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Complications and Research Priorities in Care of HIV-Infected Youth PowerPoint Presentation

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Description : Complications and Research Priorities in Care of HIV-Infected Youth

Tags : Pediatrics, Child Health, pediatric practice, pediatrician, health providers, HIV-infected infants, Adolescent Transition, HIV-infected adolescents, epidemiology

Published on : Jul 16, 2020 | Views : 1682 | Downloads : 1

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Slide 1-

Improving health worldwide www.lshtm.ac.uk It's not just HIV: Complications and Research Priorities in Care of HIV-Infected Youth Rashida A Ferrand (MD PhD) Reader in International Health
Slide 2-

Outline Unresolved management issues Spectrum of chronic complications Looking ahead
Slide 3-

Adolescents Infants 1990s 2010s Dynamics of the paediatric HIV epidemic Johnson et al PIDJ 2012 Ferrand et al AIDS 2009 UNAIDS 2014
Slide 4-

Course of paediatric HIV infection Survival prospects of HIV-infected children dramatically improved with ART: 40% reduction in mortality since 2005 HIV a chronic disease rather than a progressively fatal one Substantial reduction in mortality with early initiation of ART However only 20-30% of exposed children accessing early infant diagnosis and large numbers of children starting ART in later childhood Global update on health sector response to HIV; WHO 2014 Violari et al NEJM 2008 Hazra R et al Ann Rev Med 2010 McCoy et al JAIDS 2015
Slide 5-

Johnson et al PIDJ 2012 1 2 3 4 5 6 7 8 9 10 11 12 13 14 0 0 50,000 40,000 30,000 20,000 10,000 50,000 40,000 30,000 20,000 10,000 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 40,000 30,000 20,000 10,000 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Age (years) Receiving ART Eligible, untreated Not eligible for ART Age distribution of paediatric HIV and ART need over time: South Africa 2000 2010 2020 Assumes 53% of infants start ART by 2 months
Slide 6-

Unresolved HIV management issues Burden of infection: timely ART initiation Sub-optimal control of HIV Malnutrition→ long term effects Vaccine-preventable diseases Psychiatric morbidity Is ART enough? Heidari S et al JAIDS 2012; 59:161-169 Lowenthal E et al Lancet Infect Dis 2014 Owe-Larsson et al Afr J of Psychiatry 2009
Slide 7-

Is ART enough? HIV has pro-inflammatory as well as immunosuppressive effects HIV associated with organ damage Consequence of timing of infection Consequence of timing of ART Children expected to be on ART for >2 decades longer than adults: immature physiological mechansims when start ART Longer exposure to drugs Premature malignancy risk Lowenthal E et al Lancet ID 2015 Prendergast A et al J of Infect Dis 2016
Slide 8-

Domains of disability Devendra A et al PloS One 2013 N= 296 (age 2-9 years); HIV+ve and HIV-ve siblings OR 8.4 of disability if HIV+
Slide 9-

Cognitive impairment Progressive encephalopathy in infants and young children: improvement in locomotor and mental development with immediate ART in infants (CHER trial) No difference in cognitive performance between deferred vs immediate treatment arms in PREDICT study: both groups performed worse than HIV-uninfected children Residual cognitive and motor deficits even with ART In older children- deficits subtle, not routinely identified Fine motor function Perceptual performance Quantitative abilities Mental processing Language abilities Skills critical for adherence, education, career planning Laughton B et al AIDS 2012; 26 :1685-90 Puthanakit T et al PIDJ 2010; 32:501-8 Laughton JIAS 2013;16:18603
Slide 10-

Hearing loss 5-17yrs (mean 11yr): n=380 89% on ART (median 3 years) Nadir CD4 count 271; recent median CD4 count 725 32% had ANY hearing loss 11.4% had moderate-severe-profound hearing loss 75% hearing loss in those with Chronic inactive otitis media 87.5% hearing loss in those with Chronic suppurative otitis media Torre III et al PIDJ 2012 Chao CK et al. Otolaryngol Head Neck Surg. 2012 Chidziva et al CAJM 2016
Slide 11-

Growth Failure & pubertal delay Prevalence of growth failure : 30-50% Median HAZ: -1.7 (HIV+) vs -0.7 (HIV-ve) Pubertal delay: 17% Distinguish form wasting (1Y calorie intake): Nearly proportional declines in height/weight: and height for weight maintained Obvious in adolescence: growth spurt and puberty Sub-maximal long-term catch-up growth: effect on final height and bone age Low bone mineral density (+ effect of drugs) Ferrand RA et al Clin Infect Dis 2012; Gsponer Padiatrics 2012; Williams AIDS 2013;
Slide 12-

