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Raltegravir (Isentress) Can Cause Central Nervous System Side Effects for People with HIV

The HIV integrase inhibitor raltegravir (brand name Isentress) is generally safe and well-tolerated, but it can cause central nervous system (CNS) symptoms such as insomnia, dizziness, and mood changes, especially when used with other drugs that raise its levels in the body, researchers reported in the October 1, 2012, advance online edition of AIDS.

CNS side effects ranging from abnormal vivid dreams to anxiety and depression are most commonly associated with efavirenz (Sustiva, also in the Atripla combination pill), but they may also occur with other HIV drugs.

Giordano Madeddu from the University of Sassari and fellow investigators with the Italian Coordination Group for the Study of Allergies and HIV infection (CISAI) conducted a study of CNS symptoms in more than 400 people with HIV. A majority (about 60%) were men, the median age was 46 years, and the average CD4 T-cell count was 378 cells/mm³.

The researchers performed a medical record review and asked participants every 6 months whether they experienced CNS symptoms including dizziness, headaches, mood changes, and sleep disturbances. Follow-up continued for a median of 23 months.

Results

• 47 of 453 patients studied, or 10.4%, developed at least 1 drug-related CNS symptom.
• 4 participants discontinued treatment for this reason.
• CNS symptoms were significantly more likely when raltegravir was used with other drugs that increase raltegravir blood concentrations:

o   Tenofovir (Viread, also in the Truvada, Atripla, Complera, and Stribild coformulations): odds ratio (OR) 1.9, or nearly twice the risk.

o   Proton pump inhibitors such as omeprazole (Prilosec), esomeprazole (Nexium), lansoprazole (Prevacid), orpantoprazole (Protonix): OR 3.4, or more than 3 times higher risk.

"[O]ur data suggest a possible correlation between high raltegravir plasma concentrations and CNS symptoms and therefore [recommend] their monitoring in clinical practice," the study authors concluded.

In their discussion, they advised "careful evaluation of patients with psychiatric disease prior to starting raltegravir and a continuous monitoring of CNS symptoms in clinical practice in those starting the drug," as well as checking for drug-drug interactions that could raise raltegravir levels.

10/30/12

Reference

G Madeddu, B Menzaghi, E Ricci, et al (C.I.S.A.I Group). Raltegravir central nervous system tolerability in clinical practice: results from a multicenter observational study. AIDS. October 1, 2012 (Epub ahead of print)