Antiretroviral-treated HIV-1 patients can harbour resistant viruses in CSF despite an undetectable viral load in plasma

Background: HIV therapy reduces the CSF HIV RNA viral load (VL) and prevents disorders related to HIV encephalitis. However, these brain disorders may persist in some cases. A large population of antiretroviral-treated patients who had a VL > 1.7 log(10) copies/mL in CSF with detectable or undetectable VL in plasma associated with cognitive impairment was studied, in order to characterize discriminatory factors of these two patient populations. Methods: Blood and CSF samples were collected at the time of neurological disorders for 227 patients in 22 centres in France and 1 centre in Switzerland. Genotypic HIV resistance tests were performed on CSF. The genotypic susceptibility score was calculated according to the last Agence Nationale de Recherche sur le Sida et les he patites virales Action Coordonnee 11 (ANRS AC11) genotype interpretation algorithm. Results: Among the 227 studied patients with VL > 1.7 log10 copies/mL in CSF, 195 had VL detectable in plasma [median (IQR) HIV RNA was 3.7 (2.7-4.7) log10 copies/mL] and 32 had discordant VL in plasma (VL < 1.7 log(10) copies/mL). The CSF VL was lower (median 2.8 versus 4.0 log(10) copies/mL; P<0.001) and the CD4 cell count was higher (median 476 versus 214 cells/mm(3); P<0.001) in the group of patients with VL < 1.7 log(10) copies/mL in plasma compared with patients with plasma VL > 1.7 log(10) copies/mL. Resistance to antiretrovirals was observed in CSF for the two groups of patients. Conclusions: Fourteen percent of this population of patients with cognitive impairment and detectable VL in CSF had well controlled VL in plasma. Thus, it is important to explore CSF HIV (VL and genotype) even if the HIV VL is controlled in plasma because HIV resistance may be observed.