Impact of Early Antiretroviral Therapy, Early Life Immunity and Immune Sex Differences on HIV Disease and Posttreatment Control in Children

Overview

Journal Curr Opin HIV AIDS

Specialty Infectious Diseases

Date 2023 Jul 8

PMID 37421384

Authors

Nicholas G Herbert

Philip J R Goulder

Affiliations

Soon will be listed here.

Abstract

Purpose Of Review: To review recent insights into the factors affecting HIV disease progression in children living with HIV, contrasting outcomes: following early ART initiation with those in natural, antiretroviral therapy (ART)-naive infection; in children versus adults; and in female individuals versus male individuals.

Recent Findings: Early life immune polarization and several factors associated with mother-to-child transmission of HIV result in an ineffective HIV-specific CD8+ T-cell response and rapid disease progression in most children living with HIV. However, the same factors result in low immune activation and antiviral efficacy mediated mainly through natural killer cell responses in children and are central features of posttreatment control. By contrast, rapid activation of the immune system and generation of a broad HIV-specific CD8+ T-cell response in adults, especially in the context of 'protective' HLA class I molecules, are associated with superior disease outcomes in ART-naive infection but not with posttreatment control. The higher levels of immune activation in female individuals versus male individuals from intrauterine life onwards increase HIV infection susceptibility in females in utero and may favour ART-naive disease outcomes rather than posttreatment control.

Summary: Early-life immunity and factors associated with mother-to-child transmission typically result in rapid HIV disease progression in ART-naive infection but favour posttreatment control in children following early ART initiation.

Citing Articles

Distinct immune profiles in children living with HIV based on timing and duration of suppressive antiretroviral treatment.

Lee M, Litchford M, Vendrame E, Vergara R, Ranganath T, Fish C Virology. 2024; 602:110318.

PMID: 39612623 PMC: 11645197. DOI: 10.1016/j.virol.2024.110318.

Growth Trajectories Over the First Year of Life Among Early-Treated Infants with Human Immunodeficiency Virus and Infants Who are Human Immunodeficiency Virus-Exposed Uninfected.

Barrios-Tascon A, Strehlau R, Patel F, Burke M, Shiau S, Shen Y J Pediatr. 2024; 270:114018.

PMID: 38508485 PMC: 11176027. DOI: 10.1016/j.jpeds.2024.114018.

References

Okoye A, Duell D, Fukazawa Y, Varco-Merth B, Marenco A, Behrens H . CD8+ T cells fail to limit SIV reactivation following ART withdrawal until after viral amplification. J Clin Invest. 2021; 131(8). PMC: 8262469. DOI: 10.1172/JCI141677. View

Fouda G, Cunningham C, McFarland E, Borkowsky W, Muresan P, Pollara J . Infant HIV type 1 gp120 vaccination elicits robust and durable anti-V1V2 immunoglobulin G responses and only rare envelope-specific immunoglobulin A responses. J Infect Dis. 2014; 211(4):508-17. PMC: 4318918. DOI: 10.1093/infdis/jiu444. View

Adland E, Millar J, Bengu N, Muenchhoff M, Fillis R, Sprenger K . Sex-specific innate immune selection of HIV-1 in utero is associated with increased female susceptibility to infection. Nat Commun. 2020; 11(1):1767. PMC: 7156749. DOI: 10.1038/s41467-020-15632-y. View

Souyris M, Mejia J, Chaumeil J, Guery J . Female predisposition to TLR7-driven autoimmunity: gene dosage and the escape from X chromosome inactivation. Semin Immunopathol. 2018; 41(2):153-164. DOI: 10.1007/s00281-018-0712-y. View

Garcia-Broncano P, Maddali S, Einkauf K, Jiang C, Gao C, Chevalier J . Early antiretroviral therapy in neonates with HIV-1 infection restricts viral reservoir size and induces a distinct innate immune profile. Sci Transl Med. 2019; 11(520). PMC: 8397898. DOI: 10.1126/scitranslmed.aax7350. View

Crawford H, G Prado J, Leslie A, Hue S, Honeyborne I, Reddy S . Compensatory mutation partially restores fitness and delays reversion of escape mutation within the immunodominant HLA-B*5703-restricted Gag epitope in chronic human immunodeficiency virus type 1 infection. J Virol. 2007; 81(15):8346-51. PMC: 1951305. DOI: 10.1128/JVI.00465-07. View

Carlson J, Du V, Pfeifer N, Bansal A, Tan V, Power K . Impact of pre-adapted HIV transmission. Nat Med. 2016; 22(6):606-13. PMC: 4899163. DOI: 10.1038/nm.4100. View

Vieira V, Adland E, Malone D, Martin M, Groll A, Ansari M . An HLA-I signature favouring KIR-educated Natural Killer cells mediates immune control of HIV in children and contrasts with the HLA-B-restricted CD8+ T-cell-mediated immune control in adults. PLoS Pathog. 2021; 17(11):e1010090. PMC: 8639058. DOI: 10.1371/journal.ppat.1010090. View

Ramsuran V, Naranbhai V, Horowitz A, Qi Y, Martin M, Yuki Y . Elevated expression impairs HIV control through inhibition of NKG2A-expressing cells. Science. 2018; 359(6371):86-90. PMC: 5933048. DOI: 10.1126/science.aam8825. View

10.

Bashirova A, Martin-Gayo E, Jones D, Qi Y, Apps R, Gao X . LILRB2 interaction with HLA class I correlates with control of HIV-1 infection. PLoS Genