The human immunodeficiency virus (HIV) epidemic in India and other resource-limited countries is posing greater challenges to the containment of tuberculosis in HIV-afflicted individuals and collectively to the very control of tuberculosis. In the presence of infection with HIV, tuberculosis manifests in many ways; there may be primary tuberculosis, reactivated tuberculosis, or some patients may suffer from new TB infection (reinfection).\[[@CIT1]\] Studies conducted in rural\[[@CIT2]\] and urban\[[@CIT3]--[@CIT6]\] India revealed a rising trend of HIV-TB co-infection. This is likely to have negative impact on the well-functioning TB-control program and the existing AIDS-control program. Clinical features of HIV-associated pulmonary tuberculosis in adults are frequently atypical, particularly in the late stage of HIV infection, with noncavitary disease, lower lobe infiltrates, hilar lymphadenopathy and pleural effusion.\[[@CIT7][@CIT8]\] African countries affected by both TB and HIV are experiencing a disproportionate increase in smear-negative tuberculosis\[[@CIT9]\] and extra-pulmonary tuberculosis.\[[@CIT10]\] Diagnostic algorithms and treatment protocols must be developed for each country, taking into consideration various factors, including the commonly occurring opportunistic infections. This study provides an insight into the prevalence and clinical manifestations of HIV-TB co-infection among the patients attending for the first time the largest health care setting in India that provides care and support to such patients.

Materials and Methods {#sec1-1}
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Govt. Hospital of Thoracic Medicine, Tambaram Sanatorium, Chennai (GHTM, Tambaram), is the largest voluntary counseling and testing center in the country, providing HIV counseling and testing to more than 2,400 patients a month. All these patients are also screened for the possible coexistence of tuberculosis by performing sputum-smear microscopy for acid fast bacilli (AFB) and radiological investigations including chest radiography. Other specimens given by patients from extra-pulmonary sites are also subjected to smear microscopy.

Opportunistic infections were identified predominantly by laboratory investigations. Clinico-radiological methods and oxygen saturation were utilized in detecting pneumocystis carinii pneumonia. Computerized tomography and magnetic resonance imaging scans of brain helped in sorting out many central nervous system manifestations. Fine needle aspiration cytology and histopathological examination of the biopsied specimens were also resorted to wherever necessary.

Computerized database of Hospital Information System provides patient records and all the data analysis of various aspects of HIV-TB co-infection. This study is confined to the evaluation of manifestations of TB in adult and adolescent HIV patients who attended GHTM for the first time during 2005. Proportion test was done with the null hypothesis value of 50% to compare pulmonary *vs.* extra-pulmonary TB and the sex ratios. Chi-square test was done to compare the distribution among various age groups and smear-positive rates.

Results {#sec1-2}
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Twenty-nine thousand three hundred and eighty-six patients with HIV disease attended GHTM, Tambaram, at least once in 2005. As many as 13,348 patients visited the institution for the first time; out of them, 12,750 were aged 15 years and above, and they formed the study population for further analysis.

Among all the opportunistic infections that coexisted with 12,750 HIV patients, oral candidiasis (52%) and *Pneumocystis carinii* (jiroveci) pneumonia (42%) were found to be more frequent than tuberculosis (34%). Lower respiratory tract infection, including pneumonia, was found in 22% of the patients \[[Table 1](#T0001){ref-type="table"}\].

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Opportunistic infections

  Common ois                Patients   \%
  ------------------------- ---------- -----
  Oral candidiasis          6590       52
  PCP                       5401       42
  Tuberculosis              4383       34
  LRI/pneumonia             2761       22
  Oesophageal candidiasis   1337       10
  Diarrhoea / pathogens     1033       8
  Scabies                   611        5
  Hepatitis                 313        2
  Herpes zoster / simplex   222        2
  Malaria                   120        1
  Cryptococcois             65         \<1

Among 4,383 HIV-TB patients, 74.5% were males and the rest (25.5%) were females \[[Table 2](#T0002){ref-type="table"}\] and the difference was statistically significant (*P*\<0.001). As many as 86.5% of HIV-TB patients were in the 15-44 age group, which was significantly higher (*P*\<0.001) as compared to other age groups. However, among females, 40% of HIV-TB patients were in the 15-29 age group, which was two times significantly higher as compared to males (20%) (*P*\<0.001).

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Age and sex distribution of human immunodeficiency virus patients with tuberculosis

  Age group   Men     Women   Total   
  ----------- ------- ------- ------- ------
  15--29      646     447     1093    24.9
  30--44      2149    550     2699    61.6
  45--59      431     112     543     12.4
  \>59        40      8       48      1.1
  Total       3266    1117    4383    100
              74.5%   25.5%           

As many as 2,448 (56%) patients with HIV had pulmonary TB, which was statistically significantly higher as compared to 1,935 (44%) patients detected to have extra-pulmonary TB and disseminated TB \[[Table 3](#T0003){ref-type="table"}\] (*P*\<0.001). However, it is also true that unlike in non-HIV tuberculosis patients, almost every second patient was found to suffer from either extra-pulmonary TB or disseminated TB, apart from his/her HIV disease.

