HIV Medications: An Update and Review of Metabolic Complications

Auburn University Harrison School of Pharmacy, Auburn University, 1321 Walker Building, Auburn, AL 36849, USA.
Nutrition in Clinical Practice (Impact Factor: 2.4). 02/2012; 27(1):51-64. DOI: 10.1177/0884533611431985
Source: PubMed


In the past 30 years, medical advances for those with human immunodeficiency virus (HIV) have reduced morbidity and mortality to extend life with highly active antiretroviral therapy (HAART) and with the continued development of new therapies. With this success, HIV is being managed chronically, but other health issues of an aging HIV-infected population have emerged. The challenges of treating HIV infection have shifted from AIDS-related mortality improvements to drug-induced disease from HAART, including cardiovascular disease, metabolic disorders, and bone health. Prolonged use of antiretroviral therapy maintaining immune restoration appears to represent additional, ongoing risk factors for the development of these metabolic complications. These drug-related problems continue to challenge patients and clinicians in the management of HIV disease, as well as ongoing research for drug development improvements to minimize these risks. These health risks imposed by HAART must be vigilantly monitored and aggressively addressed to improve the overall health of those treated for HIV infection.

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Available from: Elizabeth Kelly Hester, Sep 15, 2015
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    • "The current standard of care is combinatorial antiretroviral therapy which consists of a cocktail of small molecule drugs that target multiple stages of viral replication. Although significantly improving patient survival and quality of life, combinatorial antiretroviral therapy is a lifelong, expensive treatment that is associated with an increased incidence of cardiovascular disease, lipodystrophy, and neurological complications among other clinical sequelae.2,3,4,5,6 Furthermore, with the emergence of drug-resistant viral mutants and the persistence of latent viral reservoirs, an alternative and more comprehensive approach to conventional HIV therapy is needed. "
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    ABSTRACT: Gene therapy with hematopoietic stem and progenitor cells is a promising approach to engineering immunity to HIV that may lead to a functional cure for AIDS. In support of this approach, we created lentiviral vectors with an engineered polycistronic platform derived from the endogenous MCM7 gene to express a diverse set of small antiviral RNAs and a drug resistance MGMT(P140K) marker. Multiple strategies for simultaneous expression of up to five RNA transgenes were tested. The placement and orientation of each transgene and its promoter were important determinants for optimal gene expression. Antiviral RNA expression from the MCM7 platform with U1 promoter was sufficient to provide protection from R5 tropic HIV in macrophages and resulted in reduced hematopoietic toxicity compared to constructs expressing RNA from independent Pol III promoters. The addition of HIV entry inhibitor and nucleolar TAR RNA decoy did not enhance antiviral potency over constructs that targeted only viral RNA transcripts. We also demonstrated selective enrichment of gene modified cells in vivo using a humanized mouse model. The use of these less toxic, potent anti-HIV vectors expressing a drug selection marker is likely to enhance the in vivo efficacy of our stem cell gene therapy approach to treating HIV/AIDS.Molecular Therapy (2014); doi:10.1038/mt.2014.32.
    Full-text · Article · Feb 2014 · Molecular Therapy
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    • "Such challenges include acute infection, decline of immune function, lifelong adherence to antiretroviral therapy (ART), the potential for developing opportunistic infections, and death. We will not describe these challenges further as they have been extensively covered elsewhere (Hester, 2012; Kumari & Singh, 2012; Sax, Cohen, & Kuritzkes, 2011). Increasing interest, however, has focused on life challenges that are not associated with HIV disease itself but can have a powerful impact on the course of the disease. "
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    ABSTRACT: Studies concerning persons living with HIV (PLWH) report that stressful life events (SLEs) contribute to an exacerbation of symptoms and reduced antiretroviral (ARV) adherence and quality of life (QOL). Little is known about whether these findings are site-specific. Our study's aims were to characterize the type and frequency of SLEs for PLWH in Puerto Rico, South Africa, and the United States, and to assess the impact of SLEs by national site, symptoms, and ARV adherence concerns on QOL. The sample consisted of 704 participants. The total number of SLEs correlated significantly with the total number of symptoms, adherence concerns, and QOL (p ≤ .001). Overall, 27.2% of the variance in QOL was explained by the aforementioned variables. Although SLEs were of concern to PLWH, worries about ARV adherence were of even greater concern. Routine assessment of ARV concerns and SLEs can promote ongoing ARV adherence and improved QOL.
    Full-text · Article · Mar 2013 · The Journal of the Association of Nurses in AIDS Care: JANAC
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    ABSTRACT: Introduction: HIV/AIDS continues to be a worldwide health problem and viral eradication has been an elusive goal. HIV+ patients are currently treated with combination antiretroviral therapy (cART) which is not curative. For many patients, cART is inaccessible, intolerable or unaffordable. Therefore, a new class of therapeutics for HIV is required to overcome these limitations. Cell and gene therapy for HIV has been proposed as a way to provide a functional cure for HIV in the form of a virus/infection resistant immune system. Areas covered: In this review, the authors describe the standard therapy for HIV/AIDS, its limitations, current areas of investigation and the potential of hematopoietic stem cells modified with anti-HIV RNAs as a means to affect a functional cure for HIV. Expert opinion: Cell and gene therapy for HIV/AIDS is a promising alternative to antiviral drug therapy and may provide a functional cure. In order to show clinical benefit, multiple mechanisms of inhibition of HIV entry and lifecycle are likely to be required. Among the most promising antiviral strategies is the use of transgenic RNA molecules that provide protection from HIV infection. When these molecules are delivered as gene-modified hematopoietic stem and progenitor cells, long-term repopulation of the patient's immune system with gene-modified progeny has been observed.
    No preview · Article · Mar 2013 · Expert opinion on biological therapy
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