In resource-limited countries, patients are often treated for tuberculosis at the same time that they are undergoing antiretroviral therapy (ART) for HIV. New research, published on August 6 in a special HIV/AIDS issue of JAMA, finds that virological failure is more likely to occur if patients receiving rifampicin-based anti-tuberculosis therapy also receive nevirapine-based antiretroviral therapy than rather than efavirenz-based antiretroviral therapy. The nevirapine-based antiretroviral therapy is often used to treat HIV in the developing world due to its lower cost.
Andrew Boulle, M.B.Ch.B., M.Sc. (University of Cape Town, South Africa) and colleagues suggest that either shared toxicity or adverse drug interactions are driving the complications seen when ART and anti-tubercular therapy are administered together. It is known that rifampicin-based anti-tubercular therapy has an effect of reducing concentrations of both ART agents efavirenz and nevirapine in the blood plasma, but how exactly these interactions affect the viruses remains unknown.
The researchers designed a study to compare the effectiveness of efavirenz-based ART combined with rifampicin-based anti-tubercular therapy and nevirapine-based ART combined with rifampicin-based anti-tubercular therapy. The sample consisted of South African adults who enrolled between May 2001 and June 2006 at a clinic that is part of a community-based antiretroviral treatment program. The participants were followed up until the end of 2006. Of the 3,009 individuals in the analysis, 2,035 individuals began antiretroviral therapy with efavirenz (1,074 also had tuberculosis) and 1,935 began antiretroviral therapy with nevirapine (209 also had tuberculosis).
At a six month follow-up, tuberculosis patients who began ART with nevirapine were found to be about two times as likely to have higher viral loads than those who began nevirapine without tuberculosis – 16.3% and 8.3%, respectively. In addition, a time-to-event analysis demonstrated that patients starting nevirapine with tuberculosis treatment were twice as likely to experience earlier virological failure. The researchers note, however, that 80% percent of patients taking nevirapine and rifampicin were virologically suppressed after 18 months of antiretroviral therapy. There were no significant differences found between patients free of tuberculosis on nevirapine or rifampicin and patients starting efavirenz with and without tuberculosis treatment, or in patients developing tuberculosis while on the same ART drug.
It is possible, suggest the authors, that the differences 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.”
They conclude: “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.”
Outcomes of Nevirapine- and Efavirenz-Based Antiretroviral Therapy When Coadministered With Rifampicin-Based Antitubercular Therapy
Andrew Boulle; Gilles Van Cutsem; Karen Cohen; Katherine Hilderbrand; Shaheed Mathee; Musaed Abrahams; Eric Goemaere; David Coetzee; Gary Maartens
JAMA(2008). 300[5]: pp. 530 -539.
Written by: Peter M Crosta