 |
|
|
| |
Switching From Efavirenz to Rilpivirine Combo Quells CNS Side Effects
|
| |
| |
53rd ICAAC, September 10-13, 2013, Denver
Mark Mascolini
Swapping efavirenz-containing Atripla for rilpivirine-containing Complera (Eviplera in Europe) significantly lowered rates of central nervous system (CNS) side effects and sleep disturbances in a 40-person multicenter pilot trial [1]. Everyone maintained virologic suppression after the switch from Atripla to Complera.
Atripla remains a recommended and popular one-pill once-daily antiretroviral regimen, but CNS side effects may persist beyond the first few weeks of treatment. Because CNS-related problems are less frequent with the nonnucleoside rilpivirine, researchers in the United Kingdom conducted a multicenter pilot trial to assess the impact of switching from Atripla to Complera in people with persistent CNS side effects.
The UK team enrolled 40 participants, 36 of them men. All had an undetectable viral load with Atripla but ongoing CNS toxicity after 12 or more weeks of therapy. Everyone swapped Atripla for Complera. The primary endpoint was the rate of CNS toxicity 4 weeks after the switch based on a 10-item AIDS Clinical Trials Group (ACTG) adverse event score and a 19-item sleep questionnaire. The researchers converted absolute scores into percentages.
Study participants averaged 47 years in age (range 24 to 73) and had taken efavirenz for a median of 40 months (range 4 to 165). Median CD4 count at the switch to Complera measured 640 (interquartile range [IQR] 436 to 884).
Median CNS score dropped from 40 (IQR 29 to 57) at baseline to 12 (IQR 5 to 25) at week 4, a highly significant improvement (P < 0.001). At week 12 the median CNS score had trended back up to 20 (IQR 10 to 33), still significantly lower than baseline (P < 0.001). When the investigators calculated the proportion of participants with any grade 2 to 4 CNS symptom, the 98% baseline rate fell to 38% at week 4 (P < 0.001) and to 51% at week 12, still significantly lower than the baseline proportion (P < 0.001).
This moderate rebound in proportions with grade 2 to 4 CNS adverse events from week 4 to week 12 held true for depression, anxiety, and impaired concentration, but not for dizziness aggressive mood, or abnormal dreams. Proportions of patients with grade 2 to 4 CNS events were significantly lower from baseline to week 12 for dizziness, depression, insomnia, anxiety, confusion, impaired concentration, somnolence, aggressive mood, and abnormal dreams. The only CNS symptom that did not improve significantly from baseline to week 12 was headache.
Median total sleep questionnaire score dropped from 30 (IQR 22 to 39) at baseline to 19 (IQR 12 to 29) at week 4, and to 16 (IQR 9 to 25) at week 12 (P < 0.001 for both comparisons).
Everyone maintained an undetectable viral load through study week 12. Median CD4 count dropped from 640 at baseline to 584 at week 12, a nonsignificant change (P = 0.156). Twelve weeks after the switch to Complera, the study group had significant improvements in total cholesterol (-0.6 mmol/L, P < 0.001), low-density lipoprotein cholesterol (-0.49 mmol/L, P < 0.001), and triglycerides (-0.28 mmol/L, P < 0.001).
The researchers proposed that "identification of individuals with efavirenz toxicity is essential as alternative agents lead to improvements in toxicity profile and quality of life."
Reference
1. Nelson M, Winston A, Waters L, et al. Multicentre open-label study of switching from Atripla to Eviplera for possible efavirenz associated CNS toxicity. 53rd ICAAC. September 10-13, 2013. Denver. Abstract H-672b.
|
| |
|
|
|
|
|
