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Background: In the 6-year CHER trial (2005-2011), HIV-infected infants were randomized to deferred antiretroviral therapy (ART) or early limited ART for 40 (ART-40W) or 96 (ART-96W) weeks; ART reinitiation was based on CD4 and clinical criteria. We describe a child, randomized to ART-40W in 2008, who on long term follow-up, maintains an undetectable viral load after 8.5 years off-ART.
Methods: Studies conducted to describe immunological and viral characteristics included: ultrasensitive qualitative nested and quantitative semi-nested PCR assay to assess HIV DNA reservoir; co-culture of CD4 cells with MOLT-4/CCR5 and CD8-depleted phytohaemagglutinin-activated lymphocytes to detect replication-competent virus.
Results: HIV diagnosis was confirmed by HIV-DNA PCR+ at age 32 days, and on days 39 and 60, VL was >750,000 and 151,000 copies/ml respectively. ART started at age 8.7 weeks and was interrupted at 40 weeks post randomisation. On ART, VL declined to < 50copies/ml at week 24 and was < 20 copies/ml post-interruption .During later follow-up 6-monthly VLwere also < 20copies/ml. At age 9.5 years, the child was clinically asymptomatic with CD4 802 cells/µl. Qualitative DNA PCR was negative. HIV-antibody by ELISA was negative but was weakly reactive to Gag p40 and p24 on Western blot; a weak Gag-specific CD4 T-cell response was detected by whole blood intracellular cytokine assay. Proviral DNA was positive by ultrasensitive nested (int) PCR and HIV DNA reservoir size was estimated at 2.2 copies/106 PBMCs by semi-nested quantitative (RT) assay. DNA sequencing of Gag confirmed subtype-C virus. No replication-competent virus was detected in culture supernatants by day 22 using p24 ELISA and ultrasensitive nested RT-PCR. All HLA loci were heterozygoous (A*30:02:01/66:01; B*08:01:01/44:03:01; C*04:01:01/07:01:01; DRB1*12:01:01/13:02:01; DPB1*01:01:01/18:01; B1*05:01:01/06:09:01). The KIRAA1 genotype included both full-length and truncated KIR2DS4. Immunophenotyping showed few CCR5-expressing CD4 T-cells (6.6%), low CCR5 density, low immune activation (HLA-DR, TIGIT), high PD-1expression and high % naive CD8 T-cells.
Conclusions: To our knowledge, this is the first case of sustained virological control from a randomized trial of ART interruption following early treatment of infants. Further investigation may expand our understanding of how the immune system controls HIV replication and inform future research strategies for ART interruption after early ART.