Poor Early Virologic Performance and Durability of Abacavir-based First-line Regimens for HIV-infected Children

Technau, Karl-Günter; Lazarus, Erica; Kuhn, Louise; Abrams, Elaine J.; Sorour, Gillian; Strehlau, Renate; Reubenson, Gary; Davies, Mary‐Ann; Coovadia, Ashraf

doi:10.1097/inf.0b013e31828c3738

Cited by 21 publications

(33 citation statements)

References 17 publications

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“…Eight South African sites affiliated to this collaboration contributed data including the Rahima Moosa Mother and Child Hospital (RMMCH) which previously reported poor performance of ABC-based regimens. 8 …”

Section: Methodsmentioning

confidence: 99%

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Virologic Response in Children Treated With Abacavir-compared With Stavudine-based Antiretroviral Treatment

Technau

Schomaker

Kuhn

et al. 2014

Pediatric Infectious Disease Journal

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Background Initiation criteria and pediatric antiretroviral treatment (ART) regimens have changed over the past few years in South Africa. We reported worse early virological outcomes associated with the use abacavir (ABC)-based regimens at one large site: here we expand this analysis to multiple sites in the IeDEA-Southern Africa collaboration. Methods Data for 9543 ART-naïve children <16 years at treatment initiation started on either stavudine/lamivudine (d4T/3TC) or ABC/3TC with efavirenz (EFV) or ritonavir-boosted lopinavir (LPV/r) treated at six clinics in Johannesburg and Cape Town, South Africa, were analysed with Chi-square tests and logistic regression to evaluate viral suppression at six and twelve months. Results Prevalence of viral suppression at six months in 2174 children started on a d4T-based LPV/r regimen was greater (70%) than among 438 children started on an ABC-based LPV/r regimen (54%, p<0.0001). Among 3189 children started on a d4T-based EFV regimen a higher proportion (86%) achieved suppression at six months compared to 391 children started on ABC-containing EFV regimens (78%, p<0.0001). Relative benefit of d4T vs. ABC on six month suppression remained in multivariate analysis after adjustment for pre-treatment characteristics, cohort and year of program (LPV/r – OR 0.57 [CI: 0.46–0.72]; EFV – OR 0.46 [CI: 0.32–0.65]). Conclusion This expanded analysis is consistent with our previous report of worse virological outcomes after ABC was introduced as part of first-line ART in South Africa. Whether due to the drug itself or coincident with other changes over time, continued monitoring and analyses must clarify causes and prevent suboptimal long term outcomes.

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Section: Methodsmentioning

confidence: 99%

“…8 Here we investigate whether this phenomenon is more widespread by including multiple sites in the International epidemiologic Databases to Evaluate AIDS in Southern Africa (IeDEA-SA) collaboration and whether poor virological performance in recent years may be attributed to the national programmatic switch to ABC-containing first line regimens.…”

mentioning

confidence: 99%

Virologic Response in Children Treated With Abacavir-compared With Stavudine-based Antiretroviral Treatment

Technau

Schomaker

Kuhn

et al. 2014

Pediatric Infectious Disease Journal

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“…ART failure rates for African children are significant and may vary tremendously within a country, depending on the ART regimen used. Especially high failure rates have been observed in Cote d'Ivoire (50%) and South Africa (up to 60% of children on abacavir-based first-line regimens) [8][9][10][11]. Children are generally more likely to be maintained on failing regimens for longer durations of time compared with adults, mainly due to adherence challenges and treatment option limitations.…”

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confidence: 95%

Tackling virological failure in HIV-infected children living in Africa

Jenabian

Costiniuk

Bouassa

et al. 2015

Expert Review of Anti-infective Therapy

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Drug resistance in HIV-infected children is one of the main contributors to antiretroviral treatment (ART) failure, especially in developing countries. Sub-Saharan Africa has the largest burden of pediatric HIV infection in the world. Herein, we systematically review the current status of ART failure in HIV-infected African children. A literature search for publications within 10 years was performed through PubMed to identify relevant articles. Included studies examined the impact of timing of ART initiation, criteria for diagnosing therapeutic failure, predictors of therapeutic failure, management strategies and future directions to minimize failure rates in these pediatric populations. Although there is scale-up of ART programs in Africa, novel therapeutic and management strategies are needed to overcome current challenges.

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“…South Africa's 2013 ART guidelines have recently advised that all virologically suppressed children on stavudine be automatically switched to abacavir (4), and currently around 24,000 South African children remain on stavudine out of a total of 157,000 on ART (Corry van der Walt and Jaco Stokes, South African National Department of Health, personal communication, 15 October 2013). Recent data have questioned the efficacy of abacavir-based ART in children (5), which if verified, may lead to reintroduction of stavudine. Outside of South Africa, abacavir use is limited due to its high cost.…”

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confidence: 99%

Estimation of Intracellular Concentration of Stavudine Triphosphate in HIV-Infected Children Given a Reduced Dose of 0.5 Milligrams per Kilogram Twice Daily

Innes

Derendorf

et al. 2014

Antimicrob Agents Chemother

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Poor Early Virologic Performance and Durability of Abacavir-based First-line Regimens for HIV-infected Children

Cited by 21 publications

References 17 publications

Virologic Response in Children Treated With Abacavir-compared With Stavudine-based Antiretroviral Treatment

Virologic Response in Children Treated With Abacavir-compared With Stavudine-based Antiretroviral Treatment

Tackling virological failure in HIV-infected children living in Africa

Estimation of Intracellular Concentration of Stavudine Triphosphate in HIV-Infected Children Given a Reduced Dose of 0.5 Milligrams per Kilogram Twice Daily

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