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1.
HIV Med ; 15(1): 3-12, 2014 Jan.
Article in English | MEDLINE | ID: mdl-23980620

ABSTRACT

OBJECTIVES: Low-dose stavudine therapy may have a lower toxicity profile compared with standard dose. A randomized controlled trial comparing these two doses of stavudine with tenofovir disoproxil fumarate (tenofovir DF) was performed to assess the effects on anthropometry, markers of inflammation, and lipid and glucose metabolism in Black South African patients. METHODS: Sixty patients were randomized 1:1:1 to either standard-dose (30-40 mg) or low-dose (20-30 mg) stavudine or tenofovir DF (300 mg), each combined with lamivudine and efavirenz, for 48 weeks. Anthropometry, markers of inflammation, and lipid and glucose metabolism were assessed using standard techniques. RESULTS: In all three treatment arms, there was a significant increase in lipid levels over the study period. At 48 weeks, fasting glucose level (P < 0.005) and homeostasis model assessment (HOMA) score (P < 0.05) increased significantly in the standard-dose stavudine arm, as did insulin and C-peptide levels in both the standard- and low-dose stavudine arms. At week 48, a significant decrease (P < 0.05) in adiponectin was noted in the standard-dose stavudine arm, but there was an increase (P < 0.005) in the tenofovir DF arm. In both the stavudine arms, significant increases in anthropometric measures occurred at 24 weeks but these decreased by week 48. Mitochondrial toxicities occurred in both the stavudine arms. Immunological and virological outcomes were similar for all three arms. CONCLUSIONS: This study highlights the occurrence of metabolic abnormalities with both stavudine and tenofovir DF treatment. Awareness of the potential increased cardiovascular risk should be of concern with the use of both these therapies.


Subject(s)
Adenine/analogs & derivatives , Anti-HIV Agents/administration & dosage , HIV Infections/drug therapy , HIV Infections/metabolism , Phosphorous Acids/administration & dosage , Stavudine/administration & dosage , Adenine/administration & dosage , Adenine/adverse effects , Adult , Alkynes , Analysis of Variance , Anthropometry , Anti-HIV Agents/adverse effects , Benzoxazines/administration & dosage , Benzoxazines/adverse effects , Biomarkers/metabolism , Body Composition/drug effects , Cyclopropanes , DNA, Mitochondrial/drug effects , Dose-Response Relationship, Drug , Drug Substitution , Female , Glucose/metabolism , Humans , Inflammation/metabolism , Lamivudine/administration & dosage , Lamivudine/adverse effects , Lipid Metabolism/drug effects , Male , Middle Aged , Phosphorous Acids/adverse effects , South Africa , Stavudine/adverse effects
2.
HIV Med ; 14(4): 217-25, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23036096

ABSTRACT

OBJECTIVES: Stavudine is being phased out because of its mitochondrial toxicity and tenofovir (TDF) is recommended as part of first-line highly active antiretroviral therapy (HAART) in South Africa. A prospective, open-label, randomized controlled trial comparing standard- and low-dose stavudine with TDF was performed to assess early differences in adipocyte mtDNA copy number, gene expression and metabolic parameters in Black South African HIV-infected patients. METHODS: Sixty patients were randomized 1:1:1 to either standard-dose (30-40 mg) or low-dose (20-30 mg) stavudine or TDF (300 mg) each combined with lamivudine and efavirenz. Subcutaneous fat biopsies were obtained at weeks 0 and 4. Adipocyte mtDNA copies/cell and gene expression were measured using quantitative polymerase chain reaction (qPCR). Markers of inflammation and lipid and glucose metabolism were also assessed. RESULTS: A 29% and 32% decrease in the mean mtDNA copies/cell was noted in the standard-dose (P < 0.05) and low-dose stavudine (P < 0.005) arms, respectively, when compared with TDF at 4 weeks. Nuclear respiratory factor-1 (NRF1) and mitochondrial cytochrome B (MTCYB) gene expression levels were affected by stavudine, with a significantly (P < 0.05) greater fall in expression observed with the standard, but not the low dose compared with TDF. No significant differences were observed in markers of inflammation and lipid and glucose metabolism. CONCLUSIONS: These results demonstrate early mitochondrial depletion among Black South African patients receiving low and standard doses of stavudine, with preservation of gene expression levels, except for NRF1 and MTCYB, when compared with patients on TDF.


Subject(s)
Adenine/analogs & derivatives , Adipocytes/drug effects , Anti-HIV Agents/therapeutic use , HIV Infections/drug therapy , Organophosphonates/therapeutic use , Reverse Transcriptase Inhibitors/therapeutic use , Stavudine/therapeutic use , Adenine/therapeutic use , Adipocytes/metabolism , Adult , Antiretroviral Therapy, Highly Active , Biomarkers/metabolism , DNA Copy Number Variations/drug effects , DNA, Mitochondrial/drug effects , DNA, Mitochondrial/genetics , Dose-Response Relationship, Drug , Female , Gene Expression Profiling , Glucose/metabolism , HIV Infections/genetics , HIV Infections/metabolism , Humans , Inflammation/metabolism , Lipid Metabolism/drug effects , Male , Middle Aged , Prospective Studies , South Africa , Tenofovir
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