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Boxplot graph of the urinary excretion levels of cytochrome c at different time points in patients treated with the abacavir/lamivudine (ABV) or tenofovir disoproxil fumerate (TDF) regimen. The dots and asterisks represent outliers.
Source publication
The recent introduction of new antiretroviral drugs, characterized by high efficiency and improved safety profiles, has not reduced the incidence of long-term adverse effects, in some cases manifested as selective organ damage. The presence of organ damage in patients receiving antiretroviral treatment is not only the expression of treatment toxici...
Context in source publication
Context 1
... of median values between the two groups at different time points showed that at T1 and T2 patients re- ceiving TDF excreted median urinary levels of Cyc signifi- cantly higher than patients treated by ABV ( p = 0.015 and p = 0.032 at T1 and T2, respectively), while no difference was present at T3 and T4 ( p = 0.562, and T4 p = 0.844, respectively; Fig. ...
Citations
... The exact causes of HIV-associated AKI are not well investigated, but it is associated with volume depletion, sepsis, and the intake of nephrotoxic medications [6]. It is also associated with individual risk factors, HIV-correlated factors, and antiretroviral drug toxicity [7]. AKI can lead to life-threatening complications such as end-stage renal failure, volume overload, electrolyte disturbance, and multi-organ dysfunction [8]. ...
Background
cute kidney injury(AKI) is a rapid loss of the kidney’s excretory function, resulting in an accumulation of end products of nitrogen metabolism. The causes of AKI in HIV-positive patients are not well investigated, but it may be associated with antiretroviral drug side effects and HIV itself. Even though there were studies that reported the prevalence of AKI among HIV-positive patients in Africa, their findings were inconsistent across the studies.
Methods
We searched on PubMed, Embas, Ebsco, OVID, Cochrane Library, and other supplementary search engines, including Google and Google Scholar. Articles published upto July 2023 were included in this review study. The quality of the study was assessed using the Newcastle-Ottawa Scale for cross-sectional, case-control, and cohort studies. The data were extracted using a Microsoft Excel spreadsheet and exported to Stata version 14 for analysis. A random effect meta-analysis model was used to estimate the pooled prevalence of AKI among HIV-positive patients. Heterogeneity was evaluated using Cochrane Q statistics and I squared (I ² ). Furthermore, the graphic asymmetric test of the funnel plot and/or Egger’s tests were computed to detect publication bias. Sensitivity analysis was computed to see the effect of a single study on the summary effects. To treat the publication bias, a trim and fill analysis was carried out. The protocol of this review has been registered in an international database, the Prospective Register of Systematic Reviews (PROSPERO),with reference number CRD42023446078.
Results
A total of twenty-four original articles comprising 7913HIV-positive patients were included in the study. The pooled prevalence of AKI among HI-positive patients was found to be 23.35% (95% CI: 18.14–28.56%, I ² = 97.7%, p-value <0.001). Low hemoglobin (Hgb <8mg/dl) was found to be the determinant factor for AKI among HIV-positive patients (AOR = 2.4; 95% CI:1.69–3.4, I ² = 0.0%, p-value = 0.40). In meta-regression analysis, sample size was the possible source of variation among the included studies (AOR = 3.11, 95%CI: 2.399–3.83).
Conclusions
The pooled prevalence of AKI among HIV-positive patients was high. HIV-positive patients with low hemoglobin levels are at risk of developing AKI. Hence, regular monitoring of kidney function tests is needed to prevent or delay the risk of AKI among HIV-positive patients. Healthcare workers should provide an integrated healthcare service to HIV-positive patients on the prevention, treatment, and reduction of the progression of AKI to advanced stages and complications.
... In 2020, an estimated 37.7 million people were living with the human immunodeficiency virus (HIV) worldwide, of which 1.7 million were younger than 15 years of age [1,2]. HIV infection has been associated with impaired kidney function in adults and children [3][4][5]. Generally, kidney impairment results from HIV-associated nephropathy, HIV-associated immune complex kidney disease, viral co-infections, or kidney damage induced by antiretroviral drugs [6]. While disease aetiology may differ, all HIV-associated kidney disease may potentially develop into chronic kidney disease (CKD). ...
