European Journal of Cardiovascular Medicine

The HIV/AIDS epidemic, spanning over 36 years in India, has evolved into a significant public health challenge. Globally, approximately 39 million people were living with HIV at the end of 2022, with nearly 40 million lives lost since the onset of the disease [1]. India has witnessed a decline in adult HIV prevalence (ages 15–49), dropping from 0.32% in 2010 to 0.21% in 2021. However, northeastern states like Mizoram, Nagaland, and Manipur continue to report the highest prevalence rates, followed by southern states like Andhra Pradesh, Telangana, and Karnataka. An estimated 2.5 million people are living with HIV (PLHIV) in India, with the southern states bearing the largest burden [2].

HIV in India is predominantly caused by the HIV-1 virus, particularly the M subtype C strain. Among children, perinatal transmission, breastfeeding, and blood transfusions remain the most common routes of transmission [3]. Advances in antiretroviral therapy (ART) have transformed HIV from a fatal disease into a chronic condition, significantly improving life expectancy [4]. Despite these advancements, systemic complications, especially cardiovascular diseases, remain significant concerns [5].

HIV infection and ART contribute to cardiac dysfunction through mechanisms such as direct viral effects, chronic inflammation, malnutrition, and drug-induced cardiotoxicity [6]. Globally, cardiovascular manifestations including dilated cardiomyopathy (DCM), pericardial effusion, pulmonary hypertension, and endocarditis are observed in 45–65% of HIV-infected individuals. Among children living with HIV/AIDS (CLHA), subclinical and asymptomatic cardiac conditions are common but frequently overlooked or misattributed to pulmonary issues [7].

The pathogenesis of HIV-associated cardiomyopathy is multifactorial. Myocarditis caused by opportunistic infections, such as cytomegalovirus and Toxoplasma gondii, is a key factor in DCM development [8]. Proinflammatory cytokines, such as TNF-α and IL-6, exacerbate myocardial damage, while malnutrition, selenium deficiency, and anemia further contribute to left ventricular dysfunction [9]. Additionally, certain antiretroviral drugs, such as zidovudine, are known for their cardiotoxic effects [10].

While autopsy and echocardiographic studies document high rates of cardiac abnormalities in HIV-infected children globally, Indian studies remain limited in scale and often focus on symptomatic or critically ill patients [11]. There is a pressing need for comprehensive data on the prevalence and spectrum of cardiac abnormalities among Indian CLHA [12].

Echocardiography remains the gold standard for diagnosing cardiac dysfunction, providing insights into left ventricular performance, pericardial effusion, and pulmonary hypertension [13]. Emerging biomarkers like brain natriuretic peptide (BNP) and cardiac troponins hold promise for detecting subclinical cardiac issues [14]. Early identification and management of cardiac complications are critical, as untreated conditions can significantly worsen morbidity and mortality in HIV-positive children [15].

Recognizing the increasing prevalence of cardiovascular complications among CLHA and the paucity of Indian data, the present study aims to assess the prevalence and spectrum of cardiac dysfunction in children aged 2–12 years living with HIV. This research intends to bridge critical knowledge gaps and support routine cardiac evaluations as part of the clinical management of pediatric HIV in India [16].

This descriptive, cross-sectional study was conducted at the ART Centre, MGM Hospital, Warangal, over a 22-month period from September 2022 to June 2024.

The study included 52 children living with HIV/AIDS (CLHA) aged 2–12 years who attended the ART Centre. Children with a prior diagnosis of acquired heart disease were excluded. Informed verbal consent was obtained from parents or guardians before participation. Ethical clearance was granted by the Kakatiya Institutional Ethics Committee (Ref: KIEC/PG DISS-2021-22/33). Comprehensive clinical evaluations were performed, including anthropometric measurements to assess growth parameters. CD4 cell counts were determined via flow cytometry in the Microbiology Department of Kakatiya Medical College. Cardiac assessments included chest radiography, electrocardiography (ECG), and echocardiography (ECHO).

Cardiac Investigations

• ECG: Electrocardiograms were recorded using the NIKHON KOHDEN Cardiofax 8820K machine.
• ECHO: Echocardiographic evaluations were conducted by a cardiologist using the Philips EnVisor C H.D. machine, adhering to guidelines from the American Society of Echocardiography. Standard imaging views—parasternal, apical, sub-xiphoid, and suprasternal—were utilized to measure cardiac dimensions and functional indices. Systolic function was assessed using ejection fraction (<54%) and fractional shortening (<28%). Specific diagnoses such as dilated cardiomyopathy, pericardial effusion, and valvular regurgitation were classified according to established diagnostic criteria.

