Lipodystrophy following antiretroviral therapy of primary HIV infection

Lipodystrophy has been extensively described in patients with advanced disease on long-term protease inhibitor therapy. We report lipodystrophy occurring in 20% of HIV-infected patients treated with antiretroviral therapy within 30 months of acute HIV seroconversion. Lipodystrophy syndrome, which consists of peripheral fat wasting, central fat accumulation and abnormal serum lipid and glycemic profiles has been extensively described in patients with chronic HIV disease on long-term antiretroviral therapy [1–3]. Although no unifying pathogenic process has been convincingly shown to account for these features, it has been variously purported to be a result of treatment-induced alterations in lipid receptor function, retinoic acid metabolism, or defects in mitochondrial function [3,4]. Although the contribution of antiretroviral therapy to the syndrome is becoming clearer, the impact of HIV stage and degree of immunodeficiency on the development of lipodystrophy remains unclear. Others have suggested that these features are a result of chronic HIV infection, chronic immunodeficiency, or recovery from immune dysfunction [5]. We reasoned that if lipodystrophy syndrome is related to antiretroviral therapy rather than the duration of HIV infection or the degree of immunodeficiency, the syndrome should also be seen in patients who commenced antiretroviral treatment during their HIV-seroconversion illness. We undertook to determine the prevalence of lipodystrophy in such patients. Data describing the type of antiretroviral therapy, the duration of therapy, the most recent CD4 cell count and viral load, patient- and physician-reported body shape changes and body composition were collected. For analysis, lipodystrophy was defined as any physician-assessed fat depletion (limbs, face, buttocks) or any fat accumulation (abdominal, breast, dorsocervical, lipoma). Forty-one patients who commenced treatment during acute seroconversion (mean 12 months before) were studied cross-sectionally over a 6 month period. All were homosexual men with a mean age of 38 years. The mean CD4 cell count was 920 cells/mm3 (SD 450), plasma HIV RNA was less than 400 copies/ml in 80% of patients at the time of survey and the mean time on antiretroviral therapy was 11.7 months (SD 8.4). The most frequent current antiretroviral regimen was one protease inhibitor with two nucleoside reverse transcriptase inhibitors (27 out of 41). Three patients were on no current antiretroviral therapy having discontinued therapy within the previous 3 months. Only three patients were protease inhibitor naive. Features of lipodystrophy were reported by 21 out of 41 (51%) patients; nine reported peripheral lipoatrophy and fat accumulation, seven reported peripheral lipoatrophy alone and five reported fat accumulation alone (trunk/breast/lipoma). Ten of these 21 patients reported changes in three or more body regions. Physician assessment confirmed lipodystrophy in eight (20%) patients with fewer sites identified. Patients with physician-assessed lipodystrophy were compared with those with no lipodystrophy (Table 1) and demonstrated no differences between groups for age, weight, exercise levels, CD4 cell count or viral load. The duration of treatment with any nucleoside reverse transcriptase inhibitor was significantly greater in the lipodystrophy group (median 17 months) compared with those with no lipodystrophy (median 8 months;P = 0.043). Similarly, the duration of protease inhibitor use was significantly greater in the lipodystrophy patient group (median 17 months) compared with those with no lipodystrophy (median 7 months;P = 0.015).Table 1: Clinician assessed lipodystrophy. This survey indicated that lipodystrophy is seen in early HIV disease treated with combination antiretroviral agents, and supports the theory that lipodystrophy is largely caused by antiretroviral therapy. These findings have implications for clinicians considering the commencement of combination antiretroviral therapy in patients with early HIV disease, in which long-term success will only result from long-term adherence to treatment. Prospective studies of this phenomena in patients with primary HIV infection are required to facilitate appropriate risk management decisions. John Miller Andrew Carr Don Smith Sean Emery Matthew G. Law Patricia Grey David A Cooper