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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 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: 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: 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 D3 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 D3 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 (<10th percentile), and (iii) infant stunting at 1 year of age (length-for-age z-score < −2). We also examined the effect of vitamin D3 supplementation on secondary maternal and infant health outcomes, maternal and infant serum 25-hydroxyvitamin D (25[OH]D) concentrations, and maternal hypercalcemia. An intent-to-treat analysis was used as the primary analytic approach. We enrolled 2,300 pregnant women between June 15, 2015, and April 17, 2018, and follow-up of mothers and infants was completed on October 20, 2019. There were 1,148 pregnant women randomly assigned to the vitamin D3 group, and 1,152 to the placebo group. The proportion of mothers lost to follow-up at 1 year postpartum was 6.6% in the vitamin D3 group (83 of 1,148) and 6.6% in the placebo group (76 of 1,152). The proportion of children lost to follow-up at 1 year of age was 5.5% in the vitamin D3 group (59 of 1,074 live births) and 5.2% in the placebo group (57 of 1,093 live births). There was no difference in the risk of maternal HIV progression or death, with 166 events during 1,461 person-years of follow-up in the vitamin D3 group and 141 events during 1,469 person-years of follow-up in the placebo group (hazard ratio 1.21, 95% CI 0.97 to 1.52, p = 0.09). There was no difference in the risk of SGA birth between the vitamin D3 (229 SGA births among 1,070 live births) and placebo groups (236 SGA births among 1,091 live births) (relative risk 1.03, 95% CI 0.87 to 1.22, p = 0.70). There was also no difference in the risk of infant stunting at 1 year of age between the vitamin D3 (407 events among 867 infants) and placebo groups (413 events among 873 infants) (relative risk 1.00, 95% CI 0.92 to 1.10, p = 0.95). In terms of adverse events, no cases of maternal hypercalcemia were identified. One hypersensitivity reaction to the trial supplements occurred for a pregnant woman in the placebo group. A limitation of our study is that our findings may not be generalizable to HIV-negative pregnant women or contexts where severe vitamin D deficiency is prevalent. 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. Christopher R. Sudfeld and colleagues, investigate the impact of vitamin D supplementation on clinical outcomes for pregnant women living with HIV, and growth outcomes for their infants. Author summary: Why was this study done?: Observational studies have found that vitamin D deficiency among people living with HIV is associated with an increased risk of HIV disease progression and death. Low levels of vitamin D in pregnancy are also associated with adverse birth outcomes and poor infant growth. What did the researchers do and find?: We conducted a randomized controlled trial of maternal vitamin D3 supplementation during pregnancy and lactation and found no effect on the primary trial outcomes of maternal HIV progression or death, small-for-gestational-age (SGA) live births, and infant stunting (length-for-age z-score < −2) at 1 year of age. There was no effect on most secondary outcomes; however, we found that vitamin D supplementation decreased the risk of death for mothers and increased the risk of preterm birth. Maternal vitamin D supplementation increased maternal serum 25-hydroxyvitamin D (25[OH]D) concentrations throughout follow-up and increased infant 25(OH)D at 6 weeks and 6 months of age, but not at 12 months of age. What do these findings mean?: The trial findings are not in support of routine vitamin D supplementation for pregnant and lactating women living with HIV. The mixed findings on the secondary outcomes of maternal death and preterm birth should be interpreted with caution and require replication in other randomized trials. [ABSTRACT FROM AUTHOR]

Background: CD4 T-helper 1 and T-helper 2 immune responses to Mycobacterium tuberculosis (MTB) are required to control MTB infection in humans. We, therefore, hypothesized infection with HIV or Wuchereria bancrofti (W.bancrofti) is associated with decreased MTB specific immune responses and reduction in protection against MTB infection and disease progression. Objective: To determine the CD4 T helper cell responses in individuals who are infected with HIV or W.bancrofti compared to uninfected individuals upon in-vitro stimulation with MTB strain H37Rv whole cell lysate. Methodology: A total of 122 archived whole blood samples from an on-going study were used to determine the interferon gamma (IFN-γ) Interleukin 2 (IL-2) and Interleukin 4 (IL-4) CD4 T cell responses in samples from HIV-infected (n=20), W.bancrofti infected (n=17), and HIV/W.bancrofti uninfected individuals (n=85) following stimulation with MTB antigen. Flow Cytometry was done to measure the relative amount of cytokines produced after stimulation. Data analysis was done by using Graph Pad Prism. Results: W. Bancrofti infected individuals had significantly higher frequencies of IFN-γ and IL-2 CD4 T cells responses than uninfected individuals (p =0.014 and p= 0.004). Furthermore, HIV infected individuals had higher frequencies of IFN-γ and IL2 CD4 T cells response than HIV uninfected individuals (p =0.037 and p=0.016). The frequencies of IL-4 CD4 T cells in HIV and W.bancrofti was comparable between infected and uninfected individuals (p =0.447 and p=0.599). Conclusion and recommendation: Our findings show that cytokine producing MTB-specific CD4 T cells in W.bancrofti and HIV infected individuals are not diminished. It is recommended to conduct further studies with a large sample size to confirm the impact that HIV/W.bancrofti infection has on the host immunity to TB. [ABSTRACT FROM AUTHOR]

