Improved serum cholesterol in paediatric patients switched from suppressive lopinavir‐based therapy to boosted darunavir or atazanavir: an 18‐month retrospective study

Abstract

Boosted protease inhibitor (PI)-based antiretroviral therapy (ART) in children with perinatally acquired HIV (PaHIV) infection typically includes lopinavir co-formulated with ritonavir (LPV/r), which is the preferred PI according to the 2009 Paediatric European Network for the Treatment of AIDS (PENTA) guidelines [1]. PIs adversely affect lipid parameters, and data from adult studies suggest that alternative once-daily boosted PIs may have more favourable lipid profiles compared with LPV/r [2,3]. While a switch from PIs to nonnucleoside reverse transcriptase inhibitors (NNRTIs) has been shown to improve lipid profiles in paediatric cohorts [4], data are lacking regarding the optimal PI for children who have previously failed NNRTI-based regimens.A retrospective case note audit of a single-centre cohort of paediatric patients switching from suppressive LPV/r-to ritonavir-boosted atazanavir (ATV/r)-or darunavir (DRV/r)-based ART was performed. Retrospective data were collected at two time-points; 2-7 and 11-18 months post-switch. The primary endpoint was change in mean total cholesterol. Secondary endpoints were other lipid changes, viral suppression, CD4 count and liver function.In total, 26 patients suppressed on PI-based ART switched from LPV/r to ATV/r or DRV/r. Three patients were excluded from the analysis because of incomplete lipid data. Fifteen of 23 patients (65%) and eight of 23 (35%) switched to DRV/r and ATV/r, respectively. Twelve of 23 patients (52%) were male and 23 of 23 (100%) were black African. The median age at switch was 14 years [interquartile range (IQR) 12-15 years] and the median duration of LPV/r therapy was 4 years (IQR 2.25-6.75 years).Mean total cholesterol was 4.83 mmol/L [95% confidence interval (CI) 4.36-5.30 mmol/L] pre-switch. At 2-7 months post-switch, mean cholesterol reduced to 4.43 mmol/L (95% CI 4.08-4.77 mmol/L). Analysis of variance (ANOVA) showed a significant reduction in serum cholesterol of 0.41 mmol/L (P < 0.05). At 11-18 months post-switch, mean cholesterol remained reduced at 4.37 mmol/L (95% CI 4.03-4.71 mmol/ L), a significant reduction of 0.46 mmol/L (P < 0.05) compared with pre-switch cholesterol, although the difference between the first and second time-points was not significant (Fig. 1). There were no significant changes in triglycerides or high-density lipoprotein (HDL) cholesterol.Viral suppression was maintained in all patients apart from one who stopped ART following a family bereavement. No significant change in CD4 count was seen in any patient throughout the study period. No reported side effects resulted in discontinuation of therapy; however, a significant increase in mean total bilirubin was noted in those switched to ATV/r [11 (standard deviation 5) to 51 (standard deviation 23) μmol/L]. This is a known, previously reported side effect of ATV/r [5]. This is the first report of a sustained reduction in mean total cholesterol associated with a switch from LPV/r to an alternative once-daily boosted PI in PaHIV infection. Licensed paediatric dosing is ...

Improvement in lipids after switch to boosted atazanavir or darunavir in children/adolescents with perinatally acquired HIV on older protease inhibitors: results from the Pediatric HIV/AIDS Cohort Study

“…Our results are consistent with those of studies in treatment‐naïve HIV‐infected adults, which have shown improved metabolic parameters with newer PIs . Few studies, however, have been published in the paediatric HIV‐infected population on longitudinal lipid changes over time with newer PIs such as ATV/r and DRV/r, and most have been limited by small sample sizes . Similar to our findings, a case series of HIV‐infected children who switched from lopinavir/r to ATV/r or DRV/r reported a significant reduction in TC at 18 months post switch compared with baseline levels, but no changes in TG, HDL‐C or LDL‐C .…”

“…Few studies, however, have been published in the paediatric HIV-infected population on longitudinal lipid changes over time with newer PIs such as ATV/r and DRV/r, and most have been limited by small sample sizes [27][28][29]. Similar to our findings, a case series of HIV-infected children who switched from lopinavir/r to ATV/r or DRV/r reported a significant reduction in TC at 18 months post switch compared with baseline levels, but no changes in TG, HDL-C or LDL-C [29]. Children in the Darunavir EvaLuation in Pediatric, HIVInfected, treatment-experienced patients (DELPHI) trial begun on darunavir demonstrated decreases in TG levels 48 weeks post-initiation [27].…”

Paediatric European Network for Treatment of AIDS (PENTA) guidelines for treatment of paediatric HIV‐1 infection 2015: optimizing health in preparation for adult life

“…Switching to once‐daily boosted PIs has been associated with improved lipid profiles in adult studies and now this has been demonstrated in a paediatric population 196.…”

Dyslipidemia and cardiovascular disease in Vietnamese people with HIV on antiretroviral therapy

“…Previous studies have suggested that using LPV/r can enhance renal toxicity of tenofovir and LPV/r is associated with renal dysfunction (11,12). Depending on the situation, substitution of other protease inhibitors, such as ritonavir-boosted darunavir or integrase inhibitors, for LPV/r can be used as salvage regimens (13). If this is not possible because of budget limitations, lipid-lowering therapy can be beneficial in people who are taking LPV/r with known risk factors, including older age, HT, and diabetes mellitus (14-18).…”