L Medicine, University of Rome Tor Vergata, Rome, Italy. Authors’ contributions
L Medicine, University of Rome Tor Vergata, Rome, Italy. Authors’ contributions MGL, assisted by MC, coordinated the in vivo experiments in nonhuman primates. SN, participated at the bioinformatic analyses, and generated the tissue culture data on SIVmac251 susceptibility to raltegravir. MLB and NI built the SIVmac251/IN/Mg2+/DNA model, conducted the molecular docking simulations and measured the theoretical binding energies of the complexes. BC participated in the generation of in tissue culture data on drug susceptibility. JYO and JG, respectively, organized and prepared the ex vivo plasma and PBMC sampling, and conducted the quantitative PCR assays. FT cultivated and titrated the virus for the tissue culture experiments. EG conceived the study together with AS and helped AS in the study coordination. AS conceived and coordinated the study, did the experimental design, supervised and participated at the generation of in vitro data, conducted the bioinformatic and statistical analyses and drafted the manuscript. Competing interests The authors declare that they have no competing interests. Received: 16 November 2009 Accepted: 16 March 2010 Published: 16 March 2010 References 1. Savarino A: A historical sketch of the discovery and development of HIV1 integrase inhibitors. Expert Opin Investig Drugs 2006, 15:1507-1522.7.8. 9.10.11. 12.13.14.15.16.17.18.19.20.Cotelle PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/27362935 P: Patented HIV-1 integrase inhibitors (1998-2005). Recent Pat Antiinfect Drug Discov 2006, 1:1-15. Isentress equal to Sustiva in first line therapy. Proj Inf Perspect 2009, 48:6-7. Steigbigel RT, Cooper DA, Kumar PN, Eron JE, Schechter M, Markowitz M, Loutfy MR, Lennox JL, Gatell JM, Rockstroh JK, Katlama C, Yeni P, Lazzarin A, Clotet B, Zhao J, Chen J, Ryan DM, Rhodes RR, Killar JA, Gilde LR, Strohmaier KM, Meibohm AR, Miller MD, Hazuda DJ, Nessly ML, DiNubile MJ, Isaacs RD, Nguyen BY, Teppler H, BENCHMRK Study Teams: Raltegravir with optimized background therapy for resistant HIV-1 infection. N Engl J Med 2008, 359:339-354. Neamati N: Patented small molecule inhibitors of HIV-1 integrase: a 10year saga. Expert Opin Ther Patents 2002, 12:709-724. Kulkosky J, Bray S: HAART-persistent HIV-1 latent reservoirs: their origin, mechanisms of stability and potential strategies for eradication. Curr HIV Res 2006, 4:FCCP chemical information 199-208. Chun TW, Justement JS, Moir S, Hallahan CW, Maenza J, Mullins JI, Collier AC, Corey L, Fauci AS: Decay of the HIV reservoir in patients receiving antiretroviral therapy for extended periods: implications for eradication of virus. J Infect Dis 2007, 195:1734-1736. Hamer DH: Can HIV be cured? Mechanisms of HIV persistence and strategies to combat it. Curr HIV Res 2004, 2:99-111. Chomont N, El-Far M, Ancuta P, Trautmann L, Procopio FA, Yassine-Diab B, Boucher G, Boulassel MR, Ghattas G, Brenchley JM, Schacker TW, Hill BJ, Douek DC, Routy JP, Haddad EK, S aly RP: HIV reservoir size and persistence are driven by T cell survival PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/26778282 and homeostatic proliferation. Nat Med 2009, 15:893-900. Savarino A, Mai A, Norelli S, El Daker S, Valente S, Rotili D, Altucci L, Palamara AT, Garaci E: “Shock and kill” effects of class I-selective histone deacetylase inhibitors in combination with the glutathione synthesis inhibitor buthionine sulfoximine in cell line models for HIV-1 quiescence. Retrovirology 2009, 6:52. Denton PW, Garc JV: Novel humanized murine models for HIV research. Curr HIV/AIDS Rep 2009, 6:13-9. Savarino A, Pistello M, D’Ostilio D, Zabogli E, Taglia F, Mancini F, Fe.