IAC: TB Drug Alters Power of HIV Medication

By Michael Smith
MEXICO CITY, 04 aug 2008-- TB patients treated with rifampin (Rifadin, Rimactane) are more likely to fail subsequent HIV therapy if it includes nevirapine (Viramune), researchers said here.
On the other hand, there is less risk of virological failure if TB patients start HIV treatment with a regimen that includes efavirenz (Sustiva), according to Andrew Boulle, M.B.Ch.B., of the University of Cape Town, in South Africa, and colleagues.
But when HIV patients already taking either drug began TB treatment with rifampin, outcomes were comparable to those in patients without TB, Dr. Boulle said.
The finding comes from a study that appears in the Aug. 6 issue of the Journal of the American Medical Association and was released here in conjunction with the 17th International AIDS Conference.
The issue is important in resource-poor countries, where non-nucleoside reverse transcriptase inhibitors such as nevirapine and efavirenz are recommended as components of an initial antiretroviral drug regimen.
Rifampin is a potent inducer of cytochrome P450 enzymes, which metabolize many drugs, including the non-nucleoside reverse transcriptase inhibitors.
Indeed, plasma concentrations of both nevirapine and efavirenz are reduced by the drug, although nevirapine is hardest hit with reductions of between 20% and 55%.
To see what the effects of such reductions might be, the researchers studied HIV treatment-naïve patients in a public sector antiretroviral therapy program in three centers in South Africa.
The analysis included 2,035 individuals who started antiretroviral therapy with efavirenz (including 1,074 who already had TB) and 1,935 who started with nevirapine (including 209 with concurrent TB).
Compared with patients without TB, those with TB (and on rifampin) who started nevirapine were twice as likely to have an elevated viral load six months later. The rate was 16.3%, compared with 8.3%, a difference that was significant at P<0.05.
They were also quicker to develop virological failure -- defined as two consecutive test values of more than 5,000 copies of viral RNA per milliliter of blood. The adjusted hazard ratio was 2.2, with a 95% confidence interval from 1.3 to 3.7, which was significant at P<0.05.
There were no differences between patients starting efavirenz with or without concurrent TB.
And there was no difference in time to virological rebound in patients free of TB compared with those who developed tuberculosis during follow-up while taking either nevirapine or efavirenz.
The latter finding, however, should be taken with a grain of salt, Dr. Boulle said, because the number of patients who developed TB during HIV treatment was relatively small.
Indeed, one of the main limitations of the study as a whole, he said, is that only 209 patients started nevirapine with concurrent TB, which limits the power of the analysis.
Another limitation of the study is that neither survival nor CD4 counts were affected by the antiretroviral regimen in the patients with TB. The assumption made was that virological failure would result in clinical failure.
The study was also observational so the investigators could not exclude confounding by indication for choosing nevirapine as opposed to efavirenz as the initial regimen.
There was no external support for the study.
Dr. Boulle reported no conflicts.
Primary source: Journal of the American Medical AssociationSource reference:Boulle A et al "Outcomes of Nevirapine- and Efavirenz-Based Antiretroviral Therapy When Coadministered With Rifampicin-Based Antitubercular Therapy" JAMA. 2008; 300(5): 530-539