• Monte Carlo simulations
• dosage adjustment
• population pharmacokinetics
• renal impairment
• tenofovir disoproxil fumarate

• Humans
• HIV Infections/drug therapy
• Tenofovir/pharmacokinetics
• Tenofovir/administration & dosage
• Anti-HIV Agents/pharmacokinetics
• Anti-HIV Agents/administration & dosage
• Anti-HIV Agents/adverse effects
• Renal Insufficiency/metabolism
• Monte Carlo Method
• Models, Biological
• Dose-Response Relationship, Drug
• Computer Simulation

• FF65-UoE012 University of Phayao
• SPS-66006 University of Phayao

• acquired immune deficiency syndrome (aids)
• avascular necrosis of femur
• avascular necrosis of the hip
• drug-induced acute renal failure
• femur intertrochanteric fracture
• highly active antiretroviral therapy (haart)
• human immunodeficiency virus (hiv)
• kidney failure
• tenofovir alafenamide (taf)
• tenofovir disoproxil fumarate (tdf)

• Fanconi syndrome
• antiretroviral therapy
• drug induced nephrotoxicity
• tenofovir

• HBV
• Pharmacogenetics
• TDM
• Tenofovir

• Humans
• Tenofovir/therapeutic use
• Tenofovir/pharmacokinetics
• Male
• Female
• Retrospective Studies
• Multidrug Resistance-Associated Proteins/genetics
• Middle Aged
• Pharmacogenetics/methods
• Hepatitis B virus/genetics
• Hepatitis B virus/drug effects
• Adult
• Hepatitis B, Chronic/drug therapy
• Hepatitis B, Chronic/virology
• Hepatitis B, Chronic/genetics
• Antiviral Agents/pharmacokinetics
• Antiviral Agents/therapeutic use
• Antiviral Agents/urine
• Genotype
• Cohort Studies
• Membrane Transport Proteins/genetics
• Membrane Transport Proteins/metabolism
• Polymorphism, Single Nucleotide/genetics

• 3D culture model
• Drug toxicity testing
• Human primary renal cells
• Nephrotoxicity
• Precision medicine

• R03 AI165170 NIAID NIH HHS
• R21 AI152832 NIAID NIH HHS
• National Institute of Allergy and Infectious Diseases

• infant
• bone mineral content
• renal health
• tenofovir disoproxil fumarate

• Female
• Humans
• Tenofovir/therapeutic use
• Tenofovir/pharmacology
• Anti-HIV Agents/therapeutic use
• Anti-HIV Agents/pharmacology
• Milk, Human
• HIV Infections/drug therapy
• HIV Infections/prevention & control
• Anti-Retroviral Agents/therapeutic use
• Nevirapine/therapeutic use
• Bone Density
• Kidney
• Lumbar Vertebrae

• HHSN275201800001C NICHD NIH HHS
• UM1 AI068632 NIAID NIH HHS
• UM1 AI069518 NIAID NIH HHS
• UM1 AI068616 NIAID NIH HHS
• UM1 AI069436 NIAID NIH HHS
• HHSN275201800001I NICHD NIH HHS
• UM1 AI106716 NIAID NIH HHS
• U01 AI069436 NIAID NIH HHS

• ATP-binding cassette drug transporters
• African women
• HIV
• South Africa
• Truvada®
• pre-exposure prophylaxis
• single-nucleotide polymorphisms
• tenofovir

• Humans
• Female
• Tenofovir/therapeutic use
• Polymorphism, Single Nucleotide/genetics
• ATP-Binding Cassette Transporters/genetics
• HIV Infections/drug therapy
• HIV Infections/genetics
• HIV Infections/prevention & control
• Pre-Exposure Prophylaxis
• South Africa
• RNA, Messenger
• Anti-HIV Agents/therapeutic use

• hiv
• pharmacogenetics
• renal toxicity
• tenofovir alafenamide fumarate
• tenofovir disoproxil fumarate

• Adult
• Humans
• Adenine/adverse effects
• African People
• Alanine/adverse effects
• Anti-HIV Agents/adverse effects
• HIV Infections/drug therapy
• HIV Infections/genetics
• HIV Seropositivity/drug therapy
• Pharmacogenetics
• Tenofovir/adverse effects

• 212265 Wellcome Trust
• R01 AI077505 NIAID NIH HHS
• 203135/Z/16/Z Wellcome Trust

