CROI: Abacavir may be safer than nevirapine in Africans, DART sub-study suggests

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Abacavir (Ziagen) appears to cause fewer serious adverse drug reactions than nevirapine in African patients taking part in a substudy of the DART trial, investigators reported on Tuesday at the Thirteenth Conference on Retroviruses and Opportunistic Infections in Denver.

DART is a large multicentre randomised study taking place in Uganda and Zimbabwe, sponsored by the United Kingdom’s Department for International Development and run by the United Kingdom Medical Research Council’s Uganda Research Unit.

The trial is comparing two strategies for the management of HIV disease in resource-limited settings, and is also comparing different treatment regimens.



The result of a statistical test which tells us whether the results of a study are likely to be due to chance and would not be confirmed if the study was repeated. All p-values are between 0 and 1; the most reliable studies have p-values very close to 0. A p-value of 0.001 means that there is a 1 in 1000 probability that the results are due to chance and do not reflect a real difference. A p-value of 0.05 means there is a 1 in 20 probability that the results are due to chance. When a p-value is 0.05 or below, the result is considered to be ‘statistically significant’. Confidence intervals give similar information to p-values but are easier to interpret. 


A rash is an area of irritated or swollen skin, affecting its colour, appearance, or texture. It may be localised in one part of the body or affect all the skin. Rashes are usually caused by inflammation of the skin, which can have many causes, including an allergic reaction to a medicine.


An allergic reaction.


In a clinical trial, a clearly defined outcome which is used to evaluate whether a treatment is working or not. Trials usually have a single primary endpoint (e.g. having an undetectable viral load) as well as a few secondary endpoints, covering other aspects of treatment safety, tolerability and efficacy.

secondary endpoints

Endpoints in a trial that provide supportive evidence to the primary endpoint.

The substudy reported this week has recruited 600 patients to a randomised, double-blind comparison of abacavir or nevirapine in combination with AZT/3TC, dosed as Combivir. Abacavir-based antiretroviral treatment should be evaluated in resource-limited settings, said presenter Dr Paula Munderi, because of its compatibility with TB drugs and because both nevirapine and efavirenz (Sustiva) are contraindicated in certain groups of women (nevirapine in women with off-treatment CD4 cell counts above 250 cells/mm3 and efavirenz in pregnant women or those who might become pregnant).

The study recruited individuals with CD4 cell counts below 200 cells/ mm3, approximately one-quarter of whom had CD4 cell counts below 50 cells/mm3 at baseline. Approximately 20% of participants had WHO stage 4 disease, which corresponds to an AIDS diagnosis.

The primary endpoint of the study was the number of serious adverse drug reactions probably or uncertainly related to the study drug occurring in each arm. Patients were followed for 24 weeks.

Twenty serious adverse drug reactions were reported, six in the abacavir arm and 14 in the nevirapine arm (p=0.06). Although the result showed a trend towards greater abacavir safety, it was not quite statistically significant. However, when all grade 4 adverse drug reactions were assessed (a secondary endpoint), the abacavir group were shown to have experienced significantly fewer events (59 per 100 patient years versus 88 per 100 patient years in the nevirapine group, p=0.008).

There was also a lower rate of treatment discontinuation in the abacavir arm, and the observed rate of abacavir hypersensitivity was 2%, considerably lower than rates reported in Caucasian populations.

Distinguishing between abacavir and nevirapine hypersensitivity proved quite difficult, with considerable overlap of symptoms such as rash, fever and respiratory symptoms. However, no abacavir-treated patient experienced liver enzyme elevations alongside symptoms of rash and fever.

The virological efficacy in each arm is still being assessed and will be presented at a future conference. The ACTG 5095 study suggested in 2003 that the combination of AZT/3TC/abacavir is inferior to AZT/3TC/efavirenz, leading clinicians in the United States and Europe to withdraw from prescribing triple NRTI regimens in first-line treatment. If abacavir proves to be non-inferior to nevirapine in this study, but with a lower rate of serious adverse events, it may prove an attractive alternative to nevirapine in resource-limited settings, particularly in women and TB patients.


Munderi P et al. Safety of nevirapine compared to abacavir on a background of zidovudine/lamivudine as first-line antiretroviral therapy: a randomised double-blind trial. Thirteenth Conference on Retroviruses and Opportunistic Infections, Denver, abstract 109LB, 2006.