Objectives
  • Disseminate info on TB in India
  • Improve care of TB patients in India
  • Enable doctors and NGO's interested in TB control to interact

Tuberculosis and HIV


It is now widely appreciated that the epidemiology , clinical manifestations,management and prognosis of tuberculosis are radically altered in patients with human immunodecficiency virus(HIV) infectin.It is estimated that a third of the world population has been infected with Mycobacterium tuberculosis The prevalence of HIV infection is highly variable and changing in different regions of the world.10 million persons worldwide are infected with HIV,with 60% of this latter number resident in subSaharan Africa.

Indian figures for prevalence of HIV infection

Output Using 1998 Sentinel data the current estimate is Apply a variable of 20%  Estimate ranges from 2.3 m to 3.5 m
Data from Surveillance for HIV infection/AIDS cases in India (Period of report-Since inception i.e.1986 to 31st July, 2000) viewed on 25/10/2000 .

Intersection of two global epidemics

The frequency with which HIV and M tuberculosis occur together is determined by the epidemiology of each disease in a given population. Approximately 2 billion people (one-third of the world's population) are infected with Mycobacterium tuberculosis, the cause of TB. TB is the cause of death for one out of every three people with AIDS worldwide. The spread of the HIV epidemic has significantly impacted the TB epidemic. One-third of the increase in TB cases over the last five years can be attributed to the HIV epidemic (Source: UNAIDS). Sources: **CDC Update: The Deadly Intersection Between TB and HIV
Pathogenesis:The immune response to Mycobacterium Tuberculosis in HIV infected patients
When tubercle bacilli are inhaled , mechanical barriers of the upper airways and mucociliary system of the bronchial mucosa eliminate large particles. Only particles less than 5 microns in diameter reach the alveoli,where the bacilli are ingested by the macrophages. Establishment of TB infection probably depends on the number of and viability of the bacilli versus the microbicidal activity of the macrophages.Because most alveolar macrophages are not activated ,their microbicidal activity is low, viable bacilli multiply both within the macrophages and extracellularly, and are transported by lymphatic vessels to the mediastinal lymph nodes and the blood stream, where they seed other parts of the body. Some macrophages that ingest tubercle bacilli process mycobacterial antigens and present them to T lymphocytes., which in turn release lymphokines that are chemotactants and growth factors for additional lymphocytes and macrophages. Interferon gamma is an important lymphokine that activates macrophages to more effectively ingest and kill mycobacteria. At this point, the host has mounted a cell mediated immune response and delayed type hypersensitivity response to M.tuberculosis  antigens is manifested clinically by development of a positive tuberculin skin test. In approximately 90% of immunocompetent persons infected with M.tuberculosis ,immune defenses are effective and tuberculosis disease does not develop. Cell mediated immunity is ineffective in 5% of infected persons resulting in disease within 1 year of infection. In an additional 5% ,TB develops later in life when cell mediated immune defenses wane with age or from other immuno suppressive processes.
Cd4+cells(T4 cells) and macrophages play a central role in immune defenses against M.tuberculosis  . HIV specifically infects CD4+ cells and macrophages ,resulting in progressive depletion and dysfunction of CD+ T cells. Macrophage function is also abnormal because of direct infection with HIV, coupled with lack of macrophage-activating factors produced by CD4+ cells. These factors facilitate development of progressive primary pulmonary TB (Fig 2), haematogenous dissemination of M.Tuberculosis   to extrapulmonary sites,and increased likelihood of reactivation of prior tuberculosis infection. Thirty seven per cent of HIV infected close contacts of TB patients develop disease within 5 months.

Fig2-Primary type of TB in an adult with HIV infection.

The risk of reactivation of TB in HIV infected patients previously infected with M.Tuberculosis   is 8% to 10% per year (Table 1) and one may therefore speculate that the lifetime TB risk of such patients approaches 100%.

Table 1.RISK OF CLINICAL TUBERCULOSIS IN INDIVIDUALS INFECTED WITH TB AND HIV IN THE UNITED STATES AND AFRICA.

