Outcome of protease inhibitor substitution with nevirapine in HIV-1 infected children

González-Tomé, M I; Amador, José Tomás Ramos; Peña, María José; Gómez, María Luisa Navarro; Conejo, Pablo Rojo; Fontelos, P. Martín

doi:10.1186/1471-2334-8-144

Cited by 19 publications

(8 citation statements)

References 29 publications

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“…The good outcomes of children switching from NNRTI to LPV/r-based ART in our study add to limited data on the safety of switching ART in children with virologic control 14-18 . HIV-infected children occasionally need to change ART due to adverse events, anticipated drug interactions, or formulation availability.…”

Section: Discussionmentioning

confidence: 62%

“…HIV-infected children occasionally need to change ART due to adverse events, anticipated drug interactions, or formulation availability. Prior studies have demonstrated safety in changing from PI to EFV 15 or NVP 4,18 - based ART, but to our knowledge, no randomized trials have previously reported on the safety of switching from NNRTI- to PI-based ART among children with virologic suppression…”

Section: Discussionmentioning

confidence: 91%

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Virologic and Immunologic Outcomes of HIV-Infected Ugandan Children Randomized to Lopinavir/Ritonavir or Nonnucleoside Reverse Transcriptase Inhibitor Therapy

Ruel

Kakuru

Ikilezi

et al. 2014

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Background In the PROMOTE-pediatrics trial, HIV-infected Ugandan children randomized to receive lopinavir-ritonavir (LPV/r)-based antiretroviral therapy (ART) experienced a lower incidence of malaria compared to children receiving non-nucleoside-reverse-transcriptase-inhibitor (NNRTI)-based-ART. Here we present the results of the non-inferiority (NI) analysis of virologic efficacy and comparison of immunologic outcomes. Methods ART-naïve or -experienced (HIV RNA < 400 copies/ml) children ages 2 months to 6 years received either LPV/r or NNRTI-based-ART. The proportion of children with virologic suppression (HIV RNA <400copies/ml) at 48 weeks was compared using a pre-specified NI margin of −11% in per-protocol analysis. Time to virologic failure by 96 weeks, change in CD4 counts and percentages, and incidence of adverse event rates were also compared. Results Of 185 children enrolled, 91 initiated LPV/r and 92 initiated NNRTI-based ART. At baseline, the median age was 3.1 years (range: 0.4 to 5.9) and 131 (71%) were ART-naïve. The proportion of children with virologic suppression at 48 weeks was 80% (67/84) in the LPV/r-arm vs. 76% (59/78) in the NNRTI-arm, a difference of 4% (95%CI: −9% to +17%). Time to virologic failure, CD4 changes, and the incidence of DAIDS grade III/IV adverse events were similar between arms. Conclusions LPV/r-based ART was not associated with worse virologic efficacy, immunologic efficacy, or adverse event rates compared to NNRTI-based ART. Considering these results and the reduction in malaria incidence associated with LPV/r previously reported for this trial, wider use of LPV/r to treat HIV-infected African children in similar malaria endemic settings could be considered.

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Section: Discussionmentioning

confidence: 62%

Section: Discussionmentioning

confidence: 91%

Virologic and Immunologic Outcomes of HIV-Infected Ugandan Children Randomized to Lopinavir/Ritonavir or Nonnucleoside Reverse Transcriptase Inhibitor Therapy

Ruel

Kakuru

Ikilezi

et al. 2014

JAIDS Journal of Acquired Immune Deficiency Syndromes

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“…However, Gonzalez-Tome et al . reported no significant changes in body fat composition after substitution of a PI with NVP [65]. Other investigational strategies have been identified to manage LD including the use of growth hormone (GH) and other drugs.…”

Section: Lipodystrophy Syndromementioning

confidence: 99%

“…Restoration of physiologic fat accrual and no further progression of LA was reported 96 weeks after replacement of d4T with TDF and a PI with EFV [64]. However, Gonzalez-Tome et al reported no significant changes in body fat composition after substitution of a PI with NVP [65]. Other investigational strategies have been identified to manage LD including the use of growth hormone (GH) and other drugs.…”

Section: Fat Distributionmentioning

confidence: 99%

Metabolic complications and treatment of perinatally HIV‐infected children and adolescents