Definitions and Classifications

• HIV Infection: Confirmed via rapid antigen testing.
• Vertical Transmission: Defined as mother-to-child transmission in cases where the mother was HIV-positive or had succumbed to AIDS, with no history of child abuse.
• Clinical Staging: Based on the WHO Revised Criteria for HIV clinical staging.
• Immune Status: Categorized using CDC CD4 cell count thresholds.
• Nutritional Status: Assessed using WHO growth charts.
• Anemia: Classified by hemoglobin levels into mild, moderate, or severe categories based on WHO standards.

Statistical Analysis: Data analysis was conducted using SPSS version 20.0. Continuous variables were summarized using descriptive statistics (mean, standard deviation, or median as appropriate). The Chi-square test was used to evaluate trends and associations. Diagnostic performance metrics, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), were calculated. A p-value <0.05 was considered statistically significant.

Demographics
A total of 52 children living with HIV/AIDS (CLHA) participated in the study, with a mean age of 9.38 years. The male-to-female ratio was 62:38, and no statistically significant sex difference was observed across age groups (p > 0.05) ( Table 1 & Figure 1). Perinatal transmission accounted for all cases (100%), with 53.8% of mothers deceased due to HIV/AIDS and 46.1% living with retroviral disease (RVD).

Table 1: Age and Sex Distribution

Clinical Features

Hepatosplenomegaly (46.6%) was the most common clinical finding, followed by lymphadenopathy (23%) and upper respiratory tract infections (11.5%). Tuberculosis and pneumonia were observed in 3 cases (5.7%) and 2 cases (3.8%), respectively. Chronic diarrhea and oral candidiasis were rare (1.9% each) (Table 2).

Table 2: Clinical Manifestations in CLHA

Cardiac Dysfunction and Hematological Findings

Cardiac dysfunction was found in 69.2% of children, with a slightly higher prevalence in males (75%) compared to females (60%). However, the difference was not statistically significant (p = 0.254). The mean hemoglobin level was 9.71 g/dL, and 59.6% of children were anemic, categorized as mild (13.4%), moderate (38.4%), or severe (7%).

Nutritional and Immune Status

Nutritional assessments revealed 57% of the children were undernourished (<3rd centile for weight-for-age). CD4 count evaluation indicated no immune suppression in 42.3% of cases, moderate suppression in 36.5%, and severe suppression in 21.1% (Figure 2).

Cardiac Investigations

Echocardiography identified tricuspid regurgitation and right ventricular dysfunction as the most common abnormalities (17.3% each), followed by mitral regurgitation (11.5%) and pulmonary hypertension (3.8%). Dilated cardiomyopathy was rare (1.9%) (Table 3).

Table 3: Echocardiographic Findings

Predictive Factors

Cardiac dysfunction was significantly associated with anemia (p = 0.0302) and undernutrition (p = 0.0027) (Table 4). Tachycardia and murmurs were significantly more frequent in children with cardiac dysfunction (p < 0.05).

Table 4: Association of Anemia and Nutritional Status with Cardiac Dysfunction

Symptomatology predicted cardiac dysfunction with a sensitivity of 83.3% and specificity of 87.5% (Table 5 & Figure 3).

Table 5: Diagnostic Accuracy of Cardiac Symptoms, ECG, and Chest X-ray

HIV infection continues to pose a significant global public health challenge, particularly among women of childbearing age. This contributes to pediatric HIV cases due to perinatal transmission. Although antiretroviral therapy (ART) has significantly improved survival and quality of life, it neither eradicates the virus nor fully prevents complications, including cardiovascular involvement. HIV's impact on organ systems, especially the cardiovascular system, is often underdiagnosed due to nonspecific symptoms and limited routine use of echocardiography.

This study sought to bridge this gap by evaluating cardiac abnormalities in 52 CLHA aged 2–12 years. The prevalence of cardiac dysfunction was 69.2%, which is slightly higher than that reported in similar studies, such as those by Pongprot et al. (2010) and Lubega et al. (2005) [17,8]. The most common abnormalities identified were right ventricular dysfunction, tricuspid regurgitation, and mitral regurgitation, with a low prevalence of dilated cardiomyopathy (1.9%) and pulmonary hypertension (3.8%). Notably, left ventricular dysfunction was absent in this cohort, a finding that contrasts with earlier studies like Ira Shah et al. (2006) [18]. This discrepancy may be attributed to differences in the clinical stage of HIV and the early detection of disease progression in this cohort.

