2 resultados para HIV-1 epidemic

em DRUM (Digital Repository at the University of Maryland)


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The purpose of this study is to examine organizational patterns of African American activism in response the HIV/AIDS epidemic. Given their political, economic, and social disenfranchisement, African Americans have historically developed protest and survival strategies to respond to the devaluation of their lives, health, and well-being. While Black protest strategies are typically regarded as oppositional and transformative, Black survival strategies have generally been conceptualized as accepting inequality. In the case of HIV/AIDS, African American religious and non-religious organizations were less likely to deploy protest strategies to ensure the survival and well-being of groups most at risk for HIV/AIDS—such as African American gay men and substance abusers. This study employs a multiple qualitative case study analysis of four African American organizations that were among the early mobilizers to respond to HIV/AIDS in Washington D.C. These organizations include two secular or community-based organizations and two Black churches or faith-based organizations. Given the association of HIV/AIDS with sexual sin and social deviance, I postulated that Black community-based organizations would be more responsive to the HIV/AIDS-related needs and interests of African Americans than their religious counterparts. More specifically, I expected that Black churches would be more conservative (i.e. maintain paternalistic heteronormative sexual standards) than the community-based organizations. Yet findings indicate that the Black churches in this study were more similar than different than the community-based organizations in their strategic responses to HIV/AIDS. Both the community-based organizations and Black churches drew upon three main strategies in ways that politicalize the struggle for Black survival—or what I regard as Black survival politics. First, Black survival strategies for HIV/AIDS include coalition building at the intersection of multiple systems of inequality, as well as on the levels of identity and community. Second, Black survival politics include altering aspects of religious norms and practices related to sex and sexuality. Third, Black survival politics relies on the resources of the government to provide HIV/AIDS related programs and initiatives that are, in large part, based on the gains made from collective action.

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Human immunodeficiency virus (HIV) rapidly evolves through generation and selection of mutants that can escape drug therapy. This process is fueled, in part, by the presumably highly error prone polymerase reverse transcriptase (RT). Fidelity of polymerases can be influenced by cation co-factors. Physiologically, magnesium (Mg2+) is used as a co-factor by RT to perform catalysis, however, alternative cations including manganese (Mn2+), cobalt (Co2+), and zinc (Zn2+) can also be used. I demonstrate here that fidelity and inhibition of HIV RT can be influenced differently, in vitro, by divalent cations depending on their concentration. The reported mutation frequency for purified HIV RT in vitro is typically in the 10-4 range (per nucleotide addition), making the enzyme several-fold less accurate than most polymerases. Paradoxically, results examining HIV replication in cells indicate an error frequency that is ~10 times lower than the error rate obtained in the test tube. Here, I reconcile, at least in part, these discrepancies by showing that HIV RT fidelity in vitro is in the same range as cellular results, in physiological concentrations of free Mg2+ (~0.25 mM). At low Mg2+, mutation rates were 5-10 times lower compared to high Mg2+ conditions (5-10 mM). Alternative divalent cations also have a concentration-dependent effect on RT fidelity. Presumed promutagenic cations Mn2+ and Co2+ decreases the fidelity of RT only at elevated concentrations, and Zn2+, when present in low concentration, increases the fidelity of HIV-1 RT by ~2.5 fold compared to Mg2+. HIV-1 and HIV-2 RT inhibition by nucleoside (NRTIs) and non-nucleoside RT inhibitors (NNRTIs) in vitro is also affected by the Mg2+ concentration. NRTIs lacking 3'-OH group inhibited both enzymes less efficiently in low Mg2+ than in high Mg2+; whereas inhibition by the “translocation defective RT inhibitor”, which retains the 3ʹ-OH, was unaffected by Mg2+ concentration, suggesting that NRTIs with a 3ʹ-OH group may be more potent than other NRTIs. In contrast, NNRTIs were more effective in low vs. high Mg2+ conditions. Overall, the studies presented reveal strategies for designing novel RT inhibitors and strongly emphasize the need for studying HIV RT and RT inhibitors in physiologically relevant low Mg2+ conditions.