Browsing by Subject "Tenofovir"

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    Open Access
    An exploratory pharmacogenetic screening of SLC22A6, SLC22A8, ABCC4 and ABCC10 genes in a cohort of Ghanaian HBV patients
    (2023-07-27) Thomford, Nicholas E.; Adu, Faustina; Gavor-Kwashi, Cyril; Nyarko, Samuel B.; Nsiah, Paul; Ephraim, Richard D.; Adjei, George; Anyanful, Akwasi
    Abstract Background Organic anion transporters and efflux transporters are involved in the metabolism of drugs such as tenofovir disoproxil fumarate (TDF). Given the important role of organic anions and efflux transporters in drug disposition, genetic variations lead to interindividual differences in drug response. Variations in the SLC and ABC transporters have been associated with drug-induced renal dysfunction. Looking at the prevalence of HBV infection in our population and the use of drugs such as TDF in managing this condition, this study aimed to undertake an exploratory analysis of genetic variation in renal transporters SLC22A6, SLC22A8, ABCC10 and ABCC4 in a Ghanaian HBV infected cohort. Methods We genotyped 160 HBV infected patients for SNPs in SLC22A6 (rs12293966, rs4149170, rs6591722, rs955434), SLC22A8 (rs11568487), ABCC10 (rs700008, rs831311) and ABCC4 (rs9282570) genes. Clinicodemographic data was taken, and glomerular filtration rate (eGFR) was estimated using the CKD-EPI formula. Genotyping was undertaken using Iplex gold SNP genotyping protocol on the Agena MassARRAY® system. Statistical analysis was undertaken using packages in Stata SE (v17) and GraphPad prism. Hardy–Weinberg equilibrium, haplotype inference, and linkage disequilibrium (LD) were evaluated using web-based tools LDlink and Shesis. Results The average eGFR was 79.78 ± 33.08 mL/min/1.73 m2 with 31% classified as stage 1 with normal or high GFR (eGFR > 90 mL/min/1.73 m2) and 45% with stage 2 CKD (> 60–89.99 mL/min/1.73 m2). All variants were in HWE except rs4149170, rs9282570 and rs700008 where p < 0.05. Strong LD was observed in the variants rs6591722, rs4149170, rs12293966, rs955434 and rs11568487. There was significant association between rs12293966 and eGFR stage under crude dominant inheritance model (OR 0.27, 95% CI 0.08–0.81; p = 0.019). Under crude model (OR 0.21, 95% CI 0.07–0.66; p = 0.008), adjusted model 1 (OR 76, 95% CI 0.39–7.89; p = 0.014) and adjusted model 2 (OR 0.30, 95% CI 0.12–0.78; p = 0.013) there was significant association observed between rs12293966 and eGFR stage in a codominant inheritance. Conclusion The associations observed in this study point to the need for further evaluation with the population of HBV patients on TDF treatment in addition to other factors that would lead to unfavorable outcomes. This exploratory finding may require confirmation in a larger cohort with proper phenotyping to investigate the exact pharmacogenetic mechanisms.
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    Incidence and Prevalence Of Renal Dysfunction In Antiretroviral Therapy (ART) Naïve Patients Starting A Tenofovir (TDF) Based ART Regimen In Mitchell's Plain Community Health Centre (CHC) ARV Clinic
    (2021) Fayanju, Olanrewaju Philips; Hellenberg, Derek; Ras, Tasleem
    Background: Tenofovir disoproxil fumarate (TDF) has high antiretrovirus (ARV) activity and available in fixed dose combination (FDC). However, it has been found to cause renal dysfunction. Objectives: To document the prevalence, incidence, pattern of occurence and associated factors of nephrotoxicity in patients initiated on TDF based ART regimen in Mitchell's Plain CHC ARV Clinic and make recommendations. Methodology: The study was conducted by reviewing retrospective records of all ARV naïve HIV positive adults initiated on TDF based ARV regimen from January 2016 to June 2016. The creatinine clearance (CrCl) was calculated from follow up parameters till June 2018. Results: 87 patients were included in the study and 56% were female. The mean age was 34 years. Majority, 83%, had normal renal function at ART initiation. Older age [OR = 1.11; 95% CI (1.03–1.19), p =0.005], was associated with an increased probability of non-normal renal function at baseline. The incidence of CrCl < 90ml/min were 1.5% at 1 month post ARV initiation, 3.3% at 4 months, 6.1% at 12 months and 2.8% at 24 months while the prevalence were 10.5%,11.5%, 20.4% and 16.7% respectively. Older age and male gender were independently associated with prevalence of renal impairment. Conclusion: Renal dysfunction in patients initiated on TDF based regimen in this study varied and were relatively small when compared to the prevalence of renal dysfunction at initiation. Majority of the decline in CrCl were transient and patients were found to have recovered after further follow up. It is recommended that the frequency of renal function monitoring in patients on TDF regimen be done within programmatic guidelines based on patients' risk factors and potential poor outcomes.
