Mini Review Open Access
Volume 1 | Issue 1 | DOI: https://doi.org/10.33696/AIDS.1.001

CCR5 Inhibitors and HIV-1 Infection

  • 1Institute of Human Virology, University of Maryland School of Medicine, Baltimore, Maryland, USA
  • 2Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA
  • 3School of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA
+ Affiliations - Affiliations

*Corresponding Author

Olga S. Latinovic, olatinovic@ihv.umaryland.edu

Received Date: December 10, 2018

Accepted Date: December 12, 2018


Cellular components are attractive targets for antiviral therapy because they do not mutate as readily as do viral proteins do [1-3]. The identification of CCR5 as an HIV-1 coreceptor [4-7], facilitated by the discovery of the antiviral activities of CCR5 ligand  β-chemokines [8], resulted in the development of new viral entry inhibitors to block CCR5 binding, including both- small molecules and CCR5 antibodies. In clinical trials of HIV-1 patients infected with CCR5-tropic HIV-1 only (R5 strains), these agents have achieved remarkable viral suppression by inhibiting HIV-1 entry and subsequent infection [9,10-14].

CCR5 Coreceptor as an Antiretroviral Target and the Delta 32 Mutation

The CCR5 viral coreceptor, one of a family of chemokine receptors belonging to the G protein-coupled receptor family [15], is expressed on a variety of cell types, including activated T lymphocytes, macrophages and dendritic cells [16]. These receptors consist of seven transmembrane helices, an extracellular N-terminus, three extracellular loops (ECLs) and intracellular C-terminus. Elements located in the N-terminus and second ECL of CCR5 are specifically relevant for interactions with HIV-1 during virus entry, putting focus on them as attractive targets for designing more productive antiviral therapies. In addition, CCR5 has a further advantage as a cellular target because it is relatively unnecessary for normal immune function, in contrast with receptor CD4 and the viral coreceptor CXCR4 [17]. Both have critical roles in immune function [18,19], which severely limits their utility as antiviral therapy targets. The relative dispensability of CCR5 coreceptor is demonstrated in individuals homozygous for the Δ32 mutation of CCR5. These people are highly resistant to HIV-1 infection [20,21]. In addition, Δ32 heterozygous individuals’ progress to AIDS more slowly than do homozygous with the wild-type gene [22,23]. Moreover, CCR5 density levels (molecules/cell) on CD4+ T cells positively correlate with RNA viral loads [24] and progression to AIDS [25] in untreated infected individuals. The direct impact of CCR5 surface density on the antiviral activity of CCR5 antagonists has also been clearly established in vitro where CCR5 levels inversely correlate with rates of HIV-1 entry inhibition [26,27], especially by entry inhibitors [16,22]. These findings, along with the apparent curative effect seen when Δ32 homozygous hematopoietic stem cells were transplanted into a patient with AIDS and leukemia (the Berlin patient study) [28], have given great stimulus for the use of CCR5 blockers for inhibiting HIV-1 entry and infection. It has led to extensive efforts to develop effective antiviral CCR5 inhibitors. These now include CCR5 antagonists [12,29,30,31], fusion proteins that target the CCR5 N-terminus and other relevant sites in CCR5 [32], CCR5 antibodies [33,34], and even drugs to reduce the surface density of CCR5 numbers. Some of these CCR5 blockers have achieved remarkable suppression of HIV-1 entry in clinical trials and clinical settings in vivo [12,29,34,35]. Entry inhibitors overall have a further appeal as antiviral agents, in that they immobilize HIV-1 within the extracellular environment, where it is accessible to the immune system [36].

