This review synthesises current evidence on the cardiovascular disease (CVD) burden among young people living with HIV. It explores myocardial and vascular pathology, evaluates the role of advanced imaging, and highlights critical gaps in understanding the mechanisms driving HIV-associated CVD in this population. Emerging data suggest that HIV-associated CVD in youth may be predominantly driven by non-atherosclerotic mechanisms, including direct myocardial injury, fibrosis, and remodelling, rather than traditional coronary atherosclerosis. Imaging studies have revealed subclinical myocardial changes such as increased left ventricular mass and reduced strain. Vascular studies show inconsistent findings. However, longitudinal data and multimodal imaging approaches remain scarce, particularly in high-burden regions like Africa. Young adults with HIV face a significant burden of cardiovascular pathology, often subclinical and poorly understood. The prevailing paradigm focused on atherosclerosis may not fully apply to this group, especially in African settings. There is an urgent need for longitudinal, mechanistic research to inform tailored clinical strategies and policy interventions aimed at reducing long-term cardiovascular morbidity in young people with HIV.
PURPOSE OF REVIEW:HIV-associated cardiac disease was well recognized in the preantiretroviral (ART) era among children with perinatally-acquired HIV infection (PHIV). While ART has dramatically improved survival, it has become increasingly apparent that individuals with PHIV continue to experience multisystem co-morbidities. We review the cardiac and vascular manifestations in people growing up with PHIV in the ART era. RECENT FINDINGS:ART has resulted in a drop in incidence of serious cardiac morbidity. However, there is a substantial body of evidence that demonstrates that cardiac and vascular structural and functional abnormalities, mostly subclinical, are common in people with PHIV taking ART. Studies have considerable heterogeneity with respect to types of cardiovascular assessments used. HIV-mediated chronic inflammation and potentially effects of ART contribute to these abnormalities. The long-term clinical significance of these abnormalities remains unknown as studies have mainly been cross-sectional, but it is likely that the burden of cardiovascular disease will grow as individuals with PHIV age and the prevalence of traditional risk factors increases. SUMMARY:Understanding the pathogenesis of cardiovascular disease in PHIV, is critical to inform screening and interventional strategies. Longitudinal studies are also needed to understand the natural history of cardiovascular abnormalities and incidence of clinical outcomes.
BACKGROUND:Tuberculosis (TB) continues to be a major cause of death across sub-Saharan Africa (SSA). In parallel, non-communicable disease and especially cardiovascular disease (CVD) burden has increased substantially in the region. Cardiac manifestations of TB are well-recognised but the extent to which they co-exist with pulmonary TB (PTB) has not been systematically evaluated. The aim of this study is to improve understanding of the burden of cardiac pathology in PTB in those living with and without HIV in a high-burden setting. METHODS:This is a cross-sectional and natural history study to evaluate the burden and natural history of cardiac pathology in participants with PTB in Lusaka, Zambia, a high burden setting for TB and HIV. Participants with PTB, with and without HIV will be consecutively recruited alongside age- and sex-matched TB-uninfected comparators on a 2:1 basis. Participants will undergo baseline assessments to collect clinical, socio-demographic, functional, laboratory and TB disease impact data followed by point-of-care and standard echocardiography. Participants with PTB will undergo further repeat clinical and functional examination at two- and six months follow-up. Those with cardiac pathology at baseline will undergo repeat echocardiography at six months. DISCUSSION:The outcomes of the study are to a) determine the burden of cardiac pathology at TB diagnosis, b) describe its association with patient-defining risk factors and biochemical markers of cardiac injury and stretch and c) describe the natural history of cardiac pathology during the course of TB treatment.
