Adverse events and treatment interruption in tuberculosis patients with and without HIV co-infection

Ronan AM Breen ^1*, Robert F Miller ², Thomas Gorsuch ³, Colette J Smith ², Achim Schwenk ³, William JM Holmes ¹, Jayne Ballinger ¹, Leonie Swaden ¹, Ian Cropley ¹, Margaret A Johnson ¹ and Marc CI Lipman ¹

¹ Royal Free Hospital, London, United Kingdom
² Royal Free and University College Medical School, London, United Kingdom
³ North Middlesex Hospital, London, United Kingdom

^* To whom correspondence should be addressed. E-mail: rambreen{at}doctors.org.uk.

Accepted 7 June 2006

Abstract

Rationale: Serious treatment-associated adverse events are thought to occur more frequently in individuals with tuberculosis who are co-infected with HIV.

Objectives and methods: To assess the frequency of serious (Grade III/IV) adverse events and interruption of anti-tuberculosis treatment in the era of effective anti-retroviral therapy. We retrospectively compared the incidence of serious (Grade III/IV) adverse events in 312 individuals treated for tuberculosis, of whom 156 were co-infected with HIV.

Results: 111 (71%) of HIV-infected individuals received highly active antiretroviral therapy at the same time as anti-tuberculosis treatment. Serious (Grade III/IV) adverse events were recorded in 40% HIV infected and 26% HIV-uninfected individuals respectively (p=0.008). Peripheral neuropathy and persistent vomiting were more common in co-infected patients (p<0.001; p=0.006); although all cause interruption of anti-tuberculosis therapy occurred with similar frequency within each group (13% in the HIV-infected and 15% in the HIV-uninfected groups; p=0.74). In 85% of HIV-infected and 87% of HIV-uninfected individuals respectively this was due to hepatotoxicity, which typically presented within two months of starting treatment. The median delay in restarting therapy was 4 weeks; thus most individuals required full tuberculosis re-treatment.

Conclusion: Despite a greater rate of serious (Grade III/IV) adverse events among HIV infected individuals, we found that discontinuation of anti-tuberculosis treatment occurred with similar frequency in HIV-infected and HIV-uninfected individuals.

Keywords: HIV, antiretroviral therapy, hepatotoxicity, neuropathy, tuberculosis

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