CCR5 Inhibitors

Several small-molecule CCR5 inhibitors have been developed in the last decade [37,38]. At present, the small-molecule CCR5 antagonist Maraviroc (MVC) is the only licensed CCR5 inhibitor on the market (Pfizer, 2007) [39] and is approved for use in treatment-naïve and treatment-experienced patients. It acts as an allosteric, non-competitive inhibitor of the receptor [40,41]. MVC is licensed for patients infected with only CCR5-tropic HIV-1 [42]. Oral administration of MVC has resulted in dramatic reductions in viral loads [42,43]. MVC and other small molecules have great in vitro synergy with other CCR5 blockers, including CCR5 monoclonal antibodies (mAbs) [33-35,43,44], significantly inhibiting HIV-1 entry into physiologically relevant primary cells in vitro.

Two other CCR5 inhibitors reached clinical trial phases, but both were discontinued for the different reasons. Aplaviroc (APL) administration gave significant reduction of plasma HIV-1 RNA copies during the first ten days of treatment [45], but development was terminated after reversible drug-induced hepatitis occurred in five subjects in phase II and III trials [46]. The other CCR5 antagonist, Vicriviroc (VCV), showed significant suppression of HIV-1 in combination with an optimized background regimen in placebo-controlled phase II studies in HIV treated patients, but increased rates of virologic failure in treatment-naive patients compared with an Efavirenz control arm led to the termination of a preceding phase II study [47-50].

Cenicriviroc (CVC), an experimental drug candidate for blocking CCR5 receptors, is in the phase III clinical trials [51]. Like MVC, this drug is a small-molecule CCR5 antagonist, but with a longer biological half-life than MVC. Both CCR5 inhibitors show beneficial pharmacokinetics and substantial reductions of plasma HIV-1 RNA load in HIV infected patients. It was suggested that the dosage of CVC (50-75 mg, QD, orally) may need adjustment. CVC also has additional activity as a CCR2 antagonist.

Resistance to MVC has been reported previously [52-54], and is due to three separate mechanisms. One mechanism involves selection of pre-existent minor HIV-1 variants that use CXCR4 as a coreceptor to enter target cells [55]. The second mechanism involves selection for mutants that can use inhibitor-bound CCR5 for entry [56]. The third mechanism involves selection for mutations, primarily in the V3 loop of gp120, which changes coreceptor use from CCR5 to CXCR4. The latter has been demonstrated in vitro [57], but is rare in infected patients treated with MVC [42].

Lastly, other alternative ongoing efforts on blocking CCR5 function have focused on deleting the CCR5 gene ex vivo by several gene editing technologies, including CRISPR and zinc finger nuclease (ZFN) proteins. Genome editing of the HIV co-receptor CCR5 by CRISPR-Cas9 protects CD4+ T cells from HIV-1 infection [58]. A completed Phase I clinical trial study (2015) was carried out to determine whether “zinc finger” modified CD4+T-cells are safe to give to humans and how the procedure would affect HIV-1 status (www.clinicaltrials.gov). Another clinical trial on CCR5-modified CD4+ T cells for HIV infection is about to start in mid-December 2018.

CCR5 Inhibitors and cART

The success of current cART therapies is limited by the emergence of drug-resistance, potential drug toxicity, the need for sustained adherence and costs. Advances in cART have generally resulted in reduced viral spread, but not in full viral clearance. There are numerous ongoing efforts to explore the most effective ways to intensify standard cART activity [59-61] and to more greatly impact ongoing viral propagation. Most recent efforts include combined therapies targeting reservoir reduction by a combination of cART and CCR5 blockers, due to an establishment of fewer or smaller reservoirs and a concomitant reduction in residual viral replication [62,63]. In addition, association of heterozygous CCR5Δ32 deletion with survival in HIV-infection revealed the protective role of CCR5Δ32 and extends it to the long-term survival in a large cohort of HIV-1 infected patients. Not only that CCR5Δ32 demonstrates its noticable antiretroviral effect, but it also enhances the long-term survival of patients on cART [64].


CCR5 blockers have great therapeutic potential for prevention and treatment of HIV-1 infection and perhaps (and importantly) a reduction of establishment, size, and/or persistence of reservoirs of latent HIV-1. Due to the potential beneficial effects of CCR5 inhibitors, their inclusion in clinical regimens may offer new possibilities for treating HIV-1 infection and associated disease.


