Lamivudine monotherapy as a holding regimen for HIV-positive children.

Gabriela Patten,Helena Rabie,Brian Eley,Karl Technau,Mary-Ann Davies,Jonathan Bernheimer,Shobna Sawry,Lee Fairlie,Justyna Dominika Kowalska

doi:10.1371/journal.pone.0205455

Abstract

BackgroundIn resource-limited settings holding regimens, such as lamivudine monotherapy (LM), are used to manage HIV-positive children failing combination antiretroviral therapy (cART) to mitigate the risk of drug resistance developing, whilst adherence barriers are addressed or when access to second- or third-line regimens is restricted. We aimed to investigate characteristics of children placed on LM and their outcomes.MethodsWe describe the characteristics of children (age <16 years at cART start) from 5 IeDEA-SA cohorts with a record of LM during their treatment history. Among those on LM for >90 days we describe their immunologic outcomes on LM and their immunologic and virologic outcomes after resuming cART.FindingsWe included 228 children in our study. At LM start their median age was 12.0 years (IQR 7.3–14.6), duration on cART was 3.6 years (IQR 2.0–5.9) and median CD4 count was 605.5 cells/μL (IQR 427–901). Whilst 110 (48%) had no prior protease inhibitor (PI)-exposure, of the 69 with recorded PI-exposure, 9 (13%) patients had documented resistance to all PIs. After 6 months on LM, 70% (94/135) experienced a drop in CD4, with a predicted average CD4 decline of 46.5 cells/μL (95% CI 37.7–55.4). Whilst on LM, 46% experienced a drop in CD4 to <500 cells/μL, 18 (8%) experienced WHO stage 3 or 4 events, and 3 children died. On resumption of cART the average gain in CD4 was 15.65 cells/uL per month and 66.6% (95% CI 59.3–73.7) achieved viral suppression (viral load <1000) at 6 months after resuming cART.InterpretationMost patients experienced immune decline on LM. Its use should be avoided in those with low CD4 counts, but restricted use may be necessary when treatment options are limited. Managing children with virologic failure will continue to be challenging until more treatment options and better adherence strategies are available.

Highlights

Treatment failure among HIV-positive children is a growing concern.[1]
We describe the characteristics of children from 5 International epidemiologic Database to Evaluate AIDS (IeDEA)-SA cohorts with a record of Lamivudine monotherapy (LM) during their treatment history
Managing children with virologic failure will continue to be challenging until more treatment options and better adherence strategies are available

Summary

Introduction

Treatment failure among HIV-positive children is a growing concern.[1] In resource-limited settings, where access to second- or third-line combination antiretroviral therapy (cART) for HIV-positive children is frequently restricted, managing virologic failure is especially challenging.[2] Children and adolescents face a number of adherence barriers, and drug formulations are often unpalatable with large pill burdens.[3,4,5] Switching children with virologic failure, who have suspected or proven poor adherence, to a new regimen runs the risk of increasing resistant mutations, limiting future treatment options. This commonly used holding strategy reduces the pill burden to patients and allows time for adherence barriers to be addressed It is used whilst awaiting access to second- or third-line regimens, not always readily available. In resource-limited settings holding regimens, such as lamivudine monotherapy (LM), are used to manage HIV-positive children failing combination antiretroviral therapy (cART) to mitigate the risk of drug resistance developing, whilst adherence barriers are addressed or when access to second- or third-line regimens is restricted. We aimed to investigate characteristics of children placed on LM and their outcomes.

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Conclusion