Pulmonary Function in Brazilians Living with HIV: A Comparative Cross-Sectional Study

1. INTRODUCTION

Pulmonary function and respiratory condition can be assessed through diagnostic tools that provide information on lung volumes and capacities, inspiratory and expiratory muscle strength, and gas exchange. Commonly used tests include spirometry, manovacuometry, and cardiopulmonary exercise testing (ergospirometry). Spirometry, in particular, is a clinical test performed at rest that evaluates lung volumes and capacities and may be conducted with or without the use of bronchodilators [1, 2].

The clinical interpretation of spirometry results takes into account anthropometric factors such as age, sex, body size, and ethnicity, which are essential for comparing measured values to predicted reference values. Therefore, spirometry is especially useful in identifying respiratory dysfunction in at-risk populations [2-4].

Among such populations are people living with HIV (PLHIV), who may present pulmonary alterations due to chronic inflammation, immune system compromise, and possible direct viral involvement in lung tissue. Recent scientific evidence suggests that HIV can persist in anatomical reservoirs, including the lungs and heart, contributing to both structural and functional damage in these systems [5, 6]. When pulmonary impairment is combined with cardiovascular involvement, the clinical consequences may become considerably more severe.

Although concern is growing regarding functional decline in PLHIV due to respiratory impairment, there is still a lack of studies using direct pulmonary function assessments—such as spirometry—that also report robust statistical metrics, including effect size and statistical power [5-7]. Furthermore, to minimize potential confounding variables related to sex-based physiological differences in lung function and to ensure sample homogeneity, this study included only male participants. While this decision increases the internal validity of the findings, it also limits the generalizability to women and other populations.

Given this context, the present study aimed to compare pulmonary function variables—specifically Forced Vital Capacity (FVC), Forced Expiratory Volume in the first second (FEV₁), and the FEV₁/FVC ratio—between men living with HIV and healthy male controls, to better understand the common clinical respiratory conditions associated with HIV.

2. MATERIALS AND METHODS

This is a cross-sectional analytical study with quantitative variables, with a sample composed of biologically male individuals aged between 18 and 60 years, divided into people living with HIV and a control group in the year 2024. The manuscript was developed following the STROBE checklist for cross-sectional observational studies.

3. RESULTS

The sample consisted of 34 biologically male individuals, with 17 in each group. The PVHIV group included individuals aged 24 to 60 years, while the control group ranged from 20 to 67 years, with most volunteers in both groups being between 30 and 40 years old. Each group had 15 sedentary participants and 2 active participants according to the IPAQ short version assessment. General data are presented in Table 1, demonstrating that the sample is matched for age, height, and physical condition. Regarding viral load, 16 participants had a viral load below 40 RNA/mL, and only one volunteer had a high viral load of 100,000 RNA/mL.

Regarding pulmonary function evaluation, individual reference values were considered and compared to the measurements obtained. Out of the three measurements performed, the best result was selected for analysis. Among people living with HIV, 56.25% (10 individuals) exhibited a restrictive pattern: 12.5% showed mild restriction, 12.5% moderate restriction, and 31.25% severe restriction. In contrast, the control group demonstrated 100% of pulmonary volumes within normal ranges, as shown in Table 2. Notably, there were no spirometry results indicating obstructive patterns. The Odds Ratio (OR) suggests a higher likelihood of individuals without an HIV diagnosis having normal pulmonary function compared to those living with HIV.

Regarding the predicted reference values, the PVHIV group did not meet or exceed the expected values. Even those with normal range results did not achieve their full predicted volumetric capacity, whereas the control group surpassed the predicted values. Table 3 presents the pulmonary volume values obtained by both groups in a comparative manner.

It is important to understand that the effect size and power obtained in the analyses of forced expiratory volume in the first second (FEV1) indicate a high probability of detecting real differences, as this parameter is strongly associated with expiratory force in the literature. Conversely, forced vital capacity (FVC) shows a moderate effect size; however, the statistical power is low, suggesting that larger sample sizes might be needed to confirm significant differences.

Additionally, despite the weak effect sizes and power for the other variables, the reference values for PLHIV are considerably higher compared to the values achieved during the test, with significant differences observed in FVC (0.01), FEV1 (0.01), FEF25 (0.01), and PEF (0.04), as shown in Table 4. While no statistical difference was observed between the reference values and those achieved by the control group for FVC and FEV1, as shown in Table 5.