This work was supported by NIH NIAID under grant number AI084417.


1. Scholz I, Arvidson B, Huseby D, Barklis E. Virus particle core defects caused by mutations in the human immunodeficiency virus capsid N-terminal domain. J Virol 2005 Feb 1; 79(3):1470-9.

2. Wacharapornin P, Lauhakirti D, Auewarakul P. The effect of capsid mutations on HIV-1 uncoating. Virology. 2007 Feb 5;358(1):48-54.

3. Noviello CM, López CS, Kukull B, McNett H, Still A, Eccles J, Sloan R, Barklis E. Second-site compensatory mutations of HIV-1 capsid mutations. J virol. 2011 Mar 2.

4. Alkhatib G, Combadiere C, Broder CC, , Feng Y, Kennedy PE, Murphy PM, et al. CC CKR5: a RANTES, MIP-1alpha, MIP-1beta receptor as a fusion cofactor for macrophage-tropic HIV-1. Science 1996 Jun 28; 272(5270):1955-8.

5. Choe H, Farzan M, Sun Y, Sullivan N, Rollins B, Ponath PD, Wu L, Mackay CR, LaRosa G, Newman W, Gerard N. The β-chemokine receptors CCR3 and CCR5 facilitate infection by primary HIV-1 isolates. Cell. 1996 Jun 28; 85(7):1135-48.

6. Deng H, Liu R, Ellmeier W, Choe S, Unutmaz D, Burkhart M, Marzio PD, Marmon S, Sutton RE, Hill CM, Davis CB. Identification of a major co-receptor for primary isolates of HIV-1. Nature. 1996 Jun; 381(6584):661.

7. Dragic T, Litwin V, Allaway GP, Martin SR, Huang Y, Nagashima KA, Cayanan C, Maddon PJ, Koup RA, Moore JP, Paxton WA. HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5. Nature. 1996 Jun; 381(6584):667.

8. Cocchi F, DeVico AL, Garzino-Demo A, Arya SK, Gallo RC, Lusso P. Identification of RANTES, MIP-1α, and MIP-1β as the major HIV-suppressive factors produced by CD8+ T cells. Science. 1995 Dec 15; 270(5243):1811-5.

9. Currier J, Lazzarin A, Sloan L, Clumeck N, Slims J, McCarty D, Steel H, Kleim JP, Bonny T, Millard J. Antiviral activity and safety of aplaviroc with lamivudine/zidovudine in HIV-infected, therapy-naive patients: the ASCENT (CCR102881) study. Antiviral therapy. 2008 Jan 1;13(2):297.

10. Gulick RM, Lalezari J, Goodrich J, Clumeck N, DeJesus E, Horban A, Nadler J, Clotet B, Karlsson A, Wohlfeiler M, Montana JB. Maraviroc for previously treated patients with R5 HIV-1 infection. N Eng J Med. 2008 Oct 2;359(14):1429-41.

11. Gulick RM, Su Z, Flexner C, Hughes MD, Skolnik PR, Wilkin TJ, Gross R, Krambrink A, Coakley E, Greaves WL, Zolopa A. Phase 2 study of the safety and efficacy of vicriviroc, a CCR5 inhibitor, in HIV-1-Infected, treatment-experienced patients: AIDS clinical trials group 5211. J Infect Dis. 2007 Jul 15; 196(2):304-12.

12. Latinovic O, Reitz M, Le NM, Foulke JS, Fätkenheuer G, Lehmann C, Redfield RR, Heredia A. CCR5 antibodies HGS004 and HGS101 preferentially inhibit drug-bound CCR5 infection and restore drug sensitivity of Maraviroc-resistant HIV-1 in primary cells. Virology. 2011 Mar 1;411(1):32-40.

13. Shah HR and Savjani JK. Recent updates for designing CCR5 antagonists as anti-retroviral agents. Eur J Med Chem 2018 Jan 31; 147: 115-129.

