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.

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.

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.

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.

Risk Factors for Alanine Aminotransferase Elevations in a Prospective Cohort of HIV-Infected Tanzanian Adults Initiating Antiretroviral Therapy.

INTRODUCTION: Serum alanine aminotransferase (ALT) elevations are common among HIV-infected patients on combination antiretroviral therapy (cART). APPROACH: We conducted a prospective cohort study of 3023 HIV-infected Tanzanian adults initiating cART. We assessed risk factors for mild/moderate ALT elevations >40 IU/L and severe ALT elevations >200 IU/L. RESULTS: We found that over a median follow-up of 32.5 months (interquartile range: 19.4-41.5), 44.8% of participants had at least 1 incident ALT elevation >40 IU/L of which 50.1% were persistent elevations. Risk factors for incident ALT elevation >40 IU/L included male sex, CD4 count <100 cells/µL, d4T+3TC+NVP cART, and triglycerides ≥150 mg/dL (P values <.05). Hepatitis B coinfection and alcohol consumption increased the risk of severe ALT elevations >200 IU/L (P values: <.05). CONCLUSION: Incident mild and moderate ALT elevations are common among Tanzanians initiating cART, and the clinical and demographic information can identify patients at increased risk.

Vitamin D status and risk of incident tuberculosis disease: A nested case-control study, systematic review, and individual-participant data meta-analysis.

BACKGROUND: Few studies have evaluated the association between preexisting vitamin D deficiency and incident tuberculosis (TB). We assessed the impact of baseline vitamins D levels on TB disease risk. METHODS AND FINDINGS: We assessed the association between baseline vitamin D and incident TB in a prospective cohort of 6,751 HIV-negative household contacts of TB patients enrolled between September 1, 2009, and August 29, 2012, in Lima, Peru. We screened for TB disease at 2, 6, and 12 months after enrollment. We defined cases as household contacts who developed TB disease at least 15 days after enrollment of the index patient. For each case, we randomly selected four controls from among contacts who did not develop TB disease, matching on gender and year of age. We also conducted a one-stage individual-participant data (IPD) meta-analysis searching PubMed and Embase to identify prospective studies of vitamin D and TB disease until June 8, 2019. We included studies that assessed vitamin D before TB diagnosis. In the primary analysis, we defined vitamin D deficiency as 25-(OH)D < 50 nmol/L, insufficiency as 50-75 nmol/L, and sufficiency as >75nmol/L. We estimated the association between baseline vitamin D status and incident TB using conditional logistic regression in the Lima cohort and generalized linear mixed models in the meta-analysis. We further defined severe vitamin D deficiency as 25-(OH)D < 25 nmol/L and performed stratified analyses by HIV status in the IPD meta-analysis. In the Lima cohort, we analyzed 180 cases and 709 matched controls. The adjusted odds ratio (aOR) for TB risk among participants with baseline vitamin D deficiency compared to sufficient vitamin D was 1.63 (95% CI 0.75-3.52; p = 0.22). We included seven published studies in the meta-analysis and analyzed 3,544 participants. In the pooled analysis, the aOR was 1.48 (95% CI 1.04-2.10; p = 0.03). The aOR for severe vitamin D deficiency was 2.05 (95% CI 0.87-4.87; p trend for decreasing 25-(OH)D levels from sufficient vitamin D to severe deficiency = 0.02). Among 1,576 HIV-positive patients, vitamin D deficiency conferred a 2-fold (aOR 2.18, 95% CI 1.22-3.90; p = 0.01) increased risk of TB, and the aOR for severe vitamin D deficiency compared to sufficient vitamin D was 4.28 (95% CI 0.85-21.45; p = 0.08). Our Lima cohort study is limited by the short duration of follow-up, and the IPD meta-analysis is limited by the number of possible confounding covariates available across all studies. CONCLUSION: Our findings suggest vitamin D predicts TB disease risk in a dose-dependent manner and that the risk of TB disease is highest among HIV-positive individuals with severe vitamin D deficiency. Randomized control trials are needed to evaluate the possible role of vitamin D supplementation on reducing TB disease risk.

Vitamin A and Zinc Supplementation Among Pregnant Women to Prevent Placental Malaria: A Randomized, Double-Blind, Placebo-Controlled Trial in Tanzania.

