Safety, effectiveness, and outcomes of concomitant use of highly active antiretroviral therapy with drugs for tuberculosis in resource-poor settings.

摘要

AIDS, tuberculosis, and malaria constitute "the big three" infectious diseases in resource-poor countries of the world, and nowhere are they more concentrated than in sub-Saharan Africa. In terms of mortality, HIV and tuberculosis have their largest effect in adults, whereas malaria, through Plasmodium falciparum, has its largest effect in children.Treatment for tuberculosis in most resource-poor countries comprises a four-drug initial phase (2 months of rifampicin, isoniazid, pyrazinamide, and ethambutol) and a two-drug continuation phase (either 4 months of rifampicin and isoniazid or 6 months of isoniazid and ethambutol). HIV adversely affects the outcome of such treatment by increasing case fatality rates and rates of recurrent tuberculosis after successful completion of therapy. Highly active antiretroviral therapy (HAART), which is being scaled up in most countries in the developing world where HIV is prevalent, could mitigate both these deleterious effects.HIV-positive pulmonary tuberculosis is classified in WHO clinical stage III and HIV-positive extrapulmonary tuberculosis in WHO clinical stage IV, so in principle all patients infected with HIV who also have tuberculosis should be considered eligible for HAART if facilities for CD4-lymphocyte counting are not available. In developed countries, some centres recommend that HAART is started early in patients with tuberculosis who have advanced HIV disease, but deferred until 2 months of treatment for tuberculosis has been administered in those who have CD4 counts of more than 100X106 cells/L. This approach is associated with reduced mortality, but early initiation of HAART is complicated by various adverse events and the need to interrupt or change medication. In resource-poor countries, the question of when to start HAART and the magnitude of additional benefit are unresolved, though the findings of a small study from Brazil2 indicate a better and safer outcome in patients who start HAART 4 weeks after the start of treatment for tuberculosis than inthose who start HAART at the same time. In South Africa, HAART greatly reduces the risk of tuberculosis in patients with HIV.Thus, in principle, HAART should reduce the risk of recurrent tuberculosis, but again the evidence base is poor.