• drug toxicity
• imaging
• kidney
• mitochondria
• tenofovir

• HIV
• pharmacogenomics
• renal tubular dysfunction
• risk factors
• tenofovir disoproxil fumarate

• Critical Care Nephrology and Acute Kidney Injury Series
• acute interstitial nephritis
• acute kidney injury
• acute tubular injury
• apoptosis
• chronic kidney disease
• crystalline nephropathy
• drugs
• inflammation
• nephrotoxins

Tenofovir disoproxil fumarate is part of the first-line antiretroviral therapy and can lead to Fanconi syndrome, acute kidney injury, chronic kidney disease, and reduced bone mineral density. We report the first case of simultaneous occurrence of nephrolithiasis, urolithiasis, Fanconi syndrome, and bone fracture in a 54-year-old lady who presented with pain and inability to bear weight on the right lower limb following a trivial fall. She was diagnosed with human immunodeficiency infection in the year 2000 and was on tenofovir, lamivudine, and efavirenz for the past 6 years. On evaluation, she had azotemia, glycosuria, proteinuria, normal anion gap metabolic acidosis, multiple renal stones, and a proximal ureteric calculus causing right-sided hydroureteronephrosis. The patient developed sepsis following the double “J” stenting procedure. She was managed with intravenous bicarbonate therapy and the substitution of tenofovir to abacavir with a favorable outcome.

Adefovir dipivoxil (ADV) is widely used for chronic hepatitis B therapy in China. To explore the clinical features and prognosis of ADV-induced osteomalacia and to analyze the association between osteomalacia and genetic variants in 51 drug transporters genes. Clinical and follow-up data of the ADV-treated patients were collected. Target capture sequencing was used to identify genetic variations of 51 drug transporter genes. A total of 193 hepatitis B patients treated with ADV were enrolled, of whom 140 had osteomalacia. The other 53 without osteomalacia were included in the control group. The median duration of ADV treatment before the onset of osteomalacia was 6.5 years (range:1.5–7 years). We found that most patients with osteomalacia had hypophosphatemia, high serum alkaline phosphatase levels, hypouricemia, nondiabetic glycosuria, proteinuria. Stopping ADV administration, supplementing calcitriol and calcium were effective treatments. During 3–6 months of follow-up, the clinical symptoms and biochemical indicators of patients with osteomalacia have been significantly improved. There was no significant difference in duration of adefovir treatment in patients with or without osteomalacia (p = 0.791). Through regression analysis, we found that age was a risk factor for osteomalacia [per 1 year, odds ratio (OR), 1.053; 95% confidence interval (95% CI), 1.020–1.087; p = 0.015]. 1992 single nucleotide variants were found using target capture sequencing. However, the associations of genetic variants of 51 drug transporter genes and the risk of osteomalacia were negligible. Osteomalacia is prone to occur in patients with chronic hepatitis B treated with long-term ADV at a therapeutic dose. After standard treatment, the prognosis is mostly good. We failed to find genetic variants that can predict the risk of ADV-induced osteomalacia.

• adefovir dipivoxil
• clinical characteristic
• drug-related side effects
• osteomalacia
• pharmacogenomic variants

• ATP-binding cassette transporters
• drug resistance
• drug response
• pharmacogenetics
• pharmacokinetics

• chronic hepatitis B patients
• moderate renal impairment
• tenofovir dose reduction regimens
• tenofovir-induced renal dysfunction
• viral control

• drug-induced kidney injury
• genomics
• metabolomics
• proteomics
• transcriptomics

• R01 GM107122 NIGMS NIH HHS
• R01 GM123330 NIGMS NIH HHS

• GFR
• HIV
• ethnicity
• microalbuminuria
• proximal tubule dysfunction

• APOL1
• Drug transporters
• HIV
• Kidney tubulopathy
• Pharmacogenomics
• Tenofovir

• Adult
• Anti-HIV Agents/adverse effects
• Anti-HIV Agents/therapeutic use
• Black People/genetics
• Case-Control Studies
• Cross-Sectional Studies
• Female
• HIV Seropositivity/complications
• HIV Seropositivity/drug therapy
• HIV-1
• HIV-2
• Humans
• Kidney Diseases/chemically induced
• Kidney Diseases/epidemiology
• Kidney Diseases/genetics
• Kidney Tubules/drug effects
• Kidney Tubules/pathology
• Kidney Tubules/physiology
• Male
• Nigeria/epidemiology
• Pharmacogenomic Testing
• Polymorphism, Single Nucleotide
• Prevalence
• Research Design
• Risk Factors
• Socioeconomic Factors
• Tenofovir/adverse effects
• Tenofovir/therapeutic use
• Viral Load

