Adipocyte dysfunction in response to antiretroviral therapy: clinical, tissue and in-vitro studies.
OBJECTIVE
Lipodystrophy, a major complication of antiretroviral therapy, is an adipose tissue disease involving severe alterations of fat tissue distribution and metabolic functions. Protease inhibitors and nucleoside reverse transcriptase inhibitors (NRTIs) are implicated to different extents. We review recent findings on the toxicity of HIV antiretroviral drugs at the fat cell and tissue levels and point out the underlying pathophysiological mechanisms.


RESULTS
Peripheral fat loss and central accumulation are distinct phenomena. Lipoatrophy is the dominant feature after prolonged treatment. Protease inhibitors and NRTIs promote fat tissue disease by separate mechanisms that converge and worsen adipocyte dysfunctions. The pathogenesis involves the mitochondrial toxicity of NRTIs and the adverse effects of protease inhibitors and NRTIs on adipocyte differentiation status, insulin sensitivity, survival and adipokine secretion. Oxidative stress and local inflammation induced by these drugs may participate in the setup of lipodystrophy. Partial and slow reversion can be obtained by switch strategies or drug therapy.


CONCLUSIONS
Patients using antiviral therapy develop severe fat tissue damage. The toxicity of protease inhibitors and NRTIs remains an important issue for patients and clinicians. Since fat tissue regeneration is difficult, it is important to understand the mechanisms by which these drugs alter fat tissue depots.
INSERM, U680, 75012 Paris, France. caron@st-antoine.inserm.fr
Martine
M
Caron
Corinne
C
Vigouroux
Jean Philippe
JP
Bastard
Jacqueline
J
Capeau