AbstractVitamin A and zinc are important for immune function and may improve host defense against malaria and reduce the risk of adverse pregnancy outcomes. Our objective was to determine whether daily oral supplementation with either or both nutrients starting in the first trimester reduces the risk of placental malaria and adverse pregnancy outcomes. We undertook a randomized, double-blind placebo-controlled trial with a factorial design among 2,500 human immunodeficiency virus-negative primigravid or secundigravid pregnant women in their first trimester of pregnancy in Dar es Salaam, Tanzania. We randomly allocated equal numbers of participants to 2,500 IU of vitamin A, 25 mg of zinc, both 2,500 IU of vitamin A and 25 mg of zinc, or a placebo until delivery. A total of 625 participants were allocated to each treatment group. Our primary outcome, placental malaria infection (past or current), was assessed in all randomized participants for whom placental samples were obtained at delivery (N = 1,404), which represents 56% of total participants and 62% of all pregnancies lasting 28 weeks or longer (N = 2,266). Birth outcomes were obtained for 2,434 of the 2,500 randomized participants. Secondary outcomes included small for gestational age (SGA) births and prematurity. All analyses were intent to treat. Those who received zinc had a lower risk of histopathology-positive placental malaria compared with those who did not receive zinc (risk ratio = 0.64, 95% confidence interval = 0.44, 0.91), but neither nutrient had an effect on polymerase chain reaction-positive malaria, SGA, or prematurity. No safety concerns were identified. We recommend additional studies in other geographic locations to confirm these findings.

Acceptability and adherence to Isoniazid preventive therapy in HIV-infected patients clinically screened for latent tuberculosis in Dar es Salaam, Tanzania.

BACKGROUND: Proper adherence to isoniazid preventive therapy (IPT) may depend upon the results of tuberculosis (TB) screening test and patients' understanding of their risk of developing active TB. We conducted a study to assess the acceptability, adherence and completion profile of IPT among HIV-infected patients who were clinically screened for latent TB Infection (LTBI). METHODS: A multicenter observational study was conducted in Dar es Salaam, Tanzania between February 2012 and March 2014. HIV-infected patients 10 years or older were clinically screened using a validated symptom-based screening tool to rule out active TB. Patients found to have no symptoms in the screening tool were given 300 mg of isoniazid (INH) daily for 6 months. Patients were followed up monthly at the National and Municipal hospital HIV clinics for INH refill and assessment of treatment adherence. Adherence was defined as consumption of 90 % or more of the monthly prescription of INH. RESULTS: All 1303 invited patients agreed to participate in the study. Of 1303 invited HIV-infected patients, 1283 (98.5 %) were recruited into the study. Twenty eight (2.2 %) did not complete treatment. Those who did not complete the treatment were exclusively adults aged 18 years or older, p = 0.302. The overall mean (±SD) adherence was 98.9 % (±2.9). Adherence level among children aged <18 years (92.2 %) was significantly lower than adherence level among patients aged 18-29 years (98.3 %), 30-49 years (98.8 %) and ≥ 50 years (98.5), p-value = 0.011. Sex, occupation, socio-economic status, duration of HIV infection, being on antiretroviral drugs (ARV) and duration of ARV use were not associated with adherence. CONCLUSION: IPT is highly accepted by HIV infected patients. Patients demonstrated high level of adherence to IPT. The level of adherence among children was slightly lower than that among adults. IPT non-completers were exclusively adults. Children might need adult supervision in taking IPT.

Prevalence and risk factors for skin diseases among antiretroviral-naïve HIV-infected pregnant women in Dar es Salaam, Tanzania.