Szubert et al AIDS 2015; 29:609-618 Age at ART initiation and effect on growth
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Chronic Skin disease Odds Ratio for being HIV-infected: 37.4 in adolescents (10-19y) Visible marker of HIV infection Lowe S et al Paed Infect Dis J 2010
Slide 14-

Biopsy: epidermodysplasia verruciformis EV-associated Beta-HPV type 5 HPV Type 1 and 2; multiple Treatment difficult ?malignant transformation (3/4th decade) Lowe et al CID 2012
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Burnt-out seronegative deforming arthritis (16yr old) HIV- related complications: lifelong disability Chronic uveitis: corneal deposits + perforation (17 yr old)
Slide 16-

Vaccine-preventable diseases Low immunity to vaccines if ART naïve –good antibody and lymphoproliferative responses to re-vaccination on therapy Loss of protective immunity over time: – Correlates of antibody levels with protection No specific guidelines and research gaps Necessity for & timing of repeat doses after revaccination while on ART Effect of age at ART initiation on response to revaccination Correlates of antibody levels with immunity Timing of revaccination after start of ART Sutcliffe C et al Lancet Infect Dis 2010; 10: 630–42
Slide 17-

Premature malignancy & Long term ART effects HIV-related cancers: Kaposi sarcoma and non-Hodgkins lymphoma, Burkitt’s lymphoma Premature malignancies: rare and atypical..case reports Implementation of HPV vaccine in HIV+ adolescents ART Effects: Bone mineral density (tenofovir licenced by FDA for use in children >2yrs) Metabolic complications Renal toxicity WHO 2012:Use of tenofovir in HIV-infected children and adolescents
Slide 18-

Chronic lung disease McHugh et al JAIDS 2016 In press McHugh et al IUATLD 2015
Slide 19-

Radiological findings Main morphological pattern is mosaicism, consistent with OB: strong association with FEV1 (only predictor for low FEV1z) CXR is insensitive for identifying pathology, CT needed -CT may identify pre-clinical disease Obstructive spirometry uncommon: -subclinical -other factors promoting “small lung” Emphysema rarely seen in young people -should prompt clinicians to think of HIV
Slide 20-

Spectrum of chronic lung disease Ferrand Clin Infect Dis 2012; Desai Clin Rad 2011; Mwalukomo (Pers Coms) Young children Lymphoid Intestitial Pneumonitis Diagnosed easily Responds to corticosteroids /ART Older children Small airways disease Mostly un- or mis-diagnosed Poor response to steroids/ ART Secondary heart disease
Slide 21-

Tracking lung function in children Predicted FEV1/FVC ratio and FEV1 mean values for males at ages 11, 16 and 22 years by length-adjusted infant V'max FRC quartile groups using random effects models. Predicted values were standardized to the mean height and weight for males at 11, 16 and 22 years. Stern et al Lancet 2007
Slide 22-

HIV Chro inflam nic HIV persistence Resp infection/ O mation & immune colonisation dysregulation (TB, PJP) xidative stress AGING Chronic lung disease Crothers AJRCCM 2011; Van Zyl Smit Eur Resp Journal 2010 Almovodar Viral Immunology 2014 Respiratory tract infections Growth Nutrition
Slide 23-

Left heart abnormalities (n=196) Majonga E et al CROI 2016 (manuscript in preparation)
Slide 24-

Right heart abnormalities (n=196) Majonga E et al IAS 2016 No association with lung function Association with left echocardiographic abnormalities OR: 2.5 (1.36-4.56)
Slide 25-

Research priorities Longitudinal prospective studies of prevalence and incidence of chronic systemic complications Controlled studies Combined cohorts Standard definitions Validated tools Normative data Disability and impact on function Education and mental health Pathogenesis Diagnostic and therapeutic strategies
Slide 26-

Health is a state of complete physical, mental, and social well-being and not merely the absence of disease or infirmity WHO constitution 1948
Slide 27-

Summary High burden of chronic complications, even with ART: next generation if issues Factors (evolving): -potential impact of in-utero exposure to HIV/ART -timing of infection -timing and duration of ART -persisting effects of HIV: inflammation, infection and immune- senescence -effects of treatment Surveillance and context
Slide 28-

Kusum Nathoo, Hilda Mujuru (Department of Paediatrics, University of Zimbabwe) Grace McHugh, Edith Majonga, Ethel Dauya, Tsitsi Bandason (BRTI) Collaborators at: University of Cape Town LSTM University of Oxford LSHTM University College London UCSF UCT Zvandiri Africaid Ministry of Health and Child Welfare Harare City Health Clinics Harare Hospital HIV Clinic Staff INHALE, BREATHE and ZENITH Study Teams Funders: Wellcome Trust, Norwegian Research Council, John Fell Fund, Nina-Ireland Lung Health Program Acknowledgements

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