthma patients were enrolled in the study. Females were 206 (53.5%), 232(60.3%) were non-adherent to medications and 283(73.5%) had poorly controlled asthma. Lack of health insurance, fear of medication side effects, being too busy, having alternative medication for asthma and incorrect inhaler technique were significantly associated with non-adherence to inhalers, all p-values <.05. Conclusion: The magnitude of inhaler non-adherence and poorly controlled asthma were very high. Promoting adherence through patients' education on asthma and its management, emphasis on patients' insurance coverage and setting aside time to care for ones' self are fundamental in optimising asthma care and treatment.

Prevalence and determinants of non-communicable diseases including depression among HIV patients on antiretroviral therapy in Dar es Salaam, Tanzania.

OBJECTIVE: People living with HIV/AIDS (PLHA) are experiencing growing co-morbidities due to an increase in life expectancy and the use of long-term antiretroviral therapy (ART). The lack of integrated non-communicable diseases (NCDs) screening and management at the HIV care and treatment centres (CTCs) make it difficult to determine the trends of NCD co-morbidity among patients with HIV. This study aimed to assess the burden and determinants of common NCDs, including depression among patients with HIV. METHODS: Analytical cross-sectional study of 1318 HIV patients enrolled using systematic random sampling conducted from April to November 2020. Five large CTCs in district referral hospitals were selected representing the five districts of Dar es Salaam including Mwananyamala, Temeke, and Amana regional referral hospitals and Sinza and Vijibweni hospitals. The study population consisted of adult PLHA aged 18 years and above. The primary outcome measure was the prevalence of NCDs among HIV patients. Observation of actual NCD medications or their purchase receipts or booked NCD clinic appointments that PLHA had during the study period was used to verify the reported presence of NCDs. The secondary outcome measure was the prevalence of probable depression among PLHA. The locally validated Swahili Patient Health Questionnaire (PHQ-9) was used to screen for depressive symptom severity. A logistic regression model was used to identify factors associated with common NCDs and those associated with probable depression. Potential risk factors that were statistically significant at a P-value of 0.2 or less in univariable analysis were included as potential confounders in multivariable models. RESULTS: The median age of participants was 42 (IQR 35-49) years, with 32.7% in the 36-45 years age group. The majority of patients were women (69%). Most (80.5%) had achieved HIV viral (VL) suppression (a serum HIV VL of <1000 copies/ml). Overall, 14.3% of self-reported an NCD with evidence of their current medication for the NCD from receipts for medication purchased and appointments from NCD clinics they attended. In the multivariable analyses, higher odds of NCDs were in older patients (>45 years) and those with a weight above 75 kg (P < 0.05). Male patients had 51% reduced odds of NCDs (aOR 0.49; 95% CI: 0.32-0.74) than females (P < 0.001). Probable depression prevalence was 11.8%, and depressed patients had more than twice the odds of having NCDs than those without depression (aOR 2.26; 95% CI: 1.45-3.51; P < 0.001). CONCLUSION: This study determined co-existing previously diagnosed NCDs among PLHA accessing care and high levels of depressive symptom severity. We recommend additional research on the feasibility, acceptability, and cost implications of screening and treating NCDs on HIV care platforms to provide evidence for Tanzania's integrated HIV/NCD care model.

Cholecalciferol Supplementation Does Not Affect the Risk of HIV Progression, Viral Suppression, Comorbidities, Weight Loss, and Depression among Tanzanian Adults Initiating Antiretroviral Therapy: Secondary Outcomes of a Randomized Trial.

