Study to determine the improvement in neuropsychiatric symptoms after changing the responsible antiretroviral drug to nevirapine: the RELAX study
Authors: Pedrol E , Tasias M , Clotet B , Llibre J , Curran A , Guardiola J , Deig E , Guelar A 
Published: November 2012

Objectives

Primary ‐ evaluate the improvement in psychiatric symptoms attributable to changing the antiretroviral drug responsible for such symptoms to nevirapine (NVP). The tools used were a sleep test (the Pittsburgh Sleep Quality Index [PSQI]) and the Hospital Anxiety and Depression Scale (HADS). Secondary ‐ determine the neuropsychiatric disorders and evaluate adherence to treatment and quality of life.

Methods

Prospective, observational post‐authorisation study that included HIV‐1 patients from 36 Spanish hospitals who satisfied the following criteria: age over 18 years; change of antiretroviral treatment to NVP due to CNS side‐effects; a PSQI score >5 (significant sleep disturbance); a HADS score ≥10 on the day of starting NVP treatment; and no psychoactive drug treatment initiated during the 6 weeks prior to starting treatment with NVP. Other data gathered from the patients included clinical and demographic details and administration of the Epworth somnolence scale, the Medical Outcomes Study‐short form 30 items (MOS‐SF‐30) quality of life scale and the Simplified Medication Adherence Questionnaire (SMAQ). Evaluations were performed at baseline, 1 and 3 months after the change.

Results

129 patients were included (73.6% men; mean age, 43.2 ± 9.8 years; 36.5% homosexual, 30.2% heterosexual; 28.7% drug users; 38% AIDS; 33.3% co‐infection). The drug changed was efavirenz in 89.9% of cases. The reason for the change was sleep disturbances in 75.2%, anxiety in 65.1%, other psychiatric disturbances in 38.7%, attention disturbances in 31%, and other reasons in 31%; a mean of 2.4 neuropsychiatric disturbances were detected in each patient. CD4 rose from 582 ± 261 to 619 ± 299 (non‐significant difference). Only three patients had developed an HIV viral load at the end of the study. The differences produced by the change are shown in Table 1. 29 patients withdrew from the study, for the following reasons: 9 for NVP‐related toxicity (7 cases of rash and 2 of hepatitis); 7 for loss to follow‐up; 4 for voluntary withdrawal; 9 for other reasons.

Baseline (n=129)
1 month (n=100)
3 months (n=100)
p value, baseline‐1 mo
p value, baseline‐3 mo

Percentage of patients with a PSQI score >5, suggestive of a significant alteration of sleep
96.9%
60.7%
44%
<0.001
<0.001

Percentage of patients with clinical problems of anxiety and depression, HADS
86.8%
46.4%
32%
<0.001
<0.001

Mean score and percentage of patients with normal somnolence, Epworth scale
8.3±4.7/(65.9%)
6±4 (89.3%)
5.5±3.6 (91%)
<0.001/0.001
<0.001/0.001

Percentage of compliant patients, SMAQ
65.9%
75.9%
81%
0.036
0.013

Percentage of patients with a good quality of life, MOS‐SF‐30
57.5±18.9%
69.8±19.7%
73.6±16.8%
<0.001
<0.001

Discussion

The study shows that the change to NVP from a drug that is causing neuropsychiatric disturbances (principally, efavirenz) is effective in resolving those disturbances, with an improvement in all the parameters studied (quality of sleep, anxiety/depression and somnolence). This leads to better adherence and a better quality of life with no detriment to their immunological and virological control.