CROI 2016 Abstract eBook

Abstract Listing

Poster Abstracts

Methods: HIV-infected children aged 6-16 taking ART for at least 6 months were enrolled from the Paediatric HIV clinic at Harare Central Hospital. Assessment included clinical history, New York Heart Association (NYHA) scoring, incremental shuttle walk testing, viral load, CD4 count and transthoracic echocardiography using 2-Dimensional, M-mode, pulsed wave, continuous wave and tissue Doppler imaging. Cardiac abnormalities were assessed using European reference ranges and a z-score >+2 was considered abnormal. Results: 201 children, median age 11 (IQR 9-12), 48% females and median age at HIV diagnosis of 5 (IQR 3-7) years were enrolled. The median CD4 count 726.5 (IQR 473-935) and 78.2% had a viral load of <400 copies/ml. Most of the children were stunted and wasted, 76.1% and 78.1% respectively. Chest pain on exertion was reported in 10.9%, tachypnea 10.8%, palpitations in 4.5% and 14.4% (N=29) were in New York Heart functional score II and 0.5% (N=1) in class IV. The most common cardiac abnormality was left ventricular hypertrophy (LVH) (39.5%; N=70) which was either interventricular septal (63.8%) or posterior wall (7.2%) or both (29%), LV diastolic dysfunction (23.2%; N= 41) and LV systolic dysfunction (15.8%; N=28). There was no association between symptoms and cardiac abnormalities. Conclusions: The findings show a high burden of echocardiographic abnormalities in HIV-infected older children and adolescents the majority of whomwere optimally controlled on ART. While more than a third of the HIV-infected children had evidence of left heart abnormalities, only a few were symptomatic. Further studies are needed to investigate the progression and cause of these abnormalities, in particular the strikingly high prevalence of left ventricular hypertrophy. 854 Cardiovascular Disease Biomarkers in Perinatally HIV-Infected Adolescents on ART Liesl Zuhlke 1 ; Kirsty Brittain 1 ; Linda-Gail Bekker 2 ; Helena Rabie 3 ; James Nuttall 1 ; Brian Eley 1 ; Paul Roux 4 ; Landon Myer 1 ; Heather J. Zar 1 ; for the CapeTown Adolescent Antiretroviral Cohort 1 Univ of Cape Town, Cape Town, South Africa; 2 Desmond Tutu HIV Cntr, Cape Town, South Africa; 3 Stellenbosch Univ, Cape Town, South Africa; 4 Groote Schuur Hosp, Cape Town, South Africa Background: HIV infection and antiretroviral therapy (ART) are independently associated with increases in cardiovascular disease (CVD) biomarkers in children. However little is known about CVD biomarkers in perinatally-infected adolescents in southern Africa. Methods: We enrolled perinatally HIV-infected (HIV+) adolescents ages 9-14 years on ART for at least 6 months and age- and sex-matched HIV-uninfected (HIV-) controls. Individuals underwent phlebotomy after fasting for total cholesterol (TC), low-density lipoprotein (LDL-C), high-density lipoprotein (HDL), triglycerides (TG) and highly-sensitive C-reactive protein (hs-CRP). Analyses compared biomarker levels according to current age, sex, age at ART initiation, current ART regimen, and between HIV+ and HIV- adolescents; abnormal lipid values were based on US National Heart, Lung and Blood Institute cutoffs, and hs-CRP measures excluded children with a recent history (<1 week) of or current acute illness or antibiotic use. Results: Lipid measures for 487 and 72, and hs-CRP measures for 431 and 104, HIV+ and HIV- adolescents, respectively, were included. The mean age of HIV+ adolescents was 12.0 years (median CD4 cell count, 711 cells/uL; median duration of ART use, 7.0 years; median BMI z-score, -0.24 [IQR, -0.93-0.38]). 36%were on PI-based regimens (predominantly lopinavir/ritonavir) and 10% on a regimen containing stavudine (d4T). Overall 15%, 11%, 7% and 5% of HIV+ children had abnormal TC, LDL-C, HDL and TG, respectively. The prevalence of lipid abnormalities was higher among female participants and decreased with increasing age in children on PIs (Figure). When compared to HIV- controls and adjusting for age and gender, HIV+ adolescents on PIs had elevated TC, LDL-C and TG (OR, 8.2; 95% CI, 1.9-35.5; OR, 2.7; 95% CI, 0.9-8.1; OR, 8.8; 95% CI, 1.2-67.4). Although adolescents on NNRTIs had a markedly higher level of TC abnormalities compared to controls (OR, 5.3; 95% CI: 1.3-22.8), TG and LDL-C abnormalities were similar. Current use of d4T was not associated with lipid abnormalities. The median hs-CRP was 1.1 mg/L (16%>3.0 mg/L) in HIV+ children and did not vary with age or PI use, versus 0.5 mg/L in controls (p<0.001). Conclusions: Elevated CVD biomarkers are relatively common among perinatally-infected HIV+ adolescents in this setting. The long-term implications of these abnormalities require ongoing investigation.

Poster Abstracts

855 Lipoatrophy/Lipohypertrophy Outcomes After ART Switch in Children in the UK/Ireland Steve Innes 1 ; Justin Harvey 2 ; Jeannie Collins 3 ; Mark F. Cotton 1 ; Ali Judd 3

1 Stellenbosch Univ and Tygerberg Children’s Hosp, Cape Town, South Africa; 2 Stellenbosch Univ, Cape Town, South Africa; 3 Med Rsr Council Clinical Trials Unit at Univ Coll London, London, UK Background: Following extensive use of thymidine analogue antiretroviral therapy (ART) over the past three decades, up to a third of children may have lipoatrophy (LA) and/ or lipohypertrophy (LH). Following phasing-out of stavudine, incidence of newly-diagnosed LA and LH has declined dramatically. However, the natural history of existing cases is uncertain. Previous longitudinal studies found variable (although generally poor) rates of resolution. Methods: The Collaborative HIV Paediatric Study (CHIPS) is a multicentre cohort study of virtually all HIV-infected children in care in the UK and Ireland. All with an LA/LH assessment recorded in 2003-2011 were included. Using the 0-3 grading system, unequivocal case definition was defined as grade 2 or 3. Resolution was defined as return to grade 1 or 0 in all body regions. LA and LH were assessed and analysed separately. Kaplan-Meier analysis investigated time to resolution of LA and/or LH following diagnosis (which typically occurred at the same visit as switching the drug thought to cause the LA/LH). Multivariable logistic regression identified factors predicting recovery. Results: LA/LH assessments were available on 1345 children followed for a median (IQR) of 5.5 (2.9, 8.2) years after ART initiation. Thirty developed LA and 27 developed LH. (10 had both LA and LH). Recovery was delayed until 1 year after ART switching (see figure), with a steady incidence of recovery between 1 and 2 years (for LH) or between 1 and 4 years (for LA). Cases persisting beyond 2 years (for LH) or beyond 4 years (for LA) did not recover, although only 6 (25%) and 8 (40%) of unresolved cases respectively remained in follow-up at 5 years. Thus, eventual resolution occurred in only 10 (33%) of LA cases, with a median time to resolution of 2.3 (1.8, 3.6) years, and 3 (11%) of LH cases, with a median time to resolution of 2.0 (1.7, 2.1) years.

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CROI 2016