Background: Pulmonary tuberculosis (PTB) is associated with increased cardiovascular disease (CVD) mortality. However, underlying pathophysiological mechanisms are poorly understood. This systematic review aims to synthesize the evidence on the prevalence of cardiac pathology based on cardiac imaging and circulating biomarkers in patients with PTB. Methods: We systematically searched databases for studies in patients with PTB evaluating cardiac pathology (pericardial effusion or left ventricular dysfunction) on echocardiography; late gadolinium enhancement on cardiac magnetic resonance imaging (CMR); myocardial inflammation on positron-emission tomography (PET); coronary artery stenosis on CT coronary angiography (CTCA); and cardiac troponin (cTn) and/or B-type natriuretic peptides (BNP) assessment. Results: Seven studies were included across 1,333 participants with PTB. Four studies used echocardiography (n= 1,111). The prevalence of pericardial effusion ranged from 14.1- 55.9%; and left ventricular systolic impairment from 0 - 4.25%. One study used CMR and PET-CT (n=26); and two studies used PET-CT alone (n=196). The prevalence of pericardial and/or myocardial inflammation ranged from 0.6 - 21.8%. One study evaluated cTn, Creatine Kinase-MB (CK-MB), and BNP (n=800), of whom 246 had raised cTn. No study reported cardiac pathology using CTCA. Conclusion: Pericardial effusion is the commonest reported cardiac pathology in PTB. To date, only one study has evaluated cardiac biomarkers and studies evaluating myocardial or coronary disease on advanced imaging remain limited. Our study highlights the paucity of evidence on the presence of cardiac pathology in PTB. Studies are required to determine the prevalence of, and disease mechanisms associated with cardiac pathology among patients with PTB.
Background HIV in adolescents with perinatal HIV (PHIV) is associated with an increased risk of cardiac disease, which is not well characterised. We characterised myocardial structure and function in adolescents with PHIV and established on antiretroviral therapy (ART) using advanced imaging with cardiac magnetic resonance (CMR). Methods We conducted a cross-sectional study in PHIV aged 10–19 years taking antiretroviral therapy and an HIV-negative comparison group in Harare, Zimbabwe. Participants underwent a 3-Tesla CMR examination including assessment of myocardial structure and function (cine) and myocardial fibrosis (late gadolinium enhancement, LGE). Groups were compared using unpaired t-test, and potential predictors were assessed with multiple linear regression. Results Forty-four participants were included in the analysis (n= 23 with HIV; 52% female and 21 uninfected controls; 48% female]). Participants with PHIV were older [median (IQR) 18 (16–19) vs 15 (13–17) years; p=0.002] compared to uninfected controls. They also had lower height-for-age and weight-for-age z-scores [Mean (SD), -1.84 (1.0) vs 1.17 (1.0); p=0.044] and [-1.35 (1.4) vs -0.21 (1.4); p=0.011] respectively. In the PHIV group, median age at HIV diagnosis was 5.5 (IQR, 4–8) years and 18 (82%) were virally suppressed (<19 copies/ml). The PHIV group had a larger indexed left ventricular (LV) mass [Mean (SD), 39.2 (5.4) vs 35.3 (6.4) g/m2; p=0.047] and LV end-diastolic volume [75.0 (8.2) vs 67.5 (12.5) mL/m2; p=0.026] compared to controls. LV and right ventricular systolic function measured by either ejection fraction or strain was normal in both groups, and no LGE was observed. No association of LV systolic function was observed with age, sex, and HIV viral load. Conclusion In this interim analysis, an increased indexed LV mass and end-diastolic LV volume in the PHIV group relative to those HIV-negative may suggest LV structural changes. Recruitment is ongoing and comprehensive regression modelling shall be performed. Funding: EDCTP TMA2019CDF-2776
Despite its fundamental role in diagnostic and curative care, radiology has been described as a neglected essential service in many low and middle-income countries (LMICs). Previous studies have demonstrated basic equipment and infrastructure shortages in LMIC settings, but no studies to date have gone further in understanding the perceptions and experiences of staff delivering radiology services, as a way of identifying their perspectives on barriers and facilitators for delivering services, and the potential for where improvements can be made. Our qualitative study aimed to: (a) identify barriers for delivering radiology services, and (b) suggest potential facilitators for improvement of radiology service delivery in the Zimbabwean context; from the perspective of radiology staff. We conducted semi-structured interviews (n = 13) and three focus groups (n = 24 radiographers), followed by four half- to full- days of field observations to validate insights from the interviews and focus groups in all three public hospitals and one private hospital in the Harare metropolitan area. Our study identified four main barriers for delivering radiology services: (i) poor basic infrastructure, equipment, and consumables; (ii) suboptimal equipment maintenance; (iii) shortage of radiology staff and skills development; and (iv) lack of wider integration and support for radiology services. We also identified a strong sense of motivation among staff to keep radiology services, pointing to what may be an enabler and facilitator for improving radiology services. These findings point to potential risks to patient safety and quality of delivering radiology services. More importantly, we found a strong sense of personal motivation displayed by the staff, suggesting there is the potential to maintain and improve existing practices, but this would require investments to train and remunerate more radiology staff, as well as investing in continuing professional development.