A post-hoc power analysis was conducted to validate the findings related to the FEV1 and FVC variables, based on the observed effect sizes and sample size (n = 23 per group). Using G Power software (version 3.1.9.7) and a significance level of 0.05, the estimated statistical power was approximately 82% for FEV1 (effect size = 0.87) and 46% for FVC (effect size = 0.56). These results indicate that the sample was adequate to detect significant differences in FEV1 with high reliability, while the findings for FVC should be interpreted with caution due to moderate power. These outcomes highlight the clinical relevance of the functional impairment observed, particularly the reduction in FEV1.

Although some variables showed statistical significance, such as FEV1 (p = 0.01; effect size = 0.87) and FVC (p = 0.01; effect size = 0.56), the magnitude of the observed differences also indicates clinical relevance. For FEV1, the mean difference between groups was approximately 0.68 liters, which may represent a functionally meaningful reduction in pulmonary capacity, particularly among individuals with respiratory vulnerability. For FVC, the difference was about 0.57 liters, suggesting a clinically relevant decrease in forced vital capacity. Thus, the findings are not only statistically significant but also clinically meaningful, reinforcing their importance in clinical assessments and future interventions.

4. DISCUSSION

The present sample showed patterns consistent with the literature regarding viral load. Sixteen volunteers with undetectable viral load demonstrated consistent medication use, whereas only the volunteer who did not adhere to treatment exhibited a high viral load, with potential for disease progression [11].

Regarding physical activity levels, participants aligned with studies on physical activity indices in Brazilian and global populations, which indicate a higher prevalence of sedentary individuals compared to active ones [12-16]. A study involving individuals aged 10 to 19 years reported a higher prevalence of sedentary behavior among people living with HIV, highlighting lifestyles that promote sedentarism and predispose them to cardiovascular and metabolic diseases [17].

It is known that HIV infection is associated with the development of non-infectious pulmonary diseases, due to the inflammatory characteristics of the infection and viral deposits in target organs. Numerous scientific articles highlight the association of Kaposi's sarcoma, lymphomas, and pulmonary complications such as tuberculosis with HIV, emphasizing the importance of studying respiratory conditions in people living with HIV, particularly for early disease detection [18-20].

Pulmonary alterations significantly impact human functionality. A 2021 study on individuals with HIV and frailty syndrome identified a relationship between functional decline and restrictive ventilatory patterns. Functional impairments can lead to difficulties in performing daily activities and have long-term negative effects on quality of life during aging [19].

In line with the findings of Lima et al. [19], 56.25% of the PLHIV group were diagnosed with restrictive patterns in spirometry testing. It is noteworthy that none of the participants were smokers. However, most studies emphasize obstructive diseases in the HIV population, likely influenced by the recruitment of smokers, which may explain the higher incidence of obstructive diagnoses [21-26].

The literature lacks robust evidence on the causal relationship between restrictive or obstructive respiratory patterns and mechanisms directly triggered by the virus. It is hypothesized that altered respiratory patterns may result from inflammatory processes or regional and climatic conditions, warranting further research involving imaging and tissue biopsy examinations [26].

Regarding restrictive patterns, they are identified by a reduction in vital capacity and forced expiratory volume in the first second (FEV1), as per the SBPT [9], which aligns with the findings of this study. The FEV1 of the PLHIV group was lower than that of the control group, with an effect size of 0.87 and power of 0.69, indicating a likelihood of similar findings in comparable populations.

In addition to FEV1, these findings of reduced respiratory function align with studies linking human functionality to respiratory patterns [19]. Reduced FEV1 is associated with greater functional dependency. Thus, prior FEV1 measurement could be a valuable early indicator of human functionality in people living with HIV [27].

Given the increase in HIV incidence in Brazil after the pandemic, the development of early assessments that provide insights into pulmonary function is crucial [28]. Other variables, such as FVC and PEF, also showed significant reductions, indicating compromised respiratory conditioning. Studies associate such reductions with functional dependency [27, 29].

It is worth noting that spirometry values in the control group align with the literature, while those in the PLHIV group are lower than predicted for adults with similar physical conditions. This may suggest an association between HIV and respiratory alterations, as evidenced by the aOR presented in this study [2, 30-33].

