Emma Hitt, PhD

July 20, 2011

July 20, 2011 (Rome, Italy) — Compared with efavirenz, etravirine appears to be associated with fewer neuropsychiatric adverse events, according to findings from 48 weeks of data from the randomized Study of Efavirenz Neuropsychiatric Events vs Etravirine (SENSE) trial.

Juergen Rockstroh, MD, from the University of Bonn, Medizinische Universitätsklinik, Germany, presented the findings here, during a late-breaking poster session, at the 6th International AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention.

Dr. Juergen Rockstroh

"The [nonnucleoside reverse transcriptase inhibitor (NNRTI)] etravirine is currently approved for treatment of [treatment]-experienced patients at the 200 mg twice-daily dose," said Andrew Hill, PhD, a SENSE trial statistician from Liverpool University in the United Kingdom. "This is the first clinical trial to compare first-line use of etravirine with the current standard of care, efavirenz," he told Medscape Medical News.

The SENSE trial was a comparison of etravirine with efavirenz, given in combination with 2 nucleoside reverse transcriptase inhibitors (NRTIs) to 157 treatment-naive patients for 48 weeks. The primary endpoint was neuropsychiatric adverse events measured through week 12. HIV RNA suppression at week 48 was also measured as a secondary endpoint.

Patients with a HIV RNA load of more than 5000 copies/mL were randomly assigned to receive etravirine 400 mg once daily (n = 79) or efavirenz 600 mg once daily (n = 78) plus investigator-selected NRTIs (tenofovir/emtricitabine, abacavir/lamivudine, or zidovudine/lamivudine).

Efficacy was comparable in both treatment groups. In the intent-to-treat time to loss of virologic response analysis, 76% of patients in the etravirine group had HIV RNA levels of 50 or fewer copies/mL at week 48 compared with 74% in the efavirenz group. In the on-treatment analyses, 92% of patients had HIV RNA levels lower than 50 copies/mL in the etravirine group vs 89% in the efavirenz group, indicating noninferiority for etravirine (P < .05 for noninferiority).

Four patients had virological failure in the etravirine group, but none showed NRTI or NNRTI resistance. Seven patients had virological failure in the efavirenz group, and of those, 3 had treatment-emergent NRTI and NNRTI resistance and sustained virological rebound.

Grade 1 to grade 4 drug-related neuropsychiatric adverse events peaked at week 2 (13.9% in the etravirine group and 39.7% in the efavirenz group; P < .001). At week 48, the percentage with ongoing neuropsychiatric adverse events was 6.3% for etravirine vs 21.5% for efavirenz (P = .011).

"This new analysis of the 48-week efficacy data shows 2 important results," said Dr. Hill. "First, the percentage of patients with HIV RNA [levels lower than] 50 copies/mL was similar in the two arms, which met the criteria for noninferiority, although it should be noted that this trial was not designed to demonstrate this.

"Second, the lack of treatment-emergent NRTI or NNRTI drug resistance at virological failure in the etravirine arm is the first time this has been seen in a trial of first-line NNRTI-based treatment," he said.

According to Dr. Hill, a larger trial of first-line etravirine is required to validate the results of this phase 2 trial. However, if the results can be validated, etravirine may become a new NNRTI option for first-line treatment.

"Etravirine might be considered an option in patients who do not tolerate the initial central nervous system adverse events of efavirenz or for patients considered poor candidates to start efavirenz therapy," said independent commentator José R. Arribas, MD, associate professor of medicine at the Autonoma University School of Medicine in Madrid and research director at the HIV unit of La Paz Hospital, Madrid, Spain.

"A larger clinical trial would be needed to make a definitive conclusion in regard to the comparative antiviral efficacy of etravirine and efavirenz in naive patients," he told Medscape Medical News. "It is also interesting that none of virological failures with etravirine developed NNRTI mutations, supporting a higher genetic barrier of etravirine," he added.

The study was funded by Janssen, which was involved in the development of etravirine. Dr. Hill has received consultancy payments from Tibotec. Dr. Arribas receives advisory fees, speaker fees, and grant support from Tibotec, Janssen, ViiV, Abbott, BMS, Gilead, and MSD.

6th International AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention: Abstract TULBPE025. Presented July 19, 2011.

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