BACKGROUND: Observational studies suggest that blood concentrations of 25-hydroxyvitamin D [25(OH)D] are associated with morbidity, viral suppression, and mortality among adults living with HIV. OBJECTIVES: We evaluated the effect of cholecalciferol (vitamin D3) supplementation on the risk of HIV disease progression, HIV-1 viral suppression, comorbidities, weight change, and depression among HIV-infected individuals that were initiating antiretroviral therapy (ART) in Dar es Salaam, Tanzania. METHODS: We conducted a randomized, double-blind, placebo-controlled trial of vitamin D3 supplementation among 4000 HIV-infected adult men and nonpregnant women initiating ART with insufficient serum 25(OH)D concentrations (<30 ng/mL). Participants were randomly assigned to receive either weekly 50,000-IU doses for 4 wk followed by daily 2000 IU vitamin D3 until 1 y or a matching placebo regimen given in weekly followed by daily doses until 1 y. Participants were followed up at weekly visits for the first month followed by monthly visits thereafter. We conducted intent-to-treat analyses to assess the effect of vitamin D3 supplementation on the secondary trial outcomes of HIV progression or death, viral suppression, comorbidities, change in BMI, >10% weight loss, incident wasting, and depression. RESULTS: During follow-up, 345 participants (17.2%) in the vitamin D3 group and 371 participants (18.6%) in the placebo group experienced HIV disease progression or death and there was no difference in risk between groups (RR: 0.91; 95% CI: 0.79, 1.06). Vitamin D3 supplementation did not affect the risk of an unsuppressed HIV-1 viral load (>1000 copies/mL) after 6 mo (RR: 1.10; 95% CI: 0.87, 1.41) and there was also no effect on change in BMI, risk of >10% weight loss, wasting, comorbidities, and depression (P values >0.05). CONCLUSIONS: Vitamin D supplementation did not affect the risk of HIV progression, viral suppression, common morbidities, weight-related indicators, or depression among adults initiating ART in Tanzania.This trial was registered at clinicaltrials.gov as NCT01798680.

Predictors of mortality among adolescents and young adults living with HIV on antiretroviral therapy in Dar es Salaam, Tanzania: a retrospective cohort study.

INTRODUCTION: Global AIDS-related deaths have declined by only 10% among adolescents since its peak in 2003. This is disproportionately low compared to a decline of 74% among children aged 0-9 years old. We determined the magnitude of, and predictors of mortality among adolescents and young adults living with HIV on antiretroviral therapy (ART) in Dar-es-Salaam, Tanzania. METHODS: A retrospective cohort study was conducted among adolescents (aged 10-19) and young adults (aged 20-24) living with HIV and enrolled in care and treatment centres in Dar es Salaam, Tanzania between January 2015 and December 2019. Data were analysed using STATA version 16. Cumulative hazard curves were used to estimate and illustrate 1-year mortality. Predictors for mortality were assessed by the Fine and Gray competing risk regression model. Sub-hazard ratios (SHR) and 95% confidence intervals (95% CI) were then reported. RESULTS: A total of 15,874 young people living with HIV were included: 4916 (31.3%) were adolescents and 10,913 (68.7%) were young adults. A total of 3843 (77.5%) adolescents and 9517 (87.2%) young adults were female. Deaths occurred in 2.3% (114/4961) of adolescents and 1.2% (135/10,913) of young adults (p < 0.001). Over a follow-up of 9292 person-years, the mortality rate was 3.8 per 100 person years [95% CI 3.2-4.6/100 person-years] among adolescents and 2.1 per 100 person-years among young adults [95% CI 1.8-2.5/100 person-years]. Independent predictors of mortality among adolescents were male sex (adjusted (SHR) aSHR = 1.90, 95% CI: 1.3-2.8), CD4 count < 200 cells/mm3 (aSHR = 2.7, 95% CI: 1.4-5.0) and attending a private health facility (aSHR = 1.7, 95% CI: 1.1-2.5). Predictors of mortality among young adults were CD4 count < 200 cells/mm3 (aSHR = 2.8, 95% CI 1.7-4.5), being underweight (aSHR = 2.1, 95% CI: 1.4-3.3) and using nevirapine-based therapy (aHR = 8.3, 95% CI: 3.5-19.5). CONCLUSIONS: The mortality rate for persons living with HIV and on ART in Tanzania was significantly higher in adolescents than young adults. Age- and sex-specific risk factors identify targets for intervention to reduce mortality among affected adolescents and young adults.