BACKGROUND: Reduced cell-mediated immunity associated with pregnancy may cause a flaring or exacerbation of some skin conditions. Little is known about the magnitude of and risk factors for skin diseases among human immunodeficiency virus (HIV)-infected antiretroviral therapy-naïve pregnant women. METHODS: Cross-sectional study of 1078 HIV-infected antiretroviral therapy-naïve pregnant women was conducted in Dar es Salaam, Tanzania. Skin diagnoses were mainly clinical. Log-binomial regression models were used to explore factors associated with the outcomes. RESULTS: About 84% of the women were in World Health Organization (WHO) HIV stage I. Median CD4(+) count was 405 × 10(6)  cells/l. The prevalence of any skin disease was 18%. Fungal infections (11%), genital ulcers (7%), and viral infections (5%) were the most common skin conditions. Skin infections were 2.64 times more common in HIV stage III (95% CI 1.51-4.62) compared to stage I. Fungal infections were 1.77 times common among single, divorced, and widowed women than among married women (95% CI 1.16-2.69), 2.8 times common among women in HIV stage III (95% CI 1.18-6.64) compared to stage I. Genital ulcers were significantly more common among women whose source of income was their own compared with those who got full support from partners, and among WHO HIV stage III disease compared to stage I. CONCLUSION: The burden of skin diseases was relatively low. Advanced HIV stage was associated with a range of skin conditions. CD4(+) cell count was not related to skin infection prevalence.

Effect of selenium supplementation on HIV-1 RNA detection in breast milk of Tanzanian women.

OBJECTIVE: Selenium supplementation for women infected with HIV may increase genital shedding of HIV-1, however, to our knowledge, no studies have examined the effect on viral shedding in breast milk. The aim of this study was to determine the effect of selenium supplementation on HIV-1 RNA detection in breast milk of HIV-infected women. METHODS: HIV-infected pregnant women enrolled at 12 to 27 wk gestation in a randomized, double-blind, placebo-controlled trial of daily selenium (200 µg as selenomethionine) had cell-free HIV-1 RNA quantified in breast milk at 4 to 9 wk postpartum. All participants received high-dose multivitamins containing vitamin B complex, C, and E as standard of care. RESULTS: The proportion of women with detectable (>50 copies/mL) HIV-1 RNA in breast milk appeared to be increased in the selenium group (36.4%) compared with those in the placebo group (27.5%) among the total cohort (N = 420), but results were borderline statistically significant (relative risk [RR], 1.32; 95% confidence interval [CI], 1.00-1.76; P = 0.05). In secondary analyses, the proportion of women with detectable HIV-1 RNA in breast milk was significantly greater in the selenium group (37.8%) compared with placebo group (27.5%) among women who did not receive highly active antiretroviral therapy (HAART; RR, 1.37; 95% CI, 1.03-1.82; P = 0.03). This relationship was primarily due to a significant effect of selenium among primiparous women (RR, 2.24; 95% CI, 1.30-3.86; P < 0.01), but not multiparous women (RR, 1.14; 95% CI, 0.81-1.59; P = 0.54) (P-value for interaction = 0.02). Too few women received HAART in this study (n = 12) to establish the effect of selenium supplementation. CONCLUSIONS: Selenium supplementation appears to increase HIV-1 RNA detection in breast milk among primiparous women not receiving HAART. Safety studies among pregnant women on HAART need to be conducted before administering selenium-containing supplements.

Symptom-based screening tool in ruling out active tuberculosis among HIV-infected patients eligible for isoniazid preventive therapy in Tanzania.

OBJECTIVES: We assessed the usefulness of the National TB and Leprosy Control Program (NTLP) symptom-based tuberculosis (TB) screening tool in identifying HIV-infected patients eligible for isoniazid preventive therapy in Muhimbili National Hospital, Dar es Salaam Tanzania. METHODS: Descriptive cross-sectional study. Data collected included socio-demographic and clinical data. Chest X-ray, sputum for acid-fast bacilli (AFB) microscopy, mycobacterial culture, CD4 + count and complete blood count were performed. Patients were considered not having active TB if they presented with no symptom in the screening tool, which comprised these symptoms: cough, fever and excessive night sweats for ≥2 weeks; weight loss of ≥3 kg in 4 weeks and haemoptysis of any duration. The reference standard was a negative culture for Mycobacterium tuberculosis. RESULTS: We enroled 373 patients, of whom 72.1% were females. Active pulmonary TB was found in 4.1% (14/338) of the participants as defined by a positive culture. The sensitivity and specificity of the NTLP screening tool were 71.4% (10/14) and 75.9% (246/324), respectively. False-negative rate was 28.6% (4/10). Cough, fever for ≥2 weeks and weight loss were independent predictors of NTLP-defined TB. Cough ≥2 weeks predicted TB when a positive culture was used to define TB. CONCLUSION: The screening tool had fairly good sensitivity and specificity for TB screening; however, there is a possibility that about 29% of the screened population will be given IPT while they are supposed to receive a full course of TB treatment.

