Areas of Research: Pre-clinical and clinical safety and efficacy evaluation of HIV pre-exposure prophylaxis drugs; drug pharmacokinetics/pharmacodynamics; HIV-HSV interactions; HIV eradication
Dr. Mesquita is a virologist with over 10 years of experience in HIV prevention. His research has focused on developing and optimizing models to evaluate the safety and efficacy of Pre-Exposure Prophylaxis (PrEP) modalities. He has developed several cell- and tissue-culture based models for ex-vivo and in vitro assessment of HIV PrEP formulations and APIs. He is currently studying the impact of HSV-2 infection on the establishment and maintenance of latent HIV reservoirs in specific subsets of immune cells in HSV/HIV co-infected individuals. Specifically, he is focusing on the development of novel approaches to enable HIV eradication by identifying targets that may prevent efficient virus reactivation in response to stimuli.
- Fletcher PS, Wallace GS, Mesquita PMM, Shattock RJ. Candidate polyanion microbicides inhibit HIV-1 infection and dissemination pathways in human cervical explants. Retrovirology. 2006 Aug 1;3:46.
- Madan RP*, Mesquita PMM*, Cheshenko N, Jing B, Shende V, Guzman E, Heald T, Keller MJ, Regen SL, Shattock RJ, Herold BC. Molecular umbrellas: a novel class of candidate topical microbicides to prevent human immunodeficiency virus and herpes simplex virus infections. Journal of Virology. 2007 Jul;81(14):7636-46. Epub 2007 May 9. (*authors contributed equally)
- Mesquita PMM, Wilson SS, Manlow P, Fischetti L, Keller MJ, Herold BC, Shattock RJ. Candidate microbicide PPCM blocks human immunodeficiency virus type 1 infection in cell and tissue cultures and prevents genital herpes in a murine model. Journal of Virology. 2008 Jul;82(13):6576-84. Epub 2008 Apr 23.
- Fakioglu E, Wilson SS, Mesquita PMM, Hazrati E, Cheshenko N, Blaho JA, Herold BC. Herpes simplex virus downregulates secretory leukocyte protease inhibitor: a novel immune evasion mechanism. Journal of Virology. 2008 Oct;82(19):9337-44. Epub 2008 Jul 30.
- Mesquita PMM, Cheshenko N, Wilson SS, Mhatre M, Guzman E, Fakioglu E, Keller MJ, Herold BC. Disruption of tight junctions by cellulose sulfate facilitates HIV infection: model of microbicide safety. Journal of Infectious Diseases. 2009 Aug 15;200(4):599-608.
- Wilson SS, Cheshenko N, Fakioglu E, Mesquita PMM, Keller MJ, Herold BC. Susceptibility to genital herpes as a biomarker predictive of increased HIV risk: expansion of a murine model of microbicide safety. Antiviral Therapy. 2009;14(8):1113-24.
- Keller MJ, Mesquita PMM, Torres NM, Cho S, Shust G, Madan RP, Cohen HW, Petrie J, Ford T, Soto-Torres L, Profy AT, Herold BC. Postcoital bioavailability and antiviral activity of 0.5% PRO 2000 gel: implications for future microbicide clinical trials. PLoS One. 2010 Jan 22;5(1):e8781.
- Herold BC, Mesquita PMM, Madan RP, Keller MJ. Female genital tract secretions and semen impact the development of microbicides for the prevention of HIV and other sexually transmitted infections. American Journal of Reproductive Immunology. 2011 Mar;65(3):325-33. doi: 10.1111/j.1600-0897.2010.00932.x. Epub 2010 Dec 12. Review.
- Keller MJ, Madan RP, Torres NM, Fazzari MJ, Cho S, Kalyoussef S, Shust G, Mesquita PMM, Louissaint N, Chen J, Cohen HW, Diament EC, Lee AC, Soto-Torres L, Hendrix CW, Herold BC. A randomized trial to assess anti-HIV activity in female genital tract secretions and soluble mucosal immunity following application of 1% tenofovir gel. PLoS One. 2011 Jan 25;6(1):e16475.
- Segarra TJ, Fakioglu E, Cheshenko N, Wilson SS, Mesquita PMM, Doncel GF, Herold BC. Bridging the gap between preclinical and clinical microbicide trials: blind evaluation of candidate gels in murine models of efficacy and safety. PLoS One. 2011;6(11):e27675. Epub 2011 Nov 11.
- Mesquita PMM*, Rastogi R*, Segarra TJ, Teller RS, Torres NM, Huber AM, Kiser PF, Herold BC. Intravaginal ring delivery of tenofovir disoproxil fumarate for prevention of HIV and HSV infection. Journal of Antimicrobial Chemotherapy 2012, 67(7): 1730-1738 first published online March 30, 2012 doi:10.1093/jac/dks097. * authors contributed equally.
- Kiser PF, Mesquita PMM, Herold BC. A perspective on knowledge and gaps in HIV prevention science. AIDS Research and Human Retroviruses. 2012 Nov;28(11):1373-8. doi: 10.1089/AID.2012.0277. Review
- Nixon B, Stefanidou M, Mesquita PMM, Fakioglu E, Segarra T, Rohan L, Halford W, Palmer KE, Herold BC. Griffithsin protects mice from genital herpes by preventing cell-to-cell spread. Journal of Virology. 2013 Jun;87(11):6257-69. doi: 10.1128/JVI.00012-13. Epub 2013 Mar 27.
