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.