Isoniazid preventive therapy for tuberculosis in HIV-1-infected adults

Abstract

Overall there was no statistically significant protective effect of daily isoniazid for 6 months in the prevention of tuberculosis. In the TST-positive subjects, where reactivation is likely to be the more important pathogenetic mechanism, there was some protection and some reduction in mortality, although this was not statistically significant. The small number of individuals in this subgroup made the power to detect a statistically significant difference in this subgroup low. Other influences that may have diluted the efficacy of isoniazid include a high rate of transmission of new infection and rapid progression to disease or insufficient duration of isoniazid in subjects with relatively advanced immunosuppression. The rate of drug resistance observed in subjects who received isoniazid and subsequently developed tuberculosis was low.

Ability of preventive therapy to cure latent Mycobacterium tuberculosis infection in HIV-infected individuals in high-burden settings

“…Out of 14 trials identified in the Cochrane review, two studies met our criteria (4,5). The Medline search identified 954 papers, from which 15 reported results from prospective studies on TB-preventive therapy, and one met our inclusion criteria (6).…”

“…The effect is most clearly seen in individuals with presumed Mycobacterium tuberculosis infection, as indicated by a positive tuberculin skin test (TST) (2,3). However, long-term follow-up of TB-preventive therapy trials set in sub-Saharan Africa have shown high rates of TB post IPT (2,(4)(5)(6)(7)(8), and the results of the recently published Thibela study (9) showed a rapid loss of protection following completion of IPT. It is unclear what drives this lack of durable protection from TB disease.…”

“…If preventive therapy does not cure, all noncured patients will immediately be at risk for developing TB disease through reactivation of their M. tuberculosis infection in addition to the risk of disease following reinfection. The latter scenario, where IPT does not cure latent M. tuberculosis infections (LTBI) in this population, could explain the high TB rates observed immediately post IPT (2,(4)(5)(6)(7)(8).…”

A re-examination of the potential impact of preventive therapy on the public health problem of tuberculosis in contemporary sub-Saharan Africa

“…Whereas there is ample research evidence showing that PT reduces the individual risk of active tuberculosis in HIV-positive persons with LTBI [6][7][8], the impact of this intervention toward the public health problem of tuberculosis in contemporary sub-Saharan African populations has hitherto not been adequately analyzed. Our model-based analysis that took into consideration the high prevalence of tuberculosis and HIV infection in this region provides estimates of the likely effect size of PT on tuberculosis case rates in these populations.…”

“…There is ample research evidence demonstrating that tuberculosis preventive therapy (PT) reduces the individual risk of active tuberculosis in HIV-positive persons believed to be latently infected with Mycobacterium tuberculosis [6][7][8]. In view of these findings, the World Health Organization (WHO), the Joint United Nations Programme on HIV/AIDS (UNAIDS), and the International Union Against Tuberculosis and Lung Disease (IUATLD) recommend PT for tuberculin skin test (TST)-positive, HIV-infected persons who do not have active tuberculosis [9,10].…”