Introduction

Worldwide tuberculosis (TB) takes more lives than any other infectious diseases [1]. For achieving the global tuberculosis control, early and accurate diagnosis of drug sensitive and drug resistant TB is crucial. However, underdiagnosis still remains as a pertaining obstacle especially in the countries where patient face substantial geographical and socio-economic challenges while accessing health care. Similarly, the scenario of many countries depicts that case detection relies on patients reporting symptoms to health care facility. In such condition of delays in case identification and management, there remains a higher probability of transmission and continuation of epidemic [2].

Transmission of tuberculosis depends on numerous factors, which includes the index case, the susceptibility of the exposed host, behaviour of bioaerosols, pathogen-inherent factors, and environment in which transmission occurs. Therefore, elimination of transmission relies on the ability to identify and treat the infected individuals at risk of becoming infectious, utilizing prognostic and diagnostic biomarkers to target preventive and curative therapies. Moreover, tuberculosis and HIV co-infection has fuelled the TB epidemic, presenting programmatic and treatment challenges across the world [3]. Co-morbidity of Human Immunodeficiency Virus (HIV) and tuberculosis, in the individual host, potentiate pathogens of one another, which eventually deteriorate the immunological functions. HIV coinfection is the prime risk factor for developing active TB in the high-burden settings. This in turn increases the susceptibility to primary infection or reinfection and the risk of TB reactivation for patients with latent TB. Similarly, infection of Mycobacterium tuberculosis also has a negative effect on the immune response to HIV, accelerating the progression from HIV infections to AIDS [4].

Globally HIV infection attributed 0.76 million incident TB cases along with an estimated 208,000 TB deaths among HIV positive people in 2019. Furthermore, the risk of developing TB among people living with HIV (PLHIVs) was 18 (range, 15–21) times higher than the general population [1]. Besides, estimation shows that one in every four deaths among PLHIVs was attributed to TB [5]. World Health Organization (WHO) estimates around 68,000 incident TB cases in Nepal. However, only around 27,232 new and relapse TB cases were reported in the national health management information system (HMIS) in 2019/20, resulting around 40,768 incident TB cases missing every year in Nepal [6]. Missing TB cases has posed significant challenges for the prevention, and control of TB in Nepal. Such undiagnosed TB cases has intensified transmission of TB in communities, putting vulnerable groups especially PLHIVs at higher risk of TB [7]. In 2019, the estimated number of PLHIVs in Nepal was 29,503 resulting adult (15–49 years) HIV prevalence of 0.13%. HIV epidemic in Nepal is concentrated largely among key population, notably among client of sex workers (9%), men who have sex with men and transgender (9%), male sex workers (3%), and people who inject drugs (3%). On the other hand, routine program data as of July 2020 shows only 19,410 PLHIVs on were anti-retroviral therapy (ART) along with 12% lost to follow up [8]. It reflects the urgent need to intensify the diagnosis of TB and HIV in health care settings to address the burden of HIV and TB co-morbidity in Nepal.

In the year 2004, WHO had published an interim policy on collaborative TB/HIV activities in response to demand from countries for immediate guidance on actions to decrease the dual burden of TB and HIV. This policy emphasized the need of collaboration between HIV programmes and TB control programmes to ensure access to integrated and quality-assured services for women, children, prisoners and for people who use drugs [9]. Later in the year 2009, National Tuberculosis Control Center (NTCC) in Nepal adopted TB/HIV strategy and policy with the aim to reduce the burden of TB and HIV in a population affected by both diseases in collaboration with National Center for AIDS and STD Control (NCASC). This strategy aimed to provide integrated and comprehensive TB and HIV prevention, treatment and care service as close as possible to detect more TB/HIV co-infected cases and prevent the case fatality rate from TB [10]. Despite the provision for TB screening among all PLHIVs in HIV care setting and HIV testing of all TB patients in TB care setting, yet the progress towards this indicator is very low. In 2019/20, only 51% of the TB patients were tested for HIV suggesting additional efforts to reach the target of 100% [6]. Besides, we could not find any published evidence suggesting the proportion of HIV patients who were screened for TB in HIV care setting in Nepal.

