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The novel allele KIR2DL5A*0010104 differs from that of KIR2DL5A*0010101 with eight single intronic nucleotide changes., (© 2020 The Authors. HLA published by John Wiley & Sons Ltd.)

Background: Perinatally-acquired HIV infection commonly causes stunting in children; how this affects bone and muscle development is unclear. We investigated differences in bone and muscle mass and muscle function between children with HIV (CWH) and uninfected children., Setting: Cross-sectional study of CWH (6-16 years) receiving antiretroviral therapy (ART) for >6 months and similar aged children testing HIV-negative at primary health clinics in Zimbabwe., Methods: From Dual-energy X-ray Absorptiometry (DXA) we calculated total-body less-head (TBLH) Bone Mineral Content (BMC) for lean mass adjusted-for-height (TBLH-BMC LBM ) Z-scores, and lumbar spine (LS) Bone Mineral Apparent Density (BMAD) Z-scores., Results: The 97 CWH were older (mean age 12.7 vs. 10.0 years) and taller (mean height 142 cm vs. 134 cm) than 77 uninfected. However, stunting (height-for-age Z-score ≤ -2) was more prevalent in CWH (35% vs. 5%, p < 0.001). Among CWH, 15% had low LS-BMAD (Z-score ≤ -2) and 13% low TBLH-BMC LBM , vs. 1% and 3% respectively in those uninfected (both p ≤ 0.02). After age, sex, height and puberty adjustment, LS-BMAD was 0.33 SDs (95%CI -0.01, 0.67; p = 0.06) lower in CWH, with no differences by HIV status in TBLH-BMC LBM , lean mass (0.11 [-0.03, 0.24], p = 0.11) or grip strength (0.05 [-0.16, 0.27], p = 0.62). However, age at ART initiation was correlated with both LS-BMAD Z-score (r = -0.33, p = 0.001) and TBLH-BMC LBM Z-score (r = -0.23, p = 0.027); for each year ART initiation was delayed a 0.13 SD reduction in LS-BMAD was seen., Conclusion: Size-adjusted low bone density is common in CWH. Delay in initiating ART adversely affects bone density. Findings support immediate ART initiation at HIV diagnosis., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Chronic respiratory disease is a common cause of morbidity in children with HIV infection. We investigated longitudinal lung function trends among HIV-infected children, to describe the evolution of lung disease and assess the effect of anti-retroviral therapy (ART)., Methods: Prospective follow-up of two cohorts of HIV-infected children, aged 6 to 16 years, in Harare, Zimbabwe; one group were ART-naïve at enrolment, the other established on ART for a median of 4.7-years. Standardised spirometric assessments were repeated over a 2-year follow-up period. Forced expiratory volume (FEV1) and forced vital capacity (FVC) were expressed as Global Lung Initiative defined z-scores (FEV1z and FVCz). Linear mixed-effects regression modelling of lung function was performed, with co-variate parameters evaluated by likelihood ratio comparison., Results: We included 271 ART-naïve and 197 ART-established children (median age 11 years in both groups) incorporating 1144 spirometric assessments. Changes in FEV1 and FVC were associated with age at ART initiation and body mass index for both cohorts. Our models estimate that ART initiation earlier in life could prevent a deterioration of 0.04 FVCz/year. In the ART-naïve cohort, likelihood ratio comparison suggested an improvement in 0.09 FVCz/year during the two years following treatment initiation, but no evidence for this among participants established on ART., Conclusion: Early ART initiation and improved nutrition are positively associated with lung function and are important modifiable factors. An initial improvement in lung growth was seen in the first 2-years following ART initiation, although this did not appear to be sustained beyond this timeframe., Competing Interests: The authors have declared that no competing interests exist.

Objective: Increasing numbers of children with HIV are surviving to adolescence and encountering multiple clinical and social consequences of long-standing HIV infection. We aimed to investigate the association between HIV and disability, social functioning and school inclusion among 6- to 16-year-olds in Zimbabwe., Methods: HIV-infected children receiving antiretroviral therapy from a public-sector HIV clinic and HIV-uninfected children attending primary care clinics in the same catchment area were recruited. Standardised questionnaires were used to collect socio-demographic, social functioning and disability data. Multivariable logistic regression was used to assess the relationship between HIV status and disability and functioning., Results: We recruited 202 HIV-infected and 285 HIV-uninfected children. There was no difference in age and gender between the two groups, but a higher proportion of HIV-infected children were orphaned. The prevalence of any disability was higher in HIV-infected than uninfected children (37.6% vs. 18.5%, P < 0.001). HIV-infected children were more likely to report anxiety (adjusted odds ratio (aOR) 4.4; 95% CI 2.4, 8.1), low mood (aOR 4.2; 2.1, 8.4) and difficulty forming friendships (aOR 14.8; 1.9, 116.6) than uninfected children. Children with HIV also reported more missed school days, repeating a school year and social exclusion in class. These associations remained apparent when comparing children with HIV and disability to those with HIV but no disabilities., Conclusions: Children with HIV commonly experience disabilities, and this is associated with social and educational exclusion. Rehabilitation and support services are needed to facilitate educational attainment and social participation in this group., (© 2017 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.)

