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.
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
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
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.
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
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).
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."