The central nervous system is a viral reservoir in simian immunodeficiency virus--infected macaques on combined antiretroviral therapy: a model for human immunodeficiency virus patients on highly active antiretroviral therapy.
This study used a simian immunodeficiency virus (SIV)-macaque model to determine whether virus persists in the central nervous system (CNS) of human immunodeficiency virus (HIV)-infected individuals in which plasma viral load has been suppressed by highly active antiretroviral therapy. SIV-infected macaques were treated with two reverse transcriptase inhibitors: PMPA (q- R-(2-phosphonomethoxypropyl)adenine)which does not cross the blood-brain barrier, and FTC (beta-2('),3(')-dideoxy-3 thia-5-fluorocytidine), which does. Viral DNA and RNA were quantitated in the brain after 6 months of suppression of virus replication in blood and cerebrospinal fluid (CSF). Viral DNA was detected in brain from all macaques, including those in which peripheral viral replication had been suppressed either by antiretroviral therapy or host immune responses. Significant neurological lesions were observed only in one untreated macaque that had active virus replication in the CNS. Expression of the inflammatory markers, major histocmopatibility complex (MHC) II and CD68 was significantly lower in macaques treated with PMPA/FTC. Thus, although antiretroviral treatment may suppress virus replication in the periphery and the brain and reduce CNS inflammation, viral DNA persists in the brain despite treatment. This suggests that the brain may serve as a long-term viral reservoir in HIV-infected individuals treated with antiretroviral drugs that suppress virus replication.
Clements
Janice E
JE
Retrovirus Laboratory, Department of Comparative Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. jclement@jhmi.edu
Li
Ming
M
Gama
Lucio
L
Bullock
Brandon
B
Carruth
Lucy M
LM
Mankowski
Joseph L
JL
Zink
M Christine
MC
D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015703:Antigens, CD / Q000096:biosynthesis; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis; D001921:Brain / Q000276:immunology / Q000473:pathology / Q000821:virology; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D007279:Injections, Subcutaneous; D008254:Macaca nemestrina; D063065:Organophosphonates / Q000008:administration & dosage / Q000627:therapeutic use*; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000134:cerebrospinal fluid; D016097:Simian Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000302:isolation & purification; D000068698:Tenofovir; D013997:Time Factors; D016047:Zalcitabine / Q000008:administration & dosage / Q000627:therapeutic use*; D000097382:CD68 Molecule
D000225:Adenine; D019380:Anti-HIV Agents; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D004279:DNA, Viral; D000949:Histocompatibility Antigens Class II; D063065:Organophosphonates; D012367:RNA, Viral; D000068698:Tenofovir; D016047:Zalcitabine; C067980:CD68 antigen, human; D000097382:CD68 Molecule