Tenofovir-associated kidney disease in Africans: a systematic review

Mtisi, Takudzwa J.; Ndhlovu, Chiratidzo E.; Maponga, Charles C.; Morse, Gene D.

doi:10.1186/s12981-019-0227-1

Cited by 27 publications

(29 citation statements)

References 53 publications

(92 reference statements)

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“…However, long-term treatment with some antiretroviral drugs may result in renal impairment [10]. Tenofovir disoproxil fumarate (TDF), a nucleotide reverse transcriptase inhibitor, is a widely used antiretroviral drug and renal impairment [11,12]. Fanconi syndrome [13], nephrogenic diabetes [14] and decline in estimated glomerular filtration rate (eGFR) [15,16] have been reported with TDF use in HIV positive persons living in different settings.…”

Section: Introductionmentioning

confidence: 99%

“…A number of studies conducted to look at the renal safety of TDF in sub-Saharan Africa and provides variable results. Most reported TDF use was associated with decline renal function [ 11 ] and some reported TDF had good renal safety [ 19 , 20 ]. However, the larger cohort studies in Africa showed the association of TDF with decline renal function but the incidence of TDF induced nephrotoxicity is low [ 21 – 23 ].…”

Section: Introductionmentioning

confidence: 99%

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Renal function in Ethiopian HIV-positive adults on antiretroviral treatment with and without tenofovir

et al. 2020

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Background: Limited data are available on the effect of antiretroviral treatment (ART) or Tenofovir disoproxil fumarate (TDF) on renal function in Ethiopians. We aimed to assess factors associated with renal function changes during the first year of ART with special focus on TDF. Methods: HIV positive persons who were ≥ 18 years of age and eligible for ART initiation were recruited. Creatinine measurement to estimate glomerular filtration rate (eGFR) and spot urine analyses were performed at baseline and after 3, 6 and 12 months of ART. Univariate and multivariate linear regression and univariate logistic regression were used to determine factors associated with eGFR as continuous and categorical variable respectively. A linear mixed model was used to assess 12 month eGFR difference in TDF and non-TDF based regimen. Result: Of 340 ART-naïve HIV patients with baseline renal function tests, 82.3% (279/339) were initiated on a TDF based ART regimen. All patients were on non-nucleoside reverse transcriptase inhibitors (NNRTI) based ART regimen. The median (IQR) change in eGFR with 12 months of ART was 0.8 (− 11.1; 10.0) ml/min/1.73m 2. About 41 and 26.9% of HIV patients had a drop of greater than 3 and 10 mL/min/1.73 m 2 in eGFR at 12 month, respectively. However, none of the HIV patients declined to < 60 ml/min/1.73m 2 within 12 months. Moreover, none of the HIV patients had persistent proteinuria or glycosuria. Older HIV patients especially age > 45 years and those with unsuppressed viral load at 6 month of ART had a significantly lower eGFR at 12 months of ART initiation. However, there was no difference in 12 month eGFR between HIV patients initiated on TDF based regimen and non-TDF based regimen. Conclusion: Renal function remained stable with no difference between HIV patients treated with TDF or non-TDF NNRTI based ART regimen over 12 months. However, older HIV patients and those with unsuppressed viral load deserve special focus on renal monitoring. Data on long-term safety of TDF (> 1 year) is still warranted in this population.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Renal function in Ethiopian HIV-positive adults on antiretroviral treatment with and without tenofovir

et al. 2020

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“… Baynes (2019) [ 51 ] SSA Meta-analysis of 15 studies ( N = 86,879) HIV+ patients on HAART Prevalence of CKD Overall pooled prevalence was 6.42% (95% CI 5.2–7.6%), and the majority of patients with CKD were diagnosed with stage 3. Mtisi (2019) [ 52 ] SSA Systematic review of 31 studies ( N = 106,406) HIV+ adults on tenofovir-based HAART Decline of renal function Some studies reported statistically significant renal function decline, but the clinical significance of this effect was not enough to contraindicate its continued use in HAART regimens. Cassidy (2019) [ 53 ] Botswana Prospective observational cohort study ( N = 493) Pregnant HIV+ women on efavirenz-based regimens Neurodevelopmental outcomes Adjusted mean scores for the efavirenz-exposed group were poorer compared to the efavirenz-unexposed group on Bayley-III Receptive Language (21.5 versus 22.5, p = 0.05), Developmental Milestones Checklist Locomotor (30.7 versus 32.0, p < 0.01), Fine Motor scales (17.8 versus 19.2, p < 0.01), Profile of Social Emotional Development (11.7 versus 9.9, p = 0.02), and Developmental Milestones Checklist Language scale (17.6 versus 16.5, p = 0.01).…”

Section: Resultsmentioning

confidence: 99%

“…Two hundred and five articles examined CKD in HIV+ individuals on HAART, of which one meta-analysis [ 51 ] and a systematic review [ 52 ] were eligible. The pooled prevalence of CKD among HIV+ individuals on HAART was estimated to be 6.42% (95% CI 5.2–7.6%) [ 51 ].…”

Section: Resultsmentioning

confidence: 99%

Epilepsy management in pregnant HIV+ women in sub-Saharan Africa, clinical aspects to consider: a scoping review

