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Background: Adolescents and young adults (AYA) living with HIV have been shown to have lower rates of viral load testing and viral suppression as compared to older adults. We examined trends over time and predictors of HIV viral load monitoring and viral suppression among AYA in a large HIV treatment programme in Dar es Salaam, Tanzania. Methods: We analysed longitudinal data of AYA aged 10–24 years initiated on antiretroviral therapy between January 2017 and October 2022. Trend models were used to assess changes in HIV viral load testing and viral suppression by calendar year. Generalised estimating equations were used to examine the relationship of sociodemographic and clinical factors with HIV viral load testing and viral suppression. Results: Out of 15,759 AYA, the percentage of those who received a 6‐month HIV viral load testing increased from 40.6% in 2017 to 64.7% in 2022 and, a notable annual increase of 5.6% (p < 0.001). A higher HIV viral load testing uptake was observed among 20‐ to 24‐year‐olds (87.7%) compared to 10‐ to 19‐year‐olds (80.2%) (p < 0.001). The likelihood of not receiving an HIV viral load test within 12 months of antiretroviral therapy initiation was higher among 10‐ to 19‐year‐olds (adjusted odds ratio [aOR] = 1.7; 95% confidence interval [CI] = 1.4–2.0), advanced HIV disease (aOR = 1.3; 95% CI = 1.12–1.53), normal nutrition status at enrolment aOR 2.6 (95% CI = 1.59–4.26) and initiation of non‐nucleoside reverse transcriptase inhibitors regimen aOR 1.2 (95% CI = 1.08–1.34). The proportion of AYA with viral suppression increased from 83.0% in 2017 to 94.6% in 2022. Notably, the overall trend in viral suppression increased significantly at 2.4% annually. The risk of not achieving viral suppression was greater among 10‐ to 14‐year‐olds (aOR = 2; 95% CI = 1.75–2.43) and 15‐ to 19‐year‐olds (aOR = 1.4; 95% CI = 1.24–1.58) as compared to 20–24 years; being male (aOR = 1.16; 95% CI = 1.02–1.32); undernourished (aOR = 1.53; 95% CI = 1.17–1.99); in WHO Stage II (aOR = 1.16; 95% CI = 1.02–1.33) and III (aOR = 1.21; 95% CI = 1.03–1.42) and being on an non‐nucleoside reverse transcriptase inhibitors regimen (aOR = 1.32; 95% CI = 1.18–1.48). Conclusion: HIV viral load testing uptake at 6 months of antiretroviral therapy initiation and viral suppression increased from 2017 to 2022; however, overall HIV viral load testing was suboptimal. Demographic and clinical characteristics can be used to identify AYA at greater risk for not having HIV viral load test and not achieving viral suppression. [ABSTRACT FROM AUTHOR]

Background/Objectives Screening and diagnosis of iron deficiency anemia (IDA) is cumbersome as it may require testing for hemoglobin, ferritin, and an inflammatory biomarker. The aim of this study was to compare the diagnostic capacity of hematologic biomarkers to detect IDA among pregnant women in Tanzania. Subjects/Methods We pooled data from an iron supplementation trial of 1500 iron-replete pregnant woman and a prospective cohort of 600 iron-deficient pregnant women. Receiver operating characteristic curves (ROC) for hematologic biomarkers were used to assess the sensitivity, specificity, and area under the curve (AUC) for iron deficiency (ID) and iron deficiency anemia (IDA), crude, or corrected for inflammation. Regression models assessed the relationship of baseline biomarker categories (gestational age Results Hemoglobin had the largest AUC for crude ID (0.96), while hepcidin had the largest AUC for corrected ID (0.80). The optimal hepcidin cutoff for the diagnosis of corrected IDA based on maximal sensitivity and specificity was [less than or equal to]1.6 [micro]g/L. An hepcidin cutoff of 110 g/L with IDA at delivery (RR = 0.73; 95% CI: 0.47, 1.13) was attenuated. Baseline hepcidin >1.6 [micro]g/L was associated with reduced risk of anemia at delivery by 49% (95% CI: 27%, 45%). Conclusions Ascertaining hemoglobin and hepcidin levels may improve the targeting of iron supplementation programs in resource-limited countries, though hepcidin's high costs may limit its use., Author(s): Ajibola I. Abioye [sup.1], Said Aboud [sup.2], Zulfiqarali Premji [sup.3], Analee J. Etheredge [sup.4] [sup.5], Nilupa S. Gunaratna [sup.6], Christopher R. Sudfeld [sup.5], Ramadhani A. Noor [sup.1] [sup.5], Ellen [...]

Background Observational studies suggest that vitamin D deficiency among people living with HIV is associated with a greater risk of disease progression and death. Low levels of vitamin D in pregnancy are also associated with poor fetal and infant growth. Therefore, vitamin D supplementation may improve clinical outcomes for pregnant women living with HIV and improve fetal and postnatal growth for their infants. Methods and findings We conducted a randomized, triple-blind, placebo-controlled trial of vitamin D.sub.3 supplementation among pregnant and lactating women living with HIV in Dar es Salaam, Tanzania (ClinicalTrials.gov NCT02305927). Participants were randomized with 1:1 allocation stratified by study clinic to receive either daily 3,000 IU vitamin D.sub.3 supplements or matching placebo supplements from the second trimester of pregnancy (12-27 weeks) until 1 year postpartum. The primary outcomes were (i) maternal HIV progression or death, (ii) small-for-gestational-age (SGA) live births ( Conclusions The trial findings do not support routine vitamin D supplementation for pregnant and lactating women living with HIV in Tanzania. Trial registration ClinicalTrials.gov Identifier: NCT02305927., Author(s): Christopher R. Sudfeld 1,2,*, Karim P. Manji 3, Alfa Muhihi 4, Christopher P. Duggan 2,5, Said Aboud 6, Fadhlun M. Alwy Al-Beity 7, Molin Wang 8,9,10, Ning Zhang 9, [...]

