Interventions for Tuberculosis Control and Elimination 2002

Based on these pharmacokinetic properties and other considerations, it
has been recommended that treatment for suspected or confirmed tuberculous
meningitis should begin with a two-month intensive phase incorporating
isoniazid, rifampicin, and pyrazinamide plus streptomycin. 571 The optimum
duration of the continuation phase is not known, but based on limited
information 572 a continuation phase associating isoniazid and rifampicin for
a duration of at least seven months has been advocated. 563 This regimen
may pose problems in patients with an isoniazid-resistant strain because of
the unpredictable concentrations of rifampicin. Where available, ethionamide
might provide a less well tolerated alternative in such a case. 570,573
Influence of HIV infection on the choice of a regimen
Among tuberculosis patients with HIV infection, two major issues need to
be addressed.
The first concerns the initial observations made by clinicians when
treating HIV-infected patients with anti-tuberculosis drugs: tolerance of the
medications was poorer than in patients without HIV infection.
A second issue concerns the efficacy of the regimens usually prescribed.
Patients with HIV infection may suffer from diarrhea, which may,
through its lowering of drug serum concentrations, adversely compromise
the efficacy of the regimen, favoring the emergence of resistance and subsequent
relapse.
Adverse drug events
Adverse drug events occur much more frequently among HIV-infected tuberculosis
patients. In particular, cutaneous hypersensitivity reactions are frequent.
These have mostly been attributable to thioacetazone, 443,445,447,574-577
and to a lesser extent to streptomycin, 575 rifampicin, 215,216,578 and isoniazid. 578
The frequent and sometimes fatal cutaneous adverse drug events among
HIV-infected tuberculosis patients due to thioacetazone preclude its use in
patients known to be HIV-infected. 8,13 It is best replaced with ethambutol.
An increased frequency of non-cutaneous adverse drug events (hepatotoxicity,
gastrointestinal disturbances, thrombocytopenia) to isoniazid 578, 579
and rifampicin has been reported. 578-580
Anti-retroviral therapy poses particular problems because of interactions
with rifampicin that preclude simultaneous use of the two regimens.
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