Once-daily nevirapine inferior to efavirenz in HIV/TB-coinfected patients
A nevirapine-based regimen associated with higher rates of both virologic failure and death
Recent studies have unequivocally demonstrated that patients with HIV/tuberculosis (TB) coinfection should begin antiretroviral therapy (ART) as soon as possible, but no later than 8 weeks, after initiation of TB therapy. The WHO recommends that ART for coinfected patients consist of two nucleosides (AZT or tenofovir + either 3TC or FTC) + efavirenz — and considers nevirapine an acceptable option when efavirenz cannot be used. Currently, nevirapine is the more widely used third drug because it is less expensive.
In this open-label noninferiority trial, conducted from mid-2006 to mid-2008, researchers directly compared once-daily nevirapine with once-daily efavirenz, each given in combination with ddI + 3TC. A total of 564 treatment-naive coinfected patients in India were screened for the study, and 116 were subsequently randomized to receive one of the two regimens after 2 months of TB treatment. The study was halted after the second interim analysis by the data and safety monitoring board showed significant differences between the treatment arms.
Twenty-four weeks after ART initiation, both groups had high adherence levels, but only 65% of patients in the nevirapine arm had viral loads <400 copies/mL, compared with 85% in the efavirenz arm. The nevirapine arm had twice as many virologic failures as the efavirenz arm (10 vs. 5) and also more deaths (5 vs. 0). In addition, there was a small (but not quite statistically significant) difference in TB treatment outcomes, with 93% of the efavirenz group versus only 84% of the nevirapine group having favorable responses to TB therapy. Rates of adverse drug reactions were similar between the groups, and overall, 21% of patients had symptoms suggestive of immune reconstitution inflammatory syndrome.
Comment: These results suggest that a once-daily nevirapine-based regimen is inferior to an efavirenz-based regimen for the treatment of HIV infection among TB-coinfected patients. Although both regimens contained ddI + 3TC rather than one of the currently recommended nucleoside pairs, the striking difference in outcomes should prompt the WHO as well as individual countries to reconsider the recommendation that nevirapine is an acceptable alternative to efavirenz in HIV/TB-coinfected patients.
By Carlos del Rio, MD
Published in Journal Watch HIV/AIDS Clinical Care September 26, 2011
Citation(s):
Swaminathan S et al. Efficacy and safety of once-daily nevirapine- or efavirenz-based antiretroviral therapy in HIV-associated tuberculosis: A randomized clinical trial. Clin Infect Dis 2011 Oct 1; 53:716.
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Journal Watch
http://aids-clinical-care.jwatch.org/cgi/content/full/2011/926/1
