Polymorphisms associated with renal adverse effects of antiretroviral therapy in a Southern Brazilian HIV cohort

Rocha, Ivete M. da; Gasparotto, Aline; Lazzaretti, Rosmeri Kuhmmer; Notti, Regina Kuhmmer; Sprinz, Eduardo; Mattevi, Vanessa Suñé

doi:10.1097/fpc.0000000000000169

Cited by 18 publications

(13 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, in spite of this success, there are still adverse effects incurred from HAART (5) including hepatotoxicity (6), nephrotoxicity (7) and neurotoxicity (8), following large-scale clinical trials on humans as well as animal experimental studies. In addition, there are concerns that the treatment-related drop in morbidity and mortality may actually be overestimated (4) as most studies relies on health-related quality of life outcomes considering only mortality and ignoring treatment-related morbidities.…”

Section: Introductionmentioning

confidence: 99%

Coconut Oil Extract Mitigates Testicular Injury Following Adjuvant Treatment with Antiretroviral Drugs

et al. 2016

View full text Add to dashboard Cite

Increased access to highly active antiretroviral therapy (HAART) has made the management of drug toxicities an increasingly crucial component of HIV. This study investigated the effects of adjuvant use of coconut oil and HAART on testicular morphology and seminal parameters in Sprague- Dawley rats. Twelve adult male Sprague-Dawley rats, weighing 153~169 g were distributed into four groups (A–D) and treated as follows: A served as control (distilled water); B (HAART cocktail- Zidovudine, Lamivudine and Nevirapine); C (HAART + Virgin coconut oil 10 mL/kg) and D (Virgin coconut oil 10 mL/kg). After 56 days of treatment, animals were killed and laparotomy to exercise the epididymis for seminal fluid analyses done whilst testicular tissues were processed for histomorphometric studies. Result showed a significant decline in sperm motility (P < 0.05) and count (P < 0.0001) in HAART-treated animals while there was insignificant changes in other parameters in groups C and D except count that was reduced (P < 0.0001) when compared with controls. Histomorphological studies showed HAART caused disorders in seminiferous tubular architecture with significant (P < 0.01) decline in epithelial height closely mirrored by extensive reticulin framework and positive PAS cells. Adjuvant Virgin coconut oil + HAART resulted in significant decrease in seminiferous tubular diameter (P < 0.05), but other morphometric and histological parameters were similar to control or Virgin coconut oil alone (which showed normal histoarchitecture levels). While derangements in testicular and seminal fluid parameters occurred following HAART, adjuvant treatment with Virgin coconut oil restored the distortions emanating thereof.

show abstract

Section: Introductionmentioning

confidence: 99%

Coconut Oil Extract Mitigates Testicular Injury Following Adjuvant Treatment with Antiretroviral Drugs

et al. 2016

View full text Add to dashboard Cite

show abstract

“… 1183491026 50 ABCB1 c.3243A>G rs1045642 Patients with the AG or GG genotype may be at increased risk of virological failure when receiving highly active antiretroviral therapy (HAART), with lamivudine, lopinavir, ritonavir or zidovudine as compared to patients with the AA genotype. 1183690892 51 ABCC1 c.*1512T>C rs212091 Patients with the CC or CT genotype may be at increased risk of virological failure when treated with highly active antiretroviral therapy (HAART) with lamivudine, lopinavir, ritonavir, or zidovudine compared to patients with the TT genotype. 1444673130 51 ITPA c.124+21A>C rs7270101 Patients with the AA genotype may be at increased risk of anemia but a decreased risk of thrombocytopenia compared to patients with the AC and CC genotype who are taking PEG-IFN α 2b and ribavirin.…”

Section: Resultsmentioning

confidence: 99%

“… 1183690892 51 ABCC1 c.*1512T>C rs212091 Patients with the CC or CT genotype may be at increased risk of virological failure when treated with highly active antiretroviral therapy (HAART) with lamivudine, lopinavir, ritonavir, or zidovudine compared to patients with the TT genotype. 1444673130 51 ITPA c.124+21A>C rs7270101 Patients with the AA genotype may be at increased risk of anemia but a decreased risk of thrombocytopenia compared to patients with the AC and CC genotype who are taking PEG-IFN α 2b and ribavirin. Studies have looked at the composite genotypes of rs1127354 CC and rs7270101 AA to identify “normal” vs “deficient” ITPase activity.…”

Section: Resultsmentioning

confidence: 99%

“…In contrast, cases of toxicity and ADRs are related to sequence variants in the UGT1A1, UGT1A7, UGT1A3, APOE, and APOC3 genes. [44][45][46][47][48]51,55,56,98 In some settings, darunavir-cobicistat may be used in the presence of tolerability or availability of the lopinavir-ritonavir combination (https://covid19 treatmentguidelines.nih.gov). Concerning the metabolism of Azatavir, the variants CYP3A5*1, CYP3A5*3, CYP3A5*6, CYP3A5*7 in CYP3A5 (rs776746) have been reported.…”