14. Yang M, Zhi R, Lu L, Dong M, Wang Y, Tian F, Xia M, Hu J, Dai Q, Jiang S, Li W. A CCR5 antagonist-based HIV entry inhibitor exhibited potent spermicidal activity: Potential application for contraception and prevention of HIV sexual transmission. Eur J Pharm Sci 2018 May 30;117:313-20.

15. Bockaert J and Pin JP. Molecular tinkering of G protein-coupled receptors: an evolutionary success. EMBO J. 1999 Apr 1;18(7):1723-9.

16. Lee B, Sharron M, Montaner LJ, Weissman D, Doms RW. Quantification of CD4, CCR5, and CXCR4 levels on lymphocyte subsets, dendritic cells, and differentially conditioned monocyte-derived macrophages. ProcNatlAcadSci USA 1999 Apr 27;96(9):5215-20.

17. Askew D, Su CA, Barkauskas DS, et al: (2016) J Immunol; 196 (9): 3653-64.

18. Berger EA, Murphy PM, Farber JM. Chemokine receptors as HIV-1 coreceptors: roles in viral entry, tropism, and disease. Annu Rev Immunol; 1999 Apr;17(1):657-700.

19. Nagasawa T, Hirota S, Tachibana K, Takakura N, Nishikawa SI, Kitamura Y, Yoshida N, Kikutani H, Kishimoto T. Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1. Nature. 1996 Aug;382(6592):635.

20. Zou YR, Kottmann AH, Kuroda M, Taniuchi I, Littman DR. Function of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar development. Nature. 1998 Jun;393(6685):595.

21. Michael NL, Louie LG, Sheppard HW. CCR5-delta 32 gene deletion in HIV-1 infected patients. Lancet. 1997 Sep 6; 350(9079):741-2.

22. Liu R, Paxton WA, Choe S, Ceradini D, Martin SR, Horuk R, MacDonald ME, Stuhlmann H, Koup RA, Landau NR. Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection. Cell. 1996 Aug 9;86(3):367-77.

23. Paxton WA, Liu R, Kang S, Wu L, Gingeras TR, Landau NR, Mackay CR, Koup RA. Reduced HIV-1 infectability of CD4+ lymphocytes from exposed-uninfected individuals: association with low expression of CCR5 and high production of β-chemokines. Virology. 1998 Apr 25;244(1):66-73.

24. de RodaHusman AM, Koot M, Cornelissen M, Keet IP, Brouwer M, Broersen SM, Bakker M, Roos MT, Prins M, de Wolf F, Coutinho RA. Association between CCR5 genotype and the clinical course of HIV-1 infection. Ann Intern Med.1997 Nov 15;127(10):882-90.

25. Reynes J, Portales P, Segondy M, Baillat V, André P, Réant B, Avinens O, Couderc G, Benkirane M, Clot J, Eliaou JF. CD4+ T cell surface CCR5 density as a determining factor of virus load in persons infected with human immunodeficiency virus type 1. J Infect Dis. 2000 Mar 1;181(3):927-32.

26. Westby M, van der Ryst E. CCR5 antagonists: host-targeted antiviral agents for the treatment of HIV infection, 4 years on. AntivirChemChemother. 2010 Jun;20(5):179-92.

27. Heredia A, Latinovic O, Gallo RC, Melikyan G, Reitz M, Le N, Redfield RR. Reduction of CCR5 with low-dose rapamycin enhances the antiviral activity of vicriviroc against both sensitive and drug-resistant HIV-1. ProcNatlAcadSci USA. 2008 Dec 23;105(51):20476-81.

28. Anastassopoulou CG, Marozsan AJ, Matet A, Snyder AD, Arts EJ, Kuhmann SE, Moore JP. Escape of HIV-1 from a small molecule CCR5 inhibitor is not associated with a fitness loss. PLoSPathog 2007 Jun 1;3(6):e79.

