HIV Co-Infection Increases Mortality and Impairs Functional Independence and Physical Performance in Hospitalized Tuberculosis Patients

1. INTRODUCTION

Tuberculosis (TB) remains a major global public health challenge, ranking as a leading cause of morbidity and the second most lethal infectious disease worldwide, surpassed only by COVID-19 and exceeding the mortality burden of Human Immunodeficiency Virus (HIV)/Acquired Immunodeficiency Syndrome (AIDS) [1]. According to the World Health Organization (WHO), an estimated 10.6 million people developed TB in 2021, resulting in 1.6 million deaths, including approximately 187,000 among patients living with HIV. HIV co-infection is the most substantial known risk factor for both the development of active TB and the reactivation of latent TB infection [2]. Individuals living with HIV are approximately 18 times more likely to develop active TB when compared to those without HIV [1]. Conversely, TB increases HIV viral replication at the site of Mycobacterium tuberculosis infection, thereby accelerating HIV disease progression as well as the onset of AIDS [3].

Although Mycobacterium tuberculosis primarily targets the lungs and causes diverse patterns of pulmonary damage, it can also affect different human systems, leading to systemic symptoms, such as fever, fatigue, loss of appetite, and weight loss. Additionally, peripheral muscle strength is also often compromised in TB patients. Muscle weakness is a key feature of cachexia, a hallmark of pulmonary TB, which is characterized by severe, disproportionate muscle wasting, leading to progressive weight loss, fatigue, and reduced muscle function [4]. Consequently, impaired muscular function leads to lower exercise tolerance, reduced daily physical activity, and impaired quality of life [5]. Physical function limitations are also observed in patients with HIV without TB co-infection, even in those with effectively treated infection [6, 7]. Although the literature provides extensive information on the physical functioning of patients with either TB or HIV infection, the impact of TB/HIV co-infection on functional status remains poorly understood. Therefore, this study aimed to assess the impact of HIV co-infection on functional independence and physical performance among hospitalized TB patients, as well as to investigate the associated mortality rate.

2. MATERIALS AND METHODS

2.5. Data Analysis

Descriptive statistics were used to characterize the patient population and assess differences between the TB-only group and the TB/HIV co-infected group. Categorical variables were analyzed descriptively and presented as absolute (n) and relative (%) frequencies. Numerical variables are represented as mean and standard deviation. The comparison of proportions was performed using Fisher's exact test or the chi-squared test. The Mann-Whitney test was carried out to compare differences between the TB-only and TB/HIV co-infected groups (intergroup analysis). The Wilcoxon test was conducted to assess changes within each group between admission and discharge (intragroup analysis). The level of significance was set at p <0.05. A commercial statistical software was used for all statistical analyses (Stata, version 14).

3. RESULTS

4. DISCUSSION

To our knowledge, this is the first study to compare functional independence and physical function between hospitalized patients co-infected with TB and HIV and those infected with TB only. We demonstrated that HIV co-infection significantly increased mortality and negatively impacted both functional independence and physical function in patients with TB during hospitalization. The demographic characteristics of this cohort were predominantly male, characterized by low levels of education, and a high prevalence of vulnerable living conditions, such as unemployment, homelessness, or incarceration. Among those employed, the majority reported low income levels. The demographic profile of our sample aligns with the Brazilian TB scenario [10], including average income and poverty levels, which are factors recognized by the WHO as key determinants of TB, particularly in the context of the coronavirus disease 2019 (COVID-19) pandemic [1].

In this study, we first evaluated functional independence using the FIM, a self-report instrument designed to evaluate an individual's ability to perform activities of daily living [8]. It was observed that in the TB-only infected group, the FIM score at hospital discharge significantly improved compared to the score at admission, which was not observed in the TB/HIV co-infected group. Following the FIM assessment, we conducted the SPPB, a specific and objective test widely used to evaluate physical performance, which also serves as a predictor of disability and mortality [11, 12].