Country Year of report Study methods % Annual risk of TB
HIV+/TB+     HIV-/TB+
United States 1989 Prospective study ,intravenous drug users 7.9 0
Zaire 1991 Retrospective study, women of child bearing age 6.2 0.2
Zaire 1991 Prospective study, factory workers and spouses 5.6 0.8
Rwanda 1991 Prospective study women attending prenatal clinics 5.5 0.2
Clinical featuresThere are two distinct clinical patterns of tuberculosis in HIV infected patients that depend on when in the course of evolving HIV infection the tuberculosis develops.Of the two the one that has received the greater attention develops when tuberculosis complicates the late stages of HIV disease;in other words , just before or even after the onset of AIDS.In this circumstance , the clinical and radiographic features are likely to differ substantially from those in non HIV infected patients with "ordinary" tuberculosis. Among the important differences that have been observed are:
  1. that patients with tuberculosis and HIV infection often have a negative tuberculin reaction
  2. that more than half will have extrapulmonary (especially lymph node involvement) and
  3. that upper lobe cavitary disease is infrequent and the chest radiographs are usually atypical.
The late stage of HIV infection is recognised clinically by the presence of other markers of AIDS eg (Herpes etc Fig 3) and or low CD4 cells.
herpes
Fig 3:Patient with TB and Herpes Zoster ( advanced HIV infection)

Patients with advanced HIV infection and virtual absence of cellular immunity cannot develop or maintain hypersensitivity to tuberculoprotein;this explains many of the unususal features of tuberculosis in this setting,including dissemination.In contrast ,patients with less advanced HIV infection have relatively well preserved cellular immunity,and the usual clinico radiographic features are observed.

Reported Indian experience

Centre Number of cases screened Number Positive
Elisa       WB 		Reference
Sivaraman et al Pondicherry 225 6          6 Ind J Tub 1992,39,35-39
NIV Pune 359 4          4 Quoted by Banavalikar et al 1997
Anuradha et al Chennai 392 3          - Ind J Tub 1993,40,13-15
Chennai and Vellore 3071 12          - Quoted by Banavalikar
Mumbai 5024 296          - Mohanty .K.C. and Basheer PM.m.95-119
Banavalikar et al Delhi 1002 13          5 Banavalikar et al 1997 44,17-20

The radiolgical presentations of TB in HIV seropositives

Authors Cavitary Hilar adenopathy Diffuse/miliary Pleural effusion
Sivaraman et al 1992 3 2 2 0
Anuradha et al 1993 3 - - -
Mohanty and Basheer(1995) 144 - 6 12
Banavalikar et al (1995) - - 2 1

Treatment of HIV infection with TB

Treatment guidelines for HIV-infected patients are identical to the standard regimens recommended for those without HIV . All therapeutic combinations should include rifampicin, and patients should be monitored for drug interactions with protease inhibitors. Treatment duration is also the same unless therapeutic response is slow. Directly observed therapy is the standard of care.
The response to treatment if given adequately and regularly is reported to be the same in Hiv and non HIV patients.However the significant difference in the TB patient coinfected with HIV are
  1. Median survival of about 18 months after diagnosis
  2. High frequency of adverse reactions that occur(in below 20% of cases)
Recent recommendations of WHO state that one course of immunoglobulins could prolong the life expectancy and delay the development of full blown AIDS.

Patients with risk factors for drug-resistant M tuberculosis infection may need treatment with four or more drugs. There are many reports in western literature on multi drug resistant TB in HIV infected patients.Where facilities are available,it would be ideal to have drug sensitivty tests done and chemotherapy started accordingly.
Recently, an increasing prevalence of tuberculosislike disease due to infection with other mycobacteria (eg, M kansasii, M bovis) has been observed in HIV-infected populations in USA and some western countries.

Patients with HIV infection should undergo a tuberculin skin test yearly, and those with an induration of 5 mm or more who lack manifestations of active tuberculosis should receive prophylactic treatment with isoniazid for 1 year . Many HIV-infected patients have anergy, which recent investigations have shown may wax and wane. Past recommendations that anergic patients in environments highly endemic for tuberculosis should also undergo prophylaxis are controversial , because recent studies have failed to show benefit from this practice .

Click here for info on Antiretroviraltherapy

For updated guidelines on antiretoviral therapy please see HIV/ATIS Treatment information service website(http://www.hivatis.org)

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