The Stages of HIV Infection and the Risk of Opportunistic Tuberculosis Infection

Background: Opportunistic infection (OI) by tuberculosis is the most common cause of death for peopleinfected with HIV worldwide, mainly in persons with untreated HIV infection. The aim of the study wasto determine the risk factors associated with TB as an OI of HIV-infected patients.Methods: The study conducted in Voluntary Counseling Testing (VCT) clinics in several hospitals ofseven provinces (North Sumatera, West Sumatera, Riau Islands, South Sulawesi, North Sulawesi, Maluku,and Papua). This was a cross sectional study and the respondents selected by purposive sampling. Therewere 490 HIV patients included in this study. Data were collected using a specific questionnaire. Statisticalanalyses were done using STATA 9.0 version.Results: Among 490 HIV patients, there were 238 (48.6%) patients with TB as IO. The precentage ofTB as OI in the younger HIV-infected group was higher than the older group. Among the HIV-infectedpersons, males had a 24 % higher risk of becoming infected with TB than females [adjusted relative risk(RRa)=1.24; P=0.023]. Stage 4 HIV-infected persons had 52% risk of TB as OI compared to stages 1-3(RRa=1.55; P=0.000).Conclusion: Patients with stage 4 HIV infection and male were more at risk for developing opportunistictuberculosis infection. (Health Science Journal of Indonesia 2015;6:121-5)

Indonesia has the 4 th highest number patients with Tuberculosis in the world. Tuberculosis or TB is an infection caused by Mycobacterium tuberculosis and has been recognized a long time ago, especially in developing countries such as Indonesia. At the beginning of infection, tuberculosis may cause no symptoms. People infected with HIV are more likely than others to become sick with TB. HIV infection will significantly increase the risk of progression from latent to active TB disease. This risk can be expected to be different if infection occurs in an HIV-negative person, where more than 90% will not develop into active TB disease. Active TB will occur more rapidly in HIV cases with approximately 50% probability to develop into active TB disease. Detection of TB in people with HIV disease is more difficult. 1 The World Health Organization reported in 2013, that around 9 million people developed TB and 1.5 million will die. Among the 1.5 million deaths from TB, 360,000 had HIV. The report also stated that 320,000 of the 1.3 million people with tuberculosis who died were people with HIV-AIDS. 2 TB negatively impacts the natural history of HIV infection. The opportunistic infection (OI) by tuberculosis is the most common cause of death for people infected with HIV worldwide, mainly in persons with untreated HIV disease. Once people get infected with HIV, the immune system will weaken and lead to the development of TB rapidly. 3,4 Several studies found that the prevalence of HIV among new TB cases in several provinces was varied. In 2006, the prevalence of HIV among new TB cases was 2% in Yogyakarta province. In 2008, the prevalence in East Java, Bali, and Papua were 0.8%, 3.8%, and 14% respectively. In Indonesia, TB infection was a challenge for AIDS control since TB is the most infectious disease that infects people with HIV-AIDS (31.8%). In 2013, WHO estimated the number TB patients with HIV positive in Indonesia was 7.5%, this number has increased from 3.3% in 2012. 5 Most of the data on TB related to HIV came from HIV control programs, therefore it was important to analyze the risk factors of TB infection among HIV patients. The aim of this study was to determine the risk factors of TB as OI among HIV patients in seven provinces in Indonesia in 2007.

