Raltegravir Inclusion Decreases CD4 T-Cells Intra-Cellular Viral Load and Increases CD4 and CD28 Positive T-Cells in Selected HIV Patients

被引:1
作者
Kumar, Gaurav [1 ,2 ]
Cottalorda-Dufayard, Jacqueline [3 ]
Garraffo, Rodolphe [4 ]
De Salvador-Guillouet, Francine [5 ]
Cua, Eric [5 ]
Roger, Pierre-Marie [1 ,5 ,6 ]
机构
[1] Univ Nice Sophia Antipolis, Unite 576, Ctr Hosp Univ Nice, Inst Natl Sante & Rech Med, F-06200 Nice, France
[2] Oklahoma Med Res Fdn, Arthrit & Clin Immunol, 825 NE 13th St, Oklahoma City, OK 73104 USA
[3] Univ Nice Sophia Antipolis, Virol, Hop Archet 2, Ctr Hosp Univ Nice, F-06200 Nice, France
[4] Univ Nice Sophia Antipolis, Pharmacol, Hop Pasteur, Ctr Hosp Univ Nice, F-06200 Nice, France
[5] Univ Nice Sophia Antipolis, Infectiol, Hop Archet 1, Ctr Hosp Univ Nice, F-06200 Nice, France
[6] Ctr Hosp Univ Pointe A Pitre, Serv Malad Infect & Trop, F-97159 Pointe A Pitre, Guadeloupe, France
关键词
HIV infection; raltegravir; CD4; T-cells; pharmacokinetics; viral load; HUMAN-IMMUNODEFICIENCY-VIRUS; MONOCYTE-DERIVED MACROPHAGES; INFECTED PATIENTS; ANTIRETROVIRAL THERAPY; COMBINATION THERAPY; ACTIVATION MARKERS; DOWN-REGULATION; UP-REGULATION; INTENSIFICATION; REPLICATION;
D O I
10.3390/cells11020208
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Raltegravir (RLT) prevents the integration of HIV DNA in the nucleus, but published studies remain controversial, suggesting that it does not decrease proviral DNA. However, there are only a few studies focused on virus-targeted cells. We aimed our study on the impact of RLT inclusion on total intra-cellular viral DNA (TID) in cellular subsets and immune effects in patients with newly acquired undetectable plasmatic viral load (UVL). Six patients having UVL using an antiretroviral combination for 6 months and CD4 T-cells > 350/mL and <500/mL were selected to receive RLT for 3 months from M0 to M3. Patients had 7 sequential viro-immunological determinations from M-1 to M5. Immune phenotypes were determined by flow cytometry and TID quantification was performed using PCR assay on purified cells. TID (median values) at the initiation of RLT in CD4 T-cells was 117 copies/millions of cells, decreased to 27.5 on M3, and remained thereafter permanently under the cut-off (<10 copies/millions of cells) in 4 out of 6 patients. This was associated with an increase of CD4 and CD4 + CD28+ T-cells and a decrease of HLA-DR expression and apoptosis of CD4 T-cells. RLT inclusion led to decreases in the viral load along with positive immune reconstitution, mainly for CD4 T-cells in HIV patients.
引用
收藏
页数:13
相关论文
共 49 条
[1]   Reduced antiretroviral drug efficacy and concentration in HIV-infected microglia contributes to viral persistence in brain [J].
Asahchop, Eugene L. ;
Meziane, Oussama ;
Mamik, Manmeet K. ;
Chan, Wing F. ;
Branton, William G. ;
Resch, Lothar ;
Gill, M. John ;
Haddad, Elie ;
Guimond, Jean V. ;
Wainberg, Mark A. ;
Baker, Glen B. ;
Cohen, Eric A. ;
Power, Christopher .
RETROVIROLOGY, 2017, 14
[2]   Upregulation of fas ligand expression by human immunodeficiency virus in human macrophages mediates apoptosis of uninfected T lymphocytes [J].
Badley, AD ;
McElhinny, JA ;
Leibson, PJ ;
Lynch, DH ;
Alderson, MR ;
Paya, CV .
JOURNAL OF VIROLOGY, 1996, 70 (01) :199-206
[3]   LYMPHOCYTE-ACTIVATION IN HIV-1 INFECTION .2. FUNCTIONAL DEFECTS OF CD28- T-CELLS [J].
