HIV and Tuberculosis

V.H.Balasangameshwara

National Tuberculosis Institute, Bangalore - 560 003

One third of the world's population is infected with tubercle bacillus. More than 8 million new cases and 3 million deaths occur every year and 80-90% of these are in developing countries. India accounts for nearly 30% of all tuberculosis cases in the world today and more adults die from TB than from any other infectious disease. IT is estimated that more than four million in India will die from tuberculosis in the next decade (WHO/SEARO report 2000).

There has been a global resurgence of TB during the last decade and HIV has contributed significantly towards this scenario (Murray et al 1990). Close to 40 million persons have been infected with this virus and over 10 million have developed AIDS. In 1999 alone 5.6 million new cases of HIV were recorded. Every day 16,000 new HIV infections occur globally and every minute about 11 people are getting infected. Most of these infections are now occurring the developing world.

In India, state specific estimates of HIV infections have been developed, based on assumptions derived from the available data. This has provided the state specific current estimates for urban male to be 1.361 million, rural male as 0.507 million, urban female and rural female as 0.860 million and 0.204 million respectively and among intravenous drug users as 0.036 million adults. Thus the total estimate of HIV infected adults in India would be 2.97 million or 3.5 million people living with HIV and AIDS in India in mid 1998, which is about ten times lower than the rates observed in some African countries (Cristopher et al 1999)

India also has a high prevalence of tuberculosis-infected persons in the sexually active age group (TPT Report 1980). HIV infection is one of the strongest risk factor for breakdown to tuberculosis among those who have tuberculosis infection (CDC 1986; Riede and Snider 1986). World over tuberculosis is the commonest opportunistic disease seen in HIV infected persons (Murray 1989). A number of social and epidemiological features are common to both. The impact of HIV infection on tuberculosis situation is related to the prevalence of TB infection in the area, exposure to infectious patients, the quality of TB control program in the country and degree of the immune compromise (CD4 counts). In general TB occurs early in HIV infection with higher rates of reactivation (7-10% per yr) compared to non-HIV individuals (10% per lifetime) Narain et al 1992). Assuming an annual 7% to 10% breakdown rate to tuberculosis among HIV/AIDS positive persons, a total of about 1,20,000 to 2,75,000 HIV positive persons would be breaking down to tuberculosis every year in India.

The exact number of TB disease among HIV infected persons is not available from the NACO records. However, an estimate has been made that a prevalence of about 18,04,000 TB/HIV co-infected persons for India with an estimated 45,000 HIV positive tuberculosis cases (Christopher 1999) and even at this low level, the HIV epidemic threatens to wipe out the gains made in attempting to control tuberculosis.

TB is one of the important exogenous factors known to accelerate progression of HIV disease. Serial specimens obtained from involved and uninvolved lungs of HIV patients have shown that M.tuberculosis is also known to increase the mutation rate of HIV, especially in the V3 region of the E protein of the virus. M.tuberculosis infection leads to depletion of CD4 cells as well as activation of monocytes and macrophages leading to increased viral production (nakata et al 1997). The mortality among HIV infected persons with TB disease is significantly more compared to HIV positive persons without TB disease (Swaminathan et al 2000; Perriens et al 1991; Nunn et al 1992; Braun et al 1991). Thus HIV worsens TB situation and TB worsens HIV infection.

Even in HIV positive patients, pulmonary tuberculosis is still the commonest form of tuberculosis. Among various strategies to prevent breakdown to tuberculosis disease among HIV positive persons, case finding and treatment of infectious tuberculosis (sputum smear positive tuberculosis) still forms the important component, the other being preventive treatment (Narain et al 1992; kochi 1991). The emphasis is on curing more than 85% of sputum smear positive tuberculosis cases, combined with detection of more than 70% of them, while maintaining high cure rate. This tool used for diagnosing pulmonary tuberculosis is identified to be of high specificity and sensitivity in the non-HIV settings in India and with the methodology adopted for screening the chest symptomatic in the programme, the predictive value of positive sputum smear microscopy is calculated to be highest compared to radio-diagnosis (Balasangameshwara and Chakraborty 1993; Chauhan 1997).

