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and Hepatitis.com Coverage of the
XVIII International AIDS Conference (AIDS 2010) July 18 - 23, 2010, Vienna, Austria
Switching from Efavirenz to Etravirine Reduces Central Nervous System Side Effects
Efavirenz, a component of the popular Atripla combination pill, is one of the most frequently used HIV medications, and is part of one of the preferred regimens in U.S. antiretroviral treatment guidelines. It often causes central nervous system (CNS) side effects, however, leading some people to discontinue the drug.
In the first study, Brian Gazzard from Chelsea and Westminster Hospital and fellow investigators with the SENSE trial evaluate whether 12 weeks of treatment with etravirine could lead to fewer neuropsychiatric side effects than efavirenz.
The trial included 157 treatment-naive patients with HIV RNA > 5000 copies/mL and no genotypic drug-resistance mutations. Most participants (81%) were men, 85% were white, the median age was 36 years, and the baseline CD4 cell count was 302 cells/mm3.
Participants were randomly assigned to receive 400 mg once-daily etravirine or 600 mg once-daily efavirenz, both with 2 investigator-selected nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) for 48 weeks. Eligible NRTI combinations were tenofovir/emtricitabine (Truvada), abacavir/lamivudine (Epzicom), or zidovudine/lamivudine (Combivir).
The primary endpoint of the study was the percentage of patients with grade 1-4 (mild to severe) treatment-emergent drug-related neuropsychiatric adverse events. Data were presented from an interim analysis at week 12.
"After 12 weeks, first-line treatment with etravirine 400 mg once-daily + 2NRTIs led to significantly fewer neuropsychiatric adverse events than efavirenz + 2 NRTIs," the SENSE investigators concluded.
"There were larger rises in total cholesterol and LDL cholesterol during treatment with efavirenz plus 2 NRTIs, compared with etravirine + 2 NRTIs," they continued. "The short-term virologic and immunologic efficacy profiles were similar in the 2 arms."
In the second study, Laura Waters, also from Chelsea and Westminster, investigate the impact of switching from efavirenz -- the preferred drug in the British HIV treatment guidelines -- to etravirine in patients with ongoing CNS adverse events.
4 study included 38 patients recruited at 3 U.K. study sites (Chelsea
and Westminster and St. Mary's Hospital in London, and Royal Sussex
County Hospital in Brighton). All were men, all but 1 were white, and
the median age was 43 years. All had HIV RNA < 50 copies/mL at baseline
and median CD4 cell count was 468 cells/mm3.
They were randomly assigned to continue taking efavirenz (600 mg once-daily) plus an etravirine placebo, or else switch to etravirine (400 mg once-daily) plus an efavirenz placebo for 12 weeks. All participants then received open-label etravirine for an additional 12 weeks. In addition, 58% were taking the tenofovir/emtricitabine NRTI backbone at baseline (29% using the Atripla coformulation), 29% were using abacavir/lamivudine, and the rest were using other NRTI combinations.
The researchers assessed occurrence of 12 CNS side effects: insomnia, abnormal dreams, somnolence, fatigue, dizziness, depression, anxiety, nervousness, pain, impaired concentration, headache, and hallucinations. They considered the proportion of patients with grade 2-4 CNS adverse events, the median number of such events, and a CNS score, calculated as the sum of all grades of side effects (for example, a person with grade 1 dizziness + grade 3 abnormal dreams would have a CNS score of 4).
endpoint was the change in the proportion of patients with grade 2-4
CNS adverse events from baseline to week 12. Secondary endpoints included
changes in CNS score and median number of CNS side effects from baseline
to week 12, and from week 12 to week 24, as well as changes in lipid
levels, viral load, and CD4 counts.
"Switching efavirenz to etravirine led to significant reductions in grade 2-4 CNS adverse events overall, insomnia, abnormal dreams and nervousness," the investigators concluded. "Lack of improvement for some adverse events and patients suggests causes other than [ART]."
Taken together, these studies indicate that etravirine is an effective and well-tolerated option, whether started as part of a first-line regimen or substituted for efavirenz.
B Gazzard, G Di Perri, H Furrer, and others. The SENSE Trial: Etravirine (ETR) shows fewer Neuropsychiatric Adverse Events than Efavirenz (EFV) in Treatment-naive HIV-1 Infected Patient. XVIII International AIDS Conference (AIDS 2010). Vienna, July 18-23, 2010. Abstract LBPE19 (E-poster).
M Fisher, A Winston, and others. A phase IV, double blind, multi centre,
randomised, placebo controlled, pilot study to assess the feasibility
of switching individuals receiving efavirenz (EFV) with continuing central
nervous system (CNS) adverse events (AE) to etravirine (ETR). XVIII
International AIDS Conference (AIDS 2010). Vienna, July 18-23, 2010.