Effect of Methamphetamine on Residual Latent HIV Disease Study

Summary

The most commonly used illicit stimulant in HIV-infected individuals is methamphetamine (MA). Prior studies demonstrate strong evidence that MA promotes increased HIV transcription as well as immune dysregulation. A challenge in achieving worldwide HIV eradication is targeting specific marginalized populations who are most likely to benefit from an HIV cure but possess poorer immune responses. For this study, HIV+ infected ART-suppressed individuals with no prior history of MA use disorder will be administered oral methamphetamine (the maximum FDA approved daily dose for the treatment of childhood obesity) to determine the effects of short-term MA exposure on residual virus production, gene expression, and inflammation. Measures of MA exposure in urine and serum will then be associated with residual virus production, gene expression, cell surface immune marker protein expression, and systemic markers of inflammation. The clinical trial data will generate advanced gene expression and immunologic data to identify potential novel targets for reversing HIV latency, reducing inflammation, and personalizing future therapies in HIV+ individuals who use MA.

Timeline

Start

2021-01-01

Primary completion

2023-01-11

Completion

2023-01-11

Publications

• Background Castillo-Mancilla JR, Brown TT, Erlandson KM, Palella FJ Jr, Gardner EM, Macatangay BJ, Breen EC, Jacobson LP, Anderson PL, Wada NI. Suboptimal Adherence to Combination Antiretroviral Therapy Is Associated With Higher Levels of Inflammation Despite HIV Suppression. Clin Infect Dis. 2016 Dec 15;63(12):1661-1667. doi: 10.1093/cid/ciw650. Epub 2016 Sep 22.
• Background Passaro RC, Pandhare J, Qian HZ, Dash C. The Complex Interaction Between Methamphetamine Abuse and HIV-1 Pathogenesis. J Neuroimmune Pharmacol. 2015 Sep;10(3):477-86. doi: 10.1007/s11481-015-9604-2. Epub 2015 Apr 8.
• Background Centers for Disease Control and Prevention (CDC). Increasing morbidity and mortality associated with abuse of methamphetamine--United States, 1991-1994. MMWR Morb Mortal Wkly Rep. 1995 Dec 1;44(47):882-6.
• Background Marquez C, Mitchell SJ, Hare CB, John M, Klausner JD. Methamphetamine use, sexual activity, patient-provider communication, and medication adherence among HIV-infected patients in care, San Francisco 2004-2006. AIDS Care. 2009 May;21(5):575-82. doi: 10.1080/09540120802385579.
• Background Wires ES, Alvarez D, Dobrowolski C, Wang Y, Morales M, Karn J, Harvey BK. Methamphetamine activates nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) and induces human immunodeficiency virus (HIV) transcription in human microglial cells. J Neurovirol. 2012 Oct;18(5):400-10. doi: 10.1007/s13365-012-0103-4. Epub 2012 May 22.
• Background Liang H, Wang X, Chen H, Song L, Ye L, Wang SH, Wang YJ, Zhou L, Ho WZ. Methamphetamine enhances HIV infection of macrophages. Am J Pathol. 2008 Jun;172(6):1617-24. doi: 10.2353/ajpath.2008.070971. Epub 2008 May 5.
• Background Toussi SS, Joseph A, Zheng JH, Dutta M, Santambrogio L, Goldstein H. Short communication: Methamphetamine treatment increases in vitro and in vivo HIV replication. AIDS Res Hum Retroviruses. 2009 Nov;25(11):1117-21. doi: 10.1089/aid.2008.0282.
• Background Jiang J, Wang M, Liang B, Shi Y, Su Q, Chen H, Huang J, Su J, Pan P, Li Y, Wang H, Chen R, Liu J, Zhao F, Ye L, Liang H. In vivo effects of methamphetamine on HIV-1 replication: A population-based study. Drug Alcohol Depend. 2016 Feb 1;159:246-54. doi: 10.1016/j.drugalcdep.2015.12.027. Epub 2016 Jan 4.
• Background Saito M, Yamaguchi T, Kawata T, Ito H, Kanai T, Terada M, Yokosuka M, Saito TR. Effects of methamphetamine on cortisone concentration, NK cell activity and mitogen response of T-lymphocytes in female cynomolgus monkeys. Exp Anim. 2006 Oct;55(5):477-81. doi: 10.1538/expanim.55.477.
• Background Harms R, Morsey B, Boyer CW, Fox HS, Sarvetnick N. Methamphetamine administration targets multiple immune subsets and induces phenotypic alterations suggestive of immunosuppression. PLoS One. 2012;7(12):e49897. doi: 10.1371/journal.pone.0049897. Epub 2012 Dec 5.
• Background Carrico AW, Flentje A, Kober K, Lee S, Hunt P, Riley ED, Shoptaw S, Flowers E, Dilworth SE, Pahwa S, Aouizerat BE. Recent stimulant use and leukocyte gene expression in methamphetamine users with treated HIV infection. Brain Behav Immun. 2018 Jul;71:108-115. doi: 10.1016/j.bbi.2018.04.004. Epub 2018 Apr 18.
• Background Jing L, Li JX. Trace amine-associated receptor 1: A promising target for the treatment of psychostimulant addiction. Eur J Pharmacol. 2015 Aug 15;761:345-52. doi: 10.1016/j.ejphar.2015.06.019. Epub 2015 Jun 16.
• Background Pei Y, Asif-Malik A, Hoener M, Canales JJ. A partial trace amine-associated receptor 1 agonist exhibits properties consistent with a methamphetamine substitution treatment. Addict Biol. 2017 Sep;22(5):1246-1256. doi: 10.1111/adb.12410. Epub 2016 May 19.
• Background Panas MW, Xie Z, Panas HN, Hoener MC, Vallender EJ, Miller GM. Trace amine associated receptor 1 signaling in activated lymphocytes. J Neuroimmune Pharmacol. 2012 Dec;7(4):866-76. doi: 10.1007/s11481-011-9321-4. Epub 2011 Oct 29.
• Background Uhl GR, Drgon T, Liu QR, Johnson C, Walther D, Komiyama T, Harano M, Sekine Y, Inada T, Ozaki N, Iyo M, Iwata N, Yamada M, Sora I, Chen CK, Liu HC, Ujike H, Lin SK. Genome-wide association for methamphetamine dependence: convergent results from 2 samples. Arch Gen Psychiatry. 2008 Mar;65(3):345-55. doi: 10.1001/archpsyc.65.3.345.
• Background Breen MS, Uhlmann A, Nday CM, Glatt SJ, Mitt M, Metsalpu A, Stein DJ, Illing N. Candidate gene networks and blood biomarkers of methamphetamine-associated psychosis: an integrative RNA-sequencing report. Transl Psychiatry. 2016 May 10;6(5):e802. doi: 10.1038/tp.2016.67.
• Background Li MD, Wang J, Niu T, Ma JZ, Seneviratne C, Ait-Daoud N, Saadvandi J, Morris R, Weiss D, Campbell J, Haning W, Mawhinney DJ, Weis D, McCann M, Stock C, Kahn R, Iturriaga E, Yu E, Elkashef A, Johnson BA. Transcriptome profiling and pathway analysis of genes expressed differentially in participants with or without a positive response to topiramate treatment for methamphetamine addiction. BMC Med Genomics. 2014 Dec 12;7:65. doi: 10.1186/s12920-014-0065-x.

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