The experience from use of fixed-dose combination, efavirenz-based treatment (Atripla) as first-line therapy in the UK was published ahead of print in the journal AIDS.
This analysis included 472 patients from the Chelsea and Westminster Hospital in London. Case notes were retrospectively reviewed to collect safety and efficacy data on the patients who changed treatment.
Patients were predominantly male (94%), median age 37 years (IQR 31-43), and white (75%). Approximately 6% were black African, 3% Asian, 5% other. Median CD4 count and viral load when starting treatment were 285 cells/mm3 (IQR 208-362) and 16,000 copies/mL (IQR 708- 54,000) respectively. Median total cholesterol at baseline was 4.3 mmol/l (IQR 3.8 - 5 mmol/L).
Over follow-up, 19% of patients (89/472) switched treatment, most commonly (71%) due to CNS-related side effects (63/89). The median time to treatment switch (in 63 patients with data) was 294 days (IQR 108-495 days) with the median duration of first CNS event (available for 53 patients) was 27 days (IQR 7-104 days). Efavirenz was switched mainly to etravirine (n=39), atazanavir/r (n=15) and darunavir/r (n=6). The commonest symptoms (in these 53 patients) were nightmares or vivid dreams in 28 (44%), insomnia in 27 (43%), depression in 22 (35%), dizziness in 12 (19%), fatigue in 9 (19%) and anxiety in 8 (13%).
The notes highlighted six patients with CNS toxicity that had a prior documented history of depression, two of whom were on antidepressants. Of three patients who stopped ART without their doctors knowledge, one later presented with PCP and another with drug resistance. Another three individuals attempted suicide by drug overdose that they directly attributed to their CNS toxicity (one on concomitant HCV treatment).
Although limited information was available for many of these parameters, the time taken for many patients to switch is important to highlight. This is likely to be for many factors, but routinely accessing patients on efavirenz-based combinations for common symptoms (sleep disturbance, depression, dizziness, fatigue and anxiety) will be important to ensure optimal patient care.
Some of these examples, with commonly prescribed drugs at an extensively experienced centre, were clearly traumatic and avoidable, given the wide range of alternative options.
The importance of individualising care in the context of broadly prescriptive treatment guidelines is also clear.
Scourfield A et al. Discontinuation of Atripla as first-line therapy in HIV-1 infected individuals. Concise communication. AIDS, published ahead of print.
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