Clinical Meetings at RH Year 2010

2010 Jan 21 - HIV-associated Tuberculosis: A Deadly Combination

Dr CK Chan and Dr WM Leung, TB & Chest Service, Department of Health In recent years, HIV-associated tuberculosis (TB) has become an increasingly important AIDS-defining illness in Hong Kong.1-2 Data from the TB-HIV Registry, set up jointly by the TB and Chest Service and Special Preventive Programme (SPP) of Department of Health (DH) since 1996, showed that TB has overtaken PCP for the first time as the most common AIDS defining illness in 2005(Fig 1).

Among the 64 AIDS cases reported to SPP in that year, 25 (39.1%) had TB as AIDS-defining illness, whereas the corresponding figure for PCP was 20 (31.3%). This raises concern among local health care workers who are fighting against HIV-associated TB, although the latter still only represents a minority of annual TB notifications at present (about 30 cases per year). The phenomenon of TB becoming a more common AIDS-defining illness has also been observed in some other cohorts in Western Europe and US in recent years.3-4 The causes for the observed phenomenon locally is not well understood, but may be related to the high local burden of latent TB infection, increased HIV test coverage among TB patients, increased use of HAART and perhaps increased prophylaxis for PCP for people living with HIV. The implication is that all people living with HIV should be screened for TB, and that all patients newly diagnosed with TB should be counselled on HIV infection and offered HIV antibody testing, which is in fact a strong recommendation from the WHO.5

An important challenge facing all health care workers managing HIV-associated TB is its atypical presentation.6 Sixty-two percent of our local HIV-associated TB patients had extra-pulmonary involvement, and in patients with pulmonary TB, nearly one third had predominantly lower lobe involvement on chest radiograph.7 These often pose diagnostic difficulties to the attending physicians. Assiduous effort to obtain specimens for Mycobacterial smear and culture is necessary. Optimization of sputum microscopy is one of the important endeavours to facilitate diagnosis of HIV-associated TB. Fluorescence microscopy using auramine stain has been shown to be more sensitive than Ziehl-Neelsen stain in detecting acid fast bacilli and is unaffected by HIV status.8 Liquefaction with bleach or other chemical processing methods can increase the sensitivity further.9 Broth-based cultures using fluorescence techniques such as Bactec 9000 and MGIT identify more TB cases than solid media cultures, and are of particular use in the diagnosis of HIV-associated TB as many of these cases are sputum smear negative or extra-pulmonary TB.10 The sensitivity of nucleic acid amplification tests for diagnosis of HIV-associated TB has been shown to be unaffected by HIV status in recent studies but the cost is considerable and the tests cannot replace culture and drug susceptibility tests.11 Newer tests including phage-based assays such as FASTPlaque TB are being examined to facilitate the diagnosis of TB but studies are required to answer the critical question of how these tests will perform in smear negative HIV patients.

HIV-associated TB is not only more difficult to diagnose, but is also more difficult to manage than TB in the non-HIV infected. Adverse effects are commonly experienced by HIV-infected subjects undergoing anti-TB treatment. In a cohort of 190 patients with HIV-associated TB managed at both TB&CS and SPP between 1996 and 2006, 103 (54.2%) experienced one or more adverse events during the course of anti-TB treatment, with rash, liver derangement and gastro-intestinal upset being the most common. Modification of TB regimen was required in 67 (65.0%) of the patients who experienced adverse effects. Modification of TB regimen because of potential interaction with anti-retroviral drugs, especially protease inhibitors, was also common. In the same cohort of 190 patients with HIV-associated TB, rifampicin-based regimens were used in 87 (45.8%), and rifabutin-based regimens were used in 77 (40.5%). Non-rifamycin based regimens were used in the remaining 26 (13.7%) patients, either because of drug interaction or adverse reactions from rifampicin. Eleven patients (5.8%) experienced immune reconstitution syndrome at a median of 4 months after initiation of anti-TB treatment, a figure lower than that reported from some other series.12 The incidence of immune reconstitution syndrome in our patients, however, may be underestimated because the TB-HIV Registry was initiated in 1996 when the condition in HIV-infected patients was starting to be described. TB treatment outcomes was less favourable compared to non-HIV infected counterparts, with a cure/treatment complete rate of only 46.2% and 71.2% at 12 and 24 month respectively. A total of 27 patients (14.2%) died at 24 months from start of anti-TB treatment. Older age was found to be significantly associated with increased mortality, whereas mortality rate was lower in those who had anti-retroviral therapy started within 3 months. Similar reduction in mortality was reported from other studies in patients with low CD4 count who had anti-retroviral therapy started early.13-14 The optimal timing of initiation of anti-retroviral therapy has remained controversial, however. High pill burden, immune reconstitution syndromes, drug interactions and adverse effects after the initiation of anti-retroviral therapy are the main concerns.

HIV-associated TB carries a high case fatality rate. Treatment of latent TB infection is an important measure to reduce the burden of TB among people living with HIV, as recommended by WHO. In fact, WHO called for an expansion of isoniazid preventive therapy as an integral part of a comprehensive HIV and TB prevention, care and treatment service.15 The limitations of tuberculin skin test as a diagnostic tool for latent TB infection, however, are well recognized. The newer interferon-γrelease tests may facilitate diagnosis of latent TB infection but further studies are needed to examine the performance of these tests in HIV-infected subjects with advanced immuno-suppression.16-17 Moreover, the acceptance rate for treatment of latent TB infection has been low in both local and oversea HIV-infected subjects. Better ways to diagnose latent TB infection and scaling up of treatment of latent TB infection among HIV-infected subjects are needed.

References

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