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Effect of selenium supplementation on CD4 T-cell recovery, viral suppression, morbidity and quality of life of HIV-infected patients in Rwanda: study protocol for a randomized controlled trial.

ABSTRACT: Low levels of serum selenium are associated with increased risk of mortality among HIV+ patients in East Africa. We aim to assess the effect of selenium supplementation on CD4 cell count, HIV viral load, opportunistic infections, and quality of life in HIV-infected patients in Rwanda.A 24-month, multi-centre, patient and provider-blinded, randomized, placebo-controlled clinical trial involving 300 pre-antiretroviral therapy (ART) HIV-infected patients will be carried out at two sites in Rwanda. Patients ? 21 years of age with documented HIV infection, CD4 cell count of 400-650 cells/mm3, and not yet on ART will be recruited. Patients will be randomized at each study site using a randomized block design to receive either the selenium micronutrient supplement or an identically appearing placebo taken once daily. The primary outcome is a composite of time from baseline to reduction of CD4 T lymphocyte count below 350 cells/mm3 (confirmed by two measures at least one week apart), or start of ART, or the emergence of a documented CDC-defined AIDS-defining illness. An intention-to-treat analysis will be conducted using stepwise regression and structural equation modeling.Micronutrient interventions that aim to improve CD4 cell count, decrease opportunistic infections, decrease HIV viral load, and ultimately delay initiation of more costly ART may be beneficial, particularly in resource-constrained settings, such as sub-Saharan Africa. Additional trials are needed to determine if micro-supplementation can delay the need for more costly ART among HIV-infected patients. If shown to be effective, selenium supplementation may be of public health importance to HIV-infected populations, particularly in sub-Saharan Africa and other resource-constrained settings.

SUBMITTER: Kamwesiga J

PROVIDER: S-EPMC3182905 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

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Effect of selenium supplementation on CD4 T-cell recovery, viral suppression, morbidity and quality of life of HIV-infected patients in Rwanda: study protocol for a randomized controlled trial.

Kamwesiga Julius J Mutabazi Vincent V Kayumba Josephine J Tayari Jean-Claude K JC Smyth Richard R Fay Heather H Umurerwa Alice A Baziruwiha Marcel M Ntizimira Christian C Murebwayire Antoinette A Haguma Jean Pierre JP Nyiransabimana Julienne J Habarurema Donatille D Mukarukundo Veneranda V Nzabandora Jean Bosco JB Nzamwita Pascal P Mukazayire Ernestine E Mills Edward J EJ Seely Dugald D McCready Douglas J DJ Warren Don D

Trials 20110813

<h4>Background</h4>Low levels of serum selenium are associated with increased risk of mortality among HIV+ patients in East Africa. We aim to assess the effect of selenium supplementation on CD4 cell count, HIV viral load, opportunistic infections, and quality of life in HIV-infected patients in Rwanda.<h4>Methods and design</h4>A 24-month, multi-centre, patient and provider-blinded, randomized, placebo-controlled clinical trial involving 300 pre-antiretroviral therapy (ART) HIV-infected patient ...[more]

