Drug side-effects place treatment scale up at risk, says Ugandan HIV expert

One of Africa's leading HIV doctors says that efforts to scale up antiretroviral treatment in sub-Saharan Africa risk being undermined by inadequate preparation throughout the health care system for drug side-effects.

Dr Elly Katabira of Makarere University, Uganda, told the Sixth International Workshop on Lipodystrophy and Adverse Drug Reactions in HIV in Washington DC, USA, that doctors risk undermining patient confidence in antiretroviral drugs if they are not prepared properly for drug side-effects in the first months of treatment.

Global pressure to scale up treatment, said Dr Katabira, was in danger of ignoring the higher risk of drug side-effects in patients eligible for treatment.

Dr Katabira pointed to patients recruited to the DART study of antiretroviral treatment strategies in Uganda and Zimbabwe. Fifty-nine per cent had CD4 cell counts below 100 cells/mm3 and 35% had CD4 cell counts below 50 cells/mm3, he said. This group of patients are well known to be at higher risk of side-effects, he went on. It can also be difficult to distinguish drug side-effects from symptoms of immune reconstitution syndrome (IRIS).

"Managing IRIS is becoming a nightmare," Dr Katabira warned. "The first reaction of the patient who develops an immune reconstitution reaction after being told he will he better is to stop treatment," he said.

Dr Katabira also warned that efforts to move responsibility for treatment supervision to nurses, clinical officers and community health care workers could backfire without full training on drug side-effects and their management in the context of immune reconstitution illnesses.

He said that nurses and other grades of health care workers lacked confidence in distinguishing between drug side-effects and immune reconstitution syndrome, and that instructions to refer these patients onto specialists were likely to founder if referral networks were not robust.

One of the key research questions for treatment scale up programmes will be to determine whether the frequency of drug side-effects differs by region or ethnicity. In South Africa rates of nevirapine (Viramune) toxicity are perceived to be lower than amongst Caucasians, although no comparative studies have taken place. However Dr Katabira warned, "it's very difficult to tell whether there is a different rate of nevirapine toxicity because people are starting treatment very late." The risk of nevirapine toxicity is greater in women with CD4 cell counts above 250 cells/mm3.

The international workshop on lipodystrophy has never previously addressed the question of drug side-effects in developing countries, and Dr Katabira's statements, parachuted into the middle of a meeting dominated by complex basic science presentations, lacked any follow-up from field research. Hopefully next year's meeting will address the question of drug toxicity and in particular the development of methods for identification and differentiation of drug side-effects in primary health care settings.