Socioepidemiological Determinants of Human Immunodeficiency Virus associated Tuberculosis Coinfection in Northern India: A 1:2 Matched Case Control Study

INTRODUCTION

Human immunodeficiency virus infection-associated tuberculosis (HIV-TB) poses an imperative and severe threat to healthcare system globally.¹ Tuberculosis (TB) is one of the first opportunistic infections to appear in HIV-infected people and indeed, one of the key manifestations of HIV. The burden of HIV-TB poses unprecedented challenges on the public health systems, with India bearing the third highest burden in the world.²

Globally, 30% of HIV-infected persons are estimated to have concomitant infection caused by Mycobacterium tuberculosis with prevalence rates varying from 14% in Europe to 46% in the Southeast Asian region.³ There are 2.1 million people living with HIV-AIDS (PLHAs) in India, with an estimated adult HIV prevalence of 0.27%.⁴ Although only 5% of incident TB patients are HIV-infected, India bears about 10% of the global burden of HIV-TB.⁵ Tuberculosis, indeed, causes more than 25% mortality in PLHAs and hence is the leading preventable cause of death among the latter.^6,7

The HIV-TB coinfection is further complicated by complex socioeconomic factors such as unemployment, poverty, malnutrition, overcrowding, and poor living conditions.⁸ Moreover, it has also been found to be intricately linked to male gender, smoking, alcoholism, and drug abuse.^9,10 The prevalence of TB shows a bimodal distribution at the extremes of age.⁹ While active TB is more frequent in immune-compromised people, the odds of TB increases as the CD4 cell count decreases in PLHAs.^9–11 The direct and indirect costs of illness due to HIV-TB have been observed to be more than 30% of the annual household income in developing countries and can have an appalling impact on the economy of the developing world. Thus, HIV-TB is not only a medical woe but a grave socioeconomic disaster, being aptly described as the “cursed duo.”^12,13

In a resource-limited setting like India, HIV seropositivity among TB patients varies from 9.4% in New Delhi to 30% in Mumbai.^13,14 Moreover, the importance of concurrent treatment of HIV-TB cannot be undermined, since up to 50% of patients with HIV (without treatment) and concurrent TB would die prior to completion of antitubercular therapy (ATT). With the emergence of TB as a fatal complement in HIV-AIDS epidemiology, there is an urgent need to explore the probable multifactorial associations of HIV-TB coinfection.¹⁵

Our study attempts to do that by unfolding the underlying correlates of HIV-TB. It has been designed to assess the sociodemographic correlates of HIV-TB and elucidate its risk factors among patients attending a tertiary care health facility in Northern India.

MATERIALS AND METHODS

RESULTS

Our ART center had registered a total of 2,947 HIV cases during the study period (2016–2018), of which 1,857 were males, 901 were females, and 35 were transgenders and 154 were less than 15 years. While the total number of patients on ART was 1,456, the total number of HIV-TB patients were 950 (approximately a third of HIV cases).

As per Table 1, of the 420 patients studied, 267 (63.6%) were males, 147 (35.0%) females, and 6 (1.4%) were transgenders. A greater proportion of male patients (n = 100, 71.4%) were observed in the case group as compared to CGI (n = 74, 52.9%) and CGII (n = 93, 66.4%). The mean age of the case group was 34.91 ± 8.57 years, with an age range of 20–65 years. Among the CGI, the mean age was observed to be 29.79 ± 12.65 years (range = 16–70 years), while the mean age in CGII was found to be 35.21 ± 8.71 years (range = 20–65 years). Both age and sex differences were found to be significantly different among case group vs CGI (p = 0.000).

As per Table 2, the case group subjects were more likely to be residents of urban areas as compared to CGI and CGII (p ≤ 0.001) (the majority of whom were slum dwellers). A significant difference was observed in marital status on comparing cases with CGI (p %3C; 0.001), with case group individuals being more likely to be married. Among the case group, a relatively higher proportion of individuals (n = 41, 29.3%) had attained primary education in comparison to CGI, while CGII comprised maximum number of subjects with complete secondary education. More than 60% of the study subjects were Hindus; however, there was a significantly greater proportion of self-reported Muslims (p < 0.001) in CGI. Majority of the subjects in all the three groups were housewives (22.6%) followed by businessmen (16.4%) and skilled workers (15.2%).

As per Table 3, the vast majority of our subjects belonged to the upper lower socioeconomic class (case group = 74, 52.9% and CGI = 70, 50.0% and CGII = 73, 52.1%). The CGI had a significantly lower per capita income compared to the case group patients (p = 0.035).

As per Table 4, HIV testing during the course of prolonged illness was the commonest mode of HIV detection among our study subjects. An appreciable number of case group subjects (p %3C; 0.001) were diagnosed with HIV during TB testing, whereas a larger number of CGII were diagnosed either during voluntary testing (p = 0.09) or during blood donation (p = 0.06). More than 75% of the case group was known to be retrovirus positive for last 3 years, while it was vice versa for CGII.

More than 90% of the subjects in the case group reported to have unprotected sexual intercourse followed by CGII (87.9%). An almost equal proportion of subjects mentioned blood transfusion, injury with contaminated materials, and drug abuse as their exposures, with a significant difference (p < 0.05) being observed between case group (HIV-TB) and CGII when compared to CGI. The CD4 count of less than 200 was observed in 35.0% subjects belonging to the case group as compared to CGII (27.9%). This difference in CD4 count was statistically nonsignificant (p = 0.19).