Background and aims: Perinatal HIV infection (PHIV) and prolonged use of antiretroviral therapy (ART) may increase the likelihood of developing subclinical vascular dysfunction at an early age. We conducted a systematic review to assess the effect of PHIV and ART on intima-media thickness (IMT), arterial stiffness and endothelial function in individuals aged 6-25 years. Methods: Medline, Embase and Web of Science were searched, and studies screened by two independent reviewers. We performed a meta-analysis on selected studies reporting on IMT. Results: A total of 680 studies were retrieved from the databases, with 21 studies deemed eligible for qualitative analysis. There were few studies assessing IMT, arterial stiffness and endothelial function. More than half of the studies found either increased IMT, stiffer arteries or impaired endothelial function in PHIV compared to uninfected controls. A minority of the studies reported that the two groups had similar vascular parameters, a conflicting finding. There was a lack of standardisation for IMT assessment and reporting in numerous studies. In a meta-analysis of seven studies with matching methodologies, IMT was higher in PHIV compared to uninfected controls, (mean difference, 0.05 (0.01-0.09; p = 0.01) but heterogeneity between the studies was substantial (I-2, 96.7%; p < 0.001). Conclusions: PHIV may affect vascular structure and function. Existing studies are generally small, often contradictory, and predominantly cross-sectional in design. Further studies are required to understand vascular health in PHIV to identify cardiovascular disease risk and improve interventional strategies aimed at prevention and treatment of early vascular changes in this population.
Importance:HIV-associated cardiovascular disease is increasing in prevalence, but its mechanisms remain poorly understood. Objective:To systematically review data from advanced cardiovascular imaging studies evaluating computed tomographic coronary angiography, positron emission tomography (PET), and cardiac magnetic resonance (MR), in people living with HIV compared with uninfected individuals. Data Sources:Three databases and Google Scholar were searched for studies assessing cardiovascular pathology using computed tomographic coronary angiography, cardiac MR, PET, and HIV from inception to February 11, 2022. Study Selection:Two reviewers selected original studies without any restrictions on design, date, or language, investigating HIV and cardiovascular pathology. Data Extraction and Synthesis:One investigator extracted data checked by a second investigator. Prevalence ratios (PRs) and differences in inflammation among people living with HIV and uninfected individuals were qualitatively synthesized in terms of cardiovascular pathology. Study quality was assessed using the National Heart, Lung, and Blood Institute quality assessment tool for observational studies. Main Outcomes and Measures:Primary outcomes were computed tomographic coronary angiography-defined moderate to severe (≥50%) coronary stenosis, cardiac MR-defined myocardial fibrosis identified by late gadolinium enhancement, and PET-defined vascular and myocardial target to background ratio. Prevalence of moderate to severe coronary disease, as well as myocardial fibrosis, and PRs compared with uninfected individuals were reported alongside difference