Patients coinfected with HIV and tuberculosis (TB) may benefit from raltegravir as an alternative to efavirenz, new research suggests.
Standard doses of raltegravir, 400 mg twice daily, had fewer treatment-related serious adverse events compared to efavirenz 600 mg once daily. Also, compared to patients in the efavirenz group and in a double-dose raltegravir group (800 mg twice daily), fewer patients on the standard raltegravir dose discontinued HIV treatment, the authors wrote online April 10 in The Lancet Infectious Diseases.
"This is the first available data of a randomized study to explore the safety and efficacy of raltegravir in patients coinfected with HIV and tuberculosis," said lead author Dr. Beatriz Grinsztejn of the STD/AIDS Clinical Research Laboratory, Evandro Chagas Clinical Research Institute (IPEC), Oswaldo Cruz Foundation (FIOCRUZ) in Rio de Janeiro, Brazil, by email to Reuters Health.
"Although the trial was not powered for comparisons between the two raltegravir doses evaluated, the standard dose of raltegravir seems to be as good as the recommended double dose in patients with HIV and tuberculosis. This is an important result, given the lower price and better tolerability of this regimen," she said.
As to who should receive raltegravir, Dr. Grinsztejn advised, "Raltegravir might be an alternative to efavirenz in patients unable to tolerate efavirenz or who have a contraindication to efavirenz."
The randomized phase II parallel-group open-label (ANRS) 12180 Reflate TB trial was conducted at eight sites in Brazil and France. Researchers looked for virological suppression (HIV RNA <50 copies per mL) at 24 weeks.
The authors randomized antiretroviral-naive adult patients 18 years of age and older who had HIV-1 and TB with a plasma HIV RNA concentration over 1,000 copies per mL. Patients in one group received raltegravir 400 mg twice daily, those in the second group received raltegravir 800 mg twice daily, and those in the third group received efavirenz 600 mg once daily plus lamivudine and tenofovir. Patients began their study treatment after starting TB treatment.
Ultimately, 153 patients (51 in each group) received at least one dose of the study drug and were included in the primary analysis. Overall, 133 patients (87%) completed follow up through week 48.
At week 24, 39 patients (76%) had virological suppression in the raltegravir 400 mg group, as did 40 patients (78%) in the raltegravir 800 mg group and 32 patients (63%) in the efavirenz group. The adverse-event profile was similar in all three groups.
Three (6%) patients taking efavirenz and three (6%) patients taking raltegravir 800 mg discontinued the study drugs due to adverse events. Seven patients died during the study, though none of the deaths were considered related to the study treatment.
"These findings suggest that raltegravir can be used at standard doses with rifampin without compromising the efficacy of the antiretroviral therapy," said Dr. Graeme Meintjes of the University of Cape Town in South Africa, in email to Reuters Health.
"This is the best evidence to date that informs as to whether raltegravir can be used with rifampin and the appropriate dose," added Dr. Meintjes, who along with Dr. Gary Maartens, also of the University of Cape Town, wrote an editorial accompanying the study.
Dr. Ernie-Paul Barrette of Washington University in St. Louis, Missouri, said in an email, "Although efavirenz has had long-term success, there is a higher rate of neuropsychiatric adverse events, and patients with trouble sleeping, depression, psychosis, and dizziness would likely do better with an alternate antiretroviral medication. The strengths of raltegravir are its limited drug-drug interactions, its limited impact on lipids, and its high tolerability compared to many other antiretrovirals.
Dr. Russell Kempker of Emory University in Atlanta, Georgia, said in an email, "Raltegravir is a very well-tolerated antiretroviral medication and is an ideal alternative for patients who have to stop efavirenz due to side effects (most commonly neuropsychiatric or rash), have resistance to efavirenz or who are in their first trimester of pregnancy."
"The findings of this study provide the best available data on the use of raltegravir among HIV and TB coinfected patients and suggest that, when given with rifampicin, an antiretroviral treatment regimen including a standard dose of raltegravir is effective," he added.
"These findings will serve as the basis for a large phase III multicountry comparative study to be initiated later this year," Dr. Grinsztejn said in an email.
Drs. Meintjes, Maartens, Barrette and Kempker were not involved in the study.
SOURCE: http://bit.ly/1mzu1Sh
Lancet Infect Dis 2014.
Source: Medscape