Human immunodeficiency virus protease inhibitors accumulate into cultured human adipocytes and alter expression of adipocytokines.

Early human evidence such as case series or small samples is exploring possible benefits.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Lipodystrophic syndrome is a major side effect of highly active antiviral therapy. Fat tissue redistribution is associated with changes in adipocyte gene expression and in circulating levels of adipocytokines involved in the development of insulin resistance. However, the evidence that HIV drugs accumulate into human adipocytes and have a direct effect on the expression of adipocyte-specific genes is still lacking. To address these questions, we used adipocytes derived from adult stem (hMADS) cells isolated from human adipose tissue. We showed by ELISA that two inhibitors of the HIV protease, lopinavir and ritonavir, accumulated at similar levels during the development of hMADS cells in adipocytes, whereas a non-nucleoside reverse transcriptase inhibitor, the nevirapine, accumulated at lower levels. Two fluorescent protease inhibitors then have been generated to investigate their subcellular localization. The data showed that HIV drugs accumulated into adipocytes and displayed various effects on hMADS cell-derived adipocytes. Indinavir, amprenavir, and nevirapine did not alter differentiation of precursor cells. In contrast, lopinavir, saquinavir, and ritonavir inhibited the development of preadipocytes into adipocytes. In adipocytes, amprenavir increased leptin expression and ritonavir was able to up-regulate tumor necrosis factor-alpha, interleukin 6, and leptin expression an

Evidence level

Early human evidence such as case series or small samples is exploring possible benefits.

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