Effect of aspirin on HIV disease progression among HIV-infected individuals initiating antiretroviral therapy: study protocol for a randomised controlled trial.

INTRODUCTION: An increase in cardiovascular disease (CVD) among people living with HIV infection is linked to platelet and immune activation, a phenomenon unabolished by antiretroviral (ARV) drugs alone. In small studies, aspirin (acetylsalicylic acid [ASA]) has been shown to control immune activation, increase CD4+ count, halt HIV disease progression and reduce HIV viral load (HVL). We present a protocol for a larger ongoing randomised placebo controlled trial on the effect of an addition of ASA to ARV drugs on HIV disease progression. METHODS AND ANALYSIS: A single-centre phase IIA double-blind, parallel-group randomised controlled trial intends to recruit 454 consenting ARV drug-naïve, HIV-infected adults initiating ART. Participants are randomised in blocks of 10 in a 1:1 ratio to receive, in addition to ARV drugs, 75 mg ASA or placebo for 6 months. The primary outcome is the proportion of participants attaining HVL of <50 copies/mL by 8, 12 and 24 weeks. Secondary outcomes include proportions of participants with HVL of >1000 copies/mL at week 24, attaining a >30% rise of CD4 count from baseline value at week 12, experiencing adverse events, with normal levels of biomarkers of platelet and immune activation at weeks 12 and 24 and rates of morbidity and all-cause mortality. Intention-to-treat analysis will be done for all study outcomes. ETHICS AND DISSEMINATION: Ethical approval has been obtained from institutional and national ethics review committees. Findings will be submitted to peer-reviewed journals and presented in scientific conferences. TRIAL REGISTRATION NUMBER: PACTR202003522049711.

Factors hindering integration of care for non-communicable diseases within HIV care services in Dar es Salaam, Tanzania: The perspectives of health workers and people living with HIV.

BACKGROUND: Global mortality attributable to non-communicable diseases (NCDs) occurs in more than 36 million people annually with 80% of these deaths occurring in resource limited countries. Among people living with HIV and AIDS (PLHA) studies have reported higher prevalence's of NCDs compared to the general population but most studies do report a narrow range of NCDs commonly hypertension, diabetes and neoplasms and not all. In addition, there is limited reporting, integration of systematic screening and treatment for all NCDs among PLHA attending care, suggesting the NCD burden among PLHA is likely an underestimate. Little is known about factors facilitating or hindering integration of the care and treatment of NCDs within HIV care and treatment clinics (CTCs) in Tanzania. OBJECTIVE: To explore the perceptions of PLHA and health workers on factors facilitate or hinder the recognition and integration of care for NCDs within CTCs in Dar es Salaam. METHODS: Inductive content analysis of transcripts from 41 in-depth interviews were conducted with 5 CTC managers (CTC Managers), 9 healthcare providers (DHCP) and 27 people living with HIV (PLHA) attending CTCs and with co-morbid NCDs. RESULTS: Four themes emerged; the current situation of services available for care and treatment of NCDs among PLHA in CTCs, experiences of PLHA with co-morbid NCDs with access to care and treatment services for NCDs, facilitators of integrating care and treatment of NCDs within CTCs and perceived barriers for accessing and integration of care and treatment of NCDs within CTCs. CONCLUSIONS: There was a positive attitude among PLHA and healthcare workers towards integration of NCD services within CTC services. This was enhanced by perceived benefits inherent to the services. Factors hindering integration of NCD care and services included; limited and inconsistent supplies such as screening equipment, medications; insufficient awareness of NCDs within PLHA; lack of adequate training of healthcare workers on management of NCD and treatment costs and payment systems.

Clinical and Imaging Features of Adults with Recurrent Pulmonary Tuberculosis - A Prospective Case-Controlled Study.