The information collected from health management information system (HMIS) in Nepal lacks validity and reliability due to incomplete, inconsistent, untimely recording and reporting along with lack of skilled manpower, necessary infrastructure, and tools in health care setting [11]. Hence the prevalence generated from the HMIS might not be reliable. Understanding the exact prevalence of TB among PLHIVs and the associated risk factors is crucial for effective planning and implementation of interventions for preventing TB and HIV co-infection in Nepal. In this scenario, NTCC carried out this study in ART sites with comparatively high caseloads to estimate the prevalence of TB and identify the associated risk factors for TB among PLHIVs in Nepal.

Materials and methods

Results

Among the total PLHIVs who were screened for TB, 40 were diagnosed with TB indicating 9.9% prevalence of TB among PLHIVs.

More than half participants (52.9%) in the study were male (Table 1). The median age of the participants was 36 (IQR, 30–43) years. Majority of the participants (41.4%) belonged to age group 30–39 years. In terms of their ethnicity, nearly half of the PLHIVs belonged to Janajatis (44.2%), followed by Brahmin/Chhetri (33.7%) and Dalits (14.6%) (Table 1).

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Table 1. Prevalence of TB by socio demographic and clinical characteristics of PLHIVs (N = 403).

https://doi.org/10.1371/journal.pone.0262720.t001

As presented in Table 2, prevalence of TB among PLHIVs was significantly higher among male than female (13.6% Vs 5.8%, P = 0.02) and among Dalit than Brahmin/Chettri ethnic group (22.0% Vs 5.9%, P = 0.01). The odds of developing TB among male PLHIVs was nearly three times (OR = 2.62) higher than female while Dalit PLHIVs were nearly four times (OR = 3.83) at higher risk of developing TB than Brahmin/Chettri. Among different age groups, the prevalence of TB was found highest among PLHIVs aged less than 20 years (12.5%) and lowest among aged 50 year and above (7.3%). However, the association was not found statistically significant. Among the other socio-demographic characteristics of PLHIVs, prevalence of TB was found comparatively higher among Buddhist (13.3%); among unmarried (13.0%); and among agricultural workers (20.8%). Importantly, none of the association were found significant. This study also assessed the risk of developing TB among PLHIVs by the different clinical characteristics. Among different clinical characteristics of PLHIVs, TB prevalence was found comparatively high among those PLHIVs with CD4 cell count less than 200 cells/UL (13.5%); whose HIV stage progressed to WHO stage 3 and 4 (23.3%); and who did not use IPT (10.2%). Prevalence of TB was found high among PLHIVs with family history of TB (23.3%); and who were clients of female sex workers (13.3%). The risk of developing TB was significantly higher among those with HIV stage progressed to WHO stage 3 and 4 (OR = 4.85, P<0.001) and among those with family history of TB (OR = 4.50, P = 0.002) (Table 2).

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Table 2. Association between socio demographic and clinical characteristics with the development of TB in PLHIVs (N = 403).

https://doi.org/10.1371/journal.pone.0262720.t002

Discussion

Prevalence of TB among PLHIVs was found 9.9% which is slightly higher than the finding of similar study conducted by NTCC in fiscal year 2013/14 [12]. The prevalence was higher than the findings presented by other studies conducted at subnational level in Nepal [13,14]. It indicates that the prevalence of TB among PLHIVs is in increasing trend in Nepal.

In our study male PLHIVs were at greater risk of TB infection than female. This finding corresponds with similar studies conducted in different settings around the globe [15–21]. In developing countries where socio-cultural dynamics prefer male over female in terms of their movement and exposure [22], consequently exposure to TB bacilli could be high in male than female. Other reasons for this might be higher burden of HIV among male than female in general population [8]. Furthermore, burden of TB in the general population is also nearly twice among male than female [6]. A research finding shows more than a quarter of women (28%) in Nepal do not participate in decision making process resulting in low health seeking behaviour among female than male [23], it might have contributed for less number of TB diagnosis among female than male. In our study, higher risk of developing TB among Dalit PLHIVs than Brahmin/Chettri might be due to inequalities between them in accessing and utilizing health care services and resources. Evidence also show that Dalit in Nepal have been experiencing disparities in health outcomes and barriers for accessing desired health care services [24]. Significant proportion of Dalit are in lower wealth quintile, have poor households, and lack necessary infrastructure and resources as compared to non-Dalit ethnic group [25]. Inadequate nutrition and poor standards of living due to poor socio-economic status among Dalits might have increased the risk of developing TB than Brahmin/Chettri PLHIVs. This study found that PLHIVs with family history of TB were at more risk of developing TB. They were nearly five times more likely to develop TB than those without any family history of TB. PLHIVs having family members with TB could have increased their exposure to tuberculosis bacilli and have consequently increased the risk of developing TB. This finding resonates with other studies where they concluded household exposure to a known case of TB is an important risk factor for TB [26–29].

