HIV and antiretroviral drug distribution in plasma and fat tissue of HIV-infected patients with lipodystrophy

• Published in: AIDS (London) Vol. 16; no. 18; pp. 2419 - 2424
• Main Authors: DUPIN, Nicolas, BUFFET, Marc, MARCELIN, Anne-Geneviève, LAMOTTE, Claire, GORIN, Isabelle, AIT-ARKOUB, Zaina, TRELUYER, Jean-Marc, BUI, Patrick, CALVEZ, Vincent, PEYTAVIN, Gilles
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 06.12.2002
• Subjects: Adipocytes - virology; Adipose Tissue - chemistry; Adipose Tissue - virology; AIDS/HIV; Anti-HIV Agents - analysis; Anti-HIV Agents - blood; Anti-HIV Agents - therapeutic use; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiretroviral Therapy, Highly Active; Antiviral agents; Biological and medical sciences; CD4 Lymphocyte Count; Female; HIV Infections - blood; HIV Infections - drug therapy; HIV-1 - genetics; HIV-1 - isolation & purification; HIV-Associated Lipodystrophy Syndrome - blood; Human viral diseases; Humans; Infectious diseases; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Prospective Studies; Protease Inhibitors - analysis; RNA, Viral - analysis; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Immunopathology; antiretroviral drug concentration; Skin disease; Adipose tissue; Retroviridae; AIDS; Concentration; Immune deficiency; Lentivirus; Blood plasma; Infection; Virus; HIV; Viral disease; Distribution; Antiviral; Lipodystrophy; Adipose tissue disorders; Human immunodeficiency virus; Pharmacokinetics; HAART
• ISSN: 0269-9370; 1473-5571
• DOI: 10.1097/00002030-200212060-00006

To determine HIV and antiretroviral drug distribution in plasma and fat tissue of HIV-infected patients with lipodystrophy. Twenty-three consecutive HIV-infected patients (median age, 43 years; male:female ratio, 18:5; median CD4 cell count, 419 x 10(6)/l) undergoing Coleman's lipostructure were enrolled prospectively in this study. HIV-1 RNA and plasma concentration of antiretroviral drugs were determined blindly in plasma and adipocyte lysate samples. HIV-1 proviral DNA was detected by nested PCR in fresh frozen adipocytes. Mean plasma HIV-1 RNA was significantly higher than that in adipocyte lysate samples (this was below the limit of detection in all patients tested). HIV-1 proviral DNA was positive in two out of 18 adipocyte samples with a level between 2 and 5 copies; the distribution seemed to be specific and comparable within each therapeutic class--protease inhibitors (PI) or non-nucleoside reverse transcriptase inhibitors (NNRTI). NNRTI concentrations in adipocyte lysates were approximately 100-fold higher than those of PI. Efavirenz may accumulate in fat tissue as a function of treatment duration. Our results suggest that HIV does not replicate and does not integrate its genome in fat tissue in patients with fat redistribution abnormalities. In patients with effective nadir plasma concentrations of PI and NNRTI, determination of concentration in adipocyte lysates suggests that PI may diffuse in fat tissue with the same pattern of distribution for all structurally related components tested. NNRTI present a high affinity for fat tissue and may accumulate in this compartment.