Dose recommendations for lamivudine or emtricitabine in children with HIV and chronic kidney disease (CKD) are absent or not supported by clinical data. Physiologically based pharmacokinetic (PBPK) models have the potential to facilitate dose selection for these drugs in this population. Existing lamivudine and emtricitabine compound models in Simcyp® (v21) were verified in adult populations with and without CKD and in non-CKD paediatric populations. We developed paediatric CKD population models reflecting subjects with a reduced glomerular filtration and tubular secretion, based on extrapolation from adult CKD population models. These models were verified using ganciclovir as a surrogate compound. Then, lamivudine and emtricitabine dosing strategies were simulated in virtual paediatric CKD populations. The compound and paediatric CKD population models were verified successfully (prediction error within 0.5- to 2-fold). The mean AUC ratios in children (GFR-adjusted dose in CKD population/standard dose in population with normal kidney function) were 1.15 and 1.23 for lamivudine, and 1.20 and 1.30 for emtricitabine, with grade-3- and -4-stage CKD, respectively. With the developed paediatric CKD population PBPK models, GFR-adjusted lamivudine and emtricitabine dosages in children with CKD resulted in adequate drug exposure, supporting paediatric GFR-adjusted dosing. Clinical studies are needed to confirm these findings.
... Although immune system dysfunction and a decrease in the number and activity of CD4+ T cells are the hallmarks of HIV infection. It is also important to remember that HIV may also affect other cell types and organs [2][3][4][5]. Peripheral blood cytopenias, such as anemia, neutropenia, and thrombocytopenia, arise in most patients with AIDS and some HIV-positive naive individuals during the early stages of disease progression, especially when high plasma levels of HIV RNA are detectable, in regards to progressive depletion of CD4+ T lymphocytes [6,7]. ...
Aims and objectives: The study's goal is to evaluate the cluster of differentiation 4(CD4) and the erythropoietin values (EPO) in people living with HIV/AIDS in Enugu North Senatorial Zone, Enugu State, Nigeria. Specifically, the effect of HAART on CD4 and EPO in HIV patients and the influence of HIV infection on the inflammatory makers of HIV infected patients. Materials and Methods: The study employed a cross-sectional, prospective, hospital based clinical research on all consenting consecutive patients scheduled for ART treatment respective of age between the period of March 2020 to August 2020 at the General Hospital Nsukka that meet the eligibility criteria. Subjects and Sample Size Determination: The sample size of 137 was determining using Cochran (1963) formula for determining sample size, after which 137 subjects were purposively selected. Statistical Analysis: Were expressed where appropriate as mean± standard deviation. T-test was used in testing hypotheses at 5 % level of significance. Results: From the study shows the outcomes of CD4 counts in HIV patients with various ranges. The mean and standard error of CD4 counts of HIV patients before (pre) and after (post) HAART administrations showed the grand mean CD4 counts before and post HAART administration were 632.37 ± 29.24cells/µl and 646.59 ± 28.9cells/µl, respectively. The difference in CD4 counts between pre and post, that is, before and after HAART was given to HIV patients, demonstrated that HAART enhanced CD4 levels. The increase in CD4 counts in patients was statistically significant (P <0.05). The effects of HIV infection on EPO that is a haematopoietic cytokines in HIV infected individuals with various CD4 counts showed that the mean and standard error of erythropoietin (EPO) levels in HIV patients was 7.10±0.01mg/dl and 7.74±0.03mg/dl, respectively. The change in HIV patients' EPO levels between the two periods was significant (P <0.05). Conclusion: There is an increase in CD4 counts in patients in the study and is comparable to the work of Erb et al. [18], who found out that HIV infected individuals who received a combination of antiretroviral therapy (CART) had higher CD4 counts. The change in HIV patient's EPO levels indicated that HIV infection had the ability to decrease EPO synthesis in the body. The work of Wang et al 1993 discovered that HIV-1 appeared to suppress the synthesis of EPO and some, but not all.
... Although immune system dysfunction and a decrease in the number and activity of CD4+ T cells are the hallmarks of HIV infection. It is also important to remember that HIV may also affect other cell types and [2][3][4][5]. Peripheral blood cytopenias, such as anemia, neutropenia, and thrombocytopenia, arise in most patients with AIDS and some HIV-positive naive individuals during the early stages of disease progression, especially when high plasma levels of HIV RNA are detectable, in regards to progressive depletion of CD4+ T lymphocytes [6,7]. ...
... The proposed mechanism lies in drug mitochondrial toxicity, since TFV is a mitochondrial DNA polymerase inhibitor. In vitro and animal studies suggested that drug accumulation, due to its potential intracellular entrapment, could induce mitochondrial DNA polymerase depletion in proximal tubular cells [8]. Since the source of energy derives from mitochondria, tubular dysfunction is observed, with loss of low weight proteins (β2-microglobulin/retinol binding protein, RBP), amino acids, glucose, uric acid, bicarbonate and phosphate in urines. ...
Tenofovir disoproxyl fumarate (TDF) has been associated with renal tubular abnormalities, phosphaturia and proteinuria (retinol binding protein, RBP, loss): vitamin D (VD) and PTH affect these markers. Aim was to understand if some single nucleotide polymorphisms (SNPs) were predictors of renal abnormalities in an Italian cohort of HIV-affected patients. DNA was analyzed through real-time PCR, urinary RBP corrected by creatinine (uRBP/Cr). The majority of patients received TDF. Abnormal uRBP/Cr was more frequent in TDF recipients: eGFR <90 mL/min and TDF were predictors in the whole cohort, whereas eGFR <90 mL/min, TDF concentrations and CYP24A1-3999TT in TDF-treated patients. Phosphate levels were higher low VD level patients: age <50 years, CYP27B1 + 2838CC genotype and non-European ancestry were predictors. PTH levels were border-line higher in TDF patients: non-European ancestry, females, TDF, VD levels < 30 ng/mL and SLC28A2-124CT/TT and ABCC2-24CC were predictors. For the first time, SNPs were associated with PTH, phosphate, calcium and tubular dysfunction in HIV-infected patients.
... Kidney disease in HIV-infected individuals may be due to direct effects of HIV, the chronic inflammation associated with HIV-infection, traditional risk factors of kidney disease and the toxic effects of certain ART [85]. After the introduction of ART in the 1990s, the prevalence of certain diseases traditionally associated with HIV-infection decreased; however others including kidney and liver disease, increased [86].A study in France has found that the following are risk factors for the development of renal complications in HIV-infection: female gender, older age, diabetes, hyperlipidaemia, low CD4 count and the use of tenofovir [87]. ...
Individuals living with HIV infection on antiretroviral therapy are at an increased risk of developing non-AIDS related diseases and experience incomplete immune restoration. The path physiology has been linked to HIV-specific mechanisms as well as non-specific generalized responses to infection which are thought to contribute to the ongoing activation of the immune system. Factors such as the early loss of gastrointestinal (GI) tract mucosal integrity, the pro-inflammatory cytokine milieu, co-infections and marked destruction
of lymph node architecture all contribute to the ongoing immune
activation as well as deficient immune recovery. Intensive studies on
HIV are gradually aiding us understand the processes that link HIV infection to the onset of immunodeficiency. CD4+ T cells exhaustion represents the most fundamental events in HIV infection. Also, HIV-infected individuals show a strong association with individuals of
old age: their immune systems are marked by a loss of regenerative
capacity and an aggregation of ageing T cells. This review discusses the
reason for the development of immune activation and inflammation
in the early stages of HIV infection and the long-term effect of these
processes to the immune system and health. The three major aspects
of HIV disease pathogenesis: reduction of CD4+ T cells, immune
activation and depletion of regenerative capacity shall be linked to this process.
... The renal diseases mainly associated with HCV infection are membranoproliferative glomerulonephritis, but also membranous nephropathy, IgA nephropathy, proliferative glomerulonephritis, interstitial nephritis, and focal segmental glomerulosclerosis [4]. In human immunodeficiency virus (HIV)-infected patients, other risks factors for development of renal disease are also present, related to HIV infection itself, but also to some antiretroviral therapies [5,6]. In patients coinfected with HIV/HCV, the causes of renal damage cumulate, creating a pairing of viral infection and renal disease that is commonly observed, but not inseparable. ...
