The HIV-1 antibody response: a footprint of the viral reservoir in children vertically infected with HIV

Abstract

Several assays have been developed to measure and characterise the replication-competent HIV-1 reservoir, which constitutes the barrier to cure. To date, the application of these assays to studies in children and in limited-resource settings has been minimal, primarily because of their expense, the large required blood volumes, and labour-intensive technologies. For children vertically infected with HIV-1 who initiated suppressive antiretroviral therapy (ART) regimens in infancy, HIV-1-specific antibody concentrations are associated with viral persistence and could be used to estimate the size of the residual latent reservoir on ART. This strategy could be particularly useful for screening children on suppressive ART for enrolment into therapeutic vaccine trials and other protocols aimed at achieving HIV-1 remission.

Figure 1.. Percentage of early-treated (< 3 months) children who are HIV-1 seronegative at or after 18 months of age by age.

The size of individual circles reflects the size of the study cohort. The median age at ART initiation was estimated as the mid-point of the range. As described in the text, only 4-6% of children who initiate ART between 12 and 24 weeks are HIV-1 seronegative and all children who initiate ART at 6 months or older are HIV-1 seropositive. Studies that report an association between HIV-1 antibodies and PBMC-associated HIV-1 DNA are marked with an asterisk (*); these and additional studies demonstrating a relationship between HIV-1 antibodies and PBMC-associated HIV-1 DNA are reported in the text.

Figure 2.

Association between timing of ART initiation, HIV-1 specific antibody responses, and HIV-1 persistence in virally suppressed perinatally HIV-infected children.