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.

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.

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.

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.

Hepatitis B vaccination coverage among healthcare workers at national hospital in Tanzania: how much, who and why?

BACKGROUND: Hepatitis B vaccination for healthcare workers (HCWs) is a key component of the WHO Hepatitis B Elimination Strategy 2016-2021. Data on current hepatitis B vaccine coverage among health care workers in Sub-Saharan Africa are scarce, but these data are vital for effective programming. We assessed the proportion of HCWs vaccinated for hepatitis B and the factors associated with adequate vaccination coverage at a national hospital in Tanzania. METHODS: A descriptive cross-sectional study was conducted among consenting healthcare workers between 30th July and 30th September 2015. Vaccination histories were obtained through self-administered questionnaires. Means and proportions were used to summarize the data. Student's t and chi-squared tests were used as appropriate. Logistic regression was used to determine the factors associated with vaccination. RESULTS: A total of 348 HCWs were interviewed, of whom 198 (56.9%) had received at least one dose of hepatitis B vaccination, while only 117 (33.6%) were fully vaccinated. About half of the 81 HCWs with partial vaccination (49.4%) had missed their subsequent vaccination appointments. Among unvaccinated HCWs, 14 (9.3%) had either HBV infection or antibodies against HBV infection upon pre-vaccination screening. However, the remaining participants were not vaccinated and did not know their immune status against HBV. Nearly all respondents (347, 99.3%) had heard about the hepatitis B viral vaccine. The following reasons for non-vaccination were given: 98 (65.3%) reported that they had not been offered the vaccine; 70 (46.7%) observed standard precautions to ensure infection prevention and 60 (41.3%) blamed a low level of awareness regarding the availability of the hepatitis B vaccine. CONCLUSION: The current vaccination coverage among practicing healthcare workers at Muhimbili National Hospital is low, despite a high level of awareness and the acceptance of the vaccine. Expedited and concerted efforts to scale vaccine uptake should include improved access to the vaccine, especially for newly recruited HCWs. The extension of the study to private healthcare settings and lower-level facilities would be useful.

Efficacy of vitamin D3 supplementation in reducing incidence of pulmonary tuberculosis and mortality among HIV-infected Tanzanian adults initiating antiretroviral therapy: study protocol for a randomized controlled trial.

BACKGROUND: HIV-infected adults initiating antiretroviral therapy (ART) in sub-Saharan Africa continue to experience high rates of morbidity and mortality during the initial months of treatment. Observational studies in high-income and resource-limited settings indicate that HIV-infected adults with low vitamin D levels may be at increased risk of mortality, HIV disease progression, and incidence of pulmonary tuberculosis (TB). As a result, vitamin D3 supplementation may improve survival and treatment outcomes for HIV-infected adults initiating ART. METHODS/DESIGN: The Trial of Vitamins-4 (ToV4) is an individually randomized, double-blind, placebo-controlled trial of vitamin D3 (cholecalciferol) supplementation conducted among 4000 HIV-infected adults with low vitamin D levels [25-hydroxyvitamin D (25(OH)D) <30 ng/mL] initiating ART in Dar es Salaam, Tanzania. The two primary aims of the trial are to determine the effect of a vitamin D3 supplementation regimen on incidence of (1) mortality and (2) pulmonary TB as compared to a matching placebo regimen. The primary safety outcome of the study is incident hypercalcemia. The investigational vitamin D3 regimen consists of oral supplements containing 50,000 IU vitamin D3 taken under direct observation at randomization and once a week for 3 weeks (four doses) followed by daily oral supplements containing 2000 IU vitamin D3 taken at home from the fourth week until trial discharge at 1 year post ART initiation. Trial participants are followed up at weekly clinic visits during the first month of ART and at monthly clinic visits thereafter until trial discharge at 1 year post ART initiation. Secondary aims of the trial are to examine the effect of the vitamin D3 regimen on CD4 T cell reconstitution, incidence of non-TB comorbidities, body mass index (BMI), depression and anxiety, physical activity, bone health, and immunologic biomarkers. DISCUSSION: The ToV4 will provide causal evidence on the effect of vitamin D3 supplementation on incidence of pulmonary TB and mortality among HIV-infected Tanzanian adults initiating ART. The trial will also give insight to whether vitamin D3 supplementation trials for the prevention of pulmonary TB should be pursued in HIV-uninfected populations. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01798680 . Registered on 21 February 2013.