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    Renal safety of lithium in HIV-infected patients established on tenofovir disoproxil fumarate containing antiretroviral therapy: analysis from a randomized placebo-controlled trial
    (BioMed Central, 2017-02-04) Decloedt, Eric H; Lesosky, Maia; Maartens, Gary; Joska, John A
    Background: The prevalence of bipolar disorder in HIV-infected patients is higher than the general population. Lithium is the most effective mood stabiliser, while tenofovir disoproxil fumarate (TDF) is frequently used as part of combination antiretroviral therapy (ART). Both TDF and lithium are associated with renal tubular toxicity, which could be additive, or a pharmacokinetic interaction may occur at renal transporters with a decrease in TDF elimination. Objective: We report on the change in estimated glomerular filtration rate (eGFR) using the modification of diet in renal disease formula in participants who received ART including TDF and were enrolled in a 24 week randomised trial of lithium versus placebo in patients with HIV-associated neurocognitive impairment. Methods: We included HIV-infected adults with cognitive impairment established on ART for at least 6 months with a suppressed viral load attending public sector ART clinics in Cape Town, South Africa. We excluded participants with an eGFR or increase in potassium between the two arms during the 24 weeks. Conclusions: We found that 24-week treatment of HIV-infected patients with lithium and TDF did not result in increased nephrotoxicity.
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    Renal safety of lithium in HIV-infected patients established on tenofovir disoproxil fumarate containing antiretroviral therapy: analysis from a randomized placebo-controlled trial
    (2017) Decloedt, Eric H; Lesosky, Maia; Maartens, Gary; Joska, John A
    BACKGROUND: The prevalence of bipolar disorder in HIV-infected patients is higher than the general population. Lithium is the most effective mood stabiliser, while tenofovir disoproxil fumarate (TDF) is frequently used as part of combination antiretroviral therapy (ART). Both TDF and lithium are associated with renal tubular toxicity, which could be additive, or a pharmacokinetic interaction may occur at renal transporters with a decrease in TDF elimination. OBJECTIVE: We report on the change in estimated glomerular filtration rate (eGFR) using the modification of diet in renal disease formula in participants who received ART including TDF and were enrolled in a 24 week randomised trial of lithium versus placebo in patients with HIV-associated neurocognitive impairment. METHODS: We included HIV-infected adults with cognitive impairment established on ART for at least 6 months with a suppressed viral load attending public sector ART clinics in Cape Town, South Africa. We excluded participants with an eGFR <60 mL/min and treated with medications predisposing to lithium toxicity. We reviewed participants weekly for the first month for adverse events followed by 4 weekly visits for renal function assessment, adverse event monitoring and adherence. Lithium dose was titrated to achieve the maintenance target plasma concentration of between 0.6 and 1.0 mmol/L. Sham lithium concentrations were generated for participants receiving placebo. RESULTS: We included 23 participants allocated to the lithium arm and 30 participants allocated to the placebo arm. Baseline characteristics were not statistically different with a mean age of 37.7 and 40.8 years, a median time on ART of 33 and 40 months and an eGFR of 139.3 and 131.0 mL/min in the lithium and placebo arms respectively. There was no statistical significant difference in the reduction in eGFR or increase in potassium between the two arms during the 24 weeks. CONCLUSIONS: We found that 24-week treatment of HIV-infected patients with lithium and TDF did not result in increased nephrotoxicity. Trial registration The study was registered on the Pan African Clinical Trials Registry (PACTR) with the identifier number PACTR201310000635418. Registered 11 October 2013 before the first participant was enrolled.