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1.
HIV Med ; 14(4): 217-25, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23036096

RESUMO

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.


Assuntos
Adenina/análogos & derivados , Adipócitos/efeitos dos fármacos , Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Organofosfonatos/uso terapêutico , Inibidores da Transcriptase Reversa/uso terapêutico , Estavudina/uso terapêutico , Adenina/uso terapêutico , Adipócitos/metabolismo , Adulto , Terapia Antirretroviral de Alta Atividade , Biomarcadores/metabolismo , Variações do Número de Cópias de DNA/efeitos dos fármacos , DNA Mitocondrial/efeitos dos fármacos , DNA Mitocondrial/genética , Relação Dose-Resposta a Droga , Feminino , Perfilação da Expressão Gênica , Glucose/metabolismo , Infecções por HIV/genética , Infecções por HIV/metabolismo , Humanos , Inflamação/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , África do Sul , Tenofovir
2.
S Afr Med J ; 111(5): 474-481, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-34852891

RESUMO

BACKGROUND: South Africa (SA) has among the highest rates of HIV and tuberculosis (TB) in the world. Antituberculosis and antiretroviral treatment (ART) can cause drug-induced liver injury (DILI), consequences of which are disease relapse, treatment failure and drug resistance. OBJECTIVES: To: (i) determine the demographics of patients with DILI and the proportion of patients on antituberculosis drugs v. antiretroviral therapy or both; (ii) determine the median time to DILI after starting medication, and patterns of clinical presentation; (iii) determine the numbers of patients successfully re-challenged to initial therapy as inpatients; and (iv) determine the in-hospital mortality rate and predictors of all-cause mortality. METHODS: This was a retrospective record review of adult patients with DILI admitted to a tertiary hospital in Johannesburg, SA, between October 2015 and February 2017. Data on drug history, biochemical investigations and relevant imaging were collected. RESULTS: The total sample was 129 records: 79 (61.2%) were males, 46 (35.7%) had TB DILI, 29 (22.5%) had ART DILI, and 54 (41.9%) had mixed TB/ART DILI. Only 7.4% (2/27) of those with ART DILI and 30.6% (11/36) with TB DILI were re-challenged to their original regimen by discharge. Patients were followed from admission until the earlier of death (10 with TB DILI, 2 with ART DILI and 9 with mixed DILI) or discharge (after a median (interquartile range) of 14.0 (9 - 23) days). In adjusted analysis, severe DILI at admission predicted all-cause mortality (adjusted hazard ratio 8.58; 95% confidence interval 1.13 - 65.4). CONCLUSIONS: This study is one of only a few analyses of hospitalised patients with DILI in SA. Among those with severe DILI, outcomes are poor, the majority cannot tolerate standard regimens, and mortality is high.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Antituberculosos/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Adulto , Fármacos Anti-HIV/administração & dosagem , Antituberculosos/administração & dosagem , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Doença Hepática Induzida por Substâncias e Drogas/mortalidade , Feminino , Infecções por HIV/tratamento farmacológico , Mortalidade Hospitalar , Hospitalização , Humanos , Masculino , Estudos Retrospectivos , Índice de Gravidade de Doença , África do Sul , Centros de Atenção Terciária , Tuberculose/tratamento farmacológico
3.
S Afr Med J ; 106(10): 1002-1009, 2016 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-27725021

RESUMO

BACKGROUND: Despite the large number of tuberculosis (TB) patients treated in South Africa (SA), there are few descriptions in the published literature of drug-susceptible TB patient characteristics, mode of diagnosis or treatment outcomes in routine public sector treatment programmes. OBJECTIVE: To enhance the evidence base for public sector TB treatment service delivery, we reported the characteristics of and outcomes for a retrospective cohort of adult TB patients at public sector clinics in the Johannesburg Metropolitan Municipality (JHB), SA. METHODS: We collected medical record data for a retrospective cohort of adult (≥18 years) TB patients registered between 1 April 2011 and 31 March 2012 at three public sector clinics in JHB. Data were abstracted from National TB Programme clinic cards and the TB case registers routinely maintained at study sites. We report patient characteristics, mode of diagnosis, mode of treatment supervision, treatment characteristics, HIV status and treatment outcomes for this cohort. RESULTS: A total of 544 patients were enrolled in the cohort. Most (86%) were new TB cases, 81% had pulmonary TB, 58% were smear-positive at treatment initiation and 71% were HIV co-infected. Among 495 patients with treatment outcomes reported, 80% (n=394) had successful outcomes, 11% (n=55) were lost to follow-up, 8% (n=40) died and 1% (n=6) failed treatment. CONCLUSIONS: Primary healthcare clinics in JHB are achieving relatively high rates of success in treating drug-susceptible TB. Missing laboratory results were common, including follow-up smears, cultures and drug susceptibility tests, making it difficult to assess adherence to guidelines and leaving scope for substantial improvements in record-keeping at the clinics involved.

4.
S Afr Med J ; 105(2): 157, 2014 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-26242513
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