Tuberculosis associated mortality in a prospective cohort in Sub Saharan Africa: Association with HIV and antiretroviral therapy.

OBJECTIVE: Nine out of ten tuberculosis deaths occur in tuberculosis-burdened countries, particularly Sub Saharan Africa. In these setting mortality has not been fully described. We describe the magnitude and pattern of TB mortality in Tanzania. METHODS: A multicenter prospective cohort study was conducted among HIV infected and uninfected pulmonary tuberculosis patients from time of anti-TB treatment initiation to completion. Patients were censored at the time of treatment completion, or at their last visit for those who did not complete TB treatment. Kaplan-Meier curves were used to estimate time to death; cox proportional hazards model was used to examine risk factors for mortality. RESULTS: A total of 58 deaths out of 1696 patients (3.4%) occurred, two thirds (n=39) during the first two months of treatment. Compared to HIV un-infected TB patients, mortality risk for TB/HIV co-infected patients was least when antiretroviral therapy (ART) was initiated after 14 days of anti-TB (RR=3.55; 95% CI: 1.44, 8.73 p<0.0001) and highest when ART was initiated 90 days or less prior to anti-TB and within the first 14 days of anti-TB therapy (RR=10; 95% CI: 3.28, 30.54; p<0.0001). CONCLUSION: Meticulously planned and supervised antiretroviral therapy reduces mortality among TB/HIV patients. Among patients with TB/HIV naïve of ART, withholding ART until the third week of anti-tuberculosis therapy will likely reduce TB mortality in Tanzania. Patients on ART and later develop tuberculosis should be closely monitored.

Effects of isoniazid resistance on TB treatment outcomes under programmatic conditions in a high-TB and -HIV setting: a prospective multicentre study.

Objectives: The scale and impact of background isoniazid resistance in TB- and HIV-endemic countries requires definition to improve treatment success and guide the scale-up of isoniazid preventive therapy (IPT). We describe the effects of isoniazid resistance on TB treatment outcomes among patients with or without HIV infection in Dar es Salaam, Tanzania. Methods: A multicentre, prospective observational study was conducted among TB patients commencing WHO-recommended first-line TB treatment. In multivariate analysis we ascertained the relationship between isoniazid resistance at presentation with a composite of poor treatment outcomes (death, failure or default from TB therapy). Results: Of 861 patients, 250 (29.0%) were HIV infected and 23 (2.7%) had isoniazid resistance. Seven hundred and ninety-seven (92.6%) of the patients were successfully treated and 25 (2.9%) died. Isoniazid resistance [relative risk (RR) = 6.0; 95% CI = 1.9-18.7; P < 0.01] and HIV infection with (RR = 2.3; 95% CI = 1.0-5.2; P = 0.05) or without (RR = 3.1; 95% CI = 1.5-6.2; P < 0.01) ART were independent predictors of poor treatment outcomes. Conclusions: Background isoniazid resistance and HIV infection adversely affected TB treatment outcomes. Early laboratory detection of isoniazid resistance is important for successful TB therapy. Studies on the impact of background isoniazid resistance on the efficacy of isoniazid prophylaxis are recommended.

Multi drug and other forms of drug resistant tuberculosis are uncommon among treatment naïve tuberculosis patients in Tanzania.

BACKGROUND: Surveillance and effective management of drug resistance is important to sustaining tuberculosis (TB) control efforts. We aimed to determine resistance rates to first line anti tuberculosis drugs and to describe factors associated with the resistance to any of the first line anti tuberculosis drugs in Dar es Salaam Tanzania. MATERIALS: Newly diagnosed, TB patients with neither history of tuberculosis treatment nor isoniazid prophylaxis were included into the study. Sputum specimens were cultured on either mycobacteria growth indicator tube 960 (MGIT 960) or Lowenstein Jenstein (LJ) medium supplemented with either glycerol (GLJ) or pyruvate (PLJ). Drug susceptibility for isoniazid, rifampicin, streptomycin and ethambutol was determined by either Lowenstein-Jensen (LJ) medium or mycobacteria growth indicator tube 960 (MGIT 960). RESULTS: A total of 933 newly diagnosed TB patients, were included into the study. Multi drug resistance (MDR) tuberculosis was detected among 2 (0.2%) patients. Resistance to any of the four tested drugs was detected among 54 (5.8%) patients. Mono-resistance to isoniazid, rifampicin, streptomycin and ethambutol were 21(2.3%), 3 (0.3%), 13 (1.4%), 9 (1.0%) respectively. CONCLUSION: Primary resistance to first line anti tuberculosis drugs is still low in this setting. Continued vigilance including periodic national surveillance of anti-tuberculosis resistance is recommended.

