Persistence of CCR5 usage among primary human immunodeficiency virus isolates of individuals receiving intermittent interleukin-2.
OBJECTIVE
To investigate the impact of intermittent interleukin-2 (IL-2) plus combination antiretroviral therapy (cART) on HIV-1 entry co-receptor use.


METHODS
Primary HIV-1 isolates were obtained from 54 HIV-1-positive individuals at baseline and after 12 months using co-cultivation of peripheral blood mononuclear cells (PBMC) with activated PBMC of HIV-negative healthy donors. HIV-1 co-receptor use was determined on U87-CD4 cells.


RESULTS
Fourteen out of the 21 (67%) IL-2-treated individuals harbouring a primary CCR5-dependent (R5) HIV-1 isolate at baseline confirmed an R5 virus isolation after 12 months in contrast to 3 out of 7 (43%) of those receiving cART only. After 12 months, only 1 R5X4 HIV-1 isolate was obtained from 21 cART+IL-2-treated individuals infected with an R5 virus at entry (5%) vs. 2/7 (29%) patients receiving cART alone, as confirmed by a 5-year follow-up on some individuals.


CONCLUSIONS
Intermittent IL-2 administration plus cART may prevent evolution towards CXCR4 usage in individuals infected with R5 HIV-1.
Ghezzi
S
S
Viral Pathogens and Biosafety Unit, Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, Milano, Italy.
Pacciarini
F
F
Nozza
S
S
Racca
S
S
Mariani
S A
SA
Vicenzi
E
E
Lazzarin
A
A
Veglia
F
F
Tambussi
G
G
Poli
G
G
D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes; D002478:Cells, Cultured; D018849:Controlled Clinical Trials as Topic; D018450:Disease Progression; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D015497:HIV-1 / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage*; D007963:Leukocytes, Mononuclear; D019713:Receptors, CCR5 / Q000378:metabolism*; D014766:Viremia / Q000175:diagnosis
D044966:Anti-Retroviral Agents; D007376:Interleukin-2; D019713:Receptors, CCR5