IAS: Rifampin TB treatment does not reduce response to NNRTIs, South Africans report

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Using rifampin-based therapy alongside a triple antiretroviral regimen that contains drugs from the NNRTI class (either nevirapine or efavirenz) does not result in a poorer response to treatment or greater toxicity, South African researchers reported last week at the Third International AIDS Society Conference on HIV Treatment and Pathogenesis in Rio de Janeiro, Brazil.

Concern persists over the effect of interactions between rifampin and nevirapine or efavirenz, and the possibility that rifampin will reduce blood levels of the NNRTI, leading to sub-optimal anti-HIV treatment and drug resistance. No long-term randomised study has yet reported on the effects of rifampin, and the South African study is the first substantial review of the clinical outcomes of patients in a resource-limited setting taking both regimens at the same time.

South African researchers set out to compare outcomes of patients with and without tuberculosis (TB) receiving rifampin-based treatment who commenced NNRTI-containing ART regimens. They looked at outcomes in the Medecins sans Frontieres Khayelitsha community cohort, which provides prospective follow-up.

Glossary

p-value

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. 

drug resistance

A drug-resistant HIV strain is one which is less susceptible to the effects of one or more anti-HIV drugs because of an accumulation of HIV mutations in its genotype. Resistance can be the result of a poor adherence to treatment or of transmission of an already resistant virus.

hepatotoxicity

Side-effects of drugs of medicines affecting the liver.

immune reconstitution

Improvement of the function of the immune system as a consequence of anti-HIV therapy.

trend

In everyday language, a general movement upwards or downwards (e.g. every year there are more HIV infections). When discussing statistics, a trend often describes an apparent difference between results that is not statistically significant. 

The study reviewed 1731 patients with a median CD4 cell count of 76 cells/mm3 at baseline and high viral load (median 5.4 log10 copies/ml, 250,000 copies/ml). Twenty-five per cent were receiving TB treatment at the time they began antiretroviral therapy (ART), and the vast majority had completed at least two months of TB treatment by this point (45% >2 months, 34%>4 months).

Initial regimens in the cohort were fairly evenly divided between nevirapine and efavirenz-containing regimens (EFV 808, NVP 918).

After three months of antiretroviral treatment, individuals receiving concomitant TB treatment were significantly less likely to have viral load below 400 copies/ml, but this difference was no longer apparent at month six (8.3% vs 13% at month 3, p=0.045; 8.6% vs 9.1% at month 6, p=0.91).

There was no difference in survival or immunologic outcomes at month six, nor any evidence of increased mortality due to immune reconstitution syndrome or advanced HIV disease in the TB treatment group.

Although a trend towards more treatment switches due to hepatotoxicity was observed in the nevirapine/TB treatment group, this was not associated with concomitant rifampin treatment (8% vs 4%, p=0.849).

References

Van Cutsem G et al. TB/HIV coinfected patients on rifampicin-containing treatment have equivalent ART treatment outcomes and concurrent use of nevirapine is not associated with increased hepatotoxicity. Third International AIDS Society Conference on HIV Pathogenesis and Treatment, Rio de Janeiro, Brazil, abstract WePp0303, 2005.