in vascular target to background ratio. Results:Forty-five studies including 5218 people living with HIV (mean age, 48.5 years) and 2414 uninfected individuals (mean age, 49.1 years) were identified. Sixteen studies (n = 5107 participants) evaluated computed tomographic coronary angiography; 16 (n = 1698), cardiac MRs; 10 (n = 681), vascular PET scans; and 3 (n = 146), both computed tomographic coronary angiography and vascular PET scans. No studies originated from low-income countries. Regarding risk of bias, 22% were classified as low; 47% moderate; and 31% high. Prevalence of moderate to severe coronary disease among those with vs without HIV ranged from 0% to 52% and 0% to 27%, respectively, with PRs ranging from 0.33 (95% CI, 0.01-15.90) to 5.19 (95% CI, 1.26-21.42). Prevalence of myocardial fibrosis among those with vs without HIV ranged from 5% to 84% and 0% to 68%, respectively, with PRs ranging from 1.01 (95% CI, 0.85-1.21) to 17.35 (95% CI, 1.10-274.28). Differences in vascular target to background ratio among those with vs without HIV ranged from 0.06 (95% CI, 0.01-0.11) to 0.37 (95% CI, 0.02-0.72). Conclusions and Relevance:In this systematic review of studies of advanced cardiovascular imaging, the estimates of the associations between HIV and cardiovascular pathologies demonstrated large amounts of heterogeneity. The findings provide a summary of the available data but may not be representative of all individuals living with HIV, including those from low-income countries with higher HIV endemicity.
Objectives: Children with perinatally acquired HIV (PHIV) and taking antiretroviral therapy (ART) have a high prevalence of subclinical cardiac disease. We hypothesized that cardiac disease may be a consequence of dysregulated systemic immune activation driven by HIV infection. We examined cardiovascular and proinflammatory biomarkers and their association with echocardiographic abnormalities in children with PHIV. Design: Cross-sectional analysis of soluble biomarkers from a prospective cohort of children aged 6–16 years with PHIV and age-matched HIV-uninfected comparison group. Methods: Cryopreserved plasma samples were used to measure seven soluble biomarkers using multiplex bead assay (Luminex). Multivariable logistic regression assessed how biomarker levels related to cardiac abnormalities. Results: A total of 406 children participated in this study (195 PHIV and 211 HIV-uninfected). Mean [standard deviation (SD)] ages of PHIV and HIV-uninfected participants were 10.7 (2.6) and 10.8 (2.8) years, respectively. Plasma levels of CRP, TNF-α, ST2, VCAM-1 and GDF-15 were significantly higher in the PHIV group compared with uninfected control (P < 0.001). Among children with PHIV, with one-unit representing one SD in biomarker level, a one-unit increase in CRP and GDF-15, was associated with increased odds of having left ventricular (LV) diastolic dysfunction [adjusted odds ratio (aOR), 1.49 (1.02–2.18; P < 0.040)] and [aOR 1.71 (1.18–2.53; P = 0.006)], respectively. Each one unit increase in GDF-15 was associated with increased odds of LV hypertrophy [aOR 1.84 (95% CI 1.10–3.10; P < 0.021)]. Conclusion: Children with PHIV had higher levels of proinflammatory and cardiovascular biomarkers compared with HIV-uninfected children. Increased CRP and GDF-15 were associated with cardiac abnormalities in children with PHIV.
