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Lipodystrophy in PI-naive Patients Treated with RTI Combinations: Frequency and Risk Factors C. GOUJARD1*, A. S. LASCAUX2, A. DULIOUST3, F. BOUE3, J. F. DELFRAISSY1, A. SOBEL2, F. BOUFASSA1,4, and the LipoSud Study Group.
1Hosp. Bicêtre; 2Hosp. Mondor; 3Hosp. Béclère; and 4INSERM U292, Assistance Publique Hôpitaux de Paris, France Lipodystrophy (LD) has been extensively described in patients (pts) treated with combinations including PI. More recently, cases of LD have been reported in PI-naive pts treated with NRTI therapies.
Objectives: To describe the frequency of LD and risk factors associated with RTIs.
Methods: Cross-sectional study of 646 HIV-1 infected pts, routinely followed between 1/99 and 5/99, among whom 23.1% received NRTIs+/-NNRTI, without PI. Clinical examination for LD abnormalities, treatment history and biological features were recorded.
Results: 149 pts were PI-naive: 121 pts received two RTIs (81.2%; mean duration: 24.9 months), 26 pts three RTIs (17.4%; 17.7 months) and 2 pts four RTIs (1.3%; 30.3 months). A NRTIs regimen was prescribed in 87.9% of pts whereas a NRTIs+NNRTI regimen in 12.1%. The average duration of previous ART was 41.6 months (SD: 27.7) in the whole population. Mean CD4 cell count was 309/mL (SD: 142) and mean plasma HIV-RNA was 4.3 log copies /ml (SD: 0.9) before initiation of any treatment, while at study assessment, mean CD4 cell count was 485/mL (SD: 225) and mean plasma HIV-RNA was 2.8 log copies /ml (SD: 1.0). LD was diagnosed in 59 pts (39.6%): 28.8% reported fat wasting, 39.0% fat accumulation and 32.2% mixed LD. The frequency of LD was higher in combination regimens including stavudine (54.9%) than regimens including zidovudine (30.2%) (p=0.003). Mean duration of ART was longer in stavudine (48.1 months) than in zidovudine recipients (38.2 months) but the difference was of borderline significance (p=0.07). The frequency of LD in pts with NRTIs only was 37.4% compared to 55.6% in pts receiving NRTIs+NNRTI regimens (p=0.14). Fasting metabolic variables (cholesterol, triglycerides and glucose) were identical in LD and non LD pts.
Conclusions: This study confirms that typical LD features can be observed in PI-naive pts, although less frequently than in pts treated with PI-including combinations. Use of stavudine and duration of previous treatment are associated with lipodystrophy occurrence. Although controversial, a NRTI mitochondrial toxicity has been proposed as a mechanism for LD in these patients.
Key Words: Lipodystrophy, RTIs
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