Vitamin D status and TB treatment outcomes in adult patients in Tanzania: a cohort study.

OBJECTIVES: Vitamin D is an immunomodulator and can alter response to tuberculosis (TB) treatment, though randomised trials have been inconclusive to date. We present one of the first comprehensive analysis of the associations between vitamin D status and TB treatment, T-cell counts and nutritional outcomes by HIV status. DESIGN: Cohort study. SETTING: Outpatient clinics in Tanzania. PARTICIPANTS: 25-hydroxyvitamin D levels were assessed in a cohort of 677 patients with TB (344 HIV infected) initiating anti-TB treatment at enrolment in a multivitamin supplementation (excluding vitamin D) trial (Clinicaltrials.gov identifier: NCT00197704). PRIMARY AND SECONDARY OUTCOME MEASURES: Information on treatment outcomes such as failure and relapse, HIV disease progression, T-cell counts and anthropometry was collected routinely, with a median follow-up of 52 and 30 months for HIV-uninfected and HIV-infected patients, respectively. Cox and binomial regression, and generalised estimating equations were used to assess the association of vitamin D status with these outcomes. RESULTS: Mean 25-hydroxyvitamin D concentrations at enrolment were 69.8 (±21.5) nmol/L (27.9 (±8.6) ng/mL). Vitamin D insufficiency (<75 nmol/L) was associated with a 66% higher risk of relapse (95% CI 4% to 164%; 133% higher risk in HIV-uninfected patients). Each unit higher 25-hydroxyvitamin D levels at baseline were associated with a decrease of 3 (p=0.004) CD8 and 3 (p=0.01) CD3 T-cells/µL during follow-up in patients with HIV infection. Vitamin D insufficiency was also associated with a greater decrease of body mass index (BMI; -0.21 kg/m(2); 95% CI -0.39 to -0.02), during the first 8 months of follow-up. No association was observed for vitamin D status with mortality or HIV disease progression. CONCLUSIONS: Adequate vitamin D status is associated with a lower risk of relapse and with improved nutritional indicators such as BMI in patients with TB, with or without HIV infection. Further research is needed to determine the optimal dose of vitamin D and effectiveness of daily vitamin D supplementation among patients with TB.

Weight change at 1 mo of antiretroviral therapy and its association with subsequent mortality, morbidity, and CD4 T cell reconstitution in a Tanzanian HIV-infected adult cohort.

BACKGROUND: The development of low-cost point-of-care technologies to improve HIV treatment is a major focus of current research in resource-limited settings. OBJECTIVE: We assessed associations of body mass index (BMI; in kg/m(2)) at antiretroviral therapy (ART) initiation and weight change after 1 mo of treatment with mortality, morbidity, and CD4 T cell reconstitution. DESIGN: A prospective cohort of 3389 Tanzanian adults initiating ART enrolled in a multivitamin trial was followed at monthly clinic visits (median: 19.7 mo). Proportional hazard models were used to analyze mortality and morbidity associations, whereas generalized estimating equations were used for CD4 T cell counts. RESULTS: The median weight change at 1 mo of ART was +2.0% (IQR: -0.4% to +4.6%). The association of weight loss at 1 mo with subsequent mortality varied significantly by baseline BMI (P = 0.011). Participants with ≥2.5% weight loss had 6.43 times (95% CI: 3.78, 10.93 times) the hazard of mortality compared with that of participants with weight gains ≥2.5%, if their baseline BMI was <18.5 but only 2.73 times (95% CI: 1.49, 5.00 times) the hazard of mortality if their baseline BMI was ≥18.5 and <25.0. Weight loss at 1 mo was also associated with incident pneumonia (P = 0.002), oral thrush (P = 0.007), and pulmonary tuberculosis (P < 0.001) but not change in CD4 T cell counts (P > 0.05). CONCLUSIONS: Weight loss as early as 1 mo after ART initiation can identify adults at high risk of adverse outcomes. Studies identifying reasons for and managing early weight loss are needed to improve HIV treatment, with particular urgency for malnourished adults initiating ART. The parent trial was registered at clinicaltrials.gov as NCT00383669.

Association of serum albumin concentration with mortality, morbidity, CD4 T-cell reconstitution among tanzanians initiating antiretroviral therapy.