29. Heredia A, Amoroso A, Davis CL, Le N, Reardon E, Dominique JK, Klingebiel E, Gallo RC, Redfield RR. Rapamycin causes down-regulation of CCR5 and accumulation of anti-HIV β-chemokines: an approach to suppress R5 strains of HIV-1. ProcNatlAcadSci USA.2003 Sep 2;100(18):10411-6.

30. Li L, Sun T, Yang K, Zhang P, Jia WQ. Monoclonal CCR5 antibody for treatment of people with HIV infection. Cochrane Database Syst Rev 2010(12).

31. Maeda K, Das D, Yin PD, Tsuchiya K, Ogata-Aoki H, Nakata H, Norman RB, Hackney LA, Takaoka Y, Mitsuya H. Involvement of the second extracellular loop and transmembrane residues of CCR5 in inhibitor binding and HIV-1 fusion: insights into the mechanism of allosteric inhibition. J Mol Biol.2008 Sep 12;381(4):956-74.

32. Heng Y, Han GW, Abagyan R, Wu B, Stevens RC, Cherezov V, Kufareva I, Handel TM. Structure of CC chemokine receptor 5 with a potent chemokine antagonist reveals mechanisms of chemokine recognition and molecular mimicry by HIV. Immunity. 2017 Jun 20;46(6):1005-17.

33. Huang CC, Lam SN, Acharya P, Tang M, Xiang SH, Hussan SS, Stanfield RL, Robinson J, Sodroski J, Wilson IA, Wyatt R. Structures of the CCR5 N terminus and of a tyrosine-sulfated antibody with HIV-1 gp120 and CD4. Science. 2007 Sep 28;317(5846):1930-4.

34. Ji C, Zhang J, Dioszegi M, Chiu S, Rao E, Derosier A, et al. CCR5 Small-Molecule antagonists and monoclonal antibodies exert potent synergistic antiviral effects by co-binding to the receptor. Molecular Pharmacology MolPharmacol. 2007 Jul;72(1):18-28.

35. Lalezari J, Yadavalli GK, Para M, Richmond G, DeJesus E, Brown SJ, Cai W, Chen C, Zhong J, Novello LA, Lederman MM. Safety, Pharmacokinetics, and Antiviral Activity of HGS004, a Novel Fully Human IgG4 Monoclonal Antibody against CCR5, in HIV-1—zInfected Patients. J Infect Dis.2008 Mar 1;197(5):721-7.

36. Moore JP and Doms RW. The entry of entry inhibitors: a fusion of science and medicine. ProcNatlAcad Sci. 2003 Sep 16;100(19):10598-602.

37. Henrich TJ and Kuritzkes DR. HIV-1 Entry Inhibitors: Recent Development and Clinical Use. CurrOpinVirol.2013 Feb 1;3(1):51-7.

38. Berro R, Klasse PJ, Lascano D, Flegler A, Nagashima KA, Sanders RW, Sakmar TP, Hope TJ, Moore JP. Multiple CCR5 conformations on the cell surface are used differentially by human immunodeficiency viruses resistant or sensitive to CCR5 inhibitors. J Virol.2011 Jun 15:JVI-00767.

39. Carter PH. Progress in the discovery of CC chemokine receptor 2 antagonists, 2009-2012. Expert OpinTher Pat. 2013 May 1;23(5):549-68.

40. FDA notifications. Maraviroc approved as a CCR5 co-receptor antagonist. AIDS Alert.2007 Sep;22(9):103.

41. Tsibris AM, Korber B, Arnaout R, Russ C, Lo CC, Leitner T, Gaschen B, Theiler J, Paredes R, Su Z, Hughes MD. Quantitative deep sequencing reveals dynamic HIV-1 escape and large population shifts during CCR5 antagonist therapy in vivo. PloS one. 2009 May 25;4(5):e5683.