• MC_PC_16100 Medical Research Council
• GSK Africa Non-Communicable Disease Open Lab Grant

There are increasing reports of antiretroviral therapy (ART) drug-related kidney dysfunction. Traditional markers of kidney dysfunction such as urine protein/creatinine ratio and estimated glomerular filtration rate (eGFR) have thus far proven ineffective at detecting some sub-clinical forms of ART-related kidney injury. This is a cross-sectional examination of 114 people living with HIV (PLWH), either naïve (N =104) or treatment experienced (N =10). Urinary kidney injury molecule-1 (KIM-1 ng/mg) thresholds were estimated using electrochemiluminescent assays from stored urine samples and normalised for urinary creatinine excretion (KIM-1/Cr). Correlation coefficients and predictors of kidney tubular injury were compared and derived for both adjusted and unadjusted urinary KIM-1/CR (ng/mg). In PLWH (both ART-naïve and treatment experienced) had a higher baseline unadjusted and adjusted median (≥3.7 ng/mg) and upper tertile (≥6.25 ng/mg) urinary KIM-1/Cr levels compared to either non-normal volunteers (0.39 ng/mg) or those with acute kidney injury in the general population (0.57 ng/mg). When upper tertile KIM-1/Cr (≥6.25 ng/mg) was utilised as a marker of kidney injury, eGFR (ml/min/1.73 m²), white Caucasian ethnicity, and protease inhibitor exposure were significantly associated with increased risk of kidney injury in multivariate analyses (odds ratio 0.91, confidence interval [CI] 0.68–0.98, P = 0.02; odds ratio 8.9, CI 1.6–48.6, p = 0.01; and odds ratio 0.05, CI 0.03–0.9, p =0.04, respectively). We found a significant degree of sub-clinical kidney injury (high unadjusted and adjusted KIM-1/Cr) in PLWH with normal kidney function (eGFR ≥60 ml/min/1.73 m²). We also found a higher baseline KIM-1/Cr (ng/mg) in our study cohort than reported both in normal volunteers and patients with kidney injury in the general population.

• HIV
• Kidney injury molecule-1
• antiretroviral therapy drugs
• proteinuria

Tenofovir disoproxil fumarate (TDF)-induced nephrotoxicity is related to high plasma tenofovir concentrations. Tenofovir alafenamide (TAF) is a tenofovir prodrug with 90% lower plasma tenofovir concentrations. The aim of this study was to evaluate changes in tenofovir-induced nephrotoxicity in Human Immunodeficiency Virus (HIV)-positive patients who switched from TDF to TAF.

We identified all HIV-positive patients who switched from elvitegravir/cobicistat/emtricitabine/TDF to elvitegravir/cobicistat/emtricitabine/TAF at a tertiary hospital. We assessed tubulopathy and renal dysfunction before TDF administration, at the time TAF was used following at least 3 months of TDF use, and 3 months after TAF administration. Tubulopathy was defined by the presence of at least three abnormalities in fractional excretion of phosphate, fractional excretion of uric acid, urinary β2-microglobulin, urinary N-acetyl-β-D-glucosaminidase, glucosuria or proteinuria. Renal dysfunction was defined as decreased by more than 25% in the estimated glomerular filtration rate (eGFR) relative to baseline.

In 80 patients, the mean eGFR was 96.8 mL/min/1.73 m² before administration of TDF, 81.2 (P <0.001) at the time of change to TAF, 90.9 (P <0.001) after TAF administration. Renal dysfunction occurred in 19 patients (23.8%) after TDF use for a median 15 months, 11 (57.9%) of these patients recovered from renal dysfunction after TAF administration. Six patients (7.5%) had tubulopathy before TDF administration, 36 (45.0%) after TDF administration (P <0.001), 12 (15.0%) after TAF administration (P = 0.002).

Tenofovir-induced nephrotoxicity in HIV-positive patients receiving TDF was mostly reversible after changing to TAF. Thus, TAF-containing regimens can be administered safely to HIV-positive patients with tenofovir-induced nephrotoxicity.