METHODS
This study is a part of HIV/AIDS cross-sectional study in seven provinces in Indonesia in 2011. The subjects consisted of HIV/AIDS cases visited by the Voluntary Counseling Testing (VCT) clinics in purposive selected from seven provinces in Indonesia (North Sumatera, West Sumatera, Riau islands, South Sulawesi, North Sulawesi, Maluku, and Papua). In each province, 1 or 2 hospitals were selected purposively.
The subjects consisted of confirmed positive HIV/ AIDS using 3 rapid test by different methods or 2 rapid tests by different methods and 1 timed test by ELISA method. Severe cases were excluded.
The subjects were also selected by purposive sampling. There were 490 HIV-AIDS infected patients included in this study. Interviewers and data collection lasted 1 week and carried out by the team from Center for Biomedical and Basic Technology of Health, National Institute of Health Research and Development, Ministry of Health Republic of Indonesia.
The data were obtained by interview using a structured questionnaire. Data were analyzed to obtain the percentage of the variables studied.
This analysis used a part of HIV/AIDS cross sectional study in seven provinces in Indonesia in 2011. The subjects consisted of HIV/AIDS cases visited Volunteer Care and Treatment (VCT) clinics in purposive selected seven provinces (North Sumatera, West Sumatera, Riau islands, South Sulawesi, North Sulawesi, Maluku, and Papua). For each province was selected 1 or 2 hospitals purposively.
The subjects consisted of confirmed positive HIV/ AIDS using 3 rapid test by different methods or 2 rapid tests by different and 1 time test by ELISA method in participating. We excluded severe cases.
The selection of the subjects by purposive sampling method. There were 490 HIV-infected persons included in this study. Interviewers and data collection for 1 week by researcher's personnel of the Center for Biomedical and Basic Health Technology.
The data was obtained by interview using a structured questionnaire and analyzed to obtain a percentage of the variables studied.
All of the HIV-infected persons asked for the Opportunistic infection (TB OI) during the HIV infections. Especially for TB as OI, they had to inform how the diagnosis have been enforced such as the laboratory confirm or Rontgen. The subjects were asked about the TB medication. Interviewers and data collection for 1 week by researcher of the Center for Biomedical and Basic Health Technology.
The logistic regression method were done using STATA 9.0 version to identify the dominant risk factors related to TB OI.
This study received ethical clearance from the Ethical Committee of the Litbangkes, and informed consent available from the subjects.
Logistic regression was done using STATA 9.0 version to identify the dominant risk factors related to TB OI.
This study received ethical clearance from the Ethical Committee of the Health Research and Development (Badan Penelitian dan Pengembangan Kesehatan), and informed consent were obtained from the subjects.

RESULTS
All of the 490 patients were analyzed. Table 1 showed that the proportion of active tuberculosis OI in HIV infected subjects was 48.6%. In terms of gender, the number of HIV-infected persons was higher in men compared to women (53%). While the proportion of tuberculosis OI was greater in the younger age group (64%). It appeared that active TB developed very rapidly in HIV-positive cases. Table 1 showed that persons who had and did not have opportunistic TB infection were similarly distributed in terms of age and persons with CD4 counts.
HIV-infected persons residing in the Papua province had the highest risk for opportunistic TB infection which was equal to 117% compared to those living in the province of North Sumatera. The risk for opportunistic TB infections among six other provinces was lowest in West Sumatra province or 13% compared to those who live in North Sumatera Tabel 2, the final model, gender and the stage of HIV infection were the dominant risk factors for OI TB. In terms of gender, male had a 24% higher risk for OI TB. Furthermore stage 4 HIV cases had a 52% higher risk for OI TB compared with stages 1-3 of the HIV infection. This study showed that the increase of active TB is proportionately parallel to the severity of HIV. This finding corresponded to those reported by other studies, which showed that the OI TB developed actively among HIV-positive cases especially with those with lower CD4 counts. The risk of progressing from latent to active TB is estimated to be between 12 and 20 times greater in people living with HIV than among those without HIV infection. 8 The best way to prevent the OI TB was by avoiding exposure of HIV-infected persons to TB. This was rather difficult since TB is endemic in Indonesia. 8 Knowing the early presence of TB infection in people with HIV is to do a tuberculin skin test (TST) using 5-TU purified protein derivative (PPD) by the Mantoux method (AI) at the time the person is diagnosed with HIV. If the result is a positive TST (≥ 5 mm of induration), then a chest x-ray should be done immediately and treatment started for active TB. All people with HIV and a positive TST result, even without any symptoms of active TB or TB treatment history, should be as latent TB. 10 Generally, the symptoms of pulmonary tuberculosis in HIV-infected persons have no symptoms if the CD4 count is > 350 cells/mL. But if CD4 count is down to 50 cells/uL, it will be accompanied by extrapulmonary TB. 9 In this study, it appeared that HIV-infected persons with CD4 < 350 cells/mL was at a higher risk for TB infection compared to HIVinfected persons with CD4 > 350 cells/uL.
In stages 1 and 2 of positive HIV cases, there were no TB infection reported. This was probably due to the lack of chest x-rays done among HIV 1 and 2 stages, since no TB symptoms were present. The majority (76%) cases of active TB in HIV-positive patients had more than one types of OI. The risk of HIV-infected persons developing TB infection is higher since HIV and TB are closely related. Globally, 50% of HIVinfected persons developing TB. The development of TB among HIV-infected persons is related to immunosuppression. The risk was increased with the increasing degree of the immunosuppression. 12 In this study, the same pattern was found, where stage 4 of HIV-infected persons with immunosuppression have higher risk to develop TB infection than those without immunosuppression.
In conclusion, patients with stage 4 of HIV infection and males were more at risk for developing TB IO. Therefore for early detection of TB should be a concern. Opportunistic infection can occur at the different stages of HIV infections. The incidence of TB as the OI among HIV patients in Indonesia were high and it is very important to test for TB in every HIV patients.