Persons from resource-poor countries, especially sub-Saharan Afri

Persons from resource-poor countries, especially sub-Saharan Africa, often present with TB as their first manifestation of immunosuppression. Others who are diagnosed with HIV have high rates of latent TB infection. Low CD4 cell counts and not being on antiretroviral therapy are also associated with an increased risk of reactivation of latent TB [193,194].

Widespread use of HAART has reduced the risk of developing clinical TB among persons infected with HIV. In several studies, the risk of TB was up to 80% lower in those prescribed IWR-1 mw HAART. The protective effect was greatest in symptomatic patients and those with advanced immune suppression and was not apparent in those with CD4 counts >350 cells/μL [195–197]. The effect is almost certainly related to improvements in systemic immunity (reflected by increasing CD4 cell count) to a point where the risk of new infection or reactivation is greatly diminished. There have been many short-term

controlled trials in HIV-positive persons showing the protective effect of chemo-preventative AZD1208 nmr therapy [198–204]. A significant protective effect of isoniazid is found only in those who are TST-positive, and appears to last only 2–4 years as compared with at least 19 years (suggesting protection is lifelong) in TB control programmes in non-HIV populations where active cases were also treated, limiting the risk of any reinfection occurring. This is an important point, as the HIV-infected populations studied have mainly been in areas of high TB prevalence, where most TB arises from new infection rather than reactivation [53]. Apart from recognized outbreaks, there is little evidence to suggest that reinfection

(as opposed to reactivation) is a major factor in the United Kingdom. Chemo-preventative therapy might therefore have a longer duration of effect in the United Kingdom, but there are no data to support this hypothesis. There are some data from Brazil to suggest that a combination of HAART and isoniazid may be more effective than either alone in controlling TB [196]. The epidemiological situation in the United Kingdom is different, however. Chemo-preventative therapy without HAART seemed to have little effect on HIV progression and mortality in the long term [202]. There are also theoretical concerns that widespread isoniazid monotherapy might speed Epothilone B (EPO906, Patupilone) the emergence of drug-resistant TB [205]. However, in a recent meta-analysis of 13 studies investigating the risk of developing isoniazid resistance as a result of chemo-preventative therapy, the relative risk for resistance was 1.45 (95% CI 0.85–2.47). Results were similar when studies of HIV-uninfected and HIV-infected persons were considered separately. Analyses were limited by small numbers and incomplete testing of isolates, and their findings did not exclude an increased risk for isoniazid-resistant TB after isoniazid preventative therapy [206]. The other risk of isoniazid preventative therapy is hepatotoxicity.

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