Barlow‐Mosha

Eckard

McComsey

et al. 2013

Journal of the International AIDS Society

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The benefits of long-term antiretroviral therapy (ART) are recognized all over the world with infected children maturing into adults and HIV infection becoming a chronic illness. However, the improved survival is associated with serious metabolic complications, including lipodystrophy (LD), dyslipidemia, insulin resistance, lactic acidosis and bone loss. In addition, the dyslipidemia mainly seen with protease inhibitors may increase the risk of cardiovascular disease in adulthood and potentially in children as they mature into adults. Nucleoside reverse transcriptase inhibitors, particularly stavudine, zidovudine and didanosine are linked to development of LD and lactic acidosis. Perinatally infected children initiate ART early in life; they require lifelong therapy with multiple drug regimens leading to varying toxicities, all potentially impacting their quality of life. LD has a significant impact on the mental health of older children and adolescents leading to poor self-image, depression and subsequent poor adherence to therapy. Reduced bone mineral density (BMD) is reported in both adults and children on ART with the potential for children to develop more serious bone complications than adults due to their rapid growth spurts and puberty. The role of vitamin D in HIV-associated osteopenia and osteoporosis is not clear and needs further study. Most resource-limited settings are unable to monitor lipid profiles or BMD, exposing infected children and adolescents to on-going toxicities with unclear long-term consequences. Improved interventions are urgently needed to prevent and manage these metabolic complications. Longitudinal cohort studies in this area should remain a priority, particularly in resource-limited settings where the majority of infected children reside.

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“…Switch studies in adults showed improvements in cholesterol with a switch to atazanavir 21–23 or raltegravir 24 , from zidovudine/lamivudine to tenofovir/emtricitabine 25 and from stavudine to tenofovir 26 . Children who switched from PI therapy to a PI-sparing regimen containing nevirapine showed mild decreases in total-C and increases in HDL-C 27 as did those who switched from PI to efavirenz 28 . More studies on the effect of switching ARV are needed in children as newer ARVs, such as atazanavir and darunavir which have an improved lipid profile, are approved in children older than six years of age.…”

Section: Introductionmentioning

confidence: 94%

Clinical Management and Follow-up of Hypercholesterolemia Among Perinatally HIV-Infected Children Enrolled in the PACTG 219C Study

Jacobson¹,

Williams²,

Tassiopoulos³

et al. 2011

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Background Hypercholesterolemia is common in perinatally HIV-infected (HIV+) children, but little is known about the clinical course and management in this population. Methods We studied HIV+ children in a multisite prospective cohort study (PACTG 219C) and considered follow-up for two years after development of hypercholesterolemia. We estimated the time to and factors associated with resolution of hypercholesterolemia and described changes in ARV regimen and use of lipid-lowering medications. We defined incident hypercholesterolemia as entry total cholesterol (cholesterol) < 220 mg/dl and two subsequent consecutive cholesterol ≥ 220 mg/dl, and defined resolution of hypercholesterolemia as two consecutive cholesterol < 200 mg/dl after incident hypercholesterolemia. Results Among 240 incident hypercholesterolemia cases, 81 (34%) had resolution to normal cholesterol within two years of follow-up (median follow-up = 1.9 years). The median age of cases was 10.3 years with 54% Non-Hispanic black and 53% male. Resolution to normal cholesterol was more likely in children who changed ARV regimen (adjusted Hazard Ratio (aHR) = 2.37, 95%CI 1.45, 3.88) and who were ≥ 13 years old (aHR=2.39, 95%CI 1.33, 4.27). Types of regimen changes varied greatly and 15 children began statins. Conclusions The majority of children who develop hypercholesterolemia maintain elevated levels over time, potentially placing them at risk for premature cardiovascular morbidity.

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Outcome of protease inhibitor substitution with nevirapine in HIV-1 infected children

Cited by 19 publications

References 29 publications

Virologic and Immunologic Outcomes of HIV-Infected Ugandan Children Randomized to Lopinavir/Ritonavir or Nonnucleoside Reverse Transcriptase Inhibitor Therapy

Virologic and Immunologic Outcomes of HIV-Infected Ugandan Children Randomized to Lopinavir/Ritonavir or Nonnucleoside Reverse Transcriptase Inhibitor Therapy

Metabolic complications and treatment of perinatally HIV‐infected children and adolescents

Clinical Management and Follow-up of Hypercholesterolemia Among Perinatally HIV-Infected Children Enrolled in the PACTG 219C Study

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