ORIGINAL RESEARCH ARTICLE Adverse events to antituberculosis therapy: influence of HIV and antiretroviral drugs D J B Marks MBBS PhD* , K Dheda FCP(SA) PhD †‡ , R Dawson FCP(SA) † , G Ainslie FRCP † and R F Miller FRCP § *Centre for Molecular Medicine, University College London, London, UK; † Division of Pulmonology, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa; ‡ Centre for Infectious Diseases and International Health, and; § Research Department of Infection and Population Health, University College London, London, UK Summary: This study investigated whether serious adverse events (SAEs) during antituberculosis therapy occur more frequently in HIV co-infected patients in a South African population. A retrospective analysis examined incidences of hepatotoxicity, peripheral neuropathy, severe arthralgia, persistent vomiting and severe rash in 400 patients treated for tuberculosis in a community clinic. A total of 141 patients were co-infected with HIV, among whom only 16.3% were receiving antiretrovirals. Details of SAEs were ascertainable in 331/400 patients, and occurred in 26.7% of HIV-infected and 13.3% of HIV-uninfected individuals (P ¼ 0.003). The excess was attributable to increased peripheral neuropathy (8.3% and 1.9%, respectively, P ¼ 0.009) and persistent vomiting (13.3% and 3.3%, P ¼ 0.001). SAE occurrence was not related to antiretroviral use, although median CD4 counts were lower in those experiencing side-effects (130 and 259 cells/mL, P ¼ 0.008). The treatment completion did not differ significantly between the two groups (76.6% and 84.2%, P ¼ 0.08). Keywords: tuberculosis, HIV, adverse events, neuropathy, South Africa INTRODUCTION Tuberculosis contributes an enormous global burden of disease and disability. 1 In resource-limited countries it remains a leading cause of morbidity and mortality, while Westernized countries are witnessing a recrudescence in its incidence. The situation is compounded by the concurrent HIV epidemic. 2 Despite availability of efficacious antimycobacterial chemotherapy, programmes to control tuberculosis are hampered by obstacles to effective and timely drug delivery. Among these, poor patient adherence rep- resents a key issue. 3 This frequently relates to development of adverse drug reactions, which can be severe and life-threatening. Failure of disease control both imposes substantial socioeconomic consequences and leads to emergence of multidrug-resistant (MDR) and extensively drug-resistant organisms. 4 The interaction between tuberculosis and HIV is complex and multifaceted. One aspect recently under scrutiny is the inci- dence of serious adverse reactions to antituberculosis drugs, and whether this is increased in patients co-infected with HIV. Several small studies have suggested that risk is elevated in such patients, 5–7 findings confirmed in a case-control study from the UK that demonstrated an approximate doubling in the relative risk of adverse events in HIV-infected individuals. 8 The underlying mechanism was not elucidated, although a drug interaction was considered probable given the high rates of concomitant antiretroviral medication use. The consequences of increased rates of adverse drug reac- tions could be most profound in resource-limited settings, given the considerably greater prevalence of both infections. In the current study, we aimed to determine whether the increase in SAEs also applies to a South African population. This region has high tuberculosis and HIV prevalence, and patients are genetically and culturally distinct compared with those studied in the UK. Additionally, in this environment, access to antiretroviral medication remains limited, 9,10 resulting from multiple factors including diagnostic delay, stigmatiza- tion, heavily burdened clinics, logistic delays within clinics and patient non-attendance. Consequently, this population may also provide information on the respective influences of HIV infection itself and antiretroviral medication. METHODS Data were collected retrospectively from a community treat- ment clinic in Cape Town, South Africa. An anonymized case- note review was performed in which the last 400 consecutive patients treated for tuberculosis between 2004 and 2006 were identified and medical records were analysed in an unselected manner. The study was approved by the University of Cape Town Research Ethics Committee (South Africa), the Regional Clinic Management Committee (Cape Town, South Africa) and University College London Hospitals Research Ethics Committee (UK). Demographic characteristics recorded included age, sex and ethnicity. Details of tuberculosis infection included anatomical site of involvement, and whether the case was new or re- treatment (patients who had previously received .4 weeks of antituberculosis therapy). All patients were offered screening Correspondence to: Dr D J B Marks Email: d.marks@ucl.ac.uk DOI: 10.1258/ijsa.2008.008361. International Journal of STD & AIDS 2009; 20: 339–345