HIV and antiretroviral drug distribution in plasma and fat tissue of HIV-infected patients with lipodystrophy.
OBJECTIVE
To determine HIV and antiretroviral drug distribution in plasma and fat tissue of HIV-infected patients with lipodystrophy.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Dupin
Nicolas
N
Service de Dermatologie (CRPI), Université René Descartes, Paris V, Hôpital Tarnier-Cochin, 89 rue d'Assas, 75006 Paris, France.
Buffet
Marc
M
Marcelin
Anne-Geneviève
AG
Lamotte
Claire
C
Gorin
Isabelle
I
Ait-Arkoub
Zaina
Z
Tréluyer
Jean-Marc
JM
Bui
Patrick
P
Calvez
Vincent
V
Peytavin
Gilles
G
D017667:Adipocytes / Q000821:virology; D000273:Adipose Tissue / Q000737:chemistry / Q000821:virology*; D019380:Anti-HIV Agents / Q000032:analysis / Q000097:blood / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy*; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification; D039682:HIV-Associated Lipodystrophy Syndrome / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011480:Protease Inhibitors / Q000032:analysis; D012367:RNA, Viral / Q000032:analysis
D019380:Anti-HIV Agents; D011480:Protease Inhibitors; D012367:RNA, Viral