BACKGROUND: Recurrent pulmonary tuberculosis (RPTB) is a growing, important and neglected problem affecting treated TB patients and TB health services across the world, particularly in sub-Saharan Africa. Analyses and identification of differences in clinical features between recurrent PTB and newly diagnosed PTB may lead to improved management recommendations. METHODS: Between September 1st 2019 and January 31st 2020, we performed a prospective case controlled study of clinical and imaging features of patients with recurrent pulmonary tuberculosis and compared them with those of newly diagnosed PTB cases. Recurrent PTB was defined as a patient with bacteriologically confirmed active PTB who was previously successfully treated for PTB and was cured. A control was defined as a patient who presents for the first time with bacteriologically confirmed PTB. Clinical and radiological features were assessed and documented. Chi-square and t-test were used to test the difference between proportion and continuous data, respectively. Logistic regression analysis was done to determine factors associated with RPTB using SPSS version 23 software. RESULTS: A total of 312 patients with PTB were enrolled (104 RPTB cases and 208 newly diagnosed controls). Clinically hemoptysis was more common in RPTB compared to controls 28/104 (26.9%) vs 35/208 (16.8%), P = 0.036. Chest pain was significantly less common among patients with RPTB compared to controls 33 (31.7%) vs 92 (44.2%), P = 0.034. A higher proportion of RPTB presented with cavitation 34/104 (32.7%) compared to control 44/208 (21.2%) P = 0.027. The median score for lung pathology was higher among patients with RPTB (50) compared to controls (30); P = 0.001. Lung function of patients with RPTB at diagnosis of index TB were more likely to show mixed restrictive and obstructive pattern 36/104 (34.6%) compared to controls 31/208 (14.9%). p<0.001. Multivariate analysis showed that patients older than 45 years of age (adjusted odds ratio [aOR]: 3.59, 95% CI: 1.38 - 9.32), those with hemoptysis (aOR 1.96, 95% CI: 1.04 - 3.69) p=0.04) and fibrosis on chest x rays (aOR 2.18, 95% CI: 1.16 - 4.10) were significantly associated with recurrent PTB. CONCLUSIONS: Hemoptysis, lung parenchymal damage, and patients being older than 45 years of age are significant features of RPTB. Management should focus on risk factors for recurrence, and a more holistic model of care to prevent long term lung injury.

Depression and Viral Suppression Among Adults Living with HIV in Tanzania.

Limited information is available on the association between depression and viral suppression among people living with HIV (PLH) in sub-Saharan Africa. We conducted a prospective cohort study of 3996 adults initiating antiretroviral therapy (ART) in Dar es Salaam, Tanzania. Log-binomial models were used to assess the association between depression and the risk of an unsuppressed viral load (> 400 copies/mL) after 6 months of ART. Women who had depression at both initiation and after 6 months of treatment had 1.94 times (95% CI 1.22, 3.09; z = 2.78, p < 0.01) the risk of an unsuppressed viral load after 6 months of treatment as compared to women who did not have depression at either time point. Men with the top tertile of depressive symptoms after 6 months of treatment had 1.58 times the risk of an unsuppressed viral load (95% CI 1.04, 2.38; z = 2.15, p = 0.03) as compared to the lowest tertile. Research should be pursued on interventions to prevent and address depression among adults initiating ART to potentially support achievement of viral suppression.

Factors associated with sub-microscopic placental malaria and its association with adverse pregnancy outcomes among HIV-negative women in Dar es Salaam, Tanzania: a cohort study.