PMID: 21838913

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Project description:The goal of antiretroviral therapy (ART) is to suppress HIV-1 replication and reconstitute CD4+ T cells. Here, we report on HIV-infected individuals who had a paradoxical decline in CD4+ T cells despite ART-mediated suppression of plasma HIV-1 load (pVL). We defined such an immunological outcome as extreme immune decline (EXID). EXID's clinical and immunological characteristics were compared to immunological responders (IRs), immunological nonresponders (INRs), healthy controls (HCs), and idiopathic CD4+ lymphopenia (ICL) patients. T cell immunophenotyping and assembly/activation of inflammasomes were evaluated by flow cytometry. PBMC transcriptome analysis and genetic screening for pathogenic variants were performed. Levels of cytokines/chemokines were measured by electrochemiluminescence. Luciferase immunoprecipitation system and NK-mediated antibody-dependent cellular cytotoxicity (ADCC) assays were used to identify anti-lymphocyte autoantibodies. EXIDs were infected with non-B HIV-1 subtypes and after 192 weeks of consistent ART-mediated pVL suppression had a median CD4+ decrease of 157 cells/μl, compared with CD4+ increases of 193 cells/μl and 427 cells/μl in INR and IR, respectively. EXID had reduced naive CD4+ T cells, but similar proportions of cycling CD4+ T cells and HLA-DR+CD38+CD8+ T cells compared with IR and INR. Levels of inflammatory cytokines were also similar in EXID and INR, but the IL-7 axis was profoundly perturbed compared with HC, IR, INR, and ICL. Genes involved in T cell and monocyte/macrophage function, autophagy, and cell migration were differentially expressed in EXID. Two of the 5 EXIDs had autoantibodies causing ADCC, while 2 different EXIDs had an increased inflammasome/caspase-1 activation despite consistently ART-suppressed pVL. EXID is a distinct immunological outcome compared with previously described INR. Anti-CD4+ T cell autoantibodies and aberrant inflammasome/caspase-1 activation despite suppressed HIV-1 viremia are among the mechanisms responsible for EXID.

Project description:BackgroundThere is very little data on long-term immune recovery responses in patients on suppressive antiretroviral therapy (ART) in the setting of sub-Saharan Africa (SSA). Thus, we sought to determine CD4+ T-cell, CD8+ T-cell and CD4/CD8 ratio responses in a cohort of HIV infected individuals on sustained suppressive ART followed up for more than a decade.MethodsThe cohort comprised adult patients who started ART between 2001 and 2007 and followed for up to 14 years. Trends in median CD4+ T-cells, CD8+ T-cells and CD4/CD8 ratio were reviewed retrospectively. Poisson regression models were used to identify factors associated with achieving normalized T-cell biomarkers. Kaplan-Meier curves were used to estimate the probability of attaining normalized counts while on suppressive ART.ResultsA total of 227 patients with a median duration of follow-up on ART of 12 (IQR: 10.5-13.0) years were included. CD4 cell count increased from baseline median of 138 cells (IQR: 70-202) to 555 cells (IQR: 417-830). CD4 cell increased continuously up until 5 years, after which it plateaued up until 14 years of follow up. Only 69.6% normalized their CD4 cell count within a median of 6.5 (IQR: 3.0-10.5) years. In addition, only 15.9% of the cohort were able to achieve the median reference CD4+ T-cell threshold count in Ethiopians (≈760 cells/μL). CD8+ T-cell counts increased initially until year 1, after which continuous decrease was ascertained. CD4/CD8 ratio trend revealed continuous increase throughout the course of ART, and increased from a median baseline of 0.14 (IQR: 0.09-0.22) to a median of 0.70 (IQR: 0.42-0.95). However, only 12.3% normalized their ratio (≥ 1.0) after a median of 11.5 years. In addition, only 8.8% of the cohort were able to achieve the median reference ratio of healthy Ethiopians.ConclusionDetermination of both CD4+ and CD8+ T-cells, along with CD4/CD8 ratio is highly relevant in long-term follow-up of patients to assess immune recovery. Monitoring ratio levels may serve as a better biomarker risk for disease progression among patients on long-term ART. In addition, the findings emphasize the relevance of initiation of ART at the early stage of HIV-1 infection.

