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Design and Evaluation of a Topical Rectal Specific Microbicide for HIV prevention

Jhunjhunwala, Kunal (2015) Design and Evaluation of a Topical Rectal Specific Microbicide for HIV prevention. Master's Thesis, University of Pittsburgh. (Unpublished)

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Abstract

According to the UNAIDS report 2013, there were 2.1 million new HIV infections including adults and children. This indicates that apart from the already existing therapeutic ART (Antiretroviral Therapy), there is a need for development of HIV prevention products which can reduce the risk of HIV transmission from person to person. Such products which are referred to as microbicides could be used as a means of pre exposure prophylaxis (PrEP). A vaginal gel containing 1% tenofovir, a nucleotide reverse transcriptase inhibitor (NtRTI), has been evaluated in clinical trials to be used prior to sexual intercourse for prevention of HIV infection. This vaginal gel was also evaluated for rectal use, where it showed negative side effects. However the same gel with reduced amount of glycerin did not show any side effects rectally. Physiologically, the rectum and vagina are very different. Hence, development of rectal specific microbicide products is needed. In addition to gel formulations, such products may also be in the form of a suppository, enemas, foams etc. [1]. The design of rectal specific gel and suppository products for tenofovir and its combination is the focus of this thesis work.
In addition to tenofovir, other classes of antiretroviral (ARV) drugs such as reverse transcriptase inhibitors, integrase inhibitors (IIs), entry inhibitors, and fusion inhibitors have been evaluated for the development of HIV prevention products [2, 3]. Raltegravir, an II, has shown potential to be a drug candidate for HIV preventative topical product given its anti-HIV activity when challenged post product treatment using a macaque model [4]. Elvitegravir is a potent analog of raltegravir, which is currently available on the market in the form of a combination ART. Therefore a combination of the NtRTI (tenofovir) and the II (elvitegravir) in the form of a rectal specific gel and a rectal suppository was evaluated in this body of work.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Jhunjhunwala, Kunalksj13@pitt.eduKSJ13
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Thesis AdvisorRohan, Lisa Clrohan@mwri.magee.edu
Committee MemberSant, Vinayakvis45@pitt.eduVIS45
Committee MemberYang, Haitaohtyang2000@gmail.com
Date: 4 August 2015
Date Type: Publication
Defense Date: 26 May 2015
Approval Date: 4 August 2015
Submission Date: 2 August 2015
Access Restriction: 1 year -- Restrict access to University of Pittsburgh for a period of 1 year.
Number of Pages: 64
Institution: University of Pittsburgh
Schools and Programs: School of Pharmacy > Pharmaceutical Sciences
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: HIV, rectal microbicides, tenofovir, elvitegravir, gel, suppositories
Date Deposited: 04 Aug 2015 11:55
Last Modified: 15 Nov 2016 14:29
URI: http://d-scholarship.pitt.edu/id/eprint/25845

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