Objective To systematically review and meta-analyse data from advanced cardiovascular imaging studies evaluating computed tomography coronary angiography (CTCA), positron emission tomography (PET), and cardiac magnetic resonance (CMR), in people living with HIV (PLHIV) compared to uninfected individuals. Methods Three databases were searched for studies investigating the association between cardiovascular pathology and HIV using CTCA, CMR and PET in PLHIV from inception to February 11th 2022. Primary outcomes moderate to severe (>50%) coronary stenosis (CTCA), vascular and myocardial target-to-background ratio (PET), late gadolinium enhancement prevalence (CMR). Prevalence and risk ratios (RR) (comparing PLHIV to uninfected individuals) were pooled for using a random effects model. Results Forty-five studies including 5218 PLHIV (mean age 48.5 years) and 2414 uninfected individuals (mean age 49.1 years) met the inclusion criteria. Sixteen studies (n=5107 participants) evaluated CTCA, 10 (n=681) vascular PET, 3 (n=146) both CTCA and vascular PET, and 16 (n=1698) CMR. No studies originated from low-income countries. The prevalence of moderate/severe coronary disease in 17.3% in PLHIV and 13.8% in controls (RR 1.33, 95%CI 0.96–1.82, I2= 62%). The prevalence of myocardial fibrosis was 47.5% in PLHIV and 31.7% in controls (RR 2.34, 95% confidence interval [CI] 1.34–4.08, I2=88%). PET studies indicated that PLHIV have an increase in vascular inflammation however these findings are derived from populations with well controlled HIV in middle age. Conclusion Significant associations were observed between HIV and risk of myocardial fibrosis but not moderate to severe coronary disease. These findings were derived largely from populations in regions of low HIV endemicity.
Background: Right heart abnormalities and pulmonary hypertension (PH) may be secondary to chronic lung disease. Chronic lung disease is common in children with HIV. In the BREATHE trial (Trial registration: NCT02426112), azithmmycin (AZM) reduced the risk of acute respiratory exacerbations in children aged 6-19 years with HIV-associated chronic lung disease (HCLD) taking antiretroviral therapy. We assessed the possible effect of AZM on right heart dysfunction and/or PH in the trial. Methods: A standardised transthoracic echocardiogram using M-mode, two-dimensional and Doppler was performed, at baseline and at completion of weight-based AZM given weekly for 48 weeks. Linear regression was used to compare trial arms. Results: A total of 169 participants (82 AZM arm; 87 placebo arm) were included. Participants in the placebo arm were older, median age 16.2 (13.0-18.2) vs 15.3 (12.9-17.4) years, p = 0.184 in the AZM arm. At baseline, right heart abnormalities (right ventricular systolic dysfunction (RVSD), dilatation, or PH) were observed in 7(4%). Following treatment, there was no difference in prevalence of RVSD between arms (p = 0.761). There was one incident case of suspected PH, and overall, no difference in pulmonary pressures. Conclusion: In children with HCLD, there was evidence of secondary cardiac effects, but AZM had no effect on right heart function. Long-term follow-up in children with HIV should be part of future research to understand the clinical implications of right heart abnormalities.
Abstract Background A high prevalence of cardiac abnormalities has been reported in children with human immunodeficiency virus (HIV) taking antiretroviral therapy (ART) in sub-Saharan Africa. We investigated the incidence and progression of cardiac abnormalities among children taking ART in Zimbabwe. Methods A prospective cohort study was conducted at a pediatric HIV clinic from 2014 to 2017. Children with HIV aged between 6 and 16 years and taking ART ≥6 months were enrolled. Transthoracic echocardiography was performed at baseline and after 18 months. Results Of 197 participants recruited at baseline, 175 (89%; 48% female; median age 12 years, interquartile range 10–14 years) were followed up. The incidences of left and right heart abnormalities were 3.52 and 5.64 per 100 person-years, respectively. Stunting was associated with the development of any cardiac abnormality (adjusted odds ratio 2.59, 95% confidence interval 1.03–6.49; P = .043). Right ventricular (RV) dilatation persisted at follow-up in 92% of participants and left ventricular (LV) diastolic dysfunction in 88%. Cardiac abnormalities present at baseline reverted to normal over the follow-up period in 11 (6%). There was an overall increase in mean z scores for LV, left atrium (LA), RV, interventricular septum, and LV posterior wall diameters at 18 months (P < .001). Conclusions Despite ART, children with HIV have a high incidence of cardiac abnormalities, with only a minority being transient. Mean z scores for LV, LA, RV, interventricular septum, and LV posterior wall diameters increased over a relatively short follow-up period, suggesting the potential for progression of cardiac abnormalities. Longer follow-up is required to understand the clinical implications of these abnormalities.
