Verena Linder1, Cheree Goldswain, Hugh Adler, Craig Carty, Kim Harper, Valerie Jackson, John S Lambert, Gerald Boon. 1. From the *Department of Pediatrics, Frere Hospital, Eastern Cape, South Africa; †Department of Infectious Diseases, Mater Misericordiae University Hospital, Dublin, Ireland; ‡The Relevance Network, Johannesburg, South Africa; §Infectious Diseases, Rotunda Hospital, Dublin, Ireland; and ¶ School of Medicine and Medical Sciences, University College Dublin, Dublin, Ireland.
Abstract
BACKGROUND: HIV-infected children in resource-poor settings who fail or default from first-line antiretroviral therapy have limited alternative options. By preferentially selecting the M184V mutation, lamivudine monotherapy (LM) is occasionally used while awaiting patient readiness for second- or third-line therapy, but this strategy has not been widely studied. METHODS: A retrospective review of all eligible LM events (≥3 months) from a cohort of two linked health facilities in the Eastern Cape Province, South Africa was undertaken. Events were disaggregated according to absolute CD4 count at initiation (Group 1: >200cells/μl, n=64; Group 2: ≤200cells/μl, n=7). Study endpoints were defined as a decline of absolute CD4 by ≥25% or to ≤200 cells/μl or World Health Organization stage 3 or 4 event (immunologic outcomes) or (re)initiation of second- or third-line therapy (real-world outcomes). RESULTS: Eligible LM events were identified among 71 children (56.4% male; median age at LM initiation 9.6 years). 71.8% (n = 51) had a drop in CD4 count of ≥25%, 15.6% (n = 10) of those whose CD4 counts had been >200 cells/μl dropped to ≤200 cells/μl and 8.1% (n = 6) experienced a stage 3 or 4 event; CD4 decreases and stage 3 or 4 events did not differ significantly between groups. No deaths were recorded. Children commencing LM with CD4 counts ≤200cells/μl had a shorter mean "real-world" duration of LM before switching to second/third line therapy (11.38 months vs. 26.1 months, P < 0.0001) and experienced immunologic outcomes at an earlier stage (5.29 vs. 9.2 months, P = 0.023). CONCLUSIONS: LM offers a potential alternative approach to antiretroviral therapy management in young patients pending availability and/or willingness to adhere to second- or third-line therapies but is associated with substantial immunologic decline. This strategy should be avoided in patients with CD4 ≤200 cells/μl.
BACKGROUND:HIV-infectedchildren in resource-poor settings who fail or default from first-line antiretroviral therapy have limited alternative options. By preferentially selecting the M184V mutation, lamivudine monotherapy (LM) is occasionally used while awaiting patient readiness for second- or third-line therapy, but this strategy has not been widely studied. METHODS: A retrospective review of all eligible LM events (≥3 months) from a cohort of two linked health facilities in the Eastern Cape Province, South Africa was undertaken. Events were disaggregated according to absolute CD4 count at initiation (Group 1: >200cells/μl, n=64; Group 2: ≤200cells/μl, n=7). Study endpoints were defined as a decline of absolute CD4 by ≥25% or to ≤200 cells/μl or World Health Organization stage 3 or 4 event (immunologic outcomes) or (re)initiation of second- or third-line therapy (real-world outcomes). RESULTS: Eligible LM events were identified among 71 children (56.4% male; median age at LM initiation 9.6 years). 71.8% (n = 51) had a drop in CD4 count of ≥25%, 15.6% (n = 10) of those whose CD4 counts had been >200 cells/μl dropped to ≤200 cells/μl and 8.1% (n = 6) experienced a stage 3 or 4 event; CD4 decreases and stage 3 or 4 events did not differ significantly between groups. No deaths were recorded. Children commencing LM with CD4 counts ≤200cells/μl had a shorter mean "real-world" duration of LM before switching to second/third line therapy (11.38 months vs. 26.1 months, P < 0.0001) and experienced immunologic outcomes at an earlier stage (5.29 vs. 9.2 months, P = 0.023). CONCLUSIONS: LM offers a potential alternative approach to antiretroviral therapy management in young patients pending availability and/or willingness to adhere to second- or third-line therapies but is associated with substantial immunologic decline. This strategy should be avoided in patients with CD4 ≤200 cells/μl.
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