• HIV
• Renal dysfunction
• Tenofovir alafenamide
• Tenofovir disoproxil fumarate
• Tubulopathy

• Acute kidney injury
• Antibiotics
• Antifungals
• Antivirals
• Nephrotoxicity

• ATP-Binding Cassette Transporters/blood
• ATP-Binding Cassette Transporters/genetics
• Adult
• Alanine Transaminase/blood
• Antitubercular Agents/adverse effects
• Asian People/genetics
• Chemical and Drug Induced Liver Injury/blood
• Chemical and Drug Induced Liver Injury/epidemiology
• Chemical and Drug Induced Liver Injury/genetics
• China/epidemiology
• Drug Therapy, Combination/adverse effects
• Ethambutol/adverse effects
• Female
• Genetic Predisposition to Disease
• Genotype
• Humans
• Isoniazid/adverse effects
• Male
• Middle Aged
• Multidrug Resistance-Associated Protein 2
• Polymorphism, Single Nucleotide
• Pyrazinamide/adverse effects
• Rifampin/adverse effects
• Risk Factors
• Sex Factors
• Tuberculosis/blood
• Tuberculosis/drug therapy
• Young Adult

• bantu-ancestry
• genetic diversity and pharmacogenetics
• next generation sequencing
• novel variants

• Adult
• Chromosome Mapping
• Cohort Studies
• Female
• Gene Frequency
• Genetic Variation
• High-Throughput Nucleotide Sequencing/methods
• Humans
• Male
• Pharmacogenomic Variants
• Sequence Analysis, DNA/methods
• South Africa/ethnology

• U54 HG006938 NHGRI NIH HHS

• Africans
• Renal
• Tenofovir

• Africa
• Anti-HIV Agents/adverse effects
• HIV Infections/drug therapy
• HIV Infections/ethnology
• Humans
• Kidney/drug effects
• Kidney Diseases/chemically induced
• Kidney Diseases/virology
• Renal Insufficiency/chemically induced
• Tenofovir/adverse effects

• Fogarty International Center

• Centers for Disease Control and Prevention clinical category C
• HIV-infected patients
• Nephrotoxicity
• Tenofovir

• Adult
• Anti-Retroviral Agents/adverse effects
• Female
• HIV Infections/drug therapy
• Humans
• Incidence
• Male
• Middle Aged
• Renal Insufficiency/chemically induced
• Renal Insufficiency/epidemiology
• Republic of Korea/epidemiology
• Retrospective Studies
• Risk Factors
• Tenofovir/adverse effects

Despite all these exciting developments, there remain some unmet needs in the management for patients with chronic hepatitis B (CHB). As majority of CHB patients are going to use oral nucleos(t)ide analogues (NAs) for decades, Safety profile of NAs is of no doubt an important issue. The newest nucleotide analogue tenofovir alafenamide is potent in terms of viral suppression, together with favourable renal and bone safety profile. Biochemical response as reflected by alanine aminotransferase (ALT) normalization is recently found to be prognostically important. Patients who achieved ALT normalization have reduced the risk of hepatic events by 49%. Functional cure as reflected by hepatitis B surface antigen seroclearance not only implies patients may stop NA treatment, it also confers to a reduced risk of hepatocellular carcinoma and other hepatic events. Hence functional cure should be the ultimate treatment goal in CHB patients. Preemptive antiviral treatment may reduce mother-to-child transmission of hepatitis B virus, especially if birth dose of vaccination cannot be given in the first two hours after delivery. Lastly, despite the currently first-line NAs have high-genetic barrier to drug resistance mutations, there are still are many patients who were previously treated with low barrier of resistance including lamivudine, telbivudine or adefovir dipivoxil which could lead to antiviral resistance and affecting the choice of NAs.

• Cirrhosis
• Hepatitis B
• Hepatocellular carcinoma
• Mortality
• Tenofovir alafenamide

• chronic hepatitis B
• long-term therapy
• neutrophil gelatinase-associated lipocalin (NGAL)
• nucleos(t)ide analogue
• proximal tubular nephropathy

Tenofovir disoproxil fumarate (TDF) is relatively safe, although renal toxicity has been reported. In Nigeria, there is insufficient data on renal toxicity among patients on TDF. This study assesses TDF-associated tubular dysfunction among human immunodeficiency virus (HIV) patients at a hospital in Nigeria.

In this cohort study, 104 adult HIV patients were recruited with a simple random technique from the outpatient clinic. Biochemical indices of renal function were estimated from serum and urine at the 16th and 24th week after an initial assessment at baseline.