42. Schlecht HP, Schellhorn S, Dezube BJ, Jacobson JM. New approaches in the treatment of HIV/AIDS–focus on maraviroc and other CCR5 antagonists.The Clin Risk Manag. 2008 Apr;4(2):473.

43. Westby M, Smith-Burchnell C, Mori J, Lewis M, Mosley M, Stockdale M, Dorr P, Ciaramella G, Perros M. Reduced maximal inhibition in phenotypic susceptibility assays indicates that viral strains resistant to the CCR5 antagonist maraviroc utilize inhibitor-bound receptor for entry. J Virol.2007 Mar 1;81(5):2359-71.

44. Latinovic OS, Zhang J, Tagaya Y, DeVico AL, Fouts T, Schneider K, Lakowicz J, Heredia A, Redfield RR. Synergistic inhibition of R5 HIV-1 by Maraviroc and FLSC IgG in primary cells: Implications for prevention and treatment. Current HIV Research. 2016; 14(1):24-36.

45. Lalezari J, Thompson M, Kumar P, Piliero P, Davey R, Patterson K, Shachoy-Clark A, Adkison K, Demarest J, Lou Y, Berrey M. Antiviral activity and safety of 873140, a novel CCR5 antagonist, during short-term monotherapy in HIV-infected adults. Aids. 2005 Sep 23;19(14):1443-8.

46. Nichols WG, Steel HM, Bonny T, Adkison K, Curtis L, Millard J, Kabeya K, Clumeck N. Hepatotoxicity observed in clinical trials of aplaviroc (GW873140).Antimicrob Agents Chemother. 2008 Mar 1;52(3):858-65.

47. Gulick RM, Su Z, Flexner C, Hughes MD, Skolnik PR, Wilkin TJ, Gross R, Krambrink A, Coakley E, Greaves WL, Zolopa A. Phase 2 study of the safety and efficacy of vicriviroc, a CCR5 inhibitor, in HIV-1-Infected, treatment-experienced patients: AIDS clinical trials group 5211. J Infect Dis. 2007 Jul 15;196(2):304-12.

48. Schürmann D, Fätkenheuer G, Reynes J, Michelet C, Raffi F, Van Lier J, Caceres M, Keung A, Sansone-Parsons A, Dunkle LM, Hoffmann C. Antiviral activity, pharmacokinetics and safety of vicriviroc, an oral CCR5 antagonist, during 14-day monotherapy in HIV-infected adults. Aids. 2007 Jun 1;21(10):1293-9.

49. Landovitz RJ, Angel JB, Hoffmann C, Horst H, Opravil M, Long J, Greaves W, Fätkenheuer G. Phase II study of vicriviroc versus efavirenz (both with zidovudine/lamivudine) in treatment-naive subjects with HIV-1 infection. J Infect Dis. 2008 Oct 15;198(8):1113-22.

50. Cooper DA, Heera J, Ive P, Botes M, Dejesus E, Burnside R, Clumeck N, Walmsley S, Lazzarin A, Mukwaya G, Saag M. Efficacy and safety of maraviroc vs. efavirenz in treatment-naive patients with HIV-1: 5-year findings. AIDS. 2014 Mar 13;28(5):717.

51. Tobira Therapeutics Initiates Phase 2b Trial of Cenicriviroc, The Body,July 5, 2011.

52. Xu F, P Acosta E, Liang L, He Y, Yang J, Kerstner-Wood C, Zheng Q, Huang J, Wang K. Current Status of the Pharmacokinetics and Pharmacodynamics of HIV-1 Entry Inhibitors and HIV Therapy. Curr Drug Metab. 2017 Aug 1;18(8):769-81.

53. Westby M, Smith-Burchnell C, Mori J, Lewis M, Mosley M, Stockdale M, Dorr P, Ciaramella G, Perros M. Reduced maximal inhibition in phenotypic susceptibility assays indicates that viral strains resistant to the CCR5 antagonist maraviroc utilize inhibitor-bound receptor for entry. J Virol.2007 Mar 1;81(5):2359-71.