BORTHWICK, NJ ;
BOFILL, M ;
GOMBERT, WM ;
AKBAR, AN ;
MEDINA, E ;
SAGAWA, K ;
LIPMAN, MC ;
JOHNSON, MA ;
JANOSSY, G .
AIDS, 1994, 8 (04) :431-441
[4]   HIV-1 replication and immune dynamics are affected by raltegravir intensification of HAART-suppressed subjects [J].
Buzon, Maria J. ;
Massanella, Marta ;
Llibre, Josep M. ;
Esteve, Anna ;
Dahl, Viktor ;
Puertas, Maria C. ;
Gatell, Josep M. ;
Domingo, Pere ;
Paredes, Roger ;
Sharkey, Mark ;
Palmer, Sarah ;
Stevenson, Mario ;
Clotet, Bonaventura ;
Blanco, Julia ;
Martinez-Picado, Javier .
NATURE MEDICINE, 2010, 16 (04) :460-U143
[5]   The importance of monocytes and macrophages in HIV pathogenesis, treatment, and cure [J].
Campbell, Jennifer H. ;
Hearps, Anna C. ;
Martin, Genevieve E. ;
Williams, Kenneth C. ;
Crowe, Suzanne M. .
AIDS, 2014, 28 (15) :2175-2187
[6]   Resident memory T cells are a cellular reservoir for HIV in the cervical mucosa [J].
Cantero-Perez, Jon ;
Grau-Exposito, Judith ;
Serra-Peinado, Carla ;
Rosero, Daniela A. ;
Luque-Ballesteros, Laura ;
Astorga-Gamaza, Antonio ;
Castellvi, Josep ;
Sanhueza, Tamara ;
Tapia, Gustavo ;
Lloveras, Belen ;
Fernandez, Marco A. ;
Prado, Julia G. ;
Sole-Sedeno, Josep M. ;
Tarrats, Antoni ;
Lecumberri, Carla ;
Manalich-Barrachina, Laura ;
Centeno-Mediavilla, Cristina ;
Falco, Vicenc ;
Buzon, Maria J. ;
Genesca, Meritxell .
NATURE COMMUNICATIONS, 2019, 10 (1)
[7]   Monocyte-derived macrophages and myeloid cell lines as targets of HIV-1 replication and persistence [J].
Cassol, Edana ;
Alfano, Massimo ;
Biswas, Priscilla ;
Poli, Guido .
JOURNAL OF LEUKOCYTE BIOLOGY, 2006, 80 (05) :1018-1030
[8]   HIV infection-associated immune activation occurs by two distinct pathways that differentially affect CD4 and CD8 T cells [J].
Catalfamo, Marta ;
Di Mascio, Michele ;
Hu, Zonghui ;
Srinivasula, Sharat ;
Thaker, Vishakha ;
Adelsberger, Joseph ;
Rupert, Adam ;
Baseler, Michael ;
Tagaya, Yutaka ;
Roby, Gregg ;
Rehm, Catherine ;
Follmann, Dean ;
Lane, H. Clifford .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (50) :19851-19856
[9]   Kinetics of response in lymphoid tissues to antiretroviral therapy of HIV-1 infection [J].
Cavert, W ;
Notermans, DW ;
Staskus, K ;
Wietgrefe, SW ;
Zupancic, M ;
Gebhard, K ;
Henry, K ;
Zhang, ZQ ;
Mills, R ;
McDade, H ;
Goudsmit, J ;
Danner, SA ;
Haase, AT .
SCIENCE, 1997, 276 (5314) :960-964
[10]   Effect of raltegravir intensification on HIV proviral DNA in the blood and gut mucosa of men on long-term therapy: a randomized controlled trial [J].
Chege, Duncan ;
Kovacs, Colin ;
la Porte, Charles ;
Ostrowski, Mario ;
Raboud, Janet ;
Su, Desheng ;
Kandel, Gabor ;
Brunetta, Jason ;
Kim, Connie J. ;
Sheth, Prameet M. ;
Kaul, Rupert ;
Loutfy, Mona R. .
AIDS, 2012, 26 (02) :167-174