Age of PLHIVs was not found significantly associated with the risk of developing TB. This finding corresponds with other similar studies conducted in Brazil and Tanzania [30,31]. Illiterate PLHIVs were nearly three times more likely to develop TB than the literate. Although the association was not significant, other evidence has shown that having knowledge on measures of infection prevention and TB/HIV co-infection among PLHIVs reduced the risk of developing TB [32–35]. This study could not observe any association between occupation of the PLHIVs and the risk of developing TB. Contrary to our finding, few studies had reported increased risk of developing TB among people working at mines, silica dust, factories [36,37]. Although the burden of HIV is concentrated among key population in Nepal, this study could not establish any significant association between risk group of PLHIVs and the risk of developing TB. Contrastingly, a study conducted across Europe by Kruk A. found that IDUs were comparatively at higher risk of developing TB than others [38].

TB incidence was significantly associated with HIV stages of PLHIVs. PLHIVs with HIV stage progressed to WHO stage 3 and 4 were nearly five times at risk of developing TB than those in WHO stage 1 and 2. Generally, PLHIVs with HIV stage progressed to WHO stage 3 and 4 are more immunosuppressed and are more likely to get infected with different opportunistic infections [39,40]. It could be the reasons for the observed association. On the other hand, PLHIVs with CD4 cell count less than 200 cells per/UL were found to have increased risk of developing TB than those with CD4 cell count equal or greater than 200 cells per/UL. Although the association was not found significant on multivariate analysis, studies have proven that immunocompromised people are at more risk of developing TB. Even, latent TB infection progresses more rapidly to active TB disease with the suppressed immunity [41–44]. Despite proven effectiveness of IPT to reduce the risk of TB infection among PLHIVs and general population, this study could not observe any impact in the prevention of TB. In contrast to this study, other studies conducted in different geographical settings had found significant impact of IPT on preventing the risk of developing TB among PLHIVs [45–48].

The strength of this study is major ART sites with high caseloads of PLHIVs on ART were selected. Besides, these ART sites being referral centres, PLHIVs from different geographical areas are also covered in this study.

There are some limitations of this study. Important predictors for TB, like smoking habit, alcohol consumption, diabetic status, were missed in this study which could have otherwise explored additional evidence to strengthen TB/HIV co-infection program in Nepal.

Conclusions

Prevalence of TB among PLHIVs was 9.9% in Nepal. The risk of developing TB among PLHIVs was significantly higher among male, Dalit ethnic group, those with HIV progressed to WHO stage 3 and 4 and among those with family history of TB. This study suggests that PLHIVs with certain characteristics are at greater risk of developing TB. Hence, targeted interventions are needed to minimize the risk TB among PLHIVs. Further studies are needed to explore the association between CD4 cell count, and effect of IPT with the risk of developing TB among PLHIVs. Finally, the implementation of integrated and comprehensive TB/HIV interventions is needed in health care settings to reduce the burden of TB and HIV co-infection through effective collaboration between National TB control program and HIV program in Nepal.

Supporting information

Acknowledgments

We would like to acknowledge all the Provincial TB Coordinators (Barsha Thapa, Bimal Subedi, Sailesh Bhujel, Bharati KC, Diwas Acharya, Rajesh Sah) for their support throughout the study. We express our deep gratitude to all the ART sites for their support to complete this study on time. Similarly, we would also like to thank all the laboratory technicians, survey coordinator and counsellor for their support during the study period. At last, we would like to remember and thank all the participants who gave their valuable time for interview.