Background: Chronic respiratory symptoms are common among children living with human immunodeficiency virus (HIV). We investigated the radiological features of chronic lung disease in children aged 6-16 years receiving antiretroviral therapy for ≥6 months in Harare, Zimbabwe., Methods: Consecutive participants from a HIV clinic underwent clinical assessment and chest radiography. Participants with an abnormal chest radiograph (assessed by a clinician) and/or those meeting a clinical case definition for chronic lung disease underwent high-resolution computed tomography (HRCT). Radiological studies were scored independently and blindly by 2 thoracic radiologists. Relationships between radiological abnormalities and lung function were examined., Results: Among 193 participants (46% female; median age, 11.2 years; interquartile range, 9.0-12.8 years), the median CD4 cell count was 720/µL (473-947/µL), and 79% had a human immunodeficiency virus (HIV) load of <400 copies/mL. The most common chest radiographic finding was ring/tramline opacities (55 of 193 participants; 29%). HRCT scans were evaluated in 84 participants (69%); decreased attenuation (present in 43%) was the dominant abnormality seen. The extent of decreased attenuation was strongly correlated with both the severity and extent of bronchiectasis (rs = 0.68 and P < .001 for both). The extent of decreased attenuation was also negatively correlated with forced expiratory volume in first second of expiration (rs = -0.52), forced vital capacity (rs = -0.42), and forced expiratory flow, midexpiratory phase (rs = -0.42) (P < .001 for all)., Conclusions: The HRCT findings strongly suggest that obliterative bronchiolitis may be the major cause of chronic lung disease in our cohort. Further studies to understand the pathogenesis and natural history are urgently needed., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.)

Introduction: Rapid diagnostic tests (RDT) for HIV infection have high sensitivity and specificity, but in the setting of longstanding antiretroviral therapy (ART), can give false results that can lead to misinterpretation, confusion and inadequate management. The objective of this study was to evaluate the proportion of falsely negative results of a RDT performed on oral fluid in HIV-infected children on longstanding ART., Methods: One hundred and twenty-nine children with known HIV infection and receiving ART were recruited from the HIV Clinic at the Harare Central Hospital, Zimbabwe. HIV testing was performed on oral fluid and on finger-stick blood., Results and Discussion: Children included in the study had a median age of 12 years (IQR 10-14) and 67 (51.9%) were female. Median age at HIV diagnosis was 5 years (IQR 3-6) and the median time on ART was 6.3 years (IQR 4.3-8.1). The oral fluid test was negative in 11 (8.5%) patients and indeterminate in 2 (1.6%). Finger-stick blood test was negative in 1 patient. Patients with a negative oral fluid test had a higher CD4 cell count (967 vs. 723 cells/mm 3 , p  = 0.016) and a longer time on ART (8.5 vs. 6 years, p  = 0.016)., Conclusions: This study found that a substantial proportion of false-negative HIV test results in children on longstanding ART when using an oral fluid test. This could lead to misinterpretation of HIV test results and in the false perception of cure or delayed diagnosis., Competing Interests: The authors have no conflicts of interests to declare.

Objective: Respiratory disease is a major cause of morbidity and mortality in HIV-infected children. Despite antiretroviral therapy (ART), children suffer chronic symptoms. We investigated symptom prevalence, lung function and exercise capacity among older children established on ART and an age-matched HIV-uninfected group., Design: A cross-sectional study in Zimbabwe of HIV-infected children aged 6-16 years receiving ART for over 6 months and HIV-uninfected children attending primary health clinics from the same area., Methods: Standardized questionnaire, spirometry, incremental shuttle walk testing, CD4 cell count, HIV viral load and sputum culture for tuberculosis were performed., Results: A total of 202 HIV-infected and 150 uninfected participants (median age 11.1 years in each group) were recruited. Median age at HIV diagnosis and ART initiation was 5.5 (interquartile range 2.8-7.5) and 6.1 (interquartile range 3.6-8.4) years, respectively. Median CD4 cell count was 726 cells/μl, and 79% had HIV viral load less than 400 copies/ml. Chronic respiratory symptoms were rare in HIV-uninfected children [n = 1 (0.7%)], but common in HIV-infected participants [51 (25%)], especially cough [30 (15%)] and dyspnoea [30 (15%)]. HIV-infected participants were more commonly previously treated for tuberculosis [76 (38%) vs 1 (0.7%), P < 0.001], had lower exercise capacity (mean incremental shuttle walk testing distance 771 vs 889 m, respectively, P < 0.001) and more frequently abnormal spirometry [43 (24.3%) vs 15 (11.5%), P = 0.003] compared with HIV-uninfected participants. HIV diagnosis at an older age was associated with lung function abnormality (P = 0.025). No participant tested positive for Mycobacterium tuberculosis., Conclusion: In children, despite ART, HIV is associated with significant respiratory symptoms and functional impairment. Understanding pathogenesis is key, as new treatment strategies are urgently required.