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PROPHYLAXIS AND TREATMENT OF TUBERCULOSIS IN HIV - INFECTED PATIENTS

Objectif

Step 1, Treatment of Acute Infection:
To establish the efficacy of a standard treatment of tuberculosis with INH (9 months), Rifampin (9 months) and Pyrazinamide (2 months) plus Ethambutol or no fourth drug (2 months) in HIV infected patients.

Step 2, Maintenance Treatment:
To establish the necessity of a maintenance treatment of tuberculosis, in HIV infected patients, with INH lifelong. Interim analysis will be performed every 9 months during a minimum follow-up of 27 months unless a statistically significant difference were detected before.
The objectives of the tuberculosis acute phase I were to prospectively define the characteristics and natural history of tuberculosis (TBC) in human immunodeficiency virus (HIV) patients and to compare the efficacy and tolerance of a 3 versus a 4 drug regimen. 24 centres from 6 European countries recruited HIV infected patients with a suspected or confirmed diagnosis of TBC and randomized them to receive INH (H) (9 months) plus Rifampin (R) (9 months) plus Pyrazinamide (Z) (2 months) with (group A) or without (group B) Ethambutol (E) (2 months).
592 patients have completed the trial or reached one of the trial end points. 64% were intravenous (IV) drug abusers and 14.5% heterosexuals. Both group A (297) and group B (295) were comparable with regard to age, sex, risk factors for HIV infection, CD4 cell counts and TBC localization. 8 (3%) of group A were treatment failures who died of TBC versus 10 (4%) in group B. Study drugs had to be discontinued in 10% of group A versus 9% of group B, mainly due to fever and skin rashes associated with R or liver toxicity associated with H or R. The overall mortality was similar in both groups (19% versus 15%). The percentage of initially resistant strains to more than one of the study drugs was 5.4% of the 111 strains tested.
Since the efficacy of both study regimens appears similar and the level of primary resistance remains low, the addition of a fourth drug (E) does not seem to be justified. Discontinuation of R and to a lesser extent H was frequent due to mild side effects.
A relatively high percentage of HIV infected patients develop a profound and irreversible impairment of both the cellular and the humoral immunity. Consequently, it could be anticipated that infections caused by M. tuberculosis in HIV infected patients would be more prevalent and severe when compared with control matched for age, sex and geographical area. In fact, in countries such as Spain, where the prevalence of tuberculosis in the general population is still high, tuberculosis is the most prevalent opportunistic infection among drug addicts infected with HIV. In the August of 1987 CDC criteria for AIDS case-definition, several clinical forms of tuberculosis had already been included and during 1993 pulmonary tuberculosis had been added to the list of criteria for this definition. Moreover, in countries such as the USA, where the incidence of tuberculosis is much lower, an inversion in the decreasing trend of the incidence of tuberculosis has been detected during the last few years. At present, the clinical characteristics of tuberculosis among HIV infected patients have been established. The efficacy and the optimal duration of the treatment of tuberculosis in HIV infected patients, however, still is unknown. Valid conclusions can only be obtained through a large, multicentric, prospective and controlled study and the, in order to do this, participation of centers from countries with a relatively high incidence of tuberculosis will be necessary.

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Instituto de Salud Carlos III
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C/ Sinesio Delgado 10-12
28029 Madrid
Espagne

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