In accordance with the FIM results, the TB-only infected group showed a significant increase in the scores obtained in each domain of the SPPB, such as balance, gait speed, and sit-to-stand, as well as in the total SPPB score at discharge compared to admission. This functional improvement during hospitalization in patients with TB-only can be attributed to comprehensive local hospital care, which integrates a multidisciplinary team approach, notably including consistent daily physiotherapy interventions. In contrast, the TB/HIV co-infected group did not show improvements in gait speed and sit-to-stand performance; it only exhibited an increase in the balance test domain of the SPPB, which corresponded with a lack of improvement in the FIM score. Collectively, these findings indicate that the presence of HIV infection alongside TB impedes enhancements in both functional independence and physical performance during hospitalization. Although no studies have directly compared physical function between patients with TB-only and those co-infected with TB/HIV, substantial evidence indicates that HIV infection contributes to functional impairment [7, 13].

It is known that HIV infection introduces early physical complications, including low muscle mass, reduced bone mineral density, and an increased risk of fractures [14], which can subsequently lead to functional impairment [6]. Although functional impairments in HIV/AIDS were initially attributed to AIDS or AIDS wasting syndrome [14], the use of ART has also been implicated in impairing physical performance through mitochondrial dysfunction and decreased muscle strength, leading to progressive skeletal muscle dysfunction [15]. Moreover, mitochondrial and muscle function may be further compromised by biochemical changes associated with HIV infection, such as carnitine deficiency [16]. Additional factors contributing to impaired performance in patients with HIV include the association between anemia and fatigue [17], as well as inspiratory muscle weakness, which may reduce exercise capacity [18]. In our study, both HIV-related and ART-related factors may have contributed to the reduced functional performance observed in TB/HIV co-infected patients, given that our sample comprised patients with high viral loads, low CD4 levels, and active ART use.

Consistent with the worst functional status observed in TB/HIV co-infected patients, mortality during hospitalization was exclusively recorded in this group. This finding aligns with the established role of functional limitations as strong predictors of disability and mortality [19]. Furthermore, it is known that HIV co-infection is associated with worsening TB treatment outcomes [1] and a significant increase in mortality risk by accelerating TB progression and impairing CD4 recovery. This immunological decline can lead to rapid HIV replication, facilitating progression to AIDS and death among affected individuals [20]. The high mortality rate among TB/HIV co-infected patients reported in our study, alongside similar findings in the literature, underscores the critical importance of WHO's guidelines advocating preventive TB treatment in patients living with HIV [1]. On the other hand, a recent study [21] demonstrated HIV status as a protective factor associated with successful TB treatment. Although this finding contrasts with numerous reports documenting poorer outcomes in TB-HIV co-infected patients, it was also found that HIV positive individuals often receive heightened medical attention and benefit from enhanced coordination among specialized healthcare units. This increased level of care and multidisciplinary collaboration may contribute to improved treatment success in this population [21].

This study provides novel and significant findings, demonstrating that HIV co-infection is associated with increased mortality, impaired functional independence, and diminished physical performance in TB patients during hospitalization. However, the study has several limitations. Patients were recruited from a single hospital, which may limit the generalizability of the results to other settings. Furthermore, the data were obtained from a limited sample size. It is also noteworthy that the study period coincided with the onset of the COVID-19 pandemic, leading to a decline in the number of people diagnosed and hospitalized with TB [1]. Moreover, the proportion of TB cases among people living with HIV has been steadily declining over recent years, making it challenging to recruit a larger number of TB/HIV co-infected individuals. Despite these limitations, this study showed significant differences in mortality rates, functional independence, and physical performance between hospitalized patients co-infected with TB/HIV and those infected with TB-only. To validate and extend these findings, future studies should involve multicenter trials with larger sample sizes across diverse clinical settings.

CONCLUSION

The present study highlights the significant adverse impact of HIV co-infection on the functional recovery of hospitalized TB patients. While patients with TB alone demonstrated notable improvements in functional independence and physical performance during the hospitalization, these improvements were not observed in the TB/HIV co-infected group. Additionally, the co-infected group exhibited a significantly higher mortality rate. These findings emphasize the detrimental effect of HIV co-infection on both functional outcomes and survival in TB patients, underscoring the urgent need for integrated care strategies targeting both infections in order to enhance functional outcomes and reduce mortality in this population.

REFERENCES