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Viral and Host Characteristics of a Child with Perinatal HIV-1 after Prolonged ART Cessation

This study examines the viral and host characteristics of a child with perinatal HIV-1 who achieved sustained virological control after a prolonged period of antiretroviral therapy (ART) cessation. The findings suggest that both viral factors and host immune response may contribute to HIV remission in early-treated infants.

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Viral and Host Characteristics of a Child with Perinatal HIV-1 after Prolonged ART Cessation

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  1. Viral and Host characteristics of a child with perinatal HIV-1 after prolonged period of ART cessation in the CHER trial Avy Violari, Mark Cotton, Louise Kuhn, Diana Schramm, Maria Paximadis, Shayne Loubser, Sharon Shalekoff, Bianca Da Costa Dias, Kennedy Otwombe, Afaaf Liberty, James McIntyre, Abdel Babiker, Diana Gibb, Caroline Tiemessen

  2. Disclosures • ViiV healthcare : • funded some of the viral load analysis through the EPIICAL grant • provided AZT/3TC for the CHER trial

  3. Case History • DNA PCR positive at 32 days of life • Initiated AZT/3TC/Lopinavir-ritonavirat 8.5 weeks of life • Interrupted ART after 40 weeks (age 1 year), as per trial randomisation • 3-monthly clinical and CD4 evaluations in CHER until age 4 years • 3-monthly follow up as part of PEPFAR and the NICHD-funded CHANGES study to date • Undetectable VL after 8.75 years off ART on stored and current specimens

  4. Summary of key findings Viral features • HIV-1 viral load remained below detectable levels (<20 cpm) from time of treatment interruption to date • HIV-1 total DNA reservoir: • 5 copies/106 PBMCs – similar at one year and 9.5 years of age • Currently, no replication-competent virus detected using two co-culture methods • HIV-1 subtype C Host features • HIV-specific Abs: mostly weak responses ; high IgA2 response (mucosal) to gp41 • Cell mediated responses: weak CD4 T cell response only to Gag, no detectable HIV-specific CD8 T cell responses • CCR5 expression on T cells low (surface density) compared to uninfected children and adults; similar to elite controllers • Immune activation low and similar to uninfected children and adults, but lower than elite controllers • High PD-1 expression relative to uninfected children/adults/elite controllers (CD4), and uninfected children/elite controllers (CD8) • Host genetic features – potentially disadvantageous for acquiring infection (HLA DQB1*06; KIRAA1), others potentially advantageous (heterozygosity) for control of infection (HLA class II?)

  5. Conclusions • To our knowledge, this is the first case of sustained virological control from a randomized ART interruption trial following early infant treatment. • Virus produced in vivo could be defective, sustaining the CD4 Gag response; alternatively the immune response may be controlling low levels of replication-competent virus (too small to detect with methods used, or is from a source other than peripheral CD4 cells). • Host factors, in addition to early ART, likely contributed to remission. • Further investigation may expand our understanding of how the immune system controls HIV replication and inform future research strategies to achieve HIV remission after early ART.

  6. AcknowledgementsThanks to the family for allowing us to perform and present this work

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