Association of Prenatal and Postnatal Exposure to Lopinavir-Ritonavir and Adrenal Dysfunction Among Uninfected Infants of HIV-Infected Mothers

Simon, Albane; Warszawski, Josiane; Kariyawasam, Dulanjalee; Chenadec, Jérôme Le; Benhammou, Valérie; Czernichow, P; Foissac, Frantz; Laborde, Kathleen; Tréluyer, Jean‐Marc; Firtion, Ghislaine; Layouni, I.; Munzer, Martine; Bavoux, F; Polak, Michel; Blanche, Stéphane

doi:10.1001/jama.2011.915

Cited by 80 publications

(55 citation statements)

References 33 publications

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“…LPV/r should not be administered to premature neonates or to term neonates below 2 weeks of postnatal age because of the increased risk of toxicities reported in premature and very young babies 66, 67.…”

Section: Which Art Regimen To Start As First‐line Therapymentioning

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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Section: Which Art Regimen To Start As First‐line Therapymentioning

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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“…Unfortunately, the use of boosted protease inhibitors (PIs) in preterm newborns is associated with life-threatening side effects. They should not be used or only with extreme caution (3).…”

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confidence: 99%

One-Month Transplacental Pharmacokinetics of Raltegravir in a Premature Newborn after Short-Course Treatment of the HIV-1-Infected Mother

Clavel-Osorio¹,

Cazassus²,

Stegmann³

et al. 2013

Antimicrob Agents Chemother

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eWe describe the pharmacokinetics of raltegravir of a preterm newborn after short-course treatment of the mother tested HIV ؉ the day of delivery. At age 1 month, the circulating concentration of raltegravir in the newborn was 29 ng/ml (the IC95 of RAL against HIV-1 is 15 ng/ml). Raltegravir should therefore be considered a potential transplacental postexposure prophylaxis for HIV-1 and an alternative to the use of boosted lopinavir in this context.

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“…Regarding safety data, to our knowledge, there is no evidence-based medicine to evaluate the tolerance of LPV/r at Ͻ6 weeks of age, but a few case reports on toxicity have been provided. Those reports mainly concerned premature babies and infants with cardiac dysfunction (and cases of overdosing) (21). A general warning from the FDA about the use of LPV/r in infants aged less than 14 days followed (22).…”

Section: Discussionmentioning

confidence: 99%

Are Prophylactic and Therapeutic Target Concentrations Different?: the Case of Lopinavir-Ritonavir or Lamivudine Administered to Infants for Prevention of Mother-to-Child HIV-1 Transmission during Breastfeeding

Foissac

Blume

Tréluyer

et al. 2017

Antimicrob Agents Chemother

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The ANRS 12174 trial assessed the efficacy and tolerance of lopinavir (LPV)-ritonavir (LPV/r) prophylaxis versus those of lamivudine (3TC) prophylaxis administered to breastfed infants whose HIV-infected mothers were not on antiretroviral therapy. In this substudy, we assessed LPV/r and 3TC pharmacokinetics to evaluate the percentage of infants with therapeutic plasma concentrations and to discuss these data in the context of a prophylactic treatment. Infants from the South African trial site underwent blood sampling for pharmacokinetic study at weeks 6, 26, and 38 of life. We applied a Bayesian approach to derive the 3TC and LPV pharmacokinetic parameters on the basis of previously published pharmacokinetic models for HIV-infected children. We analyzed 114 LPV and 180 3TC plasma concentrations from 69 infants and 92 infants, respectively. A total of 30 LPV and 20 3TC observations were considered missing doses and discarded from the Bayesian analysis. The overall population analysis showed that 30 to 40% of the infants did not reach therapeutic targets, regardless of treatment group. The median LPV trough concentrations at weeks 6, 26, and 38 were 2.8 mg/liter (interquartile range [IQR], 1.7 to 4.4 mg/liter), 5.6 mg/liter (IQR, 3.2 to 7.7 mg/liter), and 3.4 mg/liter (IQR, 2.3 to 7.3 mg/ liter), respectively. The median 3TC area under the curve from 0 to 12 h after the last drug intake were 5.6 mg · h/liter (IQR, 4.1 to 7.8 mg · h/liter), 5.9 mg · h/liter (IQR, 5.1 to 7.5 mg · h/liter), and 7.3 mg · h/liter (IQR, 4.9 to 8.5 mg · h/liter) at weeks 6, 26, and 38, respectively. Use of the therapeutic doses recommended by the WHO would have resulted in a higher proportion of infants achieving the targets. However, no HIV-1 infection was reported among these infants. These results suggest that the prophylactic targets for both 3TC and LPV may be lower than the ther-

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Association of Prenatal and Postnatal Exposure to Lopinavir-Ritonavir and Adrenal Dysfunction Among Uninfected Infants of HIV-Infected Mothers

Abstract: Among newborn children of HIV-1-infected mothers exposed in utero to lopinavir-ritonavir, postnatal treatment with a lopinavir-ritonavir-based regimen, compared with a zidovudine-based regimen, was associated with transient adrenal dysfunction.

Cited by 80 publications

References 33 publications

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

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

One-Month Transplacental Pharmacokinetics of Raltegravir in a Premature Newborn after Short-Course Treatment of the HIV-1-Infected Mother

Are Prophylactic and Therapeutic Target Concentrations Different?: the Case of Lopinavir-Ritonavir or Lamivudine Administered to Infants for Prevention of Mother-to-Child HIV-1 Transmission during Breastfeeding

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