Menon

Beňová

Mabeya

2020

BMC Med

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Background Since the introduction of highly active antiretroviral therapy (HAART), acquired immune deficiency syndrome (AIDS) related mortality has markedly declined. As HAART is becoming increasingly available, the infection with human immunodeficiency virus (HIV+) in sub-Saharan Africa (SSA) is becoming a chronic condition. While pregnancy in HIV+ women in SSA has always been considered a challenging event for the mother and the fetus, for pregnant HIV+ women also diagnosed with epilepsy (WWE), there are additional risks as HIV increases the odds of developing seizures due to the vulnerability of the central nervous system to other infections, immune dysfunction, and overall metabolic disturbances. In light of a growing proportion of HIV+ WWE on HAART and an increasing number of pregnant women accessing mother-to-child transmission of HIV programs through provision of HAART in SSA, there is a need to develop contextualized and evidenced-based clinical strategies for the management of epilepsy in this population. In this study, we conduct a literature scoping review to identify issues that warrant consideration for clinical management. Result Twenty-three articles were retained after screening, which covered six overarching clinical aspects: status epilepticus (SE), Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), dyslipidemia, congenital malformation (CM), chronic kidney disease (CKD), and neurological development. No studies for our population of interest were identified, highlighting the need for a cautionary approach to be employed when extrapolating findings. Conclusion High risks of CM and drug interactions with first-line antiepileptic drugs (AEDs) warrant measures to increase the accessibility and choices of safer second-line AEDs. To ensure evidence-based management of epilepsy within this population, the potential high prevalence of SE, CKD, dyslipidemia, and SJS/TEN and the cumulative effect of drug-drug interactions should be considered. Further understanding of the intersections between pregnancy and drug-drug interactions in SSA is needed to ensure evidenced-based management of epilepsy in pregnant HIV+ WWE. To prevent SE, the barriers for AED treatment adherence in pregnant HIV+ women should be explored. Our review underscores the need to conduct cohort studies of HIV+ WWE in reproductive age over time and across pregnancies to capture the cumulative effect of HAART and AED to inform clinical management.

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“…However, statistically significant reductions in renal function after the initiation of TDF, compared with after the initiation of other drugs, have been reported in other studies [ 35 , 41 , 42 ]. In this regard, results from a systematic review identified studies in Africans reporting statistically significant renal function decline associated with TDF use [ 49 ]. In the Ethiopian cohort study by Yazie et al [ 50 ], an eGFR decrease of >25% from baseline was observed in 25.4% of patients initiating TDF containing combination ART.…”

Section: Discussionmentioning

confidence: 99%

Renal function in a cohort of HIV-infected patients initiating antiretroviral therapy in an outpatient setting in Ethiopia

Fiseha

Gebreweld

2021

PLoS ONE

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Aim To evaluate the prevalence and associated factors of abnormal renal function among Ethiopian HIV-infected patients at baseline prior to initiation of antiretroviral therapy (ART) and during follow-up. Methods We conducted a retrospective observational cohort study of HIV infected patients who initiated ART at the outpatient ART clinic of Mehal Meda Hospital of North Shewa, Ethiopia from January 2012 to August 2018. Demographic and clinical data were abstracted from the medical records of patients. Renal function was assessed by estimated glomerular filtration rate (eGFR) calculated using the Modification of Diet in Renal Disease (MDRD) equation. Univariate and multivariate analysis were conducted to determine the factors associated with abnormal renal function at baseline and during follow-up. Results Among 353 patients, 70 (19.8%) had baseline eGFR <60 ml/min/1.73m2 and 102 (28.9%) had eGFR = 60–89.9 ml/min/1.73m2. Factors associated with baseline renal impairment (eGFR <60 ml/min/1.73m2) included female sex (AOR = 3.52, CI 1.75–7.09), CD4 count < 200 cells/mm3 (AOR = 2.75, CI 1.40–5.42), BMI < 25 Kg/m2 (AOR = 3.04, CI 1.15–8.92), low hemoglobin (AOR = 2.19, CI 1.16–4.09) and high total cholesterol (AOR = 3.15, CI 1.68–5.92). After a median of 3.0 years of ART, the mean eGFR declined from 112.9 ± 81.2 ml/min/1.73m2 at baseline to 93.9 ± 60.6 ml/min/1.73m2 (P < 0.001). The prevalence of renal impairment increased from 19.8% at baseline to 22.1% during follow-up. Of 181 patients with baseline normal renal function, 49.7% experienced some degree of renal impairment. Older age (AOR = 3.85, 95% CI 2.03–7.31), female sex (AOR = 4.18, 95% CI 2.08–8.40), low baseline CD4 (AOR = 2.41, 95% CI 1.24–4.69), low current CD4 count (AOR = 2.32, 95% CI 1.15–4.68), high BMI (AOR = 2.91, 95% CI 1.49–5.71), and low hemoglobin (AOR = 3.38, 95% CI 2.00–7.46) were the factors associated with renal impairment during follow-up. Conclusion Impaired renal function was common in HIV-infected patients initiating ART in an outpatient setting in Ethiopia, and there appears to be a high prevalence of renal impairment after a median ART follow-up of 3 years. There is a need for assessment of renal function at baseline before ART initiation and regular monitoring of renal function for patients with HIV during follow-up.

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Tenofovir-associated kidney disease in Africans: a systematic review

Cited by 27 publications

References 53 publications

Renal function in Ethiopian HIV-positive adults on antiretroviral treatment with and without tenofovir

Renal function in Ethiopian HIV-positive adults on antiretroviral treatment with and without tenofovir

Epilepsy management in pregnant HIV+ women in sub-Saharan Africa, clinical aspects to consider: a scoping review

Renal function in a cohort of HIV-infected patients initiating antiretroviral therapy in an outpatient setting in Ethiopia

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