Patterns of detectable viraemia among children and adults with HIV infection taking antiretroviral therapy in Zimbabwe.

OBJECTIVE: To investigate the incidence and predictors of viraemia among individuals on antiretroviral therapy (ART) in Harare, Zimbabwe. METHODS: Children (0-19 years) and adults (>19 years) starting ART between 2013 and 2015 were followed for a median of 2.8 and 2.7 years, respectively. The incidence rates of virological failure (VF), low-level viraemia (LLV), and viral blips were assessed and the predictors of viraemia were determined using logistic and parametric survival regression analyses. RESULTS: A total of 630 individuals initiated ART, and 19.7% of children and 5.6% of adults did not achieve viral suppression by 12 months. Younger age and CD4 count ≤200 cells/mm3 at baseline were associated with not being virally suppressed at 12 months in adults. Among those who achieved viral suppression during the follow-up period, the incidence of VF was higher in children (4.0/100 person-years vs. 0.4/100 person-years in adults; p<0.001), as was the incidence of LLV (1.9/100 person-years vs. 0.3/100 person-years in adults; p=0.03). The incidence rate of blips was 10.9 per 100 person-years in children and 4.0 per 100 person-years in adults. CONCLUSIONS: Children are less likely to reach viral suppression and are at higher risk of viraemia while on ART than adults. The significance of LLV and blips needs further study

Soluble biomarkers associated with chronic lung disease in older children and adolescents with perinatal HIV infection.

OBJECTIVE: HIV-associated chronic lung disease (HCLD) is a common comorbidity in children and adolescents in sub-Saharan Africa (SSA). The pathogenesis of HCLD is unclear and may be driven by underlying dysregulated systemic immune activation and inflammation. We investigated the association between 26 plasma soluble biomarkers and HCLD. DESIGN: Case--control analysis of baseline biomarker data from 336 children and adolescents (6-19 years old) with perinatal HIV infection (PHIV) and HCLD (cases) and 74 age-matched and sex-matched controls with PHIV but no CLD. HCLD was defined as having a forced expiratory volume in one second (FEV1) z score less than -1 with no reversibility. METHODS: Cryopreserved plasma collected at recruitment was used in a multiplex bead assay (Luminex) to measure baseline levels of soluble biomarkers. Logistic regression alongside data-reduction and techniques quantifying the interconnectedness of biomarkers were used to identify biomarkers associated with odds of HCLD. RESULTS: Biomarkers of general immune activation and inflammation (β2M, CRP, sCCL5, GCSF, IFN-γ, IP-10), T-cell activation (sCD25, sCD27), platelet activation (sCD40-L), monocyte activation (sCD14), coagulation (D-Dimer), cellular adhesion (E-selectin), and extracellular matrix degradation (MMP-1, MMP-7, MMP-10) were associated with increased odds of HCLD. Exploratory PCA and assessment of biomarker interconnectedness identified T-cell and platelet activation as centrally important to this association. CONCLUSION: HCLD was associated with a large number of soluble biomarkers representing a range of different pathways. Our findings suggest a prominent role for T-cell and platelet activation in HCLD

"The effect of 48-weeks azithromycin therapy on levels of soluble biomarkers associated with HIV-associated chronic lung disease".

OBJECTIVES: HIV-associated immune activation contributes to chronic lung disease (CLD) in children and adolescents living with HIV. Azithromycin has immunomodulatory and anti-microbial properties that may be useful for treating HIV-associated CLD (HCLD). This study describes the effect of azithromycin on expression of plasma soluble biomarkers in children and adolescents with HCLD. METHODS: This study was nested within a multi-site double-blind, placebo controlled, randomised controlled trial (RCT) of azithromycin in individuals aged 6-19 years with HCLD (defined as FEV1 z-score < -1) in Malawi and Zimbabwe (BREATHE (NCT02426112)). Participants were randomized 1:1 to once-weekly oral azithromycin with weight-based dosing, for 48 weeks, or placebo. Twenty-six plasma soluble biomarkers were measured on a MagPix Luminex instrument at enrolment, after 48-weeks of treatment and 24-weeks after treatment cessation. Mixed effects models were constructed to compare biomarker expression across treatment and placebo groups. RESULTS: Weekly azithromycin was associated with reduced levels of C-Reactive Protein (CRP), E-Selectin, Matrix metalloproteinase 10 (MMP-10). Treatment effects for all soluble biomarkers were not sustained 24-weeks after treatment cessation with biomarker expression returning to pre-treatment levels. CONCLUSIONS: We observed real-world effects of azithromycin on acute inflammation, neutrophil accumulation, and extracellular matrix degradation, that were not sustained after treatment cessation. These results are pertinent when using azithromycin for its immunomodulatory properties, or targeting pathways represented by the soluble biomarkers in this study