Anemia at the initiation of tuberculosis therapy is associated with delayed sputum conversion among pulmonary tuberculosis patients in Dar-es-Salaam, Tanzania.

BACKGROUND: Pulmonary tuberculosis and anemia are both prevalent in Tanzania. There is limited and inconsistent literature on the association between anemia and sputum conversion following tuberculosis treatment. METHODS: Newly diagnosed sputum smear positive pulmonary tuberculosis patients aged ≥15 years initiating on standard anti tuberculosis therapy were recruited from 14 of 54 tuberculosis clinics in Dar es Salaam. Patients were receiving medication according to the recommended short course Directly Observed Therapy (DOT) strategy and were followed up prospectively until completion of treatment (six months). Patients were evaluated before initiation of TB treatment by performing the following; clinical history, physical examination, complete blood counts, serum biochemistry and sputum microscopy. Sputum smears were re-examined at two months of anti-tuberculosis therapy for presence of acid fast bacilli. Anemia was defined as hemoglobin <13 g/dl (males) or <12 g/dl (females). Log-binomial regression was used to assess the association between anemia and sputum conversion at two months. RESULTS: Of the 1245 patients included in the study, 86% were anemic and 7% were sputum smear positive at two months of anti-tuberculosis therapy. Anemic patients were three times more likely to have sputum positive smear as compared to non-anemic patients at two months (RR = 3.05; 95% CI 1.11-8.40) p = 0.03. The risk for sputum positive smear results increased with severity of anemia (P for trend <0.01). CONCLUSION: Baseline anemia is associated with increased risk for persistent positive sputum smears at two months of tuberculosis treatment. Future studies should evaluate the mechanisms for TB-associated anemia as well as the role of intervention for anemia among TB patients.

Hepatitis A, B and C viral co-infections among HIV-infected adults presenting for care and treatment at Muhimbili National Hospital in Dar es Salaam, Tanzania.

BACKGROUND: Tanzania is currently scaling-up access to anti-retro viral therapy (ART) to reach as many eligible persons as possible. Hepatitis viral co-infections are known to influence progression, management as well as outcome of HIV infection. However, information is scarce regarding the prevalence and predictors of viral hepatitis co-infection among HIV-infected individuals presenting at the HIV care and treatment clinics in the country. METHODS: A cross-sectional study conducted between April and September 2006 enrolled 260 HIV-1 infected, HAART naïve patients aged > or = 18 years presenting at the HIV care and treatment clinic (CTC) of the Muhimbili National Hospital (MNH). The evaluation included clinical assessment and determination of CD4+ T-lymphocyte count, serum transaminases and serology for Hepatitis A, B and C markers by ELISA. RESULTS: The prevalence of anti HAV IgM, HBsAg, anti-HBc IgM and anti-HCV IgG antibodies were 3.1%, 17.3%, 2.3% and 18.1%, respectively. Dual co-infection with HBV and HCV occurred in 10 individuals (3.9%), while that of HAV and HBV was detected in two subjects (0.8%). None of the patients had all the three hepatitis viruses. Most patients (81.1%) with hepatitis co-infection neither had specific clinical features nor raised serum transaminases. History of blood transfusion and jaundice were independent predictors for HBsAg and anti-HBc IgM positivity, respectively. CONCLUSION: There is high prevalence of markers for hepatitis B and C infections among HIV infected patients seeking care and treatment at MNH. Clinical features and a raise in serum alanine aminotransferase were of limited predictive values for the viral co-infections. Efforts to scale up HAART should also address co-infections with Hepatitis B and C viruses.