Immune correlates of HIV-1 rebound during broadly neutralizing antibody treatment in young children
Aischa Niesar, Melanie Lancien, Seohyun Hong, Chloe Naasz, Gbolahan Ajibola, Kenneth Maswabi, Maureen Sakoi-Mosetlhi, Oganne Batlang, Sikhulile Moyo, Terence Mohammed, Comfort Maphorisa, Leah Carrere, Isabelle Roseto, Ciputra Adijaya Hartana, Toong Seng Tan, Ce Gao, Elizabeth Parsons, Renee Hua, Molly Pretorius Holme, Shahin Lockman, Kathleen M. Powis, Mary Carrington, Joseph Makhema, Xu G. Yu, Daniel R. Kuritzkes, Roger L. Shapiro, Mathias Lichterfeld
Aischa Niesar, Melanie Lancien, Seohyun Hong, Chloe Naasz, Gbolahan Ajibola, Kenneth Maswabi, Maureen Sakoi-Mosetlhi, Oganne Batlang, Sikhulile Moyo, Terence Mohammed, Comfort Maphorisa, Leah Carrere, Isabelle Roseto, Ciputra Adijaya Hartana, Toong Seng Tan, Ce Gao, Elizabeth Parsons, Renee Hua, Molly Pretorius Holme, Shahin Lockman, Kathleen M. Powis, Mary Carrington, Joseph Makhema, Xu G. Yu, Daniel R. Kuritzkes, Roger L. Shapiro, Mathias Lichterfeld
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Research Article AIDS/HIV Immunology

Immune correlates of HIV-1 rebound during broadly neutralizing antibody treatment in young children

Abstract

Broadly neutralizing antibodies (bnAbs) are evaluated as possible alternatives to standard antiretroviral treatment (ART) for maintaining control of HIV-1 replication and may enhance immune responses to reduce or control the viral reservoir. However, the immunological and virological effects of bnAbs in infants and children are unknown. We conducted a detailed analysis of proviral reservoir dynamics and antiviral immune responses in a unique group of young children from Botswana who started ART at birth and then stopped standard ART while receiving the bnAbs 10-1074 and VRC01-LS in a subsequent clinical trial. No quantitative changes in frequencies of proviral sequences were observed during bnAb treatment, but selection of genome-intact proviruses in transcriptionally repressive heterochromatin regions occurred in some study participants. Faster viral rebound following standard ART cessation was linked to elevated proportions of KIR2DL1-positive NK cells. In contrast, delayed viral rebound and more limited viral reservoir size were associated with elevated proportions of NKG2A-positive NK cells and with the HLA-B-21M signal peptide polymorphism. HIV-specific T cell responses were low in all study participants and unrelated to viral reservoir sizes or clinical outcomes following ART interruption. These results suggest that, in young children, specific NK cell subsets and KIR-HLA interactions might be linked to HIV-1 rebound kinetics after substitution of standard ART with bnAbs.

Authors

Aischa Niesar, Melanie Lancien, Seohyun Hong, Chloe Naasz, Gbolahan Ajibola, Kenneth Maswabi, Maureen Sakoi-Mosetlhi, Oganne Batlang, Sikhulile Moyo, Terence Mohammed, Comfort Maphorisa, Leah Carrere, Isabelle Roseto, Ciputra Adijaya Hartana, Toong Seng Tan, Ce Gao, Elizabeth Parsons, Renee Hua, Molly Pretorius Holme, Shahin Lockman, Kathleen M. Powis, Mary Carrington, Joseph Makhema, Xu G. Yu, Daniel R. Kuritzkes, Roger L. Shapiro, Mathias Lichterfeld

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Figure 1

Viral reservoir dynamics in participants of the Tatelo study.

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Viral reservoir dynamics in participants of the Tatelo study. (A and B) ...
(A and B) Frequency of intact (A) and defective (B) proviruses in controllers and rebounders from the Tatelo study, measured at indicated timepoints (wk0, birth; wk84, week 84 after birth). Data from elite controllers (EC), long-term ART-treated adults who initiated treatment during chronic infection, and adults who started ART during acute infection in the RIVER cohort (27) are presented for comparative purposes. Limit of defection (LOD) was calculated as 0.5 copies per maximum number of cells tested without target identification. Data were obtained by near full-length proviral sequencing (FLIP-Seq) or by matched integration site and proviral sequencing (MIP-Seq). (C) Decay kinetics of intact and defective proviral HIV-1 sequences before, during, and after the Tatelo study. Mean and SEM are shown. (A and B) Significance was tested using 2-tailed Mann-Whitney-U or Wilcoxon matched-pairs signed-rank tests; nominal P values are indicated. (A and B) Medians are indicated by horizontal lines.