Chronic lung disease in children and adolescents with HIV: a case-control study.

OBJECTIVE: To describe the features of HIV-associated chronic lung disease (CLD) in older children and adolescents living with HIV and to examine the clinical factors associated with CLD. This is a post hoc analysis of baseline data from the BREATHE clinical trial (ClinicalTrials.gov, NCT02426112). METHODS: Children and adolescents aged 6-19 years were screened for CLD (defined as a FEV1 z-score 0 as controls [median age 15.6 years (IQR 12.1-18.2); 62.2% female]. Among cases, current respiratory symptoms including cough and shortness of breath were reported infrequently (9.3% and 1.8%, respectively). However, 152 (43.8%) of cases had a respiratory rate above the 90th centile for their age. Wasting and taking second-line ART were independently associated with CLD. CONCLUSIONS: The presence of CLD indicates the need to address additional treatment support for youth living with HIV, alongside ART provision, to ensure a healthier adulthood

Table des illustrations

Vasiliki Boura Fig. 1 : Grotte Pitsa, Péloponnèse, plaquette peinte sur bois (dite Pitsa), Vers 540-530 av. J.-C., musée archéologique d’Athènes, reproduit dans Lydakis Stelios, Αρχαία Ελληνική ζωγραφικη και οι απηχήσεις της στους νεότερους χρόνου, Athènes, Ekdot, Oikos Melissa, 2002, planche 38. Fig. 2 : Verghina, tombe II de Bella, façade marbre, Macédoine, Imathía nomós, ive siècle av. J.-C., reproduit dans Drougou Stella, Saatsoglou-Paliadeli Chrysoula, Βεργίνα. Περιδιαβάζοντας τον αρχαιο..

High lactose whey cheese consumption and risk of colorectal cancer - The Norwegian Women and Cancer Study

The incidence of colorectal cancer (CRC) has increased among Norwegian women, and is among the highest in the world. In order to understand this increase, country specific dietary exposures have been investigated. The aim of this study was to quantify the association between consumption of brown cheese, a common bread topping in Norway, and colorectal, colon, and rectal cancer in the prospective Norwegian Women and Cancer (NOWAC) Study. Data on brown cheese consumption and adjustment factors was available for 82 527 women. During a mean of 14.6 years of follow-up (1.2 million person-years), there were 1360 cases of colorectal cancer (907 colon; 453 rectal). Multivariable Cox proportional hazards models were used to calculate hazard ratios (HR) with 95% confidence intervals (CI) for colorectal, colon, and rectal cancer sites. We modelled restricted cubic splines with 4 knots, to assess a possible non-linear relationship between brown cheese intake and the investigated cancer sites. In the age-adjusted model, consumption of more than 2 slices (>16 grams) of brown cheese per day was associated with 13% reduced risk of colon cancer (95% CI 4%-21%) compared to women who did not consume brown cheese. The multivariable-adjusted model, however, showed no association between brown cheese consumption and the risk of colorectal, colon, or rectal cancer (colorectal: HR = 0.93, 95% CI 0.76–1.13, p-trend 0.37; colon: HR = 0.83, 95% CI 0.65–1.06; p-trend = 0.10; rectal: HR = 1.16, 95% CI 0.84–1.1.61, p-trend = 0.41). In this large, prospective cohort study of women, consumption of brown cheese was suggestively protective against colon cancer. However, adjustment attenuated the inverse risk association. Brown cheese consumption was not associated with rectal cancer, or colorectal cancer overall

