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Tsibris, Athe

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Tsibris

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Athe

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Tsibris, Athe
Author's Publications: search.filters.isAuthorOfPublication.6aa22266-ab21-43c6-ab93-9e91349fc5e6

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    Barriers to a cure for HIV in women
    (International AIDS Society, 2016) Gianella, Sara; Tsibris, Athe; Barr, Liz; Godfrey, Catherine
    Introduction: Distinct biological factors exist that affect the natural history of HIV and the host immune response between women and men. These differences must be addressed to permit the optimal design of effective HIV eradication strategies for much of the HIV-positive population. Methods and results Here, we review the literature on sex-based differences in HIV pathogenesis and natural history in tissues and anatomic compartments, HIV latency and transcriptional activity, and host immunity including the role of sex hormones. We then outline the potential effects of these differences on HIV persistence, and on the safety and efficacy of HIV eradication and curative interventions. Finally, we discuss the next steps necessary to elucidate these factors to achieve a cure for HIV, taking in account the complex ethical issues and the regulatory landscape in the hopes of stimulating further research and awareness in these areas. Conclusions: Targeted enrolment of women in clinical trials and careful sex-based analysis will be crucial to gain further insights into sex-based differences in HIV persistence and to design sex-specific approaches to HIV eradication, if required.
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    Quantitative deep sequencing reveals dynamic HIV-1 escape and large population shifts during CCR5 antagonist therapy in vivo
    (Public Library of Science, 2009) Korber, Bette; Russ, Carsten; Lo, Chien-Chi; Leitner, Thomas; Gaschen, Brian; Theiler, James; Paredes, Roger; Su, Zhaohui; Gulick, Roy M.; Greaves, Wayne; Coakley, Eoin; Flexner, Charles; Nusbaum, Chad; Tsibris, Athe; Arnaout, Ramy; Hughes, Michael; Kuritzkes, Daniel
    High-throughput sequencing platforms provide an approach for detecting rare HIV-1 variants and documenting more fully quasispecies diversity. We applied this technology to the V3 loop-coding region of env in samples collected from 4 chronically HIV-infected subjects in whom CCR5 antagonist (vicriviroc [VVC]) therapy failed. Between 25,000–140,000 amplified sequences were obtained per sample. Profound baseline V3 loop sequence heterogeneity existed; predicted CXCR4-using populations were identified in a largely CCR5-using population. The V3 loop forms associated with subsequent virologic failure, either through CXCR4 use or the emergence of high-level VVC resistance, were present as minor variants at 0.8–2.8% of baseline samples. Extreme, rapid shifts in population frequencies toward these forms occurred, and deep sequencing provided a detailed view of the rapid evolutionary impact of VVC selection. Greater V3 diversity was observed post-selection. This previously unreported degree of V3 loop sequence diversity has implications for viral pathogenesis, vaccine design, and the optimal use of HIV-1 CCR5 antagonists.