Section: Atazanavir and Darunavirmentioning

confidence: 99%

See 1 more Smart Citation

<p>Pharmacogenomics and Pharmacogenetics: In Silico Prediction of Drug Effects in Treatments for Novel Coronavirus SARS-CoV2 Disease</p>

Cafiero¹,

Re²,

Micera³

et al. 2020

PGPM

View full text Add to dashboard Cite

The latest developments in precision medicine allow the modulation of therapeutic approaches in different pathologies on the basis of the specific molecular characterization of the patient. This review of the literature coupled with in silico analysis was to provide a selected screening of interactions between single-nucleotide polymorphisms (SNPs) and drugs (repurposed, investigational, and biological agents) showing efficacy and toxicityin counteracting Covid-19 infection. In silico analysis of genetic variants related to each drug was performed on such databases as PharmGKB, Ensembl Genome Browser, www.drugs.com, and SNPedia, with an extensive literature review of papers (to May 10, 2020) on Covid-19 treatments using Medline, Embase, International Pharmaceutical Abstracts, PharmGKB, and Google Scholar. The clinical relevance of SNPs, known as both drug targets and markers, considering genetic variations with known drug responses, and the therapeutic consequences are discussed. In the context of clinical treatment of Covid-19, including infection prevention, control measures, and supportive care, this review highlights the importance of a personalized approach in the final selection of therapy, which is probably essential in the management of the Covid-19 pandemic.

show abstract

“…The kidney plays a significant role in the metabolism and excretion of some antiretroviral (ARV) medications and this causes the kidney to be more susceptible to various types of injuries, including acute renal failure, tubular dysfunction, nephrolithiasis, obstructive nephropathy, and interstitial nephritis [5]. Abnormal renal function has been identified in about 30% of HIV infected patients [6].…”

Section: Introductionmentioning

confidence: 99%

Chronic kidney disease in patients infected with human immunodeficiency virus (HIV) in an urban cohort

et al. 2019

View full text Add to dashboard Cite

Background and objectives HIV-infected patients are at risk for developing chronic kidney disease (CKD), defined by estimated glomerular filtration rate (eGFR) <60 ml/min/1.73m 2 . Our purpose was to understand the genesis of CKD in HIV patients from a large urban clinic in Houston, Texas, USA, and to characterize progression of CKD in the cohort. Design, setting, participants and measurements A retrospective cohort study (2012–2016) was conducted in all HIV-infected patients seen in a federally qualified community health center in Houston, Texas. CKD prevalence and its association with HIV viral load and CD4 count were determined. The association of the change in eGFR over time and comorbidities was assessed using linear mixed models. Results Of 3714 HIV-infected patients analyzed, 153 (4.1%) had CKD. The prevalence of CKD in the different racial groups was 5.4% White, 4.0% African American, 2.8% Hispanic/Latino and 3.2% Asian. There was no difference in the rate of decline in kidney function in White vs. African American HIV infected patients with CKD. Compared with non-CKD patients, CKD patients were older, had lived longer with HIV infection, had lower CD4 cell counts, higher proportions of hypertension, hyperlipidemia, and cerebrovascular disease, and had significantly higher rates of eGFR deterioration represented by a median decrease of 26.5% from first to last follow-up eGFR (versus 0% change). Linear mixed modeling identified older age, male gender, White race, longer time with HIV infection, hypertension, history of kidney stones, cerebrovascular disease, autoimmune disease, increased potassium and total cholesterol levels, and being treated with combination ART as associated with a worsening eGFR over time. Conclusion This study demonstrates a prevalence of CKD in HIV-infected patients of 4.1% and points to an important role for HIV medications and other common comorbidities in the genesis and progression of kidney disease. Importantly, CKD was not more prevalent in African Americans than in Whites, perhaps due to a low prevalence of IV drug abuse as inferred from the lower prevalence of HCV infection in this cohort.

show abstract

Polymorphisms associated with renal adverse effects of antiretroviral therapy in a Southern Brazilian HIV cohort

Abstract: Our data support the importance of genetic factors in the etiology of nephrotoxicity in patients treated with HAART. Studies to verify treatment implications of genotyping before HAART initiation may be advisable to guide the selection of an appropriate antiretroviral therapy regimen.

Cited by 18 publications

References 36 publications

Coconut Oil Extract Mitigates Testicular Injury Following Adjuvant Treatment with Antiretroviral Drugs

Coconut Oil Extract Mitigates Testicular Injury Following Adjuvant Treatment with Antiretroviral Drugs

<p>Pharmacogenomics and Pharmacogenetics: In Silico Prediction of Drug Effects in Treatments for Novel Coronavirus SARS-CoV2 Disease</p>

Chronic kidney disease in patients infected with human immunodeficiency virus (HIV) in an urban cohort

Contact Info

Product

Resources

About