Abstract

ObjectiveRitonavir-boosted protease inhibitors (bPI) in people living with HIV (PLWH) have been associated with renal impairment. Limited data are available from rural sub-Saharan Africa.MethodsUsing data from the Kilombero and Ulanga Antiretroviral Cohort Study (KIULARCO) in rural Tanzania from 2005-01/2020, we assessed the prevalence of renal impairment (estimated glomerular filtration rate <60 mL/min/1.73m2) at the time of switch from first-line antiretroviral treatment (ART) to bPI-regimen and the incidence of renal impairment on bPI. We assessed risk factors for renal impairment using logistic and Cox regression models.ResultsRenal impairment was present in 52/687 PLWH (7.6%) at the switch to bPI. Among 556 participants with normal kidney function at switch, 41 (7.4%) developed renal impairment after a median time of 3.5 (IQR 1.6–5.1) years (incidence 22/1,000 person-years (95%CI 16.1–29.8)). Factors associated with renal impairment at switch were older age (adjusted odds ratio (aOR) 1.55 per 10 years; 95%CI 1.15–2.11), body mass index (BMI) <18.5 kg/m2 (aOR 2.80 versus ≥18kg/m2; 95%CI 1.28–6.14) and arterial hypertension (aOR 2.33; 95%CI 1.03–5.28). The risk of renal impairment was lower with increased duration of ART use (aOR 0.78 per one-year increase; 95%CI 0.67–0.91). The renal impairment incidence under bPI was associated with older age (adjusted hazard ratio 2.01 per 10 years; 95%CI 1.46–2.78).ConclusionsIn PLWH in rural sub-Saharan Africa, prevalence and incidence of renal impairment among those who were switched from first-line to bPI-regimens were high. We found associations between renal impairment and older age, arterial hypertension, low BMI and time on ART.

Highlights

  • Factors associated with renal impairment at switch were older age (adjusted odds ratio 1.55 per 10 years; 95%confidence intervals (CI) 1.15–2.11), body mass index (BMI)

  • The risk of renal impairment was lower with increased duration of antiretroviral treatment (ART) use

  • The renal impairment incidence under boosted protease inhibitors (bPI) was associated with older age

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Summary

Introduction

Rollout and improvement in HIV care and treatment have led to a shift in the main causes of morbidity and mortality in people living with HIV (PLWH) away from opportunistic infections to chronic non-communicable diseases such as liver, cardiovascular and renal diseases [1]. With a global prevalence of 11–13% [2], chronic kidney disease (CKD) is regarded as an independent risk factor for cardiovascular diseases (CVD) and a leading cause of mortality and morbidity in PLWH [3, 4]. For second-line treatment, the same guidelines recommend the use of TDF in combination with ritonavir-boosted protease inhibitors (bPI)—either atazanavir (ATV/r) or lopinavir (LPV/r). Longer cumulative exposure to the use of TDF [12, 13] and bPIs [14, 15] has been associated with CKD or kidney dysfunction. The risk of kidney dysfunction increases when patients receive TDF in combination with a bPI [15,16,17]. The mechanism of CKD is not well understood, previous studies suggested it might be due to crystalluria, proximal tubular dysfunction, urolithiasis, and interstitial nephritis [18, 19]

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