Measuring the latent reservoir in vivo

被引:69
作者
Massanella, Marta [1 ]
Richman, Douglas D. [1 ,2 ]
机构
[1] Univ Calif San Diego, Room 329,Stein Clinical Sci Bldg,9500 Gilman Dr, La Jolla, CA 92093 USA
[2] VA San Diego Healthcare Syst, Room 329,Stein Clinical Sci Bldg,9500 Gilman Dr, La Jolla, CA 92093 USA
关键词
CD4(+) T-CELLS; ACTIVE ANTIRETROVIRAL THERAPY; HIGHLY SENSITIVE METHODS; BLOOD MONONUCLEAR-CELLS; HIV-INFECTED PATIENTS; VIRUS TYPE-1 RNA; RALTEGRAVIR INTENSIFICATION; COMBINATION THERAPY; VIRAL PERSISTENCE; CONTROLLED-TRIAL;
D O I
10.1172/JCI80567
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Current efforts toward achieving a cure for HIV are focused on developing strategies to eliminate latently infected CD4(+) T cells, which represent the major barrier to virus eradication. Sensitive, precise, and practical assays that can reliably characterize and measure this HIV reservoir and can reliably measure the impact of a candidate treatment strategy are essential. PCR-based procedures for detecting integrated HIV DNA will overestimate the size of the reservoir by detecting replication-incompetent proviruses; however, viral outgrowth assays underestimate the size of the reservoir. Here, we describe the attributes and limitations of current procedures for measuring the HIV reservoir. Characterizing their relative merits will require rigorous evaluation of their performance characteristics (sensitivity, specificity, reproducibility, etc.) and their relationship to the results of clinical studies.
引用
收藏
页码:464 / 472
页数:9
相关论文
共 97 条
  • [1] Valproic acid without intensified antiviral therapy has limited impact on persistent HIV infection of resting CD4+ T cells
    Archin, Nancy M.
    Eron, Joseph J.
    Palmer, Sarah
    Hartmann-Duff, Anne
    Martinson, Jeffery A.
    Wiegand, Ann
    Bandarenko, Nicholas
    Schmitz, John L.
    Bosch, Ronald J.
    Landay, Alan L.
    Coffin, John M.
    Margolis, David M.
    [J]. AIDS, 2008, 22 (10) : 1131 - 1135
  • [2] Residual human immunodeficiency virus type 1 viremia in some patients on Antiretroviral therapy is dominated by a small number of invariant clones rarely found in circulating CD4+ T cells
    Bailey, JR
    Sedaghat, AR
    Kieffer, T
    Brennan, T
    Lee, PK
    Wind-Rotolo, M
    Haggerty, CM
    Kamireddi, AR
    Liu, Y
    Lee, J
    Persaud, D
    Gallant, JE
    Cofrancesco, J
    Quinn, TC
    Wilke, CO
    Ray, SC
    Siliciano, JD
    Nettles, RE
    Siliciano, RF
    [J]. JOURNAL OF VIROLOGY, 2006, 80 (13) : 6441 - 6457
  • [3] Compartmentalization, Viral Evolution, and Viral Latency of HIV in the CNS
    Bednar, Maria M.
    Sturdevant, Christa Buckheit
    Tompkins, Lauren A.
    Arrildt, Kathryn Twigg
    Dukhovlinova, Elena
    Kincer, Laura P.
    Swanstrom, Ronald
    [J]. CURRENT HIV/AIDS REPORTS, 2015, 12 (02) : 262 - 271
  • [4] Lymphocyte numbers and subsets in the human blood - Do they mirror the situation in all organs?
    Blum, Katrin S.
    Pabst, Reinhard
    [J]. IMMUNOLOGY LETTERS, 2007, 108 (01) : 45 - 51
  • [5] Comparison of digital PCR platforms and semi-nested qPCR as a tool to determine the size of the HIV reservoir
    Bosman, K. J.
    Nijhuis, M.
    van Ham, P. M.
    Wensing, A. M. J.
    Vervisch, K.
    Vandekerckhove, L.
    De Spiegelaere, W.
    [J]. SCIENTIFIC REPORTS, 2015, 5
  • [6] Quantitation of HIV DNA integration: Effects of differential integration site distributions on Alu-PCR assays
    Brady, Troy
    Kelly, Brendan J.
    Male, Frances
    Roth, Shoshannah
    Bailey, Aubrey
    Malani, Nirav
    Gijsbers, Rik
    O'Doherty, Una
    Bushman, Frederic D.
    [J]. JOURNAL OF VIROLOGICAL METHODS, 2013, 189 (01) : 53 - 57
  • [7] T-cell subsets that harbor human immunodeficiency virus (HIV) in vivo: Implications for HIV pathogenesis
    Brenchley, JM
    Hill, BJ
    Ambrozak, DR
    Price, DA
    Guenaga, FJ
    Casazza, JP
    Kuruppu, J
    Yazdani, J
    Migueles, SA
    Connors, M
    Roederer, M
    Douek, DC
    Koup, RA
    [J]. JOURNAL OF VIROLOGY, 2004, 78 (03) : 1160 - 1168
  • [8] New ex vivo approaches distinguish effective and ineffective single agents for reversing HIV-1 latency in vivo
    Bullen, C. Korin
    Laird, Gregory M.
    Durand, Christine M.
    Siliciano, Janet D.
    Siliciano, Robert F.
    [J]. NATURE MEDICINE, 2014, 20 (04) : 425 - +
  • [9] Burnet FM, 1936, MED RES COUNCIL SPEC, P220
  • [10] Measuring covert HIV replication during HAART: the abundance of 2-LTR circles is not a reliable marker
    Bushman, F
    [J]. AIDS, 2003, 17 (05) : 749 - 750