Correspondence
Treatment of Tuberculosis in HIV-Infected Patients in Zaire
N Engl J Med 1995; 333:519-520August 24, 1995
- Article
To the Editor:
The study by Perriëns et al. (March 23 issue)1 demonstrates that extending antituberculous treatment from 6 to 12 months reduces the rate of relapse in patients infected with the human immunodeficiency virus (HIV) who have pulmonary tuberculosis. In spite of this, the authors considered the six-month program to be an acceptable alternative because the longer-term therapy did not prolong survival.
We question the validity of their survival analysis and therefore their recommendations for treatment. The short follow-up after treatment (1 year for patients in the 12-month treatment group) along with the unacceptable percentage of patients lost to follow-up (34 percent) lessens the statistical power of the study to reach that conclusion.
The authors argue that most relapses could be successfully retreated. As shown in Table 2 of the article, only 20 of 335 patients (6 percent) died of tuberculosis in the first episode, as compared with 3 of 9 patients (33 percent) who relapsed (P = 0.01 by Fisher's exact test). We also doubt that the patients who were lost to follow-up and those who are not enrolled in carefully controlled studies have the same opportunities for diagnosis and treatment as the patients who completed follow-up in the study by Perriëns et al. This point is even more important if patients are treated for only six months, because such patients have a greater risk of relapse. The theoretical savings afforded by a shorter course of therapy may be counteracted by the need for closer follow-up. Furthermore, close follow-up is not an easy matter in HIV-infected patients, as reflected by the 34 percent rate of loss to follow-up.
We believe that treatment of tuberculosis in HIV-infected patients must be continued for at least 9 months 2 as long as subsequent studies confirm that regimens lasting 6 months or 9 to 12 months are associated with the same rates of survival.
2 ReferencesFederico Pulido, M.D.
Hospital 12 de Octubre, 28041 Madrid, SpainJose M. Peña, M.D.
Hospital La Paz, 28046 Madrid, SpainRafael Rubio, M.D.
Hospital 12 de Octubre, 28041 Madrid, Spain1
Perriens JH ,St Louis ME ,Mukadi YB , et al. Pulmonary tuberculosis in HIV-infected patients in Zaire -- a controlled trial of treatment for either 6 or 12 months. N Engl J Med 1995;332:779-784
Full Text | Web of Science | Medline2
Initial therapy for tuberculosis in the era of multidrug resistance: recommendations of the Advisory Council for the Elimination of Tuberculosis
Medline
To the Editor:
The outcome of the study by Perriëns et al. can be viewed from opposing perspectives. In many developing countries, the overall rate of cure without relapse of 91 percent and the (approximate) 87 percent rate of cure without relapse observed in surviving HIV-positive patients treated for six months would be regarded as reflecting great success. The question is whether the level of compliance required to achieve this success could be attained outside a research setting.
It appears that the 6-month regimen was significantly less effective than the 12-month regimen in HIV-positive patients. This finding immediately suggests that either the standard six-month duration of therapy or the use of intermittent administration of drugs may be unsatisfactory in HIV-positive patients. Either conclusion has serious implications with respect to the costs and organization of therapy for tuberculosis in areas where HIV is prevalent. However, if some factor such as incomplete compliance interfered with the implementation of the regimen, then the treatment program, and not just the efficacy of the drugs, was being tested. If this was the case, then these conclusions are not justified. That this was the case is suggested by the observation that the recurrence rate in the HIV-negative group was higher than would be expected if compliance was complete and was not significantly different from that in the HIV-positive group treated for six months.
Our experience in Zambia, where we have used directly observed, intermittent therapy occasionally for difficult cases, suggests that this may sometimes actually impede compliance because patients cannot take their medication unless they attend the clinic. We found that compliance with a daily regimen of streptomycin during the intensive phase of outpatient therapy was poorer than with compliance with a regimen of oral drugs taken outside the clinic (according to patients' reports), partly because of the difficulty patients, especially sicker patients, had in making the daily trip to the “local” clinic.1 The urban population of Lusaka, Zambia, is very mobile, and patients sometimes fail to appear for their tuberculosis treatment for a week or more.
1 ReferencesAlison M. Elliott, M.D.
National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206Benita Halwiindi, R.N.
Alwyn G. Mwinga, M.B.
University Teaching Hospital, Lusaka, Zambia1
Elliott AM ,Halwiindi B ,Hayes RJ , et al. The impact of human immunodeficiency virus on response to treatment and recurrence rate in patients treated for tuberculosis: two-year follow-up of a cohort in Lusaka, Zambia. J Trop Med Hyg 1995;98:9-21
Medline
Author/Editor Response
The authors reply:
To the Editor: In response to Pulido et al., we wish to reemphasize that our recommendation to limit the duration of therapy for tuberculosis to six months was made in the specific context of the Zairian tuberculosis-control program. In countries with different epidemiologic situations and different levels of resources one could plausibly use the efficacy data in our study in a cost-effectiveness analysis and reach different conclusions about the optimal duration of treatment.
We acknowledge that the statistical power of our study to detect small differences in survival between HIV-infected patients treated for 6 months and those treated for 12 months is limited. However, after effective tuberculosis treatment, the deaths of 34 of the 37 HIV-infected patients who died in our study appeared to be unrelated to tuberculosis. These and other data1,2 suggest that, from the perspective of an HIV-infected patient, trying to avoid those other causes of death should be more efficacious in extending survival than trying to prevent relapses of tuberculosis.
We assessed compliance by recording each patient's history of drug intake and asking the patients whether they had orange urine — a side effect of rifampin use. The results are shown in Table 1Table 1
Compliance with Tuberculosis Therapy among HIV-Positive and HIV-Negative Patients.. We chose not to report these data in our paper because self-reported behavior and symptoms might be subject to important bias. However, given the circumstantial evidence that compliance was good, we believe that our observations on the efficacy of a 6-month as compared with a 12-month regimen are valid. The good rates of treatment completion in our study illustrate how supervised oral intermittent treatment by truly local tuberculosis clinics could minimize some of the problems encountered by Elliott et al.2 ReferencesJoseph H. Perriëns, Ph.D.
World Health Organization, CH-1211 Geneva 27, SwitzerlandMichael E. St. Louis, M.D.
Centers for Disease Control and Prevention, Atlanta, GA 30333Jacques Prignot, Ph.D.
Université Catholique de Louvain, B-1200 Brussels, Belgium1
Ackah AN ,Coulibaly D ,Digbeu H , et al. Response to treatment, mortality, and CD4 lymphocyte counts in HIV-infected persons with tuberculosis in Abidjan, Côte d'Ivoire. Lancet 1995;345:607-610
CrossRef | Web of Science | Medline2
Nunn P ,Brindle R ,Carpenter L , et al. Cohort study of human immunodeficiency virus infection in patients with tuberculosis in Nairobi, Kenya: analysis of early (6-month) mortality. Am Rev Respir Dis 1992;146:849-854
Web of Science | Medline
