Increased Left Ventricular Posterior Wall End-Diastolic Thickness in Adolescents With Delayed Diagnosis of Vertically Acquired HIV Infection

To the Editors: At least a third of HIV-infected infants have slow progressing disease and even without HIV treatment have a 50% probability of surviving to adolescence. Hence, substantial numbers of adolescents, infected before interventions to prevent mother-to-child HIV transmission became available, are presenting to clinical services with undiagnosed HIV in sub-Saharan Africa. A high burden of cardiac disease was recently described among vertically infected adolescents who attended HIV outpatient clinics in Harare, Zimbabwe. In that study, left ventricular (LV) hypertrophy, defined as a maximal wall thickening z-score.2 of the LV interventricular septum, the LV posterior wall (LVPW), or both, was observed in 67% (74/110) of the participants. Multivariate analysis showed no association with the participant’s age, sex, stunting, wasting, body mass index (BMI), New York Heart Association (NYHA) functional status, World Health Organization (WHO) HIV stage, CD4 count, duration or type of antiretroviral therapy (ART), and LV hypertrophy. In the general population, LVPW thickness increases with age in healthy adults, occurs in insulin-dependent diabetes mellitus in the absence of overt cardiac disease, in the morbidly obese, persisting despite weight loss, and in patients with chronic inflammatory conditions, including rheumatoid arthritis and systemic lupus erythematosus. In HIV-uninfected children, increased LVPW thickness is described to exist in association with elevated inflammatory biomarkers and in myocarditis. Among HIV-infected children, a small increase in LVPW thickness in early life predisposes these children to myocardial ischemia, and all-cause mortality, and in the general population increased LV mass is an independent predictor of cardiovascular mortality in adults. Given the significance of increased LVPW thickness among these groups, we specifically investigated the clinical associations of LVPW thickening among the previously described cohort of vertically infected adolescents. One hundred and ten adolescents aged 10–19 (median 15) years were consecutively recruited from 2 HIV outpatient clinics in Harare. Participant demographics and clinical features were recorded, and transthoracic echocardiography was performed as previously described. Echocardiographic parameters were expressed as a deviation from the body surface area–corrected mean using pediatric reference ranges; an LVPW z-score .2 was regarded as abnormal. Associations among clinical variables (age, sex, height-for-age z-score (stunting), weight-for-age z-score (wasting), BMI, WHO stage, CD4 count, NYHA functional status, duration and type of ART, and LVPW thickness were assessed, and variables showing an association at significance level P , 0.1 were included in a multivariate logistic regression analysis, where P , 0.05 was considered significant. Ethical approval was obtained from the London School of Hygiene and Tropical Medicine Ethics Committee, Medical Research Council of Zimbabwe, and the Biomedical Research and Training Institute Institutional Review Board, Harare. The participants gave their assent to participate, and written informed consent in either English or Shona was obtained from their guardians. The clinical characteristics of the study participants have been described previously. Briefly, 78 (71%) had been taking ART for a median of 20 [interquartile range (IQR) 5–40] months, 90% of whom were on the first-line ART regimen [2 nucleoside reverse transcriptase inhibitors (including stavudine or zidovudine) and a nonnucleoside reverse transcriptase inhibitor]. The median CD4 count was 384 cells per microliter (IQR 171–578), 87% (96/ 110) had WHO stage 3 or 4 disease, and the median BMI z-score was −0.69 (IQR −1.81–0.11). The median LVPW thickness z-score was +1.82 (IQR 0.69–2.63), with a z-score .2 in 48 (44%) and .3 in 17 (15%) participants. An LVPW thickness z-score .2 was associated with an ART duration of .12 months [odds ratio (OR) 2.60, P = 0.06], BMI ,18.5 kg/m2 (OR 2.31, P = 0.04), and wasting (weight-for-age zscore ,−2) (OR 2.00, P = 0.07). After adjusting for age, sex, stunting (heightfor-age z-score ,−2), WHO HIV staging, CD4 count, NYHA functional status, and ART regimen, the LVPW thickness was associated with a longer ART duration (adjusted OR 3.16, 95% confidence interval 1.10–9.05) and low BMI (adjusted OR 3.46, 95% confidence interval 1.25–9.60). The high prevalence of LVPW thickening in this cohort is striking, and contrasts with the pattern seen in HIV-infected younger children in the pre-ART era. The P2C2 study in the United States followed up HIVinfected children (median age 2.1 years) for a median of 5 years. The LVPW was thinned at baseline in HIV-infected R.A.F. is funded by The Wellcome Trust, London, United Kingdom, Grant 080815/Z/06/Z. The funders had no role in the design and conduct of the study, in data collection and analysis, decision to publish, preparation, or approval of the manuscript. R.F.M. has received honoraria for nonpromotional lectures on the clinical aspects of HIV infection from ViiV Healthcare, MSD, and Gilead. The other authors have no funding or conflicts of interest to disclose. R.F.M.: analyzed and interpreted the data, wrote the first and final drafts of the manuscript. J.M.: analyzed and interpreted the data, critically reviewed drafts of the manuscript for important intellectual content. J.P.K.: analyzed and interpreted the data, critically reviewed drafts of the manuscript for important intellectual content. J.M.: performed echocardiograms, analyzed and interpreted the data, critically reviewed drafts of the manuscript for important intellectual content. R.A.F. was responsible for the study concept and design, acquired data, analyzed and interpreted data, critically reviewed drafts of the manuscript for important intellectual content. All the authors have seen and approved the final version of the manuscript. Correspondence to: Robert F. Miller, MBBS, FRCP, Research Department of Infection and Population Health, Institute of Epidemiology and Healthcare, University College London, Mortimer Market Centre, London WC1E 6JB, United Kingdom (e-mail: [email protected]). Letters to the Editor J Acquir Immune Defic Syndr Volume 66, Number 4, August 1, 2014