Background 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 rRNA sequencing (Illumina Miseq). Results HIV 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<0.01), Finegoldia (p<0.01) and Anaerococcus (p<0.01) in HIV infected, and enrichment of Enterobacteriaceae (p=0.02) 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. Conclusion HIV infected children have altered gut microbiota. Prolonged ART may restore the richness of the microbiota closer to that of HIV-uninfected children.

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 <-1 with no reversibility post-bronchodilation with salbutamol) at two HIV clinics in Harare, Zimbabwe and Blantyre, Malawi. Eligible participants with CLD (cases) were enrolled, together with a control group without CLD (frequency-matched by age group and duration on ART) in a 4:1 allocation ratio. A clinical history and examination was undertaken. The association between CLD and a priori-defined demographic and clinical covariates was investigated using multivariable logistic regression. Results:Of the 1,585 participants screened, 419 (32%) had a FEV 1 z-score <-1, of whom 347 were enrolled as cases (median age 15.3 years ]; 48.9% female), and 74 with FEV1 z-score>0 as controls (median age 15.6 years ; 62.2% female). Amongst 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

Objective: HIV disrupts host defense mechanisms and maintains chronic inflammation in the lung. Nitric oxide is a marker of lung inflammation and can be measured in the exhaled air. We investigated the relationship between exhaled nitric oxide (eNO), HIV status and airway abnormalities in perinatally HIV-infected children aged 6–19 years. Design: A cross-sectional study. Methods: HIV-infected individuals on antiretroviral therapy and HIV-uninfected children with no active tuberculosis (TB) or acute respiratory tract infection were recruited from a public hospital in Harare, Zimbabwe. Clinical history was collected and eNO testing and spirometry was performed. The association between eNO and explanatory variables (HIV, FEV1 z -score, CD4 + cell count, viral load, history of TB) was investigated using linear regression analysis adjusted for age, sex and time of eNO testing. Results: In total, 222 HIV-infected and 97 HIV-uninfected participants were included. Among HIV-infected participants, 57 (25.7%) had a history of past TB; 56 (25.2%) had airway obstruction, but no prior TB. HIV status was associated with lower eNO level [mean ratio 0.79 (95% confidence interval, 95% CI 0.65–0.97), P = 0.03]. Within the HIV-infected group, history of past TB was associated with lower eNO levels after controlling for age, sex and time of eNO testing [0.79 (95% CI 0.67–0.94), P = 0.007]. Conclusion: HIV infection and history of TB were associated with lower eNO levels. eNO levels may be a marker of HIV and TB-induced alteration in pulmonary physiology; further studies focused on potential causes for lower eNO levels in HIV and TB are warranted.

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/mm 3 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 personyears 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.

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 twenty-six 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 and sexmatched controls with PHIV but no CLD. HCLD was defined as having a forced expiratory volume in one second (FEV1) z-score <-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.