Anemia and nutritional status were significantly associated with cardiac dysfunction, aligning with findings by Pongprot et al. (2010) and Lubega et al. (2005) [17,8]. However, no correlation was observed between cardiac abnormalities and CD4 cell counts, corroborating results from the P2C2 study (Starc et al.,2002) [19]. This suggests that immunological parameters alone may not serve as reliable predictors of cardiovascular involvement in CLHA. Moreover, this study did not find a significant impact of ART on cardiac outcomes. This aligns with some studies, but others, such as Kausalya et al. (2022) and Mladěnka et al. (2018) [20,21], have reported mixed results regarding the cardiotoxicity of specific antiretroviral drugs like zidovudine.

Diagnostic Implications

This study revealed the limitations of traditional diagnostic tools like chest X-ray, which showed low sensitivity (19.4%) and specificity (11.2%) in detecting cardiac abnormalities. While ECG demonstrated higher sensitivity (80.55%) and specificity (93.75%), it was insufficient for identifying early or subclinical cardiac dysfunction. In contrast, echocardiography emerged as the most reliable diagnostic modality, detecting abnormalities in 69.2% of cases, even in asymptomatic patients. This reinforces the findings of Alan et al. (2003) and Reinsch et al. (2011), emphasizing the critical role of echocardiography in early detection and timely intervention [22,11].

Clinical Implications

The study highlights the necessity of routine cardiac evaluations for all CLHA, regardless of their clinical presentation. Echocardiography should be prioritized as it is capable of identifying early and asymptomatic disease. ECG, while not sufficient for definitive diagnosis, remains a useful initial screening tool. Adopting this comprehensive approach can facilitate early therapeutic interventions, potentially mitigating the progression of cardiovascular complications and improving long-term outcomes for CLHA.

This study found a high prevalence of cardiac dysfunction (69.2%) among children living with HIV/AIDS (CLHA), particularly in those with advanced stages of HIV infection. The prevalence increased with age, highlighting the progressive nature of cardiac involvement in this population. While no significant association was found between cardiac dysfunction and sex, a clear correlation was observed with nutritional status, hemoglobin levels, and CD4 cell counts, emphasizing the importance of monitoring these parameters in HIV-positive children.

The findings also revealed that a substantial proportion of CLHA with cardiac dysfunction were asymptomatic or presented only subtle symptoms, reinforcing the need for routine cardiac screening. Echocardiography (ECHO) emerged as the most reliable and non-invasive diagnostic tool, detecting a range of cardiac abnormalities, including right ventricular dysfunction, tricuspid and mitral regurgitation, dilated cardiomyopathy (DCM), and pulmonary hypertension. Importantly, ECHO was particularly effective in identifying early-stage, subclinical cardiac dysfunction, underscoring its critical role in facilitating early intervention and management.

In contrast, chest X-ray and electrocardiography (ECG) demonstrated limited diagnostic utility. Chest X-rays had low sensitivity and specificity, while ECG detected abnormalities in only 57.6% of cases and often failed to identify early cardiac dysfunction. These findings highlight the inadequacy of these tools as primary diagnostic methods for cardiac evaluation in CLHA.

Based on these results, it is strongly recommended that all CLHA undergo routine echocardiographic screening, regardless of whether they exhibit symptoms of cardiac dysfunction. Periodic follow-up evaluations should also be conducted to monitor disease progression and implement timely interventions, ultimately improving long-term clinical outcomes.

SOURCE OF FUNDING : Nil

 CONFLICT OF INTEREST :None

AUTHOR’S CONTRIBUTIONS

Srivani Palley worked on conceptualization, methodology, investigation, formal analysis, validation and software, writing- original draft preparation of the article.

Subhan Basha Bukkapatnam has worked on conceptualization, methodology, software, formal analysis, data curation, validation, writing-reviewing and editing, Visualization, supervision and project administration

Vasudev Kompally has worked on conceptualization, methodology, investigation, formal analysis, validation, resources, reviewing and editing, supervision, and project administration

All authors have read and agreed to the published version of the manuscript.

ACKNOWLEDGEMENTS:

We express our appreciation and gratitude to all the parents and care givers of the babies for supporting our study by giving consent without which this can never happen. We are thankful to Department of Pediatrics, Department of Radiology, Department of Biochemistry, Hospital Administration, who have assisted and supported in this research.

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