Skeletal muscle toxicity and raltegravir

An Australian study reported higher rates of muscle toxicity associated with raltegravir in asymtomatic patients.

Prompted by higher rates of grade 3/4 creatinine kinase (CK) in registrational studies for raltegravir, and rare cases of rhabdomyolysis, Frederick Lee from St Vincent’s, Sydney and colleagues looked at differences in muscle toxicity in 318 HIV positive patients, half who were using raltegravir and half on non-raltegravir combinations.

Muscle toxicity was categorised in four ways: isolated CK elevation, myalgia without muscle weakness, proximal myopathy on examination, or rhabdomyolysis.

Characteristics of the group included: male (98%), white (89%), median age 51 years, median CD4 count 585 cells/mm3 with 91% undetectable (<50 copies/mL). Raltegravir has been used for a mean duration of 28 months. Recent vigorous exercise was reported by 42% and statins by 24%.

A higher proportion of patients on raltegravir reported at least one feature of muscle toxicity (37% vs 19%, p <0.01). Results by category were: CK elevation 14% vs 16% (NS), mylagia without weakness 19% vs 3%, p< 0.01 and proximal myopathy 4% vs 0, p=0.03, all raltgravir vs non-raltegravir respectively. No cases of rhabdomyolysis were seen.

Most CK elevations were grade 1 with the single grade 3/4 occurring in the non-raltegravir arm.

In multivariate analysis, only raltegravir use (OR 2.64; 95%CI: 1.57-4.45, p<0.01) and recent exercise (OR 2.26; 95%CI: 1.36-3.77, p<0.01) were independently associated with skeletal muscle toxicity. However, neither raltegravir drug levels nor duration of use were associated with any parameter.

Lee FJ et al. Skeletal muscle toxicity associated with raltegravir-based combination antiretroviral therapy in HIV-infected adults. 14th IWCADR, 19-21 July 2012, Washington. Oral abstract 015. Antiviral therapy 2012; 17 Suppl 2:A13.