Project description:IntroductionAiming to reach UNAIDS 90-90-90 targets, nearly all sub-Saharan African countries have expanded antiretroviral therapy (ART) to all people living with HIV (PLWH) (Treat All). Few published data exist on viral load testing and viral suppression under Treat All in this region. We assessed proportions of patients with available viral load test results and who were virally suppressed, as well as factors associated with viral suppression, among PLWH in 10 Rwandan health centres after Treat All implementation.MethodsCross-sectional study during 2018 of adults (≥15 years) engaged in HIV care at 10 Rwandan health centres. Outcomes were being on ART (available ART initiation date in the study database, with no ART discontinuation prior to 1 January 2018), retained on ART (≥2 post-ART health centre visits ≥90 days apart during 2018), available viral load test results (viral load measured in 2018 and available in study database) and virally suppressed (most recent 2018 viral load <200 copies/mL). We used modified Poisson regression models accounting for clustering by health centre to determine factors associated with being virally suppressed.ResultsOf 12,238 patients, 7050 (58%) were female and 1028 (8%) were aged 15 to 24 years. Nearly all patients (11,933; 97%) were on ART, of whom 11,198 (94%) were retained on ART. Among patients retained on ART, 10,200 (91%) had available viral load results; of these 9331 (91%) were virally suppressed. Viral suppression was less likely among patients aged 15 to 24 compared to >49 years (adjusted prevalence ratio (aPR): 0.83, 95% CI 0.76 to 0.90 and those with pre-ART CD4 counts of <200 compared to ≥500 cells/mm3 (aPR: 0.92, 95% CI 0.90 to 0.93). There was no statistically significant difference in viral suppression among patients who entered after Treat All implementation compared to those who enrolled before 2010 (aPR 0.98, 95% CI 0.94 to 1.03).ConclusionsIn this large cohort of Rwandan PLWH receiving HIV care after Treat All implementation, patients in study health centres have surpassed the third UNAIDS 90-90-90 target. To ensure all PLWH fully benefit from ART, additional efforts should focus on improving ART adherence among younger persons.

Project description:Achieving the UNAIDS 95% sustained viral suppression (VS) rate requires considerable global efforts, particularly among adolescents living with HIV (ALHIV) who are often associated with high rates of virological failure (VF). In this study, we prospectively assessed the rate of VS, and the factors associated with VF in a cohort of adolescents followed up according to the WHO guidelines in Cameroon. A cross-sectional study was carried out in 2021 among adolescents (aged 10-19 years) receiving ART in the national program in Cameroon. Socio-demographic and clinical data were collected using patients' medical files and a brief interview with the participant and/or his guardian. Thereafter, a first viral load test (VL1) was performed using the ABBOTT Platform. For adolescents with VL1 > 1000 copies/ml, adherence-enhancing interventions were routinely performed each month for 3 consecutive months, after which a second viral load (VL2) was measured. Adolescents with VL2 > 1000 copies/ml were considered in VF. Overall, 280 adolescents were enrolled, of whom 89.3% (250/280) acquired HIV infection via mother-to-child transmission. The median age was 16.0 (IQR: 13.0-18.0) years and the median duration on ART was 9.8 (IQR: 5.1-12.8) years. Females and males were almost equally represented, as 52.1% (146/280) were female, while 47.9% (134/280) were males (p = 0.47). The VS rate was 88.2% (CI: 83.8-91.7%) overall; 89.0% (CI: 82.0-93.1%) and 88.7% (CI: 81.2-93.0%) in females and males, respectively. Being on second or third-line ART, self-declared suboptimal adherence, and a history of past VF were independently associated with VF. The high rate of VS we report in this study is welcome in the era of the 95/95/95 UNAIDS goals, and indicates that improving treatment outcomes in this specific and fragile population that represent adolescents in Sub-Saharan Africa is achievable. 20/10/2020 NCT04593979 ( https://clinicaltrials.gov/ct2/show/NCT04593979 ).

Dataset Information

Effect of selenium supplementation on CD4 T-cell recovery, viral suppression, morbidity and quality of life of HIV-infected patients in Rwanda: study protocol for a randomized controlled trial.

Publications

Effect of selenium supplementation on CD4 T-cell recovery, viral suppression, morbidity and quality of life of HIV-infected patients in Rwanda: study protocol for a randomized controlled trial.

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