IMPORTANCE HIV-associated chronic lung disease (HCLD) in children is associated with small airways disease, is common despite antiretroviral therapy (ART), and is associated with substantial morbidity. Azithromycin has antibiotic and immunomodulatory activity and may be effective in treating HCLD through reducing respiratory tract infections and inflammation. OBJECTIVE To determine whether prophylactic azithromycin is effective in preventing worsening of lung function and in reducing acute respiratory exacerbations (AREs) in children with HCLD taking ART. DESIGN, SETTING, AND PARTICIPANTS This double-blind, placebo-controlled, randomized clinical trial (BREATHE) was conducted between 2016 and 2019, including 12 months of follow-up, at outpatient HIV clinics in 2 public sector hospitals in Malawi and Zimbabwe. Participants were randomized 1:1 to intervention or placebo, and participants and study personnel were blinded to treatment allocation. Participants included children aged 6 to 19 years with perinatally acquired HIV and HCLD (defined as forced expiratory volume in 1 second [FEV1] z score < -1) who were taking ART for 6 months or longer. Data analysis was performed from September 2019 to April 2020. INTERVENTION Once-weekly oral azithromycin with weight-based dosing, for 48 weeks. MAIN OUTCOMES AND MEASURES All outcomes were prespecified. The primary outcome was the mean difference in FEV1 z score using intention-to-treat analysis for participants seen at end line. Secondary outcomes included AREs, all-cause hospitalizations, mortality, and weight-for-age z score. RESULTS A total of 347 individuals (median [interquartile range] age, 15.3 [12.7-17.7] years; 177 boys [51.0%]) were randomized, 174 to the azithromycin group and 173 to the placebo group; 162 participants in the azithromycin group and 146 placebo group participants had a primary outcome available and were analyzed. The mean difference in FEV1 z score was 0.06 (95% CI, -0.10 to 0.21; P = .48) higher in the azithromycin group than in the placebo group, a nonsignificant difference. The rate of AREs was 12.1 events per 100 person-years in the azithromycin group and 24.7 events per 100 person-years in the placebo groups (hazard ratio, 0.50; 95% CI, 0.27 to 0.93; P = .03). The hospitalization rate was 1.3 events per 100 person-years in the azithromycin group and 7.1 events per 100 person-years in the placebo groups, but the difference was not significant (hazard ratio, 0.24; 95% CI, 0.06 to 1.07; P = .06). Three deaths occurred, all in the placebo group. The mean weight-for-age z score was 0.03 (95% CI, -0.08 to 0.14; P = .56) higher in the azithromycin group than in the placebo group, although the difference was not significant. There were no drug-related severe adverse events. CONCLUSIONS AND RELEVANCE In this randomized clinical trial specifically addressing childhood HCLD, once-weekly azithromycin did not improve lung function or growth but was associated with reduced AREs; the number of hospitalizations was also lower in the azithromycin group but the difference was not significant. Future research should identify patient groups who would benefit most from this intervention and optimum treatment length, to maximize benefits while reducing the risk of antimicrobial resistance.
Chronic lung disease (CLD) is a common co-morbidity for HIV-positive children and adolescents on antiretroviral therapy (ART) in sub-Saharan Africa. In this population, distinct airway microbiota may differentially confer risk of CLD. In a cross-sectional study of 202 HIV-infected children aged 6–16 years in Harare, Zimbabwe, we determined the association of sputum microbiota composition (using 16S ribosomal RNA V4 gene region sequencing) with CLD defined using clinical, spirometric, or radiographic criteria. Forty-two percent of children were determined to have CLD according to our definition. Dirichlet multinomial mixtures identified four compositionally distinct sputum microbiota structures. Patients whose sputum microbiota was dominated by Haemophilus, Moraxella or Neisseria (HMN) were at 1.5 times higher risk of CLD than those with Streptococcus or Prevotella (SP)-dominated microbiota (RR = 1.48, p = 0.035). Cell-free products of HMN sputum microbiota induced features of epithelial disruption and inflammatory gene expression in vitro, indicating enhanced pathogenic potential of these CLD-associated microbiota. Thus, HIV-positive children harbor distinct sputum microbiota, with those dominated by Haemophilus, Moraxella or Neisseria associated with enhanced pathogenesis in vitro and clinical CLD.
