Dynamics of the resting CD4+ T-cell latent HIV reservoir in infants initiating HAART less than 6 months of age

Abstract

Objectives Identification of HIV infection in exposed infants facilitates early therapy, which may limit viral reservoirs that maintain HIV infection under HAART. Methods The dynamics of the resting CD4+ T-cell latent HIV reservoir was determined over the first 2 years of life in 17 HIV-infected infants initiating lopinavir/ritonavir-based HAART at a median age of 8.1 weeks and achieving adequate suppression of plasma viral load by 24 weeks. Results The resting CD4+ T-cell latent HIV reservoir was detected in 12 of 14 (86%) infants tested at 24 weeks of HAART [median frequency 1.88 infectious units per million (IUPM); range <0.22 to 81.7), and remained measurable (median IUPM =0.32; range < 0.22 to 3.25) in six of 10 (60%) children retested at 96 weeks. The reservoir declined, from 24 to 96 weeks of HAART, at an estimated mean rate of 0.028 log10 IUPM/month, corresponding to a half-life of 11 months (95% confidence interval 6–30 months]. A strong relationship was found between the frequency of latently infected CD4+T cells at 96 weeks of HAART and time to first undetectable plasma viral load (Spearman r =0.91, P <0.001). Conclusion Although the resting CD4+ T-cell latent reservoir remains detectable over the first 2 years of HAART in a substantial proportion of infants, its size is associated with time to first undetectable viral load. To minimize HIV reservoirs in infants, rapid curtailment of viremia may limit HIV reservoirs and should be a therapeutic goal of early HAART in infants.

Influence of Age at Virologic Control on Peripheral Blood Human Immunodeficiency Virus Reservoir Size and Serostatus in Perinatally Infected Adolescents

“…This is consistent with time to first undetectable viral load being strongly correlated with the size of the resting CD4+ T-cell latent HIV reservoir at two years of age in perinatal infection. 23 It is, however, important to emphasize that undetectable levels of HIV provirus in peripheral blood likely still allow for the presence of replication-competent HIV that can rekindle viremic rebound if cART is stopped. The limitation in the current use of undetectable proviral DNA to assess HIV clearance and cure is highlighted by the two Boston patients who achieved undetectable proviral DNA levels following bone marrow transplantation, yet rebounded after cART was discontinued 24 The encouraging single case of the Mississippi Child 13 prompts the need for a more robust analysis of a larger cohort treated shortly after birth.…”

Paediatric European Network for Treatment of AIDS (PENTA) guidelines for treatment of paediatric HIV‐1 infection 2015: optimizing health in preparation for adult life

“…Recent reports in both adults and children have indicated that early and sustained full suppression of HIV may limit viral reservoirs 58, 59 and that a longer cumulative time spent with ongoing viral replication is associated with a larger viral reservoir 60. How this may relate to future ‘cure’ is yet to be determined, but it should also be borne in mind when considering ART initiation in young children who may see the advent of new curative treatments within their lifetime.…”

Immune activation and paediatric HIV-1 disease outcome

“…It is clear that early ART reduces the size of the latent HIV reservoir both in paediatric and adult infection (93, 94). Recently it has been shown that immune activation (HLA-DR, CD38) and exhaustion markers (Tim-3, PD-1, Lag-3) are strongly associated with reservoir size in ART-treated adults, the latter predicting duration of post-treatment control (that is, after ART is discontinued) (95)**.…”