People with HIV and tuberculosis who took a once-daily nevirapine regimen alongside TB treatment containing rifampicin were significantly more likely to develop a recurrence of TB than people taking efavirenz (Sustiva or Stocrin, also in the combination pill Atripla) in a randomised trial, Indian researchers reported today at the 41st Union World Conference on Lung Health in Berlin.
TB and HIV treatment are complicated by the fact that one of the key drugs used in TB treatment, rifampicin, reduces blood levels of nevirapine (Viramune) by 30 to 55% and also reduces levels of most protease inhibitors.
A further complicating factor is that nevirapine must be given at a lower dose for the first two weeks of treatment in order to reduce the risk of toxicities, further increasing the risk of sub-therapeutic drug levels when dosed with rifampicin.
For these reasons treatment guidelines now recommend the use of an efavirenz-based antiretroviral regimen.
However, nevirapine is widely used in antiretroviral therapy in resource-limited settings due to its low cost and availability in a wide range of fixed-dose combinations.
The alternative, efavirenz, is not currently recommended for pregnant women, particularly in the first trimester, due to evidence of a higher risk of birth defects in animal studies. (However a recently published meta-analysis found no elevated risk of birth defects in the offspring of women exposed to efavirenz in the first trimester.)
Indian researchers at the Tuberculosis Research Centre in Chennai designed a randomised study to investigate the extent to which responses to HIV treatment and TB treatment are compromised by drug interactions.
Virological responses to treatment in the study have already been presented (see report here, including more detailed discussion of studies examining the response to nevirapine in people receiving rifampicin), and showed that patients receiving nevirapine were significantly more likely to experience virological failure, or a lack of virological response, when compared to those who received efavirenz.
Dr Soumya Swaminathan presented a follow-up analysis of the study looking at the incidence of TB according to antiretroviral regimen.
The trial randomised 116 patients with culture-confirmed TB and HIV infection between 2002 and 2006 to a once-daily regimen of ddI/3TC and either efavirenz or nevirapine, given as directly observed therapy each morning alongside the TB regimen. All patients received the recommended Indian regimen for TB treatment.
The primary outcomes evaluated in this analysis were the proportion of patients in each arm who were culture-negative for TB after six months of treatment in cases of pulmonary TB, and the proportion of patients who experienced improvement in lesions or symptoms of extrapulmonary TB, with radiological evaluation where appropriate.
The study found a significantly higher rate of TB recurrence in the nevirapine arm (three of 54 patients in the efavirenz arm compared to nine of 46 patients in the nevirapine arm, p=0.03) during long-term follow-up to month 18, and this difference appeared to be driven by the higher rate of virological failure of antiretroviral treatment.
Although there was a trend towards a higher rate of treatment failure at month six in the nevirapine group (92 vs 81%, p=0.09), this difference was not significant.
The findings are further evidence of the difficulties of using nevirapine in antiretroviral treatment for people with TB, and of the need for affordable alternatives to efavirenz when use of that drug is considered unsuitable, particularly in pregnant women.
Swaminathan S et al. Tuberculosis treatment outcomes among patients treated with a short-course intermittent anti-TB regimen and either once-daily nevirapine or efavirenz-based antiretroviral therapy: a randomized trial. 41st Union World Conference on Lung Health, Berlin, abstract LB3, 2010.