Patterns of detectable viraemia among children and adults with HIV infection taking antiretroviral therapy in Zimbabwe

Objective To investigate the incidence and predictors of viraemia among individuals on antiretroviral therapy (ART) in Harare, Zimbabwe. Methods Children (0–19 years) and adults (>19 years) starting ART between 2013 and 2015 were followed for a median of 2.8 and 2.7 years, respectively. The incidence rates of virological failure (VF), low-level viraemia (LLV), and viral blips were assessed and the predictors of viraemia were determined using logistic and parametric survival regression analyses. Results A total of 630 individuals initiated ART, and 19.7% of children and 5.6% of adults did not achieve viral suppression by 12 months. Younger age and CD4 count ≤200 cells/mm3 at baseline were associated with not being virally suppressed at 12 months in adults. Among those who achieved viral suppression during the follow-up period, the incidence of VF was higher in children (4.0/100 person-years vs. 0.4/100 person-years in adults; p < 0.001), as was the incidence of LLV (1.9/100 person-years vs. 0.3/100 person-years in adults; p = 0.03). The incidence rate of blips was 10.9 per 100 person-years in children and 4.0 per 100 person-years in adults. Conclusions Children are less likely to reach viral suppression and are at higher risk of viraemia while on ART than adults. The significance of LLV and blips needs further study

Cytomegalovirus-SpecificImmunoglobulin G is associated with chronic lung disease in children and adolescents from sub-Saharan Africa with perinatal HIV infection

This is a pre-copyedited, author-produced version of an article accepted for publication in Clinical Infectious Diseases following peer review. The version of record Bowen, Sovershaeva E, Charlton, Schive C, Odland j, McHugh G, Bandason T, Mayin, Ferrand RA, Yindom L, Rowland-Jones. Cytomegalovirus-SpecificImmunoglobulin G is associated with chronic lung disease in children and adolescents from sub-Saharan Africa with perinatal HIV infection. Clinical Infectious Diseases. 2020 is available online at: https://doi.org/10.1093/cid/ciaa1757.In a cross-sectional study of 296 children and adolescents from Zimbabwe living with perinatal human immunodeficiency virus, individuals with the top tertile of cytomegalovirus-specific immunoglobulin G titer had an increased odds of chronic lung disease (odds ratio, 3.33; 95% confidence interval, 1.37–8.85; P = .010)

Composition of gut microbiota of children and adolescents with perinatal HIV infection taking antiretroviral therapy in Zimbabwe

Background Human immunodeficiency virus (HIV) infection causes impairment of the gastrointestinal barrier, with substantial depletion of CD4+ T cells in the gut. Antiretroviral therapy (ART) restores CD4+ counts and may have beneficial effects on gut microbiota in adults. Little is known about effect of long-term ART on gut microbiome in HIV-infected children. We investigated composition of gut microbiota in HIV-infected and -uninfected children and assessed associations between gut microbiota and patient characteristics. Methods In a cross-sectional study, rectal swabs were collected from 177 HIV-infected and 103 HIV-uninfected controls. Gut microbial composition was explored using 16S ribosomal ribonucleic acid sequencing. Results Human immunodeficiency virus-infected children had significantly lower alpha-diversity and higher beta-diversity compared to HIV-uninfected. No association was observed between microbiome diversity and CD4+ T-cell count, HIV viral load, or HIV-associated chronic lung disease. We found enriched levels of Corynebacterium (P < .01), Finegoldia (P < .01), and Anaerococcus (P < .01) in HIV-infected participants and enrichment of Enterobacteriaceae (P = .02) in participants with low CD4+ counts (<400 cells/mm3). Prolonged ART-treatment (≥10 years) was significantly associated with a richer gut microbiota by alpha diversity. Conclusions Human immunodeficiency virus-infected children have altered gut microbiota. Prolonged ART may restore the richness of the microbiota closer to that of HIV-uninfected children