Cumulative and current exposure to potentially nephrotoxic antiretrovirals and development of chronic kidney disease in HIV-positive individuals with a normal baseline estimated glomerular filtration rate: a prospective international cohort study.

Abstract:

BACKGROUND:Whether or not the association between some antiretrovirals used in HIV infection and chronic kidney disease is cumulative is a controversial topic, especially in patients with initially normal renal function. In this study, we aimed to investigate the association between duration of exposure to antiretrovirals and the development of chronic kidney disease in people with initially normal renal function, as measured by estimated glomerular filtration rate (eGFR). METHODS:In this prospective international cohort study, HIV-positive adult participants (aged ≥16 years) from the D:A:D study (based in Europe, the USA, and Australia) with first eGFR greater than 90 mL/min per 1·73 m(2) were followed from baseline (first eGFR measurement after Jan 1, 2004) until the occurrence of one of the following: chronic kidney disease; last eGFR measurement; Feb 1, 2014; or final visit plus 6 months (whichever occurred first). Chronic kidney disease was defined as confirmed (>3 months apart) eGFR lower than 60 mL/min per 1·73 m(2). The primary outcome was the occurrence of chronic kidney disease. Poisson regression was used to estimate the incidence rate of chronic kidney disease associated with cumulative exposure to tenofovir disoproxil fumarate, ritonavir-boosted atazanavir, ritonavir-boosted lopinavir, other ritonavir-boosted protease inhibitors, or abacavir. FINDINGS:Between Jan 1, 2004, and July 26, 2013, 23,905 eligible individuals from the D:A:D study were included. Participants had a median baseline eGFR of 110 mL/min per 1·73 m(2) (IQR 100-125), a median age of 39 years (33-45), and median CD4 cell count of 441 cells per mm(3) (294-628). During a median follow-up of 7·2 years (IQR 5·1-8·9), 285 (1%) of 23,905 people developed chronic kidney disease (incidence 1·76 per 1000 person-years of follow-up [95% CI 1·56-1·97]). After adjustment, we recorded a significant increase in chronic kidney disease associated with each additional year of exposure to tenofovir disoproxil fumarate (adjusted incidence rate ratio 1·14 [95% CI 1·10-1·19], p<0·0001), ritonavir-boosted atazanavir (1·20 [1·13-1·26], p<0·0001), and ritonavir-boosted lopinavir (1·11 [1·06-1·16], p<0·0001), but not other ritonavir-boosted protease inhibitors or abacavir. INTERPRETATION:In people with normal renal function, the annual incidence of chronic kidney disease increased for up to 6 years of exposure to tenofovir disoproxil fumarate, ritonavir-boosted atazanavir, or ritonavir-boosted lopinavir therapy. Although the absolute number of new cases of chronic kidney disease was modest, treatment with these antiretrovirals might result in an increasing and cumulative risk of chronic kidney disease. Patients on potentially nephrotoxic antiretrovirals or at high risk of chronic kidney disease should be closely monitored. FUNDING:The Highly Active Antiretroviral Therapy Oversight Committee.

journal_name

Lancet HIV

journal_title

The lancet. HIV

authors

Mocroft A,Lundgren JD,Ross M,Fux CA,Reiss P,Moranne O,Morlat P,Monforte Ad,Kirk O,Ryom L,Data Collection on Adverse events of Anti-HIV Drugs (D:A:D) Study.

doi

10.1016/S2352-3018(15)00211-8

subject

Has Abstract

pub_date

2016-01-01 00:00:00

pages

e23-32

issue

1

eissn

2405-4704

issn

2352-3018

pii

S2352-3018(15)00211-8

journal_volume

3

pub_type

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    abstract::Progress in the development and introduction of paediatric formulations for key infectious diseases is poor in low-income and middle-income countries (LMICs). Although major steps have been made in the scale-up of antiretroviral medicines in LMICs, the development and deployment of formulations for infants and childre...

    journal_title:The lancet. HIV

    pub_type: 杂志文章

    doi:10.1016/S2352-3018(18)30005-5

    authors: Penazzato M,Watkins M,Morin S,Lewis L,Pascual F,Vicari M,Lee J,Hargreaves S,Doherty M,Siberry GK

    更新日期:2018-05-01 00:00:00

  • Effectiveness and cost-effectiveness of potential responses to future high levels of transmitted HIV drug resistance in antiretroviral drug-naive populations beginning treatment: modelling study and economic analysis.

    abstract:BACKGROUND:With continued roll-out of antiretroviral therapy (ART) in resource-limited settings, evidence is emerging of increasing levels of transmitted drug-resistant HIV. We aimed to compare the effectiveness and cost-effectiveness of different potential public health responses to substantial levels of transmitted d...

    journal_title:The lancet. HIV

    pub_type: 杂志文章

    doi:10.1016/S2352-3018(14)70021-9

    authors: Phillips AN,Cambiano V,Miners A,Revill P,Pillay D,Lundgren JD,Bennett D,Raizes E,Nakagawa F,De Luca A,Vitoria M,Barcarolo J,Perriens J,Jordan MR,Bertagnolio S

    更新日期:2014-11-01 00:00:00