BACKGROUND: Prospective studies of serum albumin concentration measurement as a low-cost predictor of human immunodeficiency virus (HIV) disease progression are needed for individuals initiating antiretroviral therapy (ART) in resource-limited settings. METHODS: Serum albumin concentration was measured at ART initiation for 2145 adults in Tanzania who were enrolled in a trial examining the effect of multivitamins on HIV disease progression. Participants were prospectively followed for mortality, morbidity, and anthropometric outcomes at monthly visits (median follow-up duration, 21.2 months). Proportional hazard models were used to analyze mortality, morbidity, and nutritional outcomes, while generalized estimating equations were used to analyze CD4(+) T-cell counts. RESULTS: Individuals with hypoalbuminemia (defined as a serum albumin concentration of <35 g/L) at ART initiation had a hazard of death that was 4.52 times (95% confidence interval, 3.37-6.07; P < .001) that of individuals with serum albumin concentrations of ≥ 35 g/L, after multivariate adjustment. Hypoalbuminemia was also independently associated with the incidence of pulmonary tuberculosis (P < .001), severe anemia (P < .001), wasting (P = .002), and >10% weight loss (P = .012). Secondary analyses suggested that serum albumin concentrations of <38 g/L were associated with increased mortality and incident pulmonary tuberculosis. There was no association between serum albumin concentration and changes in CD4(+) T-cell counts (P = .121). CONCLUSIONS: Serum albumin concentrations can identify adults initiating ART who are at high risk for mortality and selected morbidities. Future research is needed to identify and manage conditions that reduce the serum albumin concentration.

Vitamin D status and incidence of pulmonary tuberculosis, opportunistic infections, and wasting among HIV-infected Tanzanian adults initiating antiretroviral therapy.

BACKGROUND: Maintaining vitamin D sufficiency may decrease the incidence of pulmonary tuberculosis and other infectious diseases. We present the first prospective study of vitamin D among human immunodeficiency virus (HIV)-infected adults receiving antiretrovirals in sub-Saharan Africa. METHODS: Serum 25-hydroxyvitamin D (25(OH)D) level was assessed at antiretroviral therapy (ART) initiation for 1103 HIV-infected adults enrolled in a trial of multivitamins (not including vitamin D) in Tanzania. Participants were prospectively followed at monthly visits at which trained physicians performed a clinical examination and nurses took anthropometric measurements and assessed self-reported symptoms. Cox proportional hazards models estimated hazard ratios (HRs) of morbidity outcomes. RESULTS: After multivariate adjustment, vitamin D deficiency (defined as a concentration of <20 ng/mL) had a significantly greater association with incident pulmonary tuberculosis, compared with vitamin D sufficiency (HR, 2.89; 95% confidence interval [CI], 1.31-7.41; P = .027), but no association was found for vitamin D insufficiency (defined as a concentration of 20-30 ng/mL; P = .687). Deficiency was also significantly associated with incident oral thrush (HR, 1.96; 95% CI, 1.01-3.81; P = .046), wasting (HR, 3.10; 95% CI, 1.33-7.24; P = .009), and >10% weight loss (HR, 2.10; 95% CI, 1.13-3.91; P = .019). Wasting results were robust to exclusion of individuals experiencing pulmonary tuberculosis. Vitamin D status was not associated with incident malaria, pneumonia, or anemia. CONCLUSIONS: Vitamin D supplementation trials for adults receiving ART appear to be warranted.

Vitamin D and HIV progression among Tanzanian adults initiating antiretroviral therapy.

