Consequences of Prior Use of Full-dose Ritonavir as Single Protease Inhibitor as Part of Combination Antiretroviral Regimens on the Future Therapy Choices in HIV-1–Infected Children

Feucht, Ute Dagmar; Rossouw, Theresa M.; Dyk, Gisela Van; Forsyth, Brian W.C.; Kruger, Mariana

doi:10.1097/inf.0b013e31829f2694

Cited by 3 publications

(3 citation statements)

References 19 publications

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“…Our study confirms that initiation of ART with RTV-sPI during the period of co-treatment is associated with the development of PI mutations [ 63 – 66 ]. However, not only patients on RTV-sPI developed PI mutations and not all patients initiated on RTV-sPI fail treatment [ 65 ]. Our study was too small to allow comparison between LPV/R+ and ddLPV/r, but studies have shown that ddLPV/r results in substantial reductions of LPV concentrations and should not be used in young children [ 16 , 17 ].…”

Section: Discussionmentioning

confidence: 99%

Factors Associated with the Development of Drug Resistance Mutations in HIV-1 Infected Children Failing Protease Inhibitor-Based Antiretroviral Therapy in South Africa

et al. 2015

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ObjectiveLimited data are available from the developing world on antiretroviral drug resistance in HIV-1 infected children failing protease inhibitor-based antiretroviral therapy, especially in the context of a high tuberculosis burden. We describe the proportion of children with drug resistance mutations after failed protease inhibitor-based antiretroviral therapy as well as associated factors.MethodsData from children initiated on protease inhibitor-based antiretroviral therapy with subsequent virological failure referred for genotypic drug resistance testing between 2008 and 2012 were retrospectively analysed. Frequencies of drug resistance mutations were determined and associations with these mutations identified through logistic regression analysis.ResultsThe study included 65 young children (median age 16.8 months [IQR 7.8; 23.3]) with mostly advanced clinical disease (88.5% WHO stage 3 or 4 disease), severe malnutrition (median weight-for-age Z-score -2.4 [IQR -3.7;-1.5]; median height-for-age Z-score -3.1 [IQR -4.3;-2.4]), high baseline HIV viral load (median 6.04 log10, IQR 5.34;6.47) and frequent tuberculosis co-infection (66%) at antiretroviral therapy initiation. Major protease inhibitor mutations were found in 49% of children and associated with low weight-for-age and height-for-age (p = 0.039; p = 0.05); longer duration of protease inhibitor regimens and virological failure (p = 0.001; p = 0.005); unsuppressed HIV viral load at 12 months of antiretroviral therapy (p = 0.001); tuberculosis treatment at antiretroviral therapy initiation (p = 0.048) and use of ritonavir as single protease inhibitor (p = 0.038). On multivariate analysis, cumulative months on protease inhibitor regimens and use of ritonavir as single protease inhibitor remained significant (p = 0.008; p = 0.033).ConclusionMajor protease inhibitor resistance mutations were common in this study of HIV-1-infected children, with the timing of tuberculosis treatment and subsequent protease inhibitor dosing strategy proving to be important associated factors. There is an urgent need for safe, effective, and practicable HIV/tuberculosis co-treatment in young children and the optimal timing of treatment, optimal dosing of antiretroviral therapy, and alternative tuberculosis treatment strategies should be urgently addressed.

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Section: Discussionmentioning

confidence: 99%

Factors Associated with the Development of Drug Resistance Mutations in HIV-1 Infected Children Failing Protease Inhibitor-Based Antiretroviral Therapy in South Africa

et al. 2015

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“…We included all children who started ART 2000 to 2012 with two nucleoside reverse transcriptase inhibitors (NRTI) and either a non-nucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI). We excluded children who started with ritonavir and NRTIs: this regimen is no longer used [21–23]. …”

Section: Methodsmentioning

confidence: 99%

Viral load versus CD4+ monitoring and 5-year outcomes of antiretroviral therapy in HIV-positive children in Southern Africa

Salazar‐Vizcaya¹,

Keiser²,

Technau³

et al. 2014

Aids

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Objectives Many paediatric antiretroviral therapy (ART) programmes in Southern Africa rely on CD4 counts to monitor ART. We assessed the benefit of replacing CD4 by viral load (VL) monitoring. Design Mathematical modelling study. Methods Simulation model of HIV progression over 5 years in children on ART, parameterised by data from seven South African cohorts. We simulated treatment programmes with 6-monthly CD4 count or 6- or 12-monthly VL monitoring. We compared mortality, second-line ART use, immunological failure and time spent on failing ART. In further analyses we varied the rate of virological failure, and assumed that the rate is higher with CD4 than with VL monitoring. Results About 7% of children were predicted to die within 5 years, independent of the monitoring strategy. Compared with CD4 monitoring, 12-monthly VL monitoring reduced the 5-year risk of immunological failure from 1.6% to 1.0% and the mean time spent on failing ART from 6.6 to 3.6 months; 1% of children with CD4 compared to 12% with VL monitoring switched to second-line ART. Differences became larger when assuming higher rates of virological failure. When assuming higher virological failure rates with CD4 than with VL monitoring, up to 4.2% of children with CD4 compared to 1.5% with VL monitoring experienced immunological failure; the mean time spent on failing ART was 27.3 months with CD4 monitoring and 6.0 months with VL monitoring. Conclusions VL monitoring did not affect 5-year mortality, but reduced time on failing ART, improved immunological response and increased switching to second-line ART.

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“…The frequency of NNRTI resistance prior to treatment initiation was 45% in the sdNVP-exposed group and 18% in the group that had no prior sdNVP exposure, and ART failure was more likely in the women with NNRTI resistance and prior sdNVP exposure. Similarly, prior exposure to RTV or indinavir increases PI cross-resistance and probability of failure and drug resistance from lopinavir/ritonavir (LPV/r) in both children and adults [8], and prior exposure to integrase strand transfer inhibitor exposure increases the chance of failure and drug resistance to dolutegravir [9]. Pretreatment resistance can fade over time and form minority variants, which can have an impact on outcome (covered in separate articles in this supplement).…”

Section: Pretreatment Human Immunodeficiency Virus Drug Resistancementioning

confidence: 99%

Key Factors Influencing the Emergence of Human Immunodeficiency Virus Drug Resistance in Low- and Middle-Income Countries

Wallis

Godfrey

Fitzgibbon

et al. 2017

The Journal of Infectious Diseases

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The emergence and spread of human immunodeficiency virus (HIV) drug resistance from antiretroviral roll-out programs remain a threat to long-term control of the HIV-AIDS epidemic in low- and middle-income countries (LMICs). The patterns of drug resistance and factors driving emergence of resistance are complex and multifactorial. The key drivers of drug resistance in LMICs are reviewed here, and recommendations are made to limit their influence on antiretroviral therapy efficacy.

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Consequences of Prior Use of Full-dose Ritonavir as Single Protease Inhibitor as Part of Combination Antiretroviral Regimens on the Future Therapy Choices in HIV-1–Infected Children

Cited by 3 publications

References 19 publications

Factors Associated with the Development of Drug Resistance Mutations in HIV-1 Infected Children Failing Protease Inhibitor-Based Antiretroviral Therapy in South Africa

Factors Associated with the Development of Drug Resistance Mutations in HIV-1 Infected Children Failing Protease Inhibitor-Based Antiretroviral Therapy in South Africa

Viral load versus CD4+ monitoring and 5-year outcomes of antiretroviral therapy in HIV-positive children in Southern Africa

Key Factors Influencing the Emergence of Human Immunodeficiency Virus Drug Resistance in Low- and Middle-Income Countries

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