This study utilized a case-series design comparing the hepatic expression of cholesterol regulating genes in HIV-positive (case) and HIV-negative (control) patients presenting with symptomatic gallstones. Ethical approval was obtained from the University of KwaZulu Natal (UKZN) Biomedical Research Ethics Committee (BREC) (BE276/16). Patients undergoing cholecystectomy for gallstone disease (biliary cholic, cholecystitis, jaundice, and gallstone pancreatitis) at King Edward VIII Hospital, Durban, KwaZulu Natal, South Africa, from January–December 2017 were recruited. In total, 96 Black South African women provided informed consent (standard consent form in two official main languages, i.e., English and isiZulu) for the retrieval of a liver biopsy and the recording of patient clinical parameters, including age, race, BMI, family history of gallstones, and comorbidities (HIV, hypertension, diabetes, hypercholesterolemia). The study was carried out in accordance with the institutional guidelines.
Following the analysis of clinical parameters in all subjects, five HIV-negative (control) and five HIV-positive (cases) were selected for mRNA analysis to identify if hepatic nuclear factors were differentially regulated. All patients selected were of Black African ethnicity and female gender, with no co-morbidities (diabetes and hypertensive statin therapy, hepatitis infection, or tuberculosis treatment). All HIV-positive patients were on fixed dose combination (FDC) therapy, with CD4 counts above 500 cells/mm3 and undetectable viral loads. The FDC regimen consisted of 3 drugs, namely two nucleoside reverse transcriptase inhibitors (NRTIs) drugs [tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC)] and one non-nucleoside reverse transcriptase inhibitor (NNRTI) [efavirenz (EFV)]. Common second-line agents used were protease inhibitors (PI) [lopinivar/ritonavir (Aluvia) or atazanavir/ritonavir]. None of the patients were on integrase strand transfer inhibitor (InSTI) [dolutegravir (DTG)] based therapies.
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