Efficacy of VHM After Treatment Interruption in Subjects Initiating ART During Acute HIV Infection

Summary

This study is a two-arm prospective 1:1 randomised controlled trial comparing the proportion of patients between: Group 1: vorinostat/hydroxychloroquine/maraviroc (VHM) co-administered with anti-retroviral therapy (ART) Group 2: ART only who are able to maintain HIV RNA \< 50 copies/ml following treatment interruption. Subjects will be recruited from RV254/SEARCH 010, an acute HIV infection cohort conducted by the Thai Red Cross AIDS Research Centre in Bangkok, Thailand. The study will run for a minimum of 34 weeks from screening.

Timeline

Start

2015-01

Primary completion

2015-11

Completion

2016-03

Publications

• Background Schuetz A, Deleage C, Sereti I, Rerknimitr R, Phanuphak N, Phuang-Ngern Y, Estes JD, Sandler NG, Sukhumvittaya S, Marovich M, Jongrakthaitae S, Akapirat S, Fletscher JL, Kroon E, Dewar R, Trichavaroj R, Chomchey N, Douek DC, O Connell RJ, Ngauy V, Robb ML, Phanuphak P, Michael NL, Excler JL, Kim JH, de Souza MS, Ananworanich J; RV254/SEARCH 010 and RV304/SEARCH 013 Study Groups. Initiation of ART during early acute HIV infection preserves mucosal Th17 function and reverses HIV-related immune activation. PLoS Pathog. 2014 Dec 11;10(12):e1004543. doi: 10.1371/journal.ppat.1004543. eCollection 2014 Dec.
• Background Ananworanich J, Schuetz A, Vandergeeten C, Sereti I, de Souza M, Rerknimitr R, Dewar R, Marovich M, van Griensven F, Sekaly R, Pinyakorn S, Phanuphak N, Trichavaroj R, Rutvisuttinunt W, Chomchey N, Paris R, Peel S, Valcour V, Maldarelli F, Chomont N, Michael N, Phanuphak P, Kim JH; RV254/SEARCH 010 Study Group. Impact of multi-targeted antiretroviral treatment on gut T cell depletion and HIV reservoir seeding during acute HIV infection. PLoS One. 2012;7(3):e33948. doi: 10.1371/journal.pone.0033948. Epub 2012 Mar 30.
• Background Saez-Cirion A, Bacchus C, Hocqueloux L, Avettand-Fenoel V, Girault I, Lecuroux C, Potard V, Versmisse P, Melard A, Prazuck T, Descours B, Guergnon J, Viard JP, Boufassa F, Lambotte O, Goujard C, Meyer L, Costagliola D, Venet A, Pancino G, Autran B, Rouzioux C; ANRS VISCONTI Study Group. Post-treatment HIV-1 controllers with a long-term virological remission after the interruption of early initiated antiretroviral therapy ANRS VISCONTI Study. PLoS Pathog. 2013 Mar;9(3):e1003211. doi: 10.1371/journal.ppat.1003211. Epub 2013 Mar 14.
• Background Elliott JH, Wightman F, Solomon A, Ghneim K, Ahlers J, Cameron MJ, Smith MZ, Spelman T, McMahon J, Velayudham P, Brown G, Roney J, Watson J, Prince MH, Hoy JF, Chomont N, Fromentin R, Procopio FA, Zeidan J, Palmer S, Odevall L, Johnstone RW, Martin BP, Sinclair E, Deeks SG, Hazuda DJ, Cameron PU, Sekaly RP, Lewin SR. Activation of HIV transcription with short-course vorinostat in HIV-infected patients on suppressive antiretroviral therapy. PLoS Pathog. 2014 Nov 13;10(10):e1004473. doi: 10.1371/journal.ppat.1004473. eCollection 2014 Oct.
• Background Archin NM, Liberty AL, Kashuba AD, Choudhary SK, Kuruc JD, Crooks AM, Parker DC, Anderson EM, Kearney MF, Strain MC, Richman DD, Hudgens MG, Bosch RJ, Coffin JM, Eron JJ, Hazuda DJ, Margolis DM. Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy. Nature. 2012 Jul 25;487(7408):482-5. doi: 10.1038/nature11286.
• Background Bratland A, Dueland S, Hollywood D, Flatmark K, Ree AH. Gastrointestinal toxicity of vorinostat: reanalysis of phase 1 study results with emphasis on dose-volume effects of pelvic radiotherapy. Radiat Oncol. 2011 Apr 8;6:33. doi: 10.1186/1748-717X-6-33.
• Background 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, Sekaly RP. HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation. Nat Med. 2009 Aug;15(8):893-900. doi: 10.1038/nm.1972. Epub 2009 Jun 21.
• Background Abel S, Back DJ, Vourvahis M. Maraviroc: pharmacokinetics and drug interactions. Antivir Ther. 2009;14(5):607-18.
• Background Ananworanich J, Hirschel B. Intermittent therapy for the treatment of chronic HIV infection. AIDS. 2007 Jan 11;21(2):123-34. doi: 10.1097/01.aids.0000256414.91105.8e. No abstract available.
• Background Paton NI, Goodall RL, Dunn DT, Franzen S, Collaco-Moraes Y, Gazzard BG, Williams IG, Fisher MJ, Winston A, Fox J, Orkin C, Herieka EA, Ainsworth JG, Post FA, Wansbrough-Jones M, Kelleher P; Hydroxychloroquine Trial Team. Effects of hydroxychloroquine on immune activation and disease progression among HIV-infected patients not receiving antiretroviral therapy: a randomized controlled trial. JAMA. 2012 Jul 25;308(4):353-61. doi: 10.1001/jama.2012.6936.
• Background Piconi S, Parisotto S, Rizzardini G, Passerini S, Terzi R, Argenteri B, Meraviglia P, Capetti A, Biasin M, Trabattoni D, Clerici M. Hydroxychloroquine drastically reduces immune activation in HIV-infected, antiretroviral therapy-treated immunologic nonresponders. Blood. 2011 Sep 22;118(12):3263-72. doi: 10.1182/blood-2011-01-329060. Epub 2011 May 16.
• Background Prince HM, Bishton MJ, Harrison SJ. Clinical studies of histone deacetylase inhibitors. Clin Cancer Res. 2009 Jun 15;15(12):3958-69. doi: 10.1158/1078-0432.CCR-08-2785. Epub 2009 Jun 9.
• Background Beliakova-Bethell N, Zhang JX, Singhania A, Lee V, Terry VH, Richman DD, Spina CA, Woelk CH. Suberoylanilide hydroxamic acid induces limited changes in the transcriptome of primary CD4(+) T cells. AIDS. 2013 Jan 2;27(1):29-37. doi: 10.1097/QAD.0b013e32835b3e26.
• Background Lewin SR. A cure for HIV: where we've been, and where we're headed. Lancet. 2013 Jun 15;381(9883):2057-8. doi: 10.1016/S0140-6736(13)61180-0. No abstract available.
• Background Katlama C, Deeks SG, Autran B, Martinez-Picado J, van Lunzen J, Rouzioux C, Miller M, Vella S, Schmitz JE, Ahlers J, Richman DD, Sekaly RP. Barriers to a cure for HIV: new ways to target and eradicate HIV-1 reservoirs. Lancet. 2013 Jun 15;381(9883):2109-17. doi: 10.1016/S0140-6736(13)60104-X. Epub 2013 Mar 29.

Drugs

Indications

No indication recorded.