Interventions for Tuberculosis Control and Elimination 2002

that the sputum bacillary load may not reflect the underlying number of bacilli
a patient harbors, and thus there might be a need for prolonged treatment. 587
Regimens of six to nine months duration containing rifampicin throughout
have been highly efficacious in terms of both low frequency of bacteriologic
failure 576 and relapse. 579,588,589 Eight-month regimens give acceptable
results in the field. 590 In contrast, 12-month regimens that do not
incorporate any rifampicin have shown a high frequency of failures 591,592
and relapse. 591,593,594
If antiretroviral therapy is given simultaneously with treatment for
tuberculosis, paradoxical responses have been reported with worsening of
the clinical presentation, assumed to be an immunologic response. 595 Antiretroviral
drugs such as protease inhibitors (saquinavir, indinavir, ritonavir,
and nelfinadvir) and non-nucleoside reverse transcriptase inhibitors (nevirapine,
delaviridine, and efavirenz) have substantive interactions with
rifamycins. 596 Rifampicin will reduce the blood concentrations of protease
inhibitors. The efficacy of the latter will thus be reduced when concommitantly
administered with rifampicin. The interaction with nucleoside
reverse transcriptase inhibitors (zidovudine, didanosine, zalcitabine, stavudine,
and lamivudine) is probably not clinically relevant. 596
The US Public Health Service conducted study 22, comparing the efficacy
of once-weekly isoniazid plus rifapentine with twice-weekly isoniazid
plus rifampicin in a four-month continuation phase following a four-drug,
two-month intensive phase. 597 Among 61 patients with concomitant HIV
infection, none experienced treatment failure. However, three of the 31
patients on the rifampicin-containing continuation phase relapsed, all with
fully susceptible organisms, but five of the 30 patients on the rifapentine
regimen relapsed, four of whom had acquired rifamycin resistance.
Obviously, isoniazid as a companion drug in once-weekly treatment is inadequate,
and patients effectively received rifapentine monotherapy. There
is indeed cause for concern that, by analogy, HIV-infected patients with
initial isoniazid resistance may acquire unnoticed (no apparent failure during
treatment) rifampicin resistance if treated with this drug in the continuation
phase. 598 Nevertheless, the reasons for acquisition of rifamycin resistance
in this study have not yet been fully elucidated, and there are
indications that it is attributable to an inadequate dosage of rifapentine.
Relapse following cessation of chemotherapy appears to be more frequent
among HIV-infected compared to HIV-non-infected individuals, 594,599
and post-treatment preventive chemotherapy with isoniazid appears to reduce
that risk. 599
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