BACKGROUND: Malaria infection during pregnancy has negative health consequences for both mothers and offspring. Sub-microscopic malaria infection during pregnancy is common in most African countries. We sought to identify factors associated with sub-microscopic placental malaria, and its association with adverse pregnancy outcomes among HIV-negative pregnant women in Dar es Salaam, Tanzania. METHODS: We recruited a cohort of pregnant women during their first trimester and assessed for the occurrence of placental malaria and pregnancy outcomes. The follow-up was done monthly from recruitment until delivery. Histopathology placental malaria positive results were defined as the presence of malaria pigment or parasitized erythrocytes on the slide (histology-positive (HP)), and the sub-microscopic placental infection was defined as positive Plasmodium falciparum DNA by polymerase chain reaction (DNA PCR) amplification in a negative histopathology test. Adverse pregnancy outcomes investigated included low birth weight (birth weight below 2.5 kg), prematurity (live birth below 37 weeks), and small-for-gestational-age (SGA) (live born with a birth weight below 10th percentile for gestational age and sex). Weighted baseline category logit, log-binomial, and log-Poisson models were used to assess factors associated with placental malaria, and its association with adverse pregnancy outcomes. RESULTS: Among 1115 women who had histopathology and DNA PCR performed, 93 (8%) had HP placental infection, and 136 (12%) had the sub-microscopic placental infection. The risk of sub-microscopic placental malaria was greater in women who did not use mosquito prevention methods such as bed nets, fumigation, or mosquito coils (odds ratio (OR) = 1.75; 95% confidence interval (CI): 1.05-2.92; P = 0.03) and in women who were anemic (OR = 1.59; 95% CI: 1.20-2.11; P = 0.001). Women who were underweight had reduced odds of sub-microscopic placental malaria infection (OR = 0.33; 95% CI: 0.17-0.62; P = 0.001). Women who were overweight/obese had 1.48 times higher the odds of HP placental malaria compared to normal weight (OR = 1.48; 95% CI: 1.03-2.11; P = 0.03). HP placental malaria infection was associated with an increased risk of SGA births (RR = 1.30, 95% CI: 0.98-1.72, P = 0.07). In contrast, the sub-microscopic infection was associated with a reduced risk of SGA births (RR = 0.61, 95% CI: 0.43-0.88, P = 0.01). Placental malaria was not associated with low birth weight or prematurity. CONCLUSION: Malaria prevention methods and maternal nutrition status during early pregnancy were important predictors of sub-microscopic placental malaria. More research is needed to understand sub-microscopic placental malaria and the possible mechanisms mediating the association between placental malaria and SGA.

Impaired Hematological Status Increases the Risk of Mortality among HIV-Infected Adults Initiating Antiretroviral Therapy in Tanzania.

BACKGROUND: Hematological status may predict HIV disease progression and mortality among adults initiating highly active antiretroviral therapy (HAART). OBJECTIVES: We aimed to examine the relation of anemia and iron status at HAART initiation with survival and morbidity outcomes. METHODS: We conducted a case-cohort study of 570 HIV-infected adults initiating HAART who were enrolled in a trial of multivitamins in Tanzania. Hemoglobin, serum ferritin, and hepcidin concentrations were assessed at HAART initiation and participants were followed up monthly. We adjusted serum ferritin for inflammation using a regression correction method to characterize hematological status. Cox proportional hazards models were used to estimate HRs for mortality and incident clinical outcomes. RESULTS: We found an 83% prevalence of anemia, 15% prevalence of iron deficiency anemia, and 66% prevalence of anemia of chronic diseases (ACD). The prevalence of elevated iron was 33% and 19% had iron deficiency (ID). After multivariate adjustment, severe anemia (HR: 2.57; 95% CI: 1.49, 4.45) and ACD (HR: 4.71; 95% CI: 2.91, 7.62) were associated with increased risk of mortality as compared with nonanemic participants. In addition, both ID (HR: 2.65; 95% CI: 1.08, 7.78) and elevated iron (HR: 2.83; 95% CI: 2.10, 3.82) were associated with increased risk of mortality as compared with normal iron concentrations. Severe anemia and elevated iron concentrations were associated with incident wasting and >10% weight loss (P values <0.05). CONCLUSIONS: Anemia and both ID and elevated iron were associated with increased mortality among HIV-infected adults initiating HAART. Safety and efficacy studies including anemia etiology, timing of HAART initiation, and dose of iron supplementation among HIV patients appear warranted.This trial was registered at clinicaltrials.gov as NCT00383669.