- Rastogi R, Teller RS, Mesquita PMM, Herold BC, Kiser PF. Osmotic pump tablets for delivery of antiretrovirals to the vaginal mucosa. Antiviral Research. 2013 Oct;100(1):255-8. doi: 10.1016/j.antiviral.2013.08.007. Epub 2013 Aug 20.
- Smith JM, Rastogi R, Teller RS, Srinivasan P, Mesquita PMM, Nagaraja U, McNicholl JM, Hendry RM, Dinh CT, Martin A, Herold BC, Kiser PF. Intravaginal ring eluting tenofovir disoproxil fumarate completely protects macaques from multiple vaginal simian-HIV challenges. Proceedings of the National Academy of Sciences USA. 2013 Oct 1;110(40):16145-50. doi: 10.1073/pnas.1311355110. Epub 2013 Sep 16
- Mesquita PMM, Srinivasan P, Johnson TJ, Rastogi R, Evans-Strickfaden T, Kay MS, Buckheit KW, Buckheit RW Jr, Smith JM, Kiser PF, Herold BC. Novel preclinical models of topical PrEP pharmacodynamics provide rationale for combination of drugs with complementary properties. Retrovirology. 2013 Oct 24;10:113. doi: 10.1186/1742-4690-10-113.
- Mesquita PMM and Herold BC. HIV Transmission Models: Lessons Learned for Microbicide Formulation Design. In das Neves, J and Sarmento, B (eds). Drug Delivery and Development of Anti-HIV Microbicides. Pan Stanford Publishing Pte. Ltd. 2014
- Herold, BC, Dezzutti, C, Richardson, BA, Marrazzo, J, Mesquita, PMM, Carpenter C, Louissaint N, Hillier, S and Hendrix, C, Antiviral activity of genital tract secretions following oral or topical tenofovir PrEP and the modulatory effects of mucosal immune mediators, Journal of AIDS. 2014 May 1;66(1):65-73.
- Jackson A, Else L, Mesquita PMM, Egan D, Back D, Karolia Z, Higgs C, Ringner-Nackter L, Herold B, Gazzard B.and Boffito M. A compartmental pharmacokinetic evaluation of long-acting rilpivirine in HIV negative volunteers for pre-exposure prophylaxis (PrEP). Clinical Pharmacology and Therapeutics. 2014 Sep;96(3):314-23. doi: 10.1038/clpt.2014.118. Epub 2014 May 26.
- Nel AM, Haazen W, Nuttall JP, Romano JW, Mesquita PMM, Herold BC, Rosenberg ZF and van Niekerk N. Pharmacokinetics and Safety Assessment of Anti-HIV Dapivirine Vaginal Microbicide Rings with Multiple Dosing. Journal of AIDS & Clinical Research. 2014 Oct. 5:355. doi: 10.4172/2155-6113.1000355
- Mait-Kaufman J, Fakioglu E, Mesquita PMM, Elliott J, Lo Y and Madan RP. Chronic HIV Infection is Associated with Upregulation of Proinflammatory Cytokine and Chemokine and Alpha Defensin Gene Expression in Colorectal Mucosa. AIDS Research and Human Retroviruses. 2015. doi:10.1089/aid.2014.0085
- Thurman AR, Kimble T, Herold B, Mesquita PM, Fichorova RN, Dawood HY, Fashemi T, Chandra N, Rabe L, Cunningham TD, Anderson S, Schwartz J, Doncel G. Bacterial Vaginosis and Subclinical Markers of Genital Tract Inflammation and Mucosal Immunity. AIDS Research and Human Retroviruses. 2015 Jul 23. [Epub ahead of print] PubMed PMID: 26204200
- Pereira LE*, Mesquita PMM*, Ham A, Singletary T, Deyounks F, Martin A, McNicholl J, Buckheit KW, Buckheit Jr. RW, Smith JM. Pharmacokinetic and pharmacodynamic evaluation following vaginal application of IQB3002, a dual chamber microbicide gel containing the NNRTI IQP-0528, in rhesus macaques. Antimicrobial Agents and Chemotherapy. 2015; 60(3):1393-400 (* authors contributed equally)
- Taneva E, Crooker K, Park SH, Su JT, Ott A, Cheshenko N, Szleifer I, Kiser PF, Frank B, Mesquita PMM, Herold BC. Differential Mechanisms of Tenofovir and Tenofovir Disoproxil Fumarate Cellular Transport and Implications for Topical Pre-exposure Prophylaxis. Antimicrobial Agents and Chemotherapy. 2015; 60(3):1667-75
- Thurman AR, Chandra N, Yousefieh N, Zalenskaya I, Kimble T, Asin S, Rollenhagen C, Anderson SM, Herold B, Mesquita PM, Richardson-Harman N, Cunningham T, Schwartz JL, Doncel GF. Comparison of Follicular and Luteal Phase Mucosal Markers of HIV Susceptibility in Healthy Women. AIDS Research and Human Retroviruses. 2016.
- Keller MJ, Mesquita PM, Marzinke MA, Teller R, Espinoza L, Atrio JM, Lo Y, Frank B, Srinivasan S, Fredricks DN, Rabe L, Anderson PL, Hendrix CW, Kiser PF, Herold BC. A phase 1 randomized placebo-controlled safety and pharmacokinetic trial of a tenofovir disoproxil fumarate vaginal ring. AIDS. 2016; 30(5):743-51.
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