There were no significant differences in baseline proteinuria or glycosuria between TDF and non-TDF groups. Mean baseline urine and serum parameters did not differ significantly between the two groups (P > 0.05). In the TDF group, all urine parameters differed significantly between baseline and 24th week values (P < 0.001). After 16 weeks, mean urine phosphate and urine uric acid increased significantly (P < 0.05) by 2.97 mg/dL and 50.9 mg/dL, respectively, in the TDF group. The rise in mean urine glucose from baseline to the 24th week was more marked in the TDF than the non-TDF group (0.25 vs. 0.07 mmol/L). Higher mean differences in urine albumin were also recorded in the TDF group from baseline to the 24th week.

Indicators of tubular dysfunction were markedly higher among patients on the TDF-based treatment regimen. Biomarkers of tubular dysfunction could be useful for detecting pre-symptomatic nephrotoxicity before marked reduction of glomerular filtration rate in HIV patients on TDF.

• Chronic renal insufficiency
• Proximal renal tubular dysfunction
• Renal Fanconi syndrome

• RBP
• Tenofovir
• kidney tubular dysfunction
• single nucleotide polymorphisms
• tubulopathy

Tenofovir disoproxil fumarate (TDF, commonly termed ‘tenofovir’) is the antiretroviral most commonly implicated in antiretroviral-induced nephrotoxicity. As patients on successful antiretroviral therapy (ART) age, their risk for developing renal disease may increase in part because of ART itself, but more importantly, because of HIV-associated and non-HIV-associated comorbidity. Therefore, clinicians need an approach to managing renal disease in people on TDF. TDF as a cause of acute kidney injury (AKI) or chronic kidney disease (CKD) is uncommon, and clinicians should actively exclude other causes (Box 1). In TDF-associated AKI, TDF should be interrupted in all cases, and replaced, or ART interrupted altogether. Tenofovir disoproxil fumarate toxicity can present as AKI or CKD, and as a full or partial Fanconi’s syndrome. TDF has a small but definite negative impact on kidney function (up to a 10% decrease in glomerular filtration rate [GFR]). This occurs because of altered tubular function in those exposed to TDF for treatment and as pre-exposure prophylaxis. Renal function should be assessed using creatinine-based estimated GFR at the time of initiation of TDF, if ART is changed, at 1–3 months, and then ideally every 6–12 months if stable. Specific tests of tubular function are not routinely recommended; in the case of clinical concern, a spot protein or albumin: creatinine ratio is preferable, but in resource-limited settings, urine dipstick can be used. More frequent monitoring may be required in those with established CKD (estimated glomerular filtration rate [eGFR] < 50 mL/min/1.73 m²) or risk factors for kidney disease. The most common risk factors are comorbid hypertension, diabetes, HIV-associated kidney disease, hepatitis B or C co-infection, and TDF in combination with a ritonavir-boosted protease inhibitor. Management of these comorbid conditions must be prioritised in this group. If baseline screening eGFR is < 50 mL/min/1.73 m², abacavir (the preferred option), and dose-adjusted TDF (useful if concomitant hepatitis B), zidovudine or stavudine (d4T) remain alternatives to full-dose TDF. If there is a rapid decline in kidney function (eGFR drops by more than 25% and decreases to < 50 mL/min/1.73 m² from of baseline function), or there is new onset or worsening of proteinuria or albuminuria, clinicians should review ART and other potentially nephrotoxic medications and comorbidity and conduct further testing if indicated. If kidney function does not improve after addressing reversible causes of renal failure, then referral to a nephrologist is appropriate. In the case of severe CKD, timeous referral for planning for renal replacement therapy is recommended. Tenofovir alafenamide, a prodrug of tenofovir, appears to have less renal toxicity and is likely to replace TDF in future.