Efficacy of vitamin D3 supplementation for the prevention of pulmonary tuberculosis and mortality in HIV: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Observational data suggest that low vitamin D status is associated with an increased incidence of pulmonary tuberculosis and mortality among people living with HIV. The primary aims of this study were to assess the effect of vitamin D3 supplementation on the risk of mortality and incidence of pulmonary tuberculosis among adults initiating antiretroviral therapy (ART). METHODS: This was a randomised, double-blind, placebo-controlled trial of vitamin D3 supplementation among adults living with HIV who initiated ART and had serum 25-hydroxyvitamin D concentrations of less than 30 ng/mL at four large HIV care and treatment centres in Dar es Salaam, Tanzania. Patients were excluded if they were younger than 18 years, pregnant at the time of randomisation, or were enrolled in any other clinical trial. Patients were randomly assigned 1:1 to receive either weekly oral 50 000 IU vitamin D3 supplements (cholecalciferol) for the first month of ART followed by daily 2000 IU vitamin D3 supplements or a matching weekly and daily placebo regimen. The randomisation list was computer-generated by a non-study statistician with sequence blocks of ten that were stratified by study clinic. Complete allocation concealment was ensured and patients, field team, and investigators were masked to group assignment. The trial follow-up duration was 1 year and the primary efficacy outcomes were death and incident pulmonary tuberculosis. An intention-to-treat analysis was followed for all-cause mortality; participants diagnosed with or receiving treatment for pulmonary tuberculosis at randomisation, or suspected to have tuberculosis at randomisation and who later had that diagnosis confirmed, were excluded from analyses of pulmonary tuberculosis incidence. Safety was assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT01798680, and is completed. FINDINGS: Between Feb 24, 2014, and Feb 24, 2017, 6250 adults initiating ART had serum 25-hydroxyvitamin D screening, 4000 of whom were enrolled in the trial and followed up for 1 year (follow-up of all participants was completed on March 7, 2018). 2001 patients were randomly assigned to the vitamin D3 supplementation group, and 1999 to the placebo group. 415 deaths were recorded: 211 in the vitamin D3 group and 204 in the placebo group. Among all randomly assigned participants, there was no overall effect of vitamin D3 supplementation on the risk of mortality (hazard ratio [HR] 1·04, 95% CI 0·85-1·25; p=0·73). There was also no difference in the overall incidence of pulmonary tuberculosis between the vitamin D3 (50 events in 1812 patients analysed) and placebo groups (64 events in 1827 patients; HR 0·78, 0·54-1·13; p=0·19). The vitamin D3 regimen did not increase the risk of hypercalcaemia (three events in the vitamin D3 group and two events in the placebo group; relative risk 1·25, 95% CI 0·43-3·66; Fisher's exact p=1·00). 101 hospital admissions were reported in the vitamin D3 group and 94 in the placebo group (incidence rate ratio 1·06, 95% CI 0·80-1·41; p=0·66). INTERPRETATION: Additional research is needed before vitamin D3 supplementation should be considered for implementation in HIV care and treatment programmes for the prevention of pulmonary tuberculosis or mortality. FUNDING: National Institute of Diabetes and Digestive and Kidney Diseases.

The value of hope: development and validation of a contextual measure of hope among people living with HIV in urban Tanzania a mixed methods exploratory sequential study.

