Multisystem Impairment in Perinatally HIV-infected (PHIV) South African Adolescents

Transcription

1 Multisystem Impairment in Perinatally HIV-infected (PHIV) South African Adolescents Lisa Frigati, Karryn Brown, Sana Mahtab, Leah Githinji, Diane Gray, Liesel Zuhlke, ሷ Jaqueline Hoare, Mark Cotton, Landon Myer, Heather Zar Cape Town Adolescent Antiretroviral Cohort (CTAAC) University of Cape Town Stellenbosch University

2 Background

3 Background Limited data on multisystem disease/impairment 1 Globally, younger (10-14 years) perinatally HIV-infected adolescents 2 Important for planning clinical services for aging pediatric population AIM: To describe the burden of multisystem impairment in HIVinfected adolescents enrolled in the Cape Town Adolescent Antiretroviral Cohort (CTAAC) 1. McHugh JAIDS Slogrove et al Curr Opin HIV 2018 Neurocognitive Respiratory Cardiac Renal Individual Adolescent

4 Methods Enrolled children and adolescents 9-14 years of age (515 HIV+ and 110 HIV-) Clinically stable on ART for at least 6 months 7 sites across Cape Town: 2 tertiary hospitals, 1 secondary level, 4 urban clinics History and clinical examination, lung function tests, echocardiograms, battery of neurocognitive testing, laboratory investigations were done at enrolment visit by trained study staff Cross sectional analysis of data from the baseline visit

5 Definitions: Systems: 1. Neurocognitive 2. Cardiac 3. Respiratory 4. Renal SINGLE= 1 system DUAL= Any 2 MULTISYSTEM= 3 or 4

6 Measures: Neurocognitive : International HIV Dementia Score (IHDS) <10 1 Cardiac: Echocardiogram LV mass, LVSF, MVEAR, FAC, TAPSE, PAP Respiratory: Spirometry Obstructive: (FEV 1 /FVC <LLN) Restrictive: (FVC<LLN with normal (FEV 1 /FVC) Mixed: (FEV 1 <LLN, FEV 1 /FVC<LLN and FVC<LLN) Renal: Glomerular Filtration rate < 90ml/min/1.73m 2 3 (36.2*(Ht/SCr) Courtesy of Leah Githinji LVSF: left ventricular shortening fraction MVEAR: mitral valve E/A ratio FAC: fractional area change TAPSE: tricuspid annular plane systolic excursion PAP: pulmonary artery pressure FEV 1 : forced expiratory volume in 1 second FVC : forced vital capacity LLN: lower limit of normal 1. Sacktor AIDS Githinji Ann Am Thorac Soc Schwartz Journal of the American Society of Nephrology 2009

7 Results: Characteristics of Participants Characteristics HIV+ (n=406) HIV- (n=95) P-value Age 12.0 (2) 11.8 (2) 0.35 Female 191 (47) 51 (55) 0.24 Any respiratory symptoms 112 (28) 15 (17) 0.02 Repeated a Grade * 104 (64) 16 (41) <0.01 Previous TB 244 (61) 2 (2) <0.01 Hospital admission in past 12 months 13 (3) 1 (1) 0.25 Growth measures BMI (kg/m 2) 17.0 (16-19) 18.8 (17-22) <0.01 Height 140 (10) 145 (11) <0.01 Stunting 107 (26) 4 (4) <0.01 Prepubertal (Tanner 1) 191 (48) 31 (33) <0.01 *Total n = 162 and 39

8 HIV+ participants only: ANY impairment TOTAL HIV+ 406 (100%) SINGLE 317(78.1%) DUAL 136(33.5%) MULTISYSTEM 34(8.4%)

9 Results: Type of impairment Type of impairment HIV+ (n=406) HIV- (n=95) P-value Single Cardiac 72 (18) 15 (16) 0.65 Renal 1 (0.3) 1 (1) 0.34 Neurocognitive 63 (16) 15 (16) 0.95 Respiratory 45 (11) 11 (12) 0.89 Dual Renal Cardiac 2 (0.5) Renal Respiratory Renal Neurocognitive Cardiac Respiratory 37 (9) 6 (6) 0.38 Cardiac Neurocognitive 43 (11) 7 (7) 0.35 Respiratory Neurocognitive 22 (5) 4 (4) 0.43

10 Type of impairment HIV+ (n=406) HIV- (n=95) P-value Multisystem Renal Cardiac Respiratory 1 (0.3) Renal Neurocognitive Respiratory Renal Neurocognitive Cardiac Cardiac Neurocognitive Respiratory 0 0 _ 3 (0.7) 1 (1) (6) 3 (3) 0.17 Renal Respiratory Neurocognitive Cardiac 2 (0.5)

11 Results: Impairment type (excluding renal) HIV+ (406) HIV- (95) None= 22% Cardiac 17.7 None= 36 % Cardiac Respiratory Neurocognitive 15.5 Respiratory Neurocognitive 15.8

12 None/ Single (n=272) Dual or Multisystem (134) P-value General Characteristics Age 12 (2) 12 (2) 0.56 Female 129 (47) 62 (46) 0.83 Previous TB 153 (57) 91 (68) 0.03 Hospital admissions in past 12 months 9 (3) 4 (3) 0.86 BMI 17 (16-19) 16 (15-18) 0.01 HIV related measures CD4 <350 cells/mm 3 21 (7) 15 (11) 0.26 Virally Suppressed 178 (65) 80 (60) 0.26 Age at ART initiation 4 (2-8) 4 (2-7) 0.85 Duration of ART 8 (5-9) 8 (5-10) 0.28 Current ART regimen 2 NRTI + NNRTI 159 (60) 80 (61) NRTI + PI 106 (39) 46 (35) Other 2 (1) 5 (4) Failed a regimen 74 (27) 36 (27) 0.94

13 Multivariable analysis in PHIV Variable OR(95% CI) P-value BMI 0.87 ( ) <0.01 Previous TB treatment CD4 count (at study entry) 1.58 (1-2.5) ( ) 0.51 BMI and Previous TB treatment were predictors of having 2 or more systems involved For every 1 unit increase in BMI the odds of having 2 or more systems involved decreased by 13%

14 Discussion 1st exploration of multisystem impairment in South African adolescents on ART Single system impairment is common Multisystem less common than expected Cardiac impairment was the most common impairment type Based on echocardiogram parameters and clinical significance unclear Renal impairment appears uncommon No evidence for association between duration of ART or current regimen and impairment Treatment histories are complex to interpret in real world (different eligibility criteria, drugs, reasons for switch)

15 Limitations Cross sectional Only included 4 systems: what about hearing, bone, skin, metabolic? Measures of impairment differ in assessment of severity between systems Cardiac findings of uncertain clinical significance Neurocognitive findings are more clinically concerning Explanation for similarities between HIV+ and HIV-?

16 Conclusions Single system impairment in PHIV+ adolescents is common in our population Multisystem impairment in PHIV+ adolescents is uncommon small minority require clinical attention for complex multisystem issues Next steps: To explore different ways of measuring total burden of disease in PHIV+ adolescents To look longitudinally if this changes in late adolescent period To examine this phenomenon in cohorts from different settings

17 Acknowledgements NIH R01HD CTAAC participants and staff Karryn Brown Nicole Phillips Helena Rabie John Lawrenson Heather Zar, Landon Myer, Mark Cotton