The clinical presentation is dependent on stage of HIV infection. Weightloss and fever are more common, and cough and haemoptysis are less common in HIV positive pulmonary tuberculosis patients also depends on the degree of immunosuppression. The likelihood of positive sputum smear is similar to HIV-negative patient if the degree of immunosuppression is mild. The smear positivity rate is decreased if the degree of immunosuppression is severe (Cristopher 1999). Chest x-ray appearance is often with cavities in early stage of HIv infection and shows infiltrates with no cavities in late stages of HIV based on CD 4 counts (Cristopher 1999; Keizer et al 2000).

In view of the above mentioned reasons, the diagnostic criteria for pulmonary tuberculosis adopted in tuberculosis control programme developed in HIV negative setting, may not be adequate in diagnosing tuberculosis in HIV positive persons. Also there are no published data in India for making an estimate of the proportion of patients with chest symptoms among HIV positive persons. The number of sputa to be examined for obtaining a positive persons. The number of sputa to be examined for obtaining a positive smear result may have to be altered. Methods to induce sputa may have to be included to obtain a good sputum sample (Fazio and Lafortuna 1981), whenever patients are unable to cough up sputum. More invasive techniques may have to be adopted for diagnosing extra-pulmonary tuberculosis.

The standard treatment for tuberculosis in patients with disease due to drug sensitive M. Tuberculosis is two months of isoniazid , rifampicin, pyrazinamide and ethambutol. In the absence of drug susceptibility results and at the rate of primary isoniazid in the community is 4% or more, the above regimen is followed by four months of isoniazid and rifampicin (ATS and CDC 1994).

Rifampicin, in combination with isoniazid is the most important component of standard antituberculosis treatment regimens available. Rifampicin regimens are much sorter (6 to 9 vs 18 to 24 months) and lead to faster sputum conversion rates, higher cure rates, and lower relapse rates than regimens that do not include rifampicin (Girling 1989). However, Rifampicin is contraindicated with currently available protease inhibitors (pls) and non-nucleoside reverse transcriptase inhibitors (NNRTIs) because it greatly increases the metabolism of the Pls and NNRTIs and so reduces their levels. Rifampicin is also the most potent inducer of many of the cytochrome P-450 enzymes in the liver. This induction accelerates the metabolism of innumerable drugs, causing significant drug interactions. A newer rifamycin, rifabutin is also a potent antimycobacterial agent. Three studies comparing it with rifampicin showed that the two drugs are equivalent for treating tuberculosis (Schwander et al 1995; Gonzalez-Montaner et al 1994). Rifabutin can be substituted for rifampicin for short-course treatment of tuberculosis and can be used with several of the protease inhibitors and NNRTIs. This option allows effective treatment of both HIV infection and tuberculosis in most patients (Sonal 2000). However, these have to be tried out in Indian situation before they are to be implemented on a wide scale.

The directly observed strategy (DOTS), which is implemented for more than 10 years in some of the developing countries with high rates of TB in HIV patients, has shown that the relapse rates and drug resistance could be kept at a low level (Chug et al 1996; Glynn et al 1995).

The effect of preventive chemotherapy (PT) for tuberculosis in adults infected with HIV has been studied by many authors and is found to protect adults infected with HIV against breakdown to tuberculosis, atleast in the short medium term (Wilkinson et al 1998). The prerequisites identified by WHO which should be in place before a PT service is considered are : adequate capacity for HIV counseling, sufficient trained healthcare staff, linkage between HIV care and TB control services, TB treatment services that have a high probability of curing cases of TB identified through the PT service (e.g. less than 10% combined default or failure at the end of treatment). In settings meeting these standards, WHO and UNAIDS have made the following recommendations to governments: (a) preventive therapy against tuberculosis should be part of a package of care for people living with HIV/AIDS; (b) preventive therapy should only be used in settings where it is possible to exclude therapy should only be used in settings where it is possible to exclude active tuberculosis cases; (c) to ensure appropriate monitoring and follow-up, information about tuberculosis , including preventive therapy should be made available to people with HIV; (d) preventive therapy should be provided from within settings that include established voluntary counseling and testing (VCT) services for HIV; (e) the priority for TB control programmes continues to be the detection and cure of infectious tuberculosis cases; (f) the procurement and supply of tuberculosis drugs must be regulated by national authorities, in order to prevent the development of drug resistance (WHO report 1999)

The priority for research in India now would be to identify the diagnostic and treatment strategies for TB in HIV positive persons and after fully strengthening the tuberculosis control programme in all districts, it would be prudent to develop the strategy for preventive chemotherapy among HIV positive persons.