Background: HIV infection can cause malabsorption and rapid utilization of nutrients. A randomized trial of multivitamin supplementation among people living with HIV/AIDS (PLWHA) initiating antiretroviral therapy (ART) in Tanzania was stopped early due to increased alanine aminotransferase (ALT) concentrations in the multiple recommended dietary allowances (RDA) multivitamin group. We conducted detailed analysis to assess the effect of multivitamins on ALT elevations and evaluate whether subgroups of PLWHA have greater hepatotoxicity risks associated with the use of high-dose multivitamins., Methods: We utilized data from a randomized, double-blind trial conducted in 2006-2009 that assessed the effect of high-dose multivitamins that contained vitamin B complex, vitamin C, and vitamin E at multiple RDA as compared to standard-dose multivitamins containing single RDAs among adults initiating ART in Tanzania. We evaluated the effect of high-dose multivitamins on incident mild/moderate ALT elevations > 40 IU/L, persistent ALT elevations > 40 IU/L (2 + clinic visits), and severe ALT elevations > 200IU/L using Cox proportional hazard models. We then evaluated effect modification by patient characteristics to determine if subgroups of PLWHA experienced different magnitudes of risk for ALT elevations associated with high-dose multivitamins., Results: High-dose multivitamins increased the risk of incident mild/moderate ALT elevations > 40 IU/mL as compared to standard-dose multivitamins (hazard ratio (HR): 1.41; 95%CI: 1.26,1.58) as well as incident sustained mild/moderate ALT elevations (HR: 1.19; 95%CI: 1.04,1.36), but there was no overall effect on severe ALT elevations (HR: 1.44; 95% CI: 0.91,2.28). There was no evidence that the effect of high-dose multivitamins on any or sustained mild/moderate ALT elevations was modified by any patient characteristic. However, CD4 T-cell count was found to modify the effect of high-dose multivitamins on severe ALT elevations (p-value for interaction:0.01). Among participants with a baseline CD4 T-cell count ≤ 100 cells/µL, individuals receiving high-dose multivitamins had 3.74 times (95%CI: 1.52-9.17) the risk of incident severe ALT elevations compared to standard-dose multivitamins, while participants with CD4 T-cell counts > 100 cells/µL, appeared to have no effect of high-dose multivitamins on severe ALT elevations (HR:0.92; 95% CI: 0.50,1.67)., Conclusions: High-dose RDA multivitamin supplementation increased the incidence of any mild to moderate ALT elevations among adults starting ART in Tanzania and the magnitude of the risk does not appear to differ by patient characteristics. However, immunocompromised PLWHA with CD4 T-cell counts < 100 cells/µL may experience greater risk of severe ALT elevations associated with the use of high-dose multivitamins. Although the study findings offer significant insights, it is essential to take into account limitations imposed by newer cART regimes., (© 2024. The Author(s).)

Background: A cohort of female sex workers (FSWs) was established to determine HIV prevalence and incidence, and associated factors in preparation for a phase IIb HIV vaccine and pre-exposure prophylaxis trial (PrEPVacc)., Setting: A cohort of FSWs in Dar es Salaam, Tanzania., Methods: FSWs aged 18-45 years were recruited using a respondent-driven sampling method. Social demographic data, HIV risk behavioral assessments, and blood samples for testing of HIV, syphilis, hepatitis B (HBV), and hepatitis C (HCV) infections were collected at baseline and then at 3, 6, 9, and 12 months. Poisson regressions were used to estimate the prevalence ratios for factors associated with HIV prevalence and to estimate the 12-month HIV incidence rate., Results: Between October and December 2018, a total of 773 FSWs were screened for eligibility and 700 were enrolled. The baseline prevalence of HIV, syphilis, HBV, and HCV was 7.6%, 1.2%, 1.7%, and 1.0%, respectively. HIV prevalence was associated with older age, using illicit drugs, and being infected with syphilis, HBV, or HCV. Attendance at 12 months was 80% (562/700). Twenty-one FSWs seroconverted during follow-up, giving a 12-month HIV incidence rate of 3.45 per 100 person-years at risk (95% CI; 2.25-5.28/100 person-years at risk). The HIV incidence rate was higher among FSWs aged 18-24 years, FSWs who used drugs, and those diagnosed with syphilis, HBV, or HCV., Conclusion: The high HIV incidence rate and retention rate among FSWs enrolled into the cohort demonstrate that this population is suitable for participation in HIV prevention trials., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)