Switch of predicted HIV-1 tropism in treated subjects and its association with disease progression

Dynamics of human immunodeficiency virus type 1 (HIV-1) tropism after antiretroviral therapy (ART) initiation and their association with disease progression are poorly investigated. This was a cohort study on subjects from the ICONA cohort receiving ART with persistently detectable (PD) or persistently undetectable (PU) viral load (VL) and with stored plasma or peripheral blood mononuclear cell (PBMC) samples at 2 time-points (T1, T2) after ART initiation. HIV-1 co-receptor tropism was determined by V3-loop sequencing and the geno2pheno algorithm. A switch in viral tropism was defined if the tropism classification at T2 differed from that observed at T1. Time to disease progression, defined as the occurrence of a new acquired immune deficiency syndrome (AIDS)-defining event/death from T2, was also evaluated. One hundred ninety-five patients were analyzed (124 PD, 71 PU). Over a median follow-up of 22.6 (19.8-28.1) months, PD and PU patients showed similar rates (95% confidence interval) of switch to a non-R5 virus [PD: 6.9 (3.7-11.2)/100-person-years of follow-up (PYFU); PU: 8.0 (3.4-14.5)/100-PYFU; P=0.63] and of switch to a R5 virus [PD: 15.4 (7.3-26.4)/100-PYFU; PU: 8.1 (2.5-16.7)/100-PYFU; P=0.38]. Switch to non-R5 virus was predicted by nadir CD4+ before T1. Twenty-two (18%) PD and 4 (6%) PU subjects experienced disease progression (P=0.02). The risk of disease progression was independently associated with a switch in co-receptor tropism (adjusted hazard ratio=4.06, 95% CI: 1.20-13.80, P=0.03) as well as age, AIDS diagnosis, nadir CD4+ before T2, current CD4+, and VL. Switch of HIV-1 tropism under ART occurs in both directions, with similar rates in subjects with PD or PU VL and it might be predictive of future unfavorable clinical outcome.