AZT is the only currently approved agent for the primary therapy of HIV related disease. Resistance to this agent has recently been reported in patients receiving the drug for more than 6 months. However, the clinical significance, the mechanisms and factors relating to the emergence of resistant HIV strains remains unknown. This phenomenon suggests that the development of AZT resistance may, in part, explain subsequent clinical deterioration. In this project we propose to determine the frequency and patterns of emergence of AZT resistant HIV from patients with HIV disease who are on AZT therapy and to evaluate resistance to other antiviral compounds. To accomplish this goal, 100-120 patients will be examined to determine if combination therapy with antivirals administered simultaneously or sequentially affects the emergence of HIV resistant strains, and to determine which combinations maximally inhibit the development of resistance. HIV from patients will be isolated by co-cultivation with normal PBLs, and the sensitivity to AZT and/or other compounds will be evaluated prior to initiation of therapy and at 6 monthly intervals thereafter. The relationship of the development of resistance to the virus burden of the patient (serum P24Ag), and markers of the immune response in peripheral blood (CD4:CD8, serum beta 2-microglobulin, lymphocyte transformation, and interferon-gamma production to specific and non-specific antigens) will also be evaluated. The clinical relevance of the development of HIV drug resistance will be pursued by monitoring and assessing changes in neurobehavioral testing, the frequency of development of opportunistic infections, and changes in weight and other clinical parameters of the study patients. Understanding the natural history of development of resistance should assist in designing changes in the administration of existing therapeutic agents and help identify the novel therapeutic regimens to minimize the emergence of such resistant strains. The development of this information could directly affect patient care practices and outcome.

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University of Texas Medical Br Galveston
United States
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Martin, Maureen P; Naranbhai, Vivek; Shea, Patrick R et al. (2018) Killer cell immunoglobulin-like receptor 3DL1 variation modifies HLA-B*57 protection against HIV-1. J Clin Invest 128:1903-1912
Haas, David W; Bradford, Yuki; Verma, Anurag et al. (2018) Brain neurotransmitter transporter/receptor genomics and efavirenz central nervous system adverse events. Pharmacogenet Genomics 28:179-187
Venuto, Charles S; Lim, Jihoon; Messing, Susan et al. (2018) Inflammation investigated as a source of pharmacokinetic variability of atazanavir in AIDS Clinical Trials Group protocol A5224s. Antivir Ther 23:345-351
Li, Binglan; Verma, Shefali S; Veturi, Yogasudha C et al. (2018) Evaluation of PrediXcan for prioritizing GWAS associations and predicting gene expression. Pac Symp Biocomput 23:448-459
Gupta, Samir K; Yeh, Eunice; Kitch, Douglas W et al. (2017) Bone mineral density reductions after tenofovir disoproxil fumarate initiation and changes in phosphaturia: a secondary analysis of ACTG A5224s. J Antimicrob Chemother 72:2042-2048
Verma, Anurag; Bradford, Yuki; Verma, Shefali S et al. (2017) Multiphenotype association study of patients randomized to initiate antiretroviral regimens in AIDS Clinical Trials Group protocol A5202. Pharmacogenet Genomics 27:101-111
Bednasz, Cindy J; Venuto, Charles S; Ma, Qing et al. (2017) Efavirenz Therapeutic Range in HIV-1 Treatment-Naive Participants. Ther Drug Monit 39:596-603
Verma, Shefali S; Frase, Alex T; Verma, Anurag et al. (2016) PHENOME-WIDE INTERACTION STUDY (PheWIS) IN AIDS CLINICAL TRIALS GROUP DATA (ACTG). Pac Symp Biocomput 21:57-68
Moore, Carrie B; Verma, Anurag; Pendergrass, Sarah et al. (2015) Phenome-wide Association Study Relating Pretreatment Laboratory Parameters With Human Genetic Variants in AIDS Clinical Trials Group Protocols. Open Forum Infect Dis 2:ofu113
Lehmann, David S; Ribaudo, Heather J; Daar, Eric S et al. (2015) Genome-wide association study of virologic response with efavirenz-containing or abacavir-containing regimens in AIDS clinical trials group protocols. Pharmacogenet Genomics 25:51-9

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