Lamivudine Monotherapy as a holding regimen for HIV-positive children

dc.contributor.authorPatten, Gabriela
dc.contributor.authorBernheimer, Jonathan
dc.contributor.authorLee, Fairlie
dc.contributor.authorHelena, Rabie
dc.contributor.authorShobna, Sawry
dc.contributor.authorKarl, Technau
dc.contributor.authorBrian, Eley
dc.contributor.authorMary-Ann, Davies
dc.coverage.spatialSouth Africaen_ZA
dc.date.accessioned2018-10-15T13:29:51Z
dc.date.available2018-10-15T13:29:51Z
dc.date.issued2018-10-11
dc.description.abstractBackground 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. Methods We 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. Findings We 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. Interpretation Most 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.en_ZA
dc.identifier.apacitationPatten, G., Bernheimer, J., Lee, F., Helena, R., Shobna, S., Karl, T., ... Mary-Ann, D. (2018). Lamivudine Monotherapy as a holding regimen for HIV-positive children. <i>PLoS One</i>, http://hdl.handle.net/11427/28925en_ZA
dc.identifier.chicagocitationPatten, Gabriela, Jonathan Bernheimer, Fairlie Lee, Rabie Helena, Sawry Shobna, Technau Karl, Eley Brian, and Davies Mary-Ann "Lamivudine Monotherapy as a holding regimen for HIV-positive children." <i>PLoS One</i> (2018) http://hdl.handle.net/11427/28925en_ZA
dc.identifier.citationPatten G, Bernheimer J, Fairlie L, Rabie H, Sawry S, Technau K, et al. (2018) Lamivudine monotherapy as a holding regimen for HIV-positive children. PLoS ONE 13(10): e0205455. https://doi. org/10.1371/journal.pone.0205455en_ZA
dc.identifier.ris TY - Journal Article AU - Patten, Gabriela AU - Bernheimer, Jonathan AU - Lee, Fairlie AU - Helena, Rabie AU - Shobna, Sawry AU - Karl, Technau AU - Brian, Eley AU - Mary-Ann, Davies AB - Background 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. Methods We 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. Findings We 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. Interpretation Most 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. DA - 2018-10-11 DB - OpenUCT DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2018 T1 - Lamivudine Monotherapy as a holding regimen for HIV-positive children TI - Lamivudine Monotherapy as a holding regimen for HIV-positive children UR - http://hdl.handle.net/11427/28925 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/28925
dc.identifier.vancouvercitationPatten G, Bernheimer J, Lee F, Helena R, Shobna S, Karl T, et al. Lamivudine Monotherapy as a holding regimen for HIV-positive children. PLoS One. 2018; http://hdl.handle.net/11427/28925.en_ZA
dc.languageengen_ZA
dc.publisherPLoS Oneen_ZA
dc.publisher.departmentCentre for Infectious Disease Epidemiology and Research (CIDER)en_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsCreative Commons Attribution 4.0 International (CC BY 4.0)*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttps://journals.plos.org/plosone/
dc.titleLamivudine Monotherapy as a holding regimen for HIV-positive childrenen_ZA
dc.typeJournal Articleen_ZA
uct.subject.keywordsHIVen_ZA
uct.subject.keywordsVirologic failureen_ZA
uct.subject.keywordsPaediatricen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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