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: 2.06). 02/2012; 27(1):51-64. DOI: 10.1177/0884533611431985
Source: PubMed

ABSTRACT 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.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Life expectancy has increased in HIV-positive individuals receiving combination antiretroviral therapy (cART); however, they still experience increased mortality due to ageing-associated comorbidities compared with HIV-negative individuals. A retrospective study of 314 Queensland HIV-infected males on cART was conducted. The negative impact of ageing was assessed by estimating the probability of 5-year mortality; comparisons were made between an HIV-specific predictive tool (VACS index) and the Australian Bureau of Statistics (ABS) life-tables to examine potential differences attributed to HIV. The negative impact of ageing was also assessed by the prevalence of comorbidities. Associations between comorbidity and estimates of predicted mortality by regression analysis were assessed. The mean predicted 5-year mortality rate was 6% using the VACS index compared with 2.1% using the ABS life-table (p<0.001). The proportion of patients at predicted high risk of mortality (>9%) using the VACS index or ABS life-table were 17% and 1.8% respectively. Comorbidities were also more prevalent in this cohort compared with rates of comorbidities in age-matched Australian men from the general population. Metabolic disease (38.2%) was the most prevalent comorbidity followed by renal (33.1%) and cardiovascular disease (23.9%). Multivariate analysis demonstrated that patients with a history of cardiovascular disease had a higher predicted risk of mortality (OR=1.69;95%CI:1.17-2.45) whereas ex-smokers had a lower predicted risk of mortality (OR=0.61;95%CI:0.41-0.92). Using the VACS Index there is an increased predicted risk of mortality in cART-treated HIV infected Australian men compared with age-matched men using the ABS data. This increased predicted mortality risk is associated with cardiovascular disease and the number of comorbidities per subject; which suggests that the VACS Index may discriminate between high and low predicted mortality risks in this population. However, until the VACS Index is validated in Australia this data may suggest the VACS Index overestimates predicted mortality risk in this country.
    PLoS ONE 10/2013; 8(10):e78403. DOI:10.1371/journal.pone.0078403 · 3.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    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.
    Molecular Therapy 02/2014; 22(5). DOI:10.1038/mt.2014.32 · 6.43 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Over the past 15 years we have been investigating an alternative approach to treating HIV-1/AIDS, based on the creation of a disease-resistant immune system through transplantation of autologous, gene-modified (HIV-1-resistant) hematopoietic stem and progenitor cells (GM-HSPC). We propose that the expression of selected RNA-based HIV-1 inhibitors in the CD4+ cells derived from GM-HSPC will protect them from HIV-1 infection and results in a sufficient immune repertoire to control HIV-1 viremia resulting in a functional cure for HIV-1/AIDS. Additionally, it is possible that the subset of protected T cells will also be able to facilitate the immune-based elimination of latently infected cells if they can be activated to express viral antigens. Thus, a single dose of disease resistant GM-HSPC could provide an effective treatment for HIV-1+ patients who require (or desire) an alternative to lifelong antiretroviral chemotherapy. We describe herein the results from several pilot clinical studies in HIV-1 patients and our strategies to develop second generation vectors and clinical strategies for HIV-1+ patients with malignancy who require ablative chemotherapy as part of treatment and others without malignancy. The important issues related to stem cell source, patient selection, conditioning regimen and post-infusion correlative studies become increasingly complex and are discussed herein.
    Viruses 11/2013; 5(11):2898-2919. DOI:10.3390/v5112898 · 3.28 Impact Factor


Available from