BACKGROUND: Hope or hopefulness enhances coping and improves quality of life in persons with chronic or incurable illnesses. Lack of hope is associated with depression and anxiety, which impact negatively on quality of life. In Tanzania, where HIV prevalence is high, the rates of depression and anxiety are over four times higher among people living with HIV (PLH) compared to persons not infected and contribute annual mortality among PLH. Tanzania has a shortage of human resources for mental health, limiting access to mental health care. Evidence-based psychosocial interventions can complement existing services and improve access to quality mental health services in the midst of human resource shortages. Facilitating hope can be a critical element of non-pharmacological interventions which are underutilized, partly due to limited awareness and lack of hope measures, adapted to accommodate cultural context and perspectives of PLH. To address this gap, we developed and validated a local hope measure among PLH in Tanzania. METHODS: Two-phased mixed methods exploratory sequential study among PLH. Phase I was Hope-related items identification using deductive, inductive approaches and piloting. Phase II was an evaluation of psychometric properties at baseline and 24 months. Classical test theory, exploratory, confirmatory factor analysis (CFA) were used. RESULTS: Among 722 PLH, 59% were women, mean age was 39.3 years, and majority had primary school level of education. A total of 40 hope items were reduced to 10 in a three-factor solution, explaining 69% of variance at baseline, and 93% at follow-up. Internal consistency Cronbach's alpha was 0.869 at baseline and 0.958 at follow-up. The three-factor solution depicted: positive affect; cognition of effectiveness of HIV care; and goals/plans/ future optimism. Test-retest reliability was good (r = 0.797) and a number of indices were positive for CFA model fit, including Comparative Fit Index of 0.984. CONCLUSION: The developed local hope scale had good internal reliability, validity, and its dimensionality was confirmed against expectations. The fewer items for hope assessment argue well for its use in busy clinical settings to improve HIV care in Tanzania. Hope in this setting could be more than cognitive goal thinking, pathway and motivation warranting more research. TRIAL REGISTRATION: The intervention was registered in USA ClinicalTrials.gov on September 26, 2012, Registration number: NCT01693458.

Trends in Hospitalisation for Human Immunodeficiency Virus in a Tertiary Hospital in Dar es Salaam, Tanzania: A Case study.

BACKGROUND: Reports on systematic evaluation of the impact of antiretroviral therapy(ART) on patients' hospitalisation in Sub Saharan Africa (SSA) and Tanzania in particular are scarce. We aimed at documenting the trends of hospital admissions at Muhimbili National Hospital (MNH) following scale up of free access to ART in Tanzania. METHODS: Records for all admissions at MNH from June 2005 to June 2015 were reviewed. We extracted data from Hospital Information Management System as well as from patients' charts. Data extracted included diagnosis at discharge, reason for admission and thereafter assessed admission trends over the decade. We summarised the data as frequency and percentages. We compared proportions using Chi squared test, P<0.05 was deemed significant. RESULTS: Overall there were 209,101 admissions during the study period (June 2005 to June 2015) and 7864/209,101 (3.8%) were due to HIV infection. Whereas 598/4,519 (13.2%) of all admissions in 2005 were due to HIV, only 345/13,119 (2.6%) of admissions in 2015 were HIV-related; showing a significant drop over time (P value for trend < .001). Generally, females 3887/6679 (58.2%) were more likely to be admitted than males (41.8%). Median CD4 count for admitted HIV patients was 143 cells/µl. Majority of admissions occured in the medical wards 3643/5310 (68.6%). Discharge diagnoses were Tuberculosis 1396/6482 (21.5%), anaemias 1016/6482 (15.6 %), malignancies 789/6482(12.2%), CNS infections 541/6482 (8.3%) and chronic kidney disease 308/6482 (4.8%). Three leading AIDS defining malignancies among hospitalised patients included Kaposi's sarcoma 380/789 (48.2%), carcinoma of the cervix 77/789 (9.8%), and Non-Hodgkin's lymphoma 44/789 (5.6%). CONCLUSION: Despite drastic drop of HIV related admissions at Muhimbili National Hospital over the years, the infection remains a problem of the adults, largely females suffering from medical conditions and presenting with severe immunosuppression. Tuberculosis remained the most common opportunistic infection among hospitalized HIV infected patients. Anaemia and cancers became more important causes of admission than was diarrhoea which had been the most common among HIV infected patients in pre- ART era.

