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Switching from Atripla to Eviplera reduces central nervous system side-effects
Liz Highleyman, 2013-09-23 09:10:00
People who switched single-tablet regimens from Atripla (efavirenz/tenofovir/emtricitabine) to Eviplera (rilpivirine/tenofovir/emtricitabine) maintained viral suppression and saw improvement in central nervous system (CNS) side-effects such as abnormal dreams and depression, according to a late-breaking poster presented at the 53rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) this month in Denver. Two other studies looked at the safety and efficacy of Eviplera amongst women and black patients.
Atripla, a recommended first-line regimen in European and US antiretroviral treatment guidelines, is widely used, highly effective, convenient and generally considered safe and well tolerated. But many people taking efavirenz – an ingredient in the all-in-one pill – experience neuropsychiatric symptoms that may include insomnia, vivid dreams or nightmares, and depression or anxiety.
Mark Nelson from the Chelsea and Westminster Hospital in London and colleagues evaluated outcomes amongst people with HIV who switched from Atripla to Eviplera, a similar once-daily single-tablet coformulation that substitutes a newer NNRTI, rilpivirine (sold separately as Edurant), for efavirenz. Eviplera is a recommended regimen in European guidelines and an 'alternative' in US guidelines.
This phase 4 multicentre pilot study enrolled 40 people taking Atripla who had fully suppressed viral load but continued to be bothered by efavirenz-associated CNS side-effects after at least 12 weeks on treatment. All but four were men, the average age was 47 years and the median baseline CD4 T-cell count was high at 640 cells/mm3. They had been on efavirenz-based ART for a median of 40 months (range 4 to 165 months).
The researchers assessed CNS toxicity at four and twelve weeks after the switch using ACTG adverse event scores and a 19-item sleep questionnaire, with scores converted to percentages. The CNS adverse events questionnaire asked about 10 symptoms – dizziness, depression, insomnia, anxiety or nervousness, confusion, impaired concentration, headache, somnolence or drowsiness, aggressive mood and abnormal dreams – each rated as absent, mild, moderate or severe.
The total CNS side-effects score declined significantly by four weeks after switching from Atripla to Eviplera, falling from a median of 40 to 12, with lower scores indicating fewer symptoms. By week 12 the median score rose somewhat, to 20, but was still a significant improvement over baseline.
Scores for each individual symptom, except for headache, also showed significant improvement. The largest declines in the proportion of people experiencing moderate to severe (grade 2 to 4) symptoms were seen for abnormal dreams (about 75% at baseline to 10% at week 4), insomnia (60 to 20%), depression (just over 50% to just over 10%), somnolence (50% to about 12%) and impaired concentration (about 48% to under 10%). A few symptoms rebounded by more than 10% from week 4 to 12, but dizziness, aggressive mood and headache continued to decrease, whilst insomnia, confusion, somnolence and abnormal dreams remained fairly stable.
Total sleep scores also decreased significantly, from a median of 30 at baseline to 19 at week 4, and continued to fall to 16 at week 12, with lower scores again indicating improvement.
All participants maintained viral suppression after switching to Eviplera. The median CD4 count fell to 584 cells/mm3 at week 12, but this was not a statistically significant change.
Blood lipids improved by week 12 after the switch, including significant declines in total cholesterol (-0.6mmol/l), LDL ('bad') cholesterol (-0.49mmol/l) and triglycerides (-0.28mmol/l).
"Switching Atripla to Eviplera led to significant improvement" in CNS adverse events and sleep questionnaire scores with maintenance of virological suppression, the researchers concluded. "Identification of individuals with efavirenz toxicity is essential as alternative agents lead to improvements in toxicity profile and quality of life."
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