Table 5, on univariate analysis, the factors found to be associated with HIV-TB coinfection, between case group and CGI were gender (males, OR = 2.29, 95% CI: 1.35–3.9), age (<35 years, OR = 0.43, 95% CI: 0.26–0.71), urban residence (OR = 1.63, 95% CI: 0.99–2.69), and current smoking status (OR = 1.97, 95% CI: 1.19–3.29). The factors found to be positively associated with HIV-TB, between case group and CGII, were urban residence (OR = 2.01, 95% CI: 1.21–3.34), current smoking status (OR = 2.09, 95% CI: 1.25–3.48), and duration of HIV infection (<3 years, OR = 3.10, 95% CI: 1.85–5.19). It was also observed that among the case group and CGI, the difference was highly significant for age (%3E;35 years) and male gender (p = 0.001).

DISCUSSION

Our present study seeks to examine the sociodemographic variants and the risk factors for the HIV-TB coinfection.

In a study conducted by Rajasekaran et al., 74.5% of 4,383 HIV-TB patients were males and a statistically significant difference (p < 0.001) of the prevalence of coinfection was observed between the genders.¹⁷ Per NACO estimates, HIV prevalence rate for adult females is 0.29%, while for males it is 0.43%.⁴ We found that a significantly greater proportion of male patients suffered from coinfection compared to TB alone. However, no difference in sex distribution was found on comparing coinfected patients with HIV-positive individuals. This seems to suggest that the differential sex-wise distribution arises primarily from the greater predilection of males to risk factors for HIV.

National AIDS Control Organization estimates suggest that prevalence of HIV is higher in the age group of 15–49 years (88.7%), indicating that HIV-AIDS still affects the economically productive members of the society.¹⁸ Most of our case group patients were in the age group of 25–44 years, a distribution not much different from CGII but deviated significantly from the age distribution of CGI. This again suggests that it is the population distribution of HIV infection that primarily drives the risk of coinfection.^18–20

In keeping with the population norms of our study setting, the vast majority of subjects were Hindus followed in frequency by Muslims. Most of the study subjects were married at the time of interview. When questioned about literacy levels, a significantly greater proportion of patients infected with HIV alone had higher literacy level and patients with active TB alone had lower literacy levels, when compared to the coinfected patients. This is, in turn, concordant with a study by Carvalho et al. which found that subjects with a lower educational level had a higher risk of developing TB.¹⁶ In accordance with the trends for active TB, as reported in multiple previous studies, we observed that patients with active TB alone had a significantly lower per capita income as compared to patients with coinfection and patients with HIV infection alone.^16,18,19 This reiterates the fact that HIV infection predisposes to coinfection, irrespective of the demographic profile of active TB. As regards the habitat, majority of CGI resided in urban slums, a finding backed by reports of epidemiological trends for TB.^7,15 When, however, patients acquire a predisposition for TB disease by means of HIV infection, their distribution becomes more uniform among urban areas, rural areas, and slums, mimicking the prevalence rates of HIV infection.

A majority of our coinfected patients had been known to be infected with HIV for a period of less than 3 years at the time of interview. This finding is likely confounded by the fact that a great proportion of these patients were diagnosed to have HIV infection in the course of routine investigation for active TB disease. Patients in the coinfected group had lower average CD4 counts when compared to their counterparts with HIV infection alone, the finding that authenticates the known natural history of HIV infection.^18,21–23

Our study, indirectly, reflects the success of NACP efforts as evidenced by a higher rate of HIV detection through voluntary testing. However, it reiterates the need for increasing awareness and encouraging voluntary testing, particularly among groups with high-risk social behaviors.²⁴

When questioned regarding risk factors for acquiring HIV infection, both coinfected and CGII had similar variants but were found to differ significantly from CGI. The most frequent high-risk behavior by far was unprotected sexual activity, which is in concordance with the national estimates by NACO and World Health Organization (WHO).^4,6,7

CONCLUSION

Our study was designed to determine the unique sociodemographic characteristics that distinguish HIV-TB coinfected patients from patients infected with either disease alone.

Our study is the first study conducted in the capital city of India, i.e., Delhi, which highlights the important socioepidemiological determinants of HIV-TB coinfection, in large population of Delhi. With regard to the sociodemographic variables of age, sex, literacy levels, per capita income, and habitation, we found patients in the coinfected group differ significantly from patients with active TB alone but had shown similar trends to that of the patients with only HIV infection. In a region with higher TB endemicity, this seems to suggest that the native distribution of HIV is a stronger driver for coinfection. While TB prevention and treatment is the key to reduce its prevalence in the population, controlling HIV transmission and minimizing the rates of disease progression for PLHAs are indeed the crucial facets.

Both HIV-AIDS and TB are socially driven diseases, and, hence, understanding the social characteristics of each disease individually and of their coexistence is vital to achieving infection control.

CLINICAL SIGNIFICANCE

Majority of our patients were tested for HIV status either during the course of a prolonged illness or during evaluations for active TB disease. At the time of interview, most of the patients with HIV and active TB disease had held the diagnosis for less than 3 years. These were all patients in AIDS clinical stage 3, a diagnosis that would warrant immediate initiation of ART. If the life expectancy and quality of PLHAs is to be improved, it is essential that HIV testing should occur earlier in the natural history of infection. This presents a challenge to NACP by highlighting the necessity to enhance voluntary testing, particularly in the high-risk groups.

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