54. Flynn JK, Ellenberg P, Duncan R, Ellett A, Zhou J, Sterjovski J, Cashin K, Borm K, Gray LR, Lewis M, Jubb B. Analysis of clinical HIV-1 strains with resistance to maraviroc reveals strain-specific resistance mutations, variable degrees of resistance, and minimal cross-resistance to other CCR5 antagonists. AIDS Res Hu Retroviruses. 2017 Dec 1;33(12):1220-35.

55. Jiang X, Feyertag F, Meehan C, McCormack G, Travers SA, Craig C, Westby M, Lewis M, Robertson DL. Characterising the diverse mutational pathways associated with R5-tropic maraviroc resistance: HIV-1 that uses the drug-bound CCR5 coreceptor. J virol. 2015 Sep 2:JVI-01384.

56. Westby M, Lewis M, Whitcomb J, Youle M, Pozniak AL, James IT, Jenkins TM, Perros M, van der Ryst E. Emergence of CXCR4-using human immunodeficiency virus type 1 (HIV-1) variants in a minority of HIV-1-infected patients following treatment with the CCR5 antagonist maraviroc is from a pretreatment CXCR4-using virus reservoir. J virol. 2006 May 15;80(10):4909-20.

57. Nedellec R, Coetzer M, Lederman MM, Offord RE, Hartley O, Mosier DE. Resistance to the CCR5 inhibitor 5P12-RANTES requires a difficult evolution from CCR5 to CXCR4 coreceptor use. PLoS One. 2011 Jul 8;6(7):e22020.

58. Liu Z, Chen S, Jin X, Wang Q, Yang K, Li C, Xiao Q, Hou P, Liu S, Wu S, Hou W. Genome editing of the HIV co-receptors CCR5 and CXCR4 by CRISPR-Cas9 protects CD4+ T cells from HIV-1 infection. Cell biosci. 2017 Dec;7(1):47.

59. Buzón MJ, Massanella M, Llibre JM, Esteve A, Dahl V, Puertas MC, Gatell JM, Domingo P, Paredes R, Sharkey M, Palmer S. HIV-1 replication and immune dynamics are affected by raltegravir intensification of HAART-suppressed subjects. Nature medicine. 2010 Apr;16(4):460.

60. Pace MJ, Graf EH, O'Doherty U. HIV 2-long terminal repeat circular DNA is stable in primary CD4+ T Cells. Virology. 2013 Jun 20;441(1):18-21.

61. Llibre JM, Buzón MJ, Massanella M, Esteve A, Dahl V, Puertas MC, Domingo P, Gatell JM, Larrouse M, Gutierrez M, Palmer S. Treatment intensification with raltegravir in subjects with sustained HIV-1 viraemia suppression: a randomized 48-week study. AntivirTher.2012 Jan 1;17(2):355.

62. Chaillon A, Gianella S, Lada SM, Perez-Santiago J, Jordan P, Ignacio C, Karris M, Richman DD, Mehta SR, Little SJ, Wertheim JO. Size, composition, and evolution of HIV DNA populations during early antiretroviral therapy and intensification with maraviroc. J virol. 2018 Feb 1;92(3):e01589-17.

63. Puertas MC, Massanella M, Llibre JM, Ballestero M, Buzon MJ, Ouchi D, Esteve A, Boix J, Manzardo C, Miró JM, Gatell JM. Intensification of a raltegravir-based regimen with maraviroc in early HIV-1 infection. Aids. 2014 Jan 28;28(3):325-34.

64. Ruiz-Mateos E, Tarancon-Diez L, Alvarez-Rios AI, Dominguez-Molina B, Genebat M, Pulido I, Abad MA, Muñoz-Fernandez MA, Leal M. association of heterozygous Ccr5δ32 deletion with survival in Hiv-infection: A cohort study. Antiviral res. 2018 Feb 28;150:15-9.

Author Information X