Attacking the HIV Epidemic From All Sides: Optimization of PCR Strategies to Measure Clonal Expansion and Quantitative Evaluation of Dolutegravir
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Date
2016-06-16
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Johns Hopkins University
Abstract
Although great progress has been achieved in the fight against HIV and AIDS, an epidemic continues to rage worldwide. Alongside public health and clinical efforts, scientific research plays a major role in this fight; ongoing studies focus on improving treatment options, designing a vaccine, and developing a cure. The first study described in this dissertation is a critique of research and analysis methods commonly used to characterize the latent HIV reservoir, which is considered a barrier to the cure of HIV infection. This project highlights the importance of understanding molecular biology tools and considering their inherent limitations when interpreting results. The second study presented here comprises a quantitative evaluation of the efficacy of dolutegravir, an antiretroviral drug that has emerged recently as one of our best weapons for controlling HIV infection. Results show that the high efficacy of dolutegravir in combination with other antiretroviral drugs, as well as the high genetic barrier to viral evolution of dolutegravir resistance, are consistent with the tremendous clinical success of this drug. The grand conclusion of this dissertation is that much work remains to be done. We continue to discover safer, more effective tools for the treatment of HIV infection, which may be seen as a silver lining given how far we appear to be from achieving a cure.
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HIV, antiretroviral therapy, clonal expansion, latency, latent reservoir, dolutegravir, PCR, clonal prediction score