BACKGROUND: There is growing evidence of an association between low vitamin D and HIV disease progression; however, no prospective studies have been conducted among adults receiving antiretroviral therapy (ART) in sub-Saharan Africa. METHODS: Serum 25-hydroxyvitamin D (25(OH)D) levels were assessed at ART initiation for a randomly selected cohort of HIV-infected adults enrolled in a trial of multivitamins (not including vitamin D) in Tanzania during 2006-2010. Participants were prospectively followed at monthly clinic visits for a median of 20.6 months. CD4 T-cell measurements were obtained every 4 months. Proportional hazard models were utilized for mortality analyses while generalized estimating equations were used for CD4 T-cell counts. RESULTS: Serum 25(OH)D was measured in 1103 adults 9.2% were classified as vitamin D deficient (<20 ng/ml), 43.6% insufficient (20-30 ng/mL), and 47.2% as sufficient (>30 ng/mL). After multivariate adjustment, vitamin D deficiency was significantly associated with increased mortality as compared to vitamin D sufficiency (HR: 2.00; 95% CI: 1.19-3.37; p = 0.009), whereas no significant association was found for vitamin D insufficiency (HR: 1.24; 95% CI: 0.87-1.78; p = 0.24). No effect modification by ART regimen or change in the associations over time was detected. Vitamin D status was not associated with change in CD4 T-cell count after ART initiation. CONCLUSIONS: Deficient vitamin D levels may lead to increased mortality in individuals receiving ART and this relationship does not appear to be due to impaired CD4 T-cell reconstitution. Randomized controlled trials are needed to determine the safety and efficacy of vitamin D supplementation for individuals receiving ART.

Risk factors for mortality among HIV-positive patients with and without active tuberculosis in Dar es Salaam, Tanzania.

BACKGROUND: The aim of this study was to describe risk factors for mortality and clinical characteristics of HIV-infected patients with and without tuberculosis (TB) coinfection. METHODS: A cohort of HIV-infected patients with CD4(+) T-cell counts of ≤200 cells/µl was recruited, consisting of 255 HIV-infected patients without active TB and 231 patients with active TB. All received a well-supervised treatment with an efavirenz-based HAART, and those coinfected with TB received appropriate anti-TB treatment. They were followed up for 48 weeks after HAART initiation. RESULTS: Common presenting symptoms in HIV-only patients were fever (36.5%), headache (34.5%), skin rash (34.5%) and weight loss (32%), while in HIV-TB patients the symptoms were weight loss (58%), cough (57.6%), night sweats (44.6%) and fever (34.2%). HIV-TB patients had significantly lower body mass index, Karnofsky scores and haemoglobin levels compared to those infected with HIV only, despite similar baseline CD4(+) T-cell counts. Overall, 12 (4.7%) HIV patients developed TB and 7 (3%) HIV-TB patients had worsening of their TB symptoms during the study period. Mortality was similar in the two groups, being 10.9% (16 deaths per 100 person years) and 11.3% (17 deaths per 100 person years) in HIV-only and HIV-TB patients, respectively. Overall, more males (13.1%) died compared to females (9.6%). Predictors of mortality were presence of oral candidiasis, Kaposi's sarcoma, low Karnofsky score, and low baseline white blood cell and CD4(+) T-cell counts. CONCLUSIONS: The outcomes following well-supervised treatment of HIV-TB patients are similar to those in patients with HIV alone. Predictors of mortality were those of advanced disease.

Maternal vitamin D status and child morbidity, anemia, and growth in human immunodeficiency virus-exposed children in Tanzania.

BACKGROUND: Vitamin D may help prevent adverse pediatric outcomes, including infectious diseases and growth failure, based on its role in immune and metabolic functions. We examined the association of maternal vitamin D status and pediatric health outcomes in children born to human immunodeficiency virus (HIV)-infected women. METHODS: Vitamin D status was determined in 884 HIV-infected pregnant women at 12 to 27 weeks of gestation in a trial of vitamin supplementation (not excluding vitamin D) in Tanzania. Information on child morbidities, anemia and hypochromic microcytosis, and anthropometry was recorded through monthly clinic visits. Generalized estimating equations and Cox proportional hazards models were used to assess the relationships of outcomes with maternal vitamin D status. RESULTS: A total of 39% of women had low vitamin D levels (<32 ng/mL). Children born to women with low vitamin D status were 1.11 times more likely to report cough during follow-up (relative risk [RR], 1.11; 95% confidence interval [CI], 1.02-1.21). No significant associations were noted for other respiratory symptoms, diarrhea, or anemia outcomes. Low maternal vitamin D status was associated with significantly increased risk of stunting (height-for-age z score, <-2; RR, 1.29; 95% CI, 1.05-1.59) and being underweight (weight-for-age z score, <-2; RR, 1.33; 95% CI, 1.03-1.71). CONCLUSIONS: Maternal vitamin D status may be important for preventing respiratory infections and ensuring optimal growth in HIV-exposed children.