Aflatoxin exposure in utero and birth and growth outcomes in Tanzania.

Some evidence suggests that aflatoxin may contribute to the high prevalence of stunting observed in low-income countries. Whereas several studies have been conducted in West Africa, fewer exist in East Africa and even fewer in nonagricultural contexts. We analyzed serum samples from 400 iron-replete, nonanemic pregnant women from a cohort in Dar es Salaam, Tanzania to determine the extent and magnitude of exposure to aflatoxin and to study the relationship between levels of aflatoxin exposure in utero and infant birth and growth outcomes. Ninety-nine percent of women had detectable concentrations of aflatoxin B1-lysine (AFB1-lysine), with a median level of 1.4-pg/mg albumin, indicating a much lower level compared to studies of rural populations in sub-Saharan Africa. Our results do not show a statistically significant relationship between AFB1-lysine levels and birth weight, small for gestational age, or prematurity. We observe a small statistically significant reduction in gestational age at delivery (0.47 weeks; 95% CI: -0.86, -0.07) as the natural log of AFB1-lysine levels increases by 1 unit of pg/mg of albumin, after controlling for potential confounders. Among a nonrandom set of infants who had measurements for placental weight, haemoglobin at delivery, and follow-up z-score measurements, we find no association between aflatoxin plasma concentrations and these variables. These findings suggest a high prevalence of chronic low-level exposure to aflatoxin, though its effect on birth outcomes in this population remains unclear. Our research adds to a growing body of literature finding mixed associations between aflatoxins on pregnancy outcomes and child growth.

Prenatal Zinc and Vitamin A Reduce the Benefit of Iron on Maternal Hematologic and Micronutrient Status at Delivery in Tanzania.

BACKGROUND: Zinc and vitamin A supplementation have both been shown to affect iron status, hemoglobin (Hb) concentration, and anemia in animal and human studies. However, evidence on their combined use in pregnancy, in the context of iron-folic acid (IFA) supplementation, remains limited. OBJECTIVE: This study determined the effects of prenatal zinc, vitamin A, and iron supplementation on maternal hematologic and micronutrient status at delivery in Tanzania. METHODS: We analyzed 2 large randomized controlled trials, using generalized estimating equations, and examined the effect of daily zinc (25 mg) and vitamin A (2500 IU) supplementation starting in the first trimester of pregnancy compared with placebo (n = 2500), and separately evaluated the safety and efficacy of daily iron (60 mg) supplementation among iron-replete pregnant women (n = 1500). Blood samples from baseline and delivery were tested for Hb, serum ferritin, soluble transferrin receptor, plasma zinc, and zinc protoporphyrin. RESULTS: Zinc and vitamin A supplementation were associated with lower Hb concentrations at delivery of  -0.26 g/dL (95% CI: -0.50, -0.02 g/dL) and -0.25 g/dL (95% CI: -0.49, -0.01 g/dL), respectively. Vitamin A increased mean ferritin concentrations at delivery (14.3 µg/L, 95% CI: 1.84, 29.11 µg/L), but was associated with increased risk of severe anemia (RR: 1.41; 95% CI: 1.06, 1.88). Among women who were iron replete at baseline, iron supplementation reduced the risk of iron depletion at delivery by 47% (RR: 0.53; 95% CI: 0.43, 0.65). There was no effect of zinc or iron supplements on plasma zinc concentrations. CONCLUSIONS: Our findings support existing WHO guidelines on prenatal iron, vitamin A, and zinc supplementation among pregnant women. In this setting, scaling uptake of prenatal iron supplements is warranted, but prenatal zinc and vitamin A supplementation did not benefit maternal hematologic status at delivery. In settings where vitamin A deficiency is endemic, the efficacy and safety of the WHO recommended prenatal vitamin A supplementation require further evaluation.