To review current knowledge of viral reservoirs in the central nervous system (CNS) and identify the CNS-specific barriers and strategies to cure human immunodeficiency virus type 1 (HIV-1) within the brain.
The cumulative data of HIV-1 infection of the CNS support the ability of the CNS to act as a viral reservoir for HIV-1. The HIV-1 viral strains found in the CNS are distinct to those found in other parts of the body. These differences have been well documented for env and also extend to the viral promoter, the long terminal repeat, and influence the ability of the virus to replicate, establish latency and respond to latency-reversing agents (LRAs). In addition, the bioavailability and activity of LRAs and antiretrovirals within the CNS suggest altered properties compared with the blood, which may influence their effectiveness. Selected LRAs were shown to have reduced effectiveness against CNS-derived viral strains compared with blood-derived strains from the same patients. Finally, altered immune surveillance within the CNS may also interfere with the efficiency of cure strategies within this compartment.
Together, these data suggest that the CNS viral reservoir is unique and presents a distinct set of challenges that need to be overcome to ensure successful viral elimination within this compartment. Future studies will need to develop CNS-active LRAs and biomarkers to enable monitoring and evaluation of treatment outcomes within the CNS during HIV-1 cure clinical trials.
aCenter for Biomedical Research, Burnet Institute
bDepartment of Infectious Diseases, Monash University, Melbourne, Victoria
cDepartments of Neurology, Immunology and Infectious Diseases and Peter Duncan Neurosciences Unit, St Vincent's Centre for Applied Medical Research, St Vincent's Hospital, Sydney, New South Wales
dDepartment of Microbiology, Monash University, Clayton, Victoria
eDepartment of Medicine, Monash University, Melbourne, Victoria, Australia
Correspondence to Melissa J. Churchill, PhD, Centre for Biomedical Research, Burnet Institute, 85 Commercial Rd, Melbourne, 3004 VC, Australia. Tel: +61 3 9282 2175; e-mail: email@example.com