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Types of tuberculosis

  Types of tuberculosis                        Patients   \%
  -------------------------------------------- ---------- -----
  Pulmonary tuberculosis                       2448       56
  Pulmonary tuberculosis (PTB) and extra PTB   620        14
  Extra pulmonary tuberculosis                 1315       30
  Total                                        4383       100

Lymph nodal tuberculosis and pleural tuberculosis were found to dominate the extra-pulmonary manifestations \[[Table 4](#T0004){ref-type="table"}\]. Intrathoracic lymph nodes, hilar and mediastinal, were detected in 1,523 (79%) patients.

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Manifestations of extra-pulmonary tuberculosis

  Extra pulmonary tuberculosis   Patients   \%
  ------------------------------ ---------- ----
  Intra thoracic lymphnodes      1523       79
  Extra thoracic lymphnodes      583        30
  Pleural disease                1063       55
  Pericardial effusion           113        6
  Tuberculosis abdomen           48         3
  Tuberculosis meningitis        30         2
  Tuberculoma                    19         1
  Others                         97         5

Total extra pulmonary TB: 1935

Sputum smear microscopy for AFB was performed in all the patients. Of the 3,068 HIV patients, 1,383 (44%) were found to have smear-positive pulmonary tuberculosis \[[Table 5](#T0005){ref-type="table"}\]. Sputum smear positive yield was significantly lower (31%) when all 4,383 HIV-TB patients were considered as compared to 44% of HIV and TB patients (*P*\<0.001).

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Sputum microscopy for acid fast bacilli

  Sputum acid   All types of TB   Pulmonary TB              
  ------------- ----------------- -------------- ---------- -----
                Patients          \%             Patients   \%
  Positive      1363              31             1363       44
  Negative      3020              69             1705       56
  Total         4383              100            3068       100

TB - Tuberculosis, HIV - Human immunodeficiency virus

Discussion {#sec1-3}
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The fight against tuberculosis would always remain incomplete without addressing the issues related to the control of HIV/AIDS. This study clearly brings out the important message that at least 34% of the HIV patients were found to have tuberculosis co-infection at the time of detecting or confirming their HIV disease. Significantly, a lower number of women living with HIV were found to attend the hospital, reflecting their current health remedy seeking behavior. Further, they need the support of their family members to travel long distances to attend the health institutions providing care and support to people living with HIV.

This study, apart from confirming the rising trend of HIV-TB co-infection in Tamil Nadu and other states of India where the prevalence of HIV is high, also confirmed the trend of shifting of youth peak prevalence of TB in HIV patients to the lower age group. Unlike the non-HIV immunocompetent patients, tuberculosis was found to occur more commonly in young and middle-aged adults.

Other vital factors that came out of this study were the type and severity of tuberculosis detected among the HIV patients attending GHTM, Tambaram, for the first time. While the usual pulmonary tuberculosis was detected only to the extent of 56% of HIV-TB study population, disseminated TB and extra-pulmonary TB were witnessed in 14% and 30% of the patients respectively. Increasing frequency of dissemination of tuberculosis was observed with extra-pulmonary manifestations in several developing countries\[[@CIT7]--[@CIT14]\] as the hallmark of advanced HIV disease. This is the resultant of unrecognized\[[@CIT15]\] and demonstrable\[[@CIT16]\] Mycobacteremia in severely immunosuppressed patients.

Among all the HIV-TB patients, sputum smear positive detection rate was low (31% only). Advanced HIV disease is often associated with sputum smear negative pulmonary tubercuosis,\[[@CIT1][@CIT7][@CIT9]\] atypical radiographic pictures\[[@CIT17]--[@CIT19]\] and extra-pulmonary spread. Unrecognized tuberculosis in patients with HIV disease has far-reaching consequences, including delayed diagnosis, unacceptable therapeutic delay\[[@CIT20]\] and even rapid progression to 'untreatable TB.'

Conclusion {#sec1-4}
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Tuberculosis was found to be the predominant co-infection (34%) among the symptomatic HIV patients attending the largest HIV care center in India for the first time. Significantly, 44% patients were reporting with clinical manifestations of advanced tuberculosis, indicating the associated moderate to severe immunosuppression. Smear-negative pulmonary tuberculosis and extra-pulmonary tuberculosis are likely to pose diagnostic dilemma to clinicians used to treat tuberculosis in non-HIV patients. Early detection of varied forms of tuberculosis among HIV seropositives is absolutely necessary for instituting appropriate antituberculosis treatment well before the disease gets disseminated.

The authors are grateful to all the clinicians, nurses and the entire laboratory staff of GHTM, Tambaram, for their valuable support. The assistance of Dr. L. Jeyaseelan, Professor and Head, Department of Biostatistics, Christian Medical College, Vellore, India, in providing statistical analysis is gratefully acknowledged. They are also thankful to Mr. Dhananjayan and the data entry team for providing and compiling the data of the patients.

**Source of Support:** Nil

**Conflict of Interest:** None declared.