Background. Chronic lung disease (CLD) has been reported among African children with perinatally acquired human immunodeficiency virus (HIV) infection (C-PHIV), despite combination antiretroviral therapy (cART). In adults, shorter telomere length (TL) has been reported in association with both CLD and HIV. As little is known in children, our objective was to compare TL in HIV-positive (cART-naive or -treated) and HIV-negative children with and without CLD. Methods. Participants included Zimbabwean C-PHIV, aged 6-16, who were either newly diagnosed and cART-naive, or on cART for >6 months, and HIV-negative controls of similar age and sex. Packed blood cell (granulocyte) TLs from 621 children were compared cross-sectionally between groups. For a subset of newly diagnosed C-PHIV, changes in TL following cART initiation were evaluated. Results. C-PHIV had shorter granulocyte TL compared with uninfected peers, regardless of cART. Among 255 C-PHIV without CLD, TL was shorter in cART-naive participants. In multivariable analyses adjusted for age, sex, CLD, and HIV/cART status, shorter TL was independently associated with older age, being HIV positive, and having reduced forced vital capacity (FVC). Last, cART initiation increased TL. Conclusions. In this cohort, C-PHIV and those with reduced FVC have shorter granulocyte TL, possibly the result of increased immune activation and cellular turnover due to longstanding HIV infection with delayed cART initiation.
Globally, 1·7 million children are living with HIV, of which 90% are in sub-Saharan Africa. The remarkable scale-up of combination antiretroviral therapy has resulted in increasing numbers of children with HIV surviving to adolescence. Unfortunately, in sub-Saharan Africa, HIV diagnosis is often delayed with children starting antiretroviral therapy late in childhood. There have been increasing reports from low-income settings of children with HIV who have multisystem chronic comorbidities despite antiretroviral therapy. Many of these chronic conditions show clinical phenotypes distinct from those in adults with HIV, and result in disability and reduced quality of life. In this Review, we discuss the spectrum and pathogenesis of comorbidities in children with HIV in sub-Saharan Africa. Prompt diagnosis and treatment of perinatally acquired HIV infection is a priority. Additionally, there is a need for increased awareness of the burden of chronic comorbidities. Diagnostic and therapeutic strategies need to be collectively developed if children with HIV are to achieve their full potential.
The novel allele KIR2DL5A*0010104 differs from that of KIR2DL5A*0010101 with eight single intronic nucleotide changes.
Abstract Increased carotid intima-media thickness (cIMT) is reported in both adults and children with human immunodeficiency virus (HIV) in high income settings and is associated with an increased risk of cardiovascular disease, but data from sub-Saharan Africa is lacking. We assessed cIMT using ultrasound in perinatally HIV-infected children aged 6 to 16 years taking antiretroviral therapy (ART) for ≥6 months compared with HIV-uninfected controls in Harare, Zimbabwe. Groups were compared using unpaired t test and potential predictors of cIMT were assessed using multiple linear regression. A total of 117 participants with HIV, of whom 55 (45%) were female and 75 healthy uninfected controls were included. Participants with HIV were younger than uninfected controls, 10.7 (2.4) years versus 11.9 (2.6) years (P = .001). Mean cIMT was 0.40 (0.05) mm in those with HIV versus 0.40 (0.04) mm in healthy controls (P = .377). There was no association between cluster of differentiation 4 count, HIV viral load, and duration on ART and cIMT. Children with HIV taking ART have similar cIMT to uninfected children. Increasing numbers of children with HIV are reaching adulthood and longitudinal studies to assess the effect of long-term HIV and ART on vascular changes are required.