• ABCB1
• ABCC2
• ABCG2
• SLCO1B3
• therapeutic drug monitoring
• triazoles

The first cases of AIDS in Spain were reported in 1982. Since then over 85,000 persons with AIDS have been cumulated, with 60,000 deaths. Current estimates for people living with HIV are of 145,000, of whom 20% are unaware of it. This explains the still high rate of late HIV presenters. Although the HIV epidemic in Spain was originally driven mostly by injection drug users, since the year 2000 men having sex with men (MSM) account for most new incident HIV cases. Currently, MSM represent over 80% of new yearly HIV diagnoses. In the 80s, a subset of young doctors and nurses working at Internal Medicine hospital wards became deeply engaged in attending HIV-infected persons. Before the introduction of antiretrovirals in the earlier 1990s, diagnosis and treatment of opportunistic infections was their major task. A new wave of infectious diseases specialists was born. Following the wide introduction of triple combination therapy in the late 1990s, drug side effects and antiretroviral resistance led to built a core of highly devoted HIV specialists across the country. Since then, HIV medicine has improved and currently is largely conducted by multidisciplinary teams of health care providers working at hospital-based outclinics, where HIV-positive persons are generally seen every six months. Antiretroviral therapy is currently prescribed to roughly 75,000 persons, almost all attended at clinics belonging to the government health public system. Overall, the impact of HIV/AIDS publications by Spanish teams is the third most important in Europe. HIV research in Spain has classically been funded mostly by national and European public agencies along with pharma companies. Chronologically, some of the major contributions of Spanish HIV research are being in the field of tuberculosis, toxoplasmosis, leishmaniasis, HIV variants including HIV-2, drug resistance, pharmacology, antiretroviral drug-related toxicities, coinfection with viral hepatitis, design and participation in clinical trials with antiretrovirals, immunopathogenesis, ageing, and vaccine development.

• AIDS history
• HIV education
• HIV prevention
• HIV research
• Spain
• antiretroviral therapy
• hepatitis

• Acquired Immunodeficiency Syndrome/drug therapy
• Acquired Immunodeficiency Syndrome/epidemiology
• Acquired Immunodeficiency Syndrome/history
• Anti-HIV Agents/therapeutic use
• Clinical Trials as Topic
• Epidemics/statistics & numerical data
• Europe/epidemiology
• HIV Infections/diagnosis
• HIV Infections/drug therapy
• HIV Infections/epidemiology
• History, 20th Century
• History, 21st Century
• Humans
• Physicians
• Research/statistics & numerical data
• Spain/epidemiology

• Booster
• HBV
• Hypertension
• Kidney
• Tenofovir

• tenofovir disoproxil fumarate
• tenofovir alafenamide
• proximal tubulopathy
• hepatitis b virus
• pre-exposure prophylaxis

• Adenine/adverse effects
• Adenine/analogs & derivatives
• Alanine
• Antiviral Agents/adverse effects
• Bone Density/drug effects
• Drug Interactions
• Glomerular Filtration Rate/drug effects
• HIV Infections/drug therapy
• HIV Infections/prevention & control
• Hepatitis B/drug therapy
• Humans
• Kidney Diseases/chemically induced
• Pre-Exposure Prophylaxis
• Prodrugs/adverse effects
• Tenofovir/adverse effects

• K12 HS023009 AHRQ HHS
• P01 DK056492 NIDDK NIH HHS
• R01 DK100272 NIDDK NIH HHS
• T32 DK007757 NIDDK NIH HHS
• R01 DK112258 NIDDK NIH HHS

HIV-infected patients have an increased risk of renal disease. Current first-line antiretroviral therapy contains tenofovir disoproxil fumarate (TDF), which has nephrotoxic potential, characterised by proximal tubular cell injury. This may result in acute kidney injury, chronic kidney disease or partial or complete Fanconi syndrome.

We reviewed the existing literature on acute kidney injury and TDF-associated nephrotoxicity with the aim of providing an approach to diagnosis and management, which is relevant to a general medical practitioner.

We performed a broad literature search of biomedical databases including PubMed and ScienceDirect. Our search terms included, but were not limited to, ‘tenofovir’, ‘nephrotoxicity’, ‘HIV’, ‘acute kidney injury’ and ‘renal tubular acidosis’.

Our aim was not to generate a systematic literature review with weighted evidence, but rather to provide a review of best practice from a variety of sources. Where published studies were not available from the above databases, we relied on relevant textbooks and professional guidelines.

Potential nephrotoxicity is not an impediment to the widespread use of TDF in treating HIV infection, because most patients will tolerate the medication well. However, patients with advanced disease, low body weight, advanced age, pre-existing kidney disease and concomitant use of other nephrotoxic medications are at increased risk of adverse renal events and may develop severe complications if not appropriately managed. These risk factors are unfortunately common in patients initiating antiretroviral therapy in South Africa.

Prevention of renal damage by means of careful screening and monitoring of high-risk patients is of paramount importance. Increased awareness of this problem and knowledge of how to manage kidney disease should be emphasised for general medical practitioners who work with HIV-infected patients.

• ABCC2
• ABCC4
• Thai HIV-infected patients
• population pharmacokinetics
• tenofovir