Metabolic abnormalities and body composition of HIV-infected children on Lopinavir or Nevirapine-based antiretroviral therapy

Arpadi, Stephen M.; Shiau, Stephanie; Strehlau, Renate; Martens, Leigh; Patel, Faeezah; Coovadia, Ashraf; Abrams, Elaine J.; Kuhn, Louise

doi:10.1136/archdischild-2012-302633

Cited by 58 publications

(92 citation statements)

References 42 publications

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“…For consistency with prior publications on shorter-term outcomes, we used this protocol-defined composite outcome. While the primary focus of this trial was HIV-related outcomes, studies have shown unfavorable alterations in lipid profiles and body composition among infants on LPV/r [27,28]. Longitudinal data on such outcomes are needed as, with current treatment recommendations, the duration of LPV/rbased ART exposure will only increase for perinatally infected children.…”

Section: Discussionmentioning

confidence: 99%

Nevirapine- Versus Lopinavir/Ritonavir-Based Antiretroviral Therapy in HIV-Infected Infants and Young Children: Long-term Follow-up of the IMPAACT P1060 Randomized Trial

et al. 2016

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Background. The International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT) P1060 study demonstrated short-term superiority of lopinavir/ritonavir (LPV/r) over nevirapine (NVP) in antiretroviral therapy (ART), regardless of prior NVP exposure. However, NVP-based ART had a marginal benefit in CD4 percentage (CD4%) and growth. We compared 5-year outcomes from this clinical trial.Methods. Human immunodeficiency virus (HIV)-infected, ART-eligible children were enrolled into 2 cohorts based on prior NVP exposure and randomized to NVP-or LPV/r-based ART. The data safety monitoring board recommended unblinding results in both cohorts due to superiority of LPV/r for the primary endpoint: stopping randomized treatment, virologic failure (VF), or death by 6 months. Participants were offered a switch in regimens (if on NVP) and continued observational follow-up. We compared time to VF or death, death, and CD4% and growth changes using intention-to-treat analyses. Additionally, inverse probability weights were used to account for treatment switching and censoring.Results. As of September 2014, 329 of the 451 (73%) enrolled participants were still in follow-up (median, 5.3 years; interquartile range [IQR], 4.3-6.4), with 52% on NVP and 88% on LPV/r as originally randomized. NVP arm participants had significantly higher risk of VF or death (adjusted hazard ratio [aHR], 1.90; 95% confidence interval [CI], 1.37-2.65) but not death alone (aHR, 1.65; 95% CI, .72-3.76) compared with participants randomized to LPV/r. Mean CD4% was significantly higher in the NVP arm up to 1 year after ART initiation, but not beyond. Mean weight-for-age z scores were marginally higher in the NVP arm, but height-for-age z scores did not differ. Similar trends were observed in sensitivity analyses.Conclusions. These findings support the current World Health Organization recommendation of LPV/r in first-line ART regimens for HIV-infected children.Clinical Trials Registration. NCT00307151.

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Section: Discussionmentioning

confidence: 99%

Nevirapine- Versus Lopinavir/Ritonavir-Based Antiretroviral Therapy in HIV-Infected Infants and Young Children: Long-term Follow-up of the IMPAACT P1060 Randomized Trial

et al. 2016

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“…PIs are associated with dyslipidaemia and lipodystrophy 103, 111, 112, 113. However, once‐daily PIs, such as ATV/r and DRV/r, in adults tend to cause fewer lipid abnormalities 114, 115, 116.…”

Section: Drug Toxicities and Interactionsmentioning

confidence: 99%

“…The Nevirapine Resistance Study (NEVEREST), a randomized trial of switching NVP‐exposed infants from suppressive LPV/r‐ to NVP‐based ART (after at least 3 months of VL < 400 copies/ml), showed that this strategy can be successful in infants without evidence of transmitted NVP resistance on conventional testing 64, 197. Children switched to NVP had less long‐term dyslipidaemia and subcutaneous fat loss 112. Furthermore, the recently reported results of the NEVEREST‐3 study 198 indicate that switching children fully suppressed on LPV/r to EFV‐based ART is a safe and effective strategy in the context of prophylactic NVP exposure.…”

Section: When To Switch Resistance Testing and Second And Subsequentmentioning

confidence: 99%

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

et al. 2015

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The 2015 Paediatric European Network for Treatment of AIDS (PENTA) guidelines provide practical recommendations on the management of HIV‐1 infection in children in Europe and are an update to those published in 2009. Aims of treatment have progressed significantly over the last decade, moving far beyond limitation of short‐term morbidity and mortality to optimizing health status for adult life and minimizing the impact of chronic HIV infection on immune system development and health in general. Additionally, there is a greater need for increased awareness and minimization of long‐term drug toxicity. The main updates to the previous guidelines include: an increase in the number of indications for antiretroviral therapy (ART) at all ages (higher CD4 thresholds for consideration of ART initiation and additional clinical indications), revised guidance on first‐ and second‐line ART recommendations, including more recently available drug classes, expanded guidance on management of coinfections (including tuberculosis, hepatitis B and hepatitis C) and additional emphasis on the needs of adolescents as they approach transition to adult services. There is a new section on the current ART ‘pipeline’ of drug development, a comprehensive summary table of currently recommended ART with dosing recommendations. Differences between PENTA and current US and World Health Organization guidelines are highlighted and explained.

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“…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.…”

mentioning

confidence: 99%

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

et al. 2014

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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 ...

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Metabolic abnormalities and body composition of HIV-infected children on Lopinavir or Nevirapine-based antiretroviral therapy

Cited by 58 publications

References 42 publications

Nevirapine- Versus Lopinavir/Ritonavir-Based Antiretroviral Therapy in HIV-Infected Infants and Young Children: Long-term Follow-up of the IMPAACT P1060 Randomized Trial

Nevirapine- Versus Lopinavir/Ritonavir-Based Antiretroviral Therapy in HIV-Infected Infants and Young Children: Long-term Follow-up of the IMPAACT P1060 Randomized Trial

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

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

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