In this report, we describe the coexistence of two rare and debated complications of hepatitis C virus (HCV) infection: interstitial nephritis, with associated focal glomerulosclerosis, and autoimmune hepatitis, in a 55-year-old HIV/HCV-coinfected woman. The patient was treated for the immune-mediated manifestations with mycophenolate mofetil, which she continued for 9 years, as symptoms relapsed at every attempt to discontinue immunosuppression. The patient finally cleared HCV infection thanks to new direct-acting agents and could discontinue immunosuppressive therapy maintaining stable conditions and laboratory parameters after 24-weeks follow-up.
... Kidney function has been implicated in human immunodeficiency virus (HIV) infection, which may further progress to acquired immune deficiency syndrome (AIDS) and subsequently death [1][2][3]. It may present as acute kidney injury or chronic kidney disease (CKD), with an estimated prevalence in sub-Saharan Africa ranging from 6% to 48.5% [4]. ...
... HAART includes the combination of three different types of highly effective anti-HIV drugs including nucleotide reverse transcriptase inhibitors (NRTIs), non-nucleotide reverse transcriptase inhibitors (NNRTIs) and non-peptidic viral protease inhibitors (PIs) 2 . The administration of these drugs have been associated with specific toxicities including mitochondrial toxicity, cardiovascular complications, liver toxicity, renal toxicity, gastrointestinal intolerance, glucose and lipid abnormalities 3 . These drug associated toxicities have resulted in greater proportion of patients developing chronic conditions not traditionally related to HIV such as cardiovascular, liver and kidney diseases 4 . ...
... These drug associated toxicities have resulted in greater proportion of patients developing chronic conditions not traditionally related to HIV such as cardiovascular, liver and kidney diseases 4 . The development of HAART related organ damage is a function of complex interactions between individual risk factors, HIV correlated effects and antiretroviral drug toxicity 3 . These long terms adverse effects often referred to as non infectious HIV related co-morbidities have become common source of morbidity and mortality among HIV infected individuals in developing countries 5 . ...
... This could also be as a result of absence or low prevalence of traditional risk factors such as diabetes and high blood pressure within sample population which is known to be associated with renal impairment as shown by the findings of our previous study 24 . Similar observations have been made by previous studies 3,25 . However, the eGFR of HIV sero-positve subjects on HAART were found to be higher than those of HAART naïve studied though not statistically significant. ...
Alterations in liver and renal functions are among the complications of HIV infection, and highly active antiretroviral therapy (HAART) has been implicated. The combined nephrotoxic and hepatotoxic effects of HAART were determined by assessing the renal and liver functions of HIV sero-positive subjects on HAART in a tertiary hospital. Liver enzymes activities; Aspartate and alanine aminotransferases (AST & ALT), alkaline phosphatase (ALP), gamma glutamyl-transferase (GGT), lactate dehydrogenase (LDH) and renal function parameters; uric acid and creatinine clearance were determined in sera of 90 consenting subjects comprising of 30 HIV seropositive subjects on HAART, 30 HAART naive and 30 apparently healthy HIV sero-negative controls using colorimetric methods. CD 4 + T cell count was done by flow cytometry while estimated glomerular filtration rate (eGFR) was determined by calculation. Anthropometric data and socio demographic information were obtained. Data was analyzed using ANOVA, LSD post hoc and Pearson's correlation at p<0.05. The body mass index and CD 4 + T cell count were significantly higher and AST, ALT, LDH and uric acid levels lower in HIV sero-negative controls compared to HIV on HAART and HAART naïve subjects. HIV on HAART had higher AST, ALT, GGT and LDH activities compared to HAART naïve. A significant negative correlation (r =-0.881, p = .000) was observed between uric acid and CD 4 + T cell count in HAART naïve subjects only. HIV infection and HAART is associated with low grade hepatotoxicity but no impairment of renal functions in the population studied.
... Moreover, since uric acid is highly reabsorbed at the nephron level, with a fractional excretion that usually does not exceed 10% of the filtered uric acid; an increase in urinary uric acid excretion is an early marker of proximal tubular dysfunction. 14 Glucose is normally not present in urine. When glucose is present, the condition is called glucosuria. ...
