Patient Preference, Sleep Quality, and Anxiety/Depression: A Comparison of Raltegravir and Efavirenz (Switch-ER)

• Levels of daytime sleepiness [ Time Frame: baseline, week 2 and week 4 ] [ Designated as safety issue: Yes ]
• Sleep Quality [ Time Frame: baseline, week 2 and week 4 ] [ Designated as safety issue: Yes ]
• Patient preference [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
• Symptoms of depression, anxiety and stress will be assessed [ Time Frame: baseline, week 2 and week 4 ] [ Designated as safety issue: Yes ]

Efavirenz causes neuropsychiatric side effects and sleep disturbance, including vivid dreams, dizziness, and abnormal tiredness. These symptoms are frequent during the first weeks of treatment, with subsequent attenuation but may not completely resolve even years after efavirenz initiation.

The investigators plan a four week, randomized, placebo-controlled, double-blind study. In group 1, efavirenz will be replaced with efavirenz placebo plus raltegravir, in group 2, efavirenz would be continued, and raltegravir placebo given in addition. After two weeks, patients in group 1 would switch to the regimen of group 2, and vice versa.

The primary endpoint of the trial will be patient preference. Sleep quality, daytime sleepiness, and anxiety will also be investigated.

• Sleep Disorders
• HIV Infections

• Drug: Raltegravir for the first 2 weeks
  Patient receives raltegravir and efavirenz placebo during the first 2 weeks
• Drug: Efavirenz for the last 2 weeks
  Patient receives efavirenz and raltegravir placebo during the last 2 weeks
• Drug: Efavirenz for the first 2 weeks
  Efavirenz and raltegravir placebo for the first 2 weeks
• Drug: Raltegravir for the last 2 weeks
  Raltegravir and efavirenz placebo for the last 2 weeks

• Experimental: Raltegravir first
  Patients treated with Raltegravir for first 2 weeks
  Interventions:

  • Drug: Raltegravir for the first 2 weeks
  • Drug: Efavirenz for the last 2 weeks
• Experimental: Efavirenz first
  Patients treated with Efavirenz for first 2 weeks
  Interventions:

  • Drug: Efavirenz for the first 2 weeks
  • Drug: Raltegravir for the last 2 weeks

Inclusion Criteria:

• Adult patients > 18 years
• Signing the study consent form and agree to change ART regimen
• Stable HAART including EFV since at least 3 months
• HIV-RNA below 50 copies for at least 3 months

Exclusion Criteria:

• No major psychiatric disease (psychosis, severe depression) diagnosed before the initiation of EFV
• Mentally incompetent patients
• Pregnancy or lactation Women of childbearing potential must use one or two reliable contraceptive methods during the trial, from day 1 to the end of week 12. Acceptable methods include the birth control pill, IUD, condoms with spermicides. Non-acceptable methods include (non-exhaustive list): Withdrawal, calendar (Onigo method), or spermicides alone.

• Concomitant renal or hepatic disease:

  • Creatinine above 150 micromol/L
  • Transaminases above 5 times upper normal limit
  • Prothrombin (Quick) value below 50%

• University of Bern
• University of Lausanne Hospitals
• Hospital Lugano
• University Hospital, Basel, Switzerland
• Hospital of Neuchâtel
• University Hospital, Zürich