Patients receiving rifampicin-based anti-tuberculosis therapy are more likely to experience virological failure when starting nevirapine-based antiretroviral therapy, an HIV treatment that is widely used in developing countries because of lower cost, than when starting efavirenz-based antiretroviral therapy, according to a study in the August 6 issue of JAMA, a theme issue on HIV/AIDS.
Andrew Boulle, M.B.Ch.B., M.Sc., of the University of Cape Town, South Africa, presented the findings of the study at a JAMA media briefing on HIV/AIDS.
Combination antiretroviral therapy (ART) is frequently initiated in resource-limited countries when patients are being treated for tuberculosis. Co-administration of ART and anti-tubercular therapy may be complicated by shared toxicity or adverse drug interactions, according to background information in the article. Rifampicin-based anti-tubercular therapy reduces the plasma concentrations of the antiretroviral agents efavirenz and nevirapine. The virological consequences of these interactions are not well known.
Dr. Boulle and colleagues conducted a study to assess the effectiveness of efavirenz- or nevirapine-based combination ART used with rifampicin-based anti-tubercular therapy. The researchers analyzed clinical data collected from a community-based South African antiretroviral treatment program, in which adults were enrolled between May 2001 and June 2006 and were followed up until the end of 2006. The analysis included 2,035 individuals who started antiretroviral therapy with efavirenz (1,074 with tuberculosis) and 1,935 with nevirapine (209 with tuberculosis).
The researchers found that patients with tuberculosis initiating nevirapine were about twice as likely to have elevated viral loads during follow-up than those without tuberculosis (at six months, 16.3 percent vs. 8.3 percent). In the time-to-event analysis of confirmed virological failure, patients starting nevirapine with tuberculosis treatment were more than twice as likely to develop virological failure sooner. In spite of these differences, 80 percent of patients in the initial nevirapine-rifampicin group were virologically suppressed at 18 months duration of ART. There were no differences between patients starting efavirenz with and without tuberculosis treatment, or in patients developing tuberculosis while on nevirapine or efavirenz compared to those free of tuberculosis on the same antiretroviral drug.
The authors speculate that these differences, present in patients who start nevirapine-based antiretrovirals with tuberculosis, but not in those who develop tuberculosis once already established on nevirapine-based antiretroviral therapy “… could be the result of the limited power of the latter analysis to detect a difference… An alternative explanation, however, is a drug interaction mediated by rifampicin during the lead-in dosing phase of nevirapine.”
“Given the continued reliance on nevirapine-containing ART regimens in Africa, together with the important role tuberculosis services play as an entry point for ART, further prospective studies exploring this outcome are warranted. One of the most striking aspects of our study was the demonstration that 40 percent of patients starting ART in recent years have concurrent tuberculosis, underscoring the public health importance of improving affordable treatment options for patients infected with HIV and tuberculosis in this setting.”
JAMA. 2008; 300:530-539.