COVID-19 vaccination remains to be the most important intervention in the fight against the pandemic. The immunity among the vaccinated population and its durability can significantly vary due to various factors. This study investigated the humoral immune responses among individuals who received any of the COVID-19 vaccines approved for use in Tanzania. A total of 1048 randomly selected adults who received COVID-19 vaccines at different time points were enrolled and humoral immune responses (IR) were tested at baseline and three months later (960, 91.6%). The level of SARS-CoV-2 anti-spike/receptor binding domain (RBD) IgG, anti-nucleocapsid IgG, and IgM antibodies were determined using a commercially available chemiluminescent microparticle immunoassay. Descriptive data analysis was performed using STATA version 18 and R. At baseline, serum IgG against anti-spike/RBD was detected in 1010/1048 (96.4%) participants (95%CI: 94.9–97.5) and 98.3% (95%CI: 97.3–99) three months later. The IgG against the SARS-CoV-2 nucleocapsid proteins were detected in 40.8% and 45.3% of participants at baseline and follow-up, respectively. The proportion of seroconverters following vaccination and mean titers of anti-spike/RBD antibodies were significantly more among those who had past SARS-CoV-2 infection than in those with no evidence of past infection, (p < 0.001). Only 0.5% of those who had detectable anti-spike/RBD antibodies at baseline were negative after three months of follow-up and 1.5% had breakthrough infections. The majority of participants (99.5%) had detectable anti-spike/RBD antibodies beyond 6 months post-vaccination. The proportion of Tanzanians who mounted humoral IR following COVID-19 vaccination was very high. Seroconversions, as well as the mean titers and durability of humoral IR, were significantly enhanced by exposure to natural SARS-CoV-2 infection. In view of the limited availability of COVID-19 vaccines as well as challenges to completing subsequent doses, booster doses could only be suggested to high-risk groups. [ABSTRACT FROM AUTHOR]

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 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., Author(s): Omowunmi Aibana 1, Chuan-Chin Huang 2, Said Aboud 3, Alberto Arnedo-Pena 4, Mercedes C. Becerra 2, Juan Bautista Bellido-Blasco 4, Ramesh Bhosale 5, Roger Calderon 6, Silvia Chiang 7, [...]

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. [ABSTRACT FROM AUTHOR]

Background: Environmental enteric dysfunction (EED) may contribute to poor growth and development in young children. While validated EED biomarkers are currently lacking, multiplex assays are able to capture multiple domains of the condition. The purpose of this exploratory study was to examine the relationship between biomarkers of EED and subsequent growth and development among Tanzanian HIV-exposed uninfected (HEU) infants. Methodology: We enrolled 467 infants of mothers living with HIV who had participated in a trial of vitamin D3 supplementation during pregnancy. Infant serum samples collected at 6 weeks (n = 365) and 6 months (n = 266) were analyzed for anti-flagellin and anti-lipopolysaccharide (LPS) IgA and IgG via ELISA as well as the 11-plex Micronutrient and EED Assessment Tool (MEEDAT), which incorporates two biomarkers of EED [intestinal fatty acid-binding protein (I-FABP) and soluble CD14 (sCD14)]. Outcomes were 12-month growth [length-for-age z-score (LAZ), weight-for-length z-score (WLZ), and weight-for-age z-score (WAZ)] and development [Caregiver Reported Early Development Instruments (CREDI) z-scores] and were assessed using linear regression. Findings: In primary analyses, higher quartiles of 6-month anti-LPS IgG concentrations were significantly associated with lower LAZ at 12 months (ptrend = 0.040). In secondary analyses, higher log2-transformed 6-week anti-flagellin IgA and 6-month anti-LPS IgA concentrations were significantly associated with lower LAZ at 12 months. No associations were observed between I-FABP or sCD14 and infant growth. However, higher log2-transformed 6-week sCD14 concentrations were significantly associated with lower overall CREDI z-scores, while higher log2-transformed 6-month I-FABP concentrations were significantly associated with higher overall CREDI z-scores. Conclusions: Unlike anti-flagellin and anti-LPS Igs, MEEDAT's biomarkers of EED (I-FABP and sCD14) were not associated with subsequent linear growth among HEU infants in Tanzania. The relationship between EED and infant development warrants further study. Author summary: Growth failure can begin in utero and worsen during early infancy; environmental enteric dysfunction (EED) has been hypothesized as an important causal factor. EED is an acquired, subclinical condition of the small intestine associated with chronic exposure to an unhygienic environment where enteric pathogens persist. Histologic features include mucosal inflammation, villous blunting, altered barrier integrity, and reduced intestinal absorptive capacity. Despite EED's purported link to poor health and nutrition outcomes in young children in low- and middle- income countries (LMICs), our knowledge of EED is relatively limited and is hindered by the lack of validated biomarkers across EED's various domains. In this exploratory study, we examined the relationship between biomarkers of EED, including ones in the 11-plex Micronutrient and EED Assessment Tool (MEEDAT), and growth and development in HIV-exposed uninfected (HEU) Tanzanian infants. Overall, we found that certain anti-flagellin and anti-LPS Igs assessed at 6 weeks and 6 months were significantly associated with reduced linear growth at 12 months. EED biomarkers in MEEDAT were significantly associated with subsequent developmental, but not growth, outcomes. [ABSTRACT FROM AUTHOR]