Epidemiological studies and meta-analyses have shown that people living with HIV have a higher prevalence of pulmonary function impairments, particularly obstructive patterns and, to a lesser extent, restrictive patterns. Although most studies focus on obstructive impairments, an increasing number of investigations have reported restrictive deficits, especially among individuals with longer infection duration or a history of opportunistic infections. The findings of the present study, which identified significant reductions in FVC and FEV1, are consistent with these reports, suggesting that pulmonary dysfunction in PLHIV may go beyond the classical mechanisms of airway obstruction [2-4].

Regarding antiretroviral therapy, all participants in the present study were undergoing ART. Although viral load was controlled in most cases, pulmonary functional impairments were still evident, indicating that while ART is beneficial, it may not fully prevent chronic pulmonary alterations.

The proposed biological mechanisms underlying restrictive patterns in PLHIV include chronic immune system activation, viral deposition in lung tissue, subclinical fibrosis, and persistent inflammation despite viral suppression. Histopathological and imaging studies have reported thickening of the alveolar membrane and lymphocytic infiltration as recurrent findings in individuals with HIV. Additionally, factors such as malnutrition, sarcopenia, and sedentary lifestyle, which are common in this population, may also contribute to the reduction of total lung capacity [5-7].

Based on these findings, it is recommended that spirometry be included as a routine screening tool for PLHIV, even for asymptomatic individuals with suppressed viral loads. Periodic assessments may allow early detection of functional decline, enabling preventive and rehabilitative interventions. Respiratory screening may also guide referrals to supervised physical activity programs, which have been shown to benefit both pulmonary function and overall quality of life in PLHIV.

5. LIMITATIONS

The present study has limitations, such as the sample size, considering the prejudice and stigma associated with people living with HIV in Brazil, which hinders the participation of a larger sample. Another aspect is that the sample consists exclusively of men, preventing the evaluation of individuals of the female biological sex. The selection bias was considered during the participant recruitment phase. Well-defined inclusion and exclusion criteria were adopted, and recruitment was conducted at a single center with a standardized approach for all volunteers. However, no specific statistical analyses were applied to measure selection bias, and this limitation is acknowledged as a potential influencing factor on the results. Therefore, it is essential to conduct studies that include both sexes for comparative analysis, as well as studies that consider gender in addition to biological sex. Another limitation that can be observed in the study is the possibility of recall bias, even with the use of the IPAQ as an assessment tool. Although the IPAQ is a validated and widely used instrument for estimating physical activity levels, it still relies on the participants' ability to accurately recall and report their activities over time.

CONCLUSION

This study showed that the values obtained in spirometry are lower in the population living with HIV compared to the control group, indicating a higher likelihood of individuals without an HIV diagnosis having normal patterns compared to those with HIV.

Regarding the predicted values, people living with HIV (PLHIV) exhibited lower values during the test compared to the reference values for their age, weight, and height. It is important to consider the feasibility of analyzing indicators while taking viral load into account, as values may be underestimated if the duration of illness and its effects on target organs are not considered.

The restrictive pattern, although not the most common in people living with HIV in other countries, was more frequent among Brazilians residing in the Federal District. This may be related to the region's hot and dry climate. However, further comparative studies across Brazilian regions are needed, as the control group showed no impact from the geographical region, raising the question of whether people living with HIV may be more vulnerable to climate change.

The findings of this study highlight the importance of including spirometry as part of the clinical routine for people living with HIV (PLHIV), particularly in regions with specific climatic conditions, such as the Federal District. The higher prevalence of a restrictive pattern in this population suggests that environmental factors and the pathophysiology of HIV infection itself may contribute to pulmonary alterations that are not yet fully understood. Furthermore, the underestimation of spirometric values when viral load or duration of infection is not considered underscores the need for an individualized approach, integrating immunological and clinical markers for a more accurate interpretation of results.

Future studies should explore, in larger and more representative samples, the interaction between variables such as time since diagnosis, adherence to antiretroviral therapy, associated comorbidities, and environmental conditions. A comparison across different Brazilian regions, focusing on factors like humidity, altitude, and pollution, could clarify whether PLHIV’s pulmonary vulnerability is influenced by these elements. Finally, incorporating complementary techniques, such as respiratory muscle strength assessment and imaging exams, could provide a more comprehensive understanding of pulmonary dysfunction in this population, supporting the development of more effective preventive and therapeutic protocols.

It is suggested that studies assess forced expiratory volume in the first second (FEV1) while associating it with expiratory strength evaluation, as the values that showed greater deviations compared to the control group were linked to expiratory volume and vital capacity. It is also important to conduct comparative studies with larger samples across both sexes.

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