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.
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).
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).
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.
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.
Accepted for publication November 29, 2015.
H. Adler’s current affiliation: Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
Presented as a poster at HIV Drug Therapy (Glasgow, November 2014) and the Children’s HIV Association Annual Conference (Leicester, May 2015).
Financial support for this project was received from ViiV Healthcare in the form of an unrestricted grant from their Pediatric Seed Fund to Dr Lambert. ViiV Healthcare had no role in study design, interpretation, writing or decision to submit for publication. All other authors have no conflicts of interest or funding to disclose.
Address for correspondence: Gerald Boon FCPaed(SA), Department of Pediatrics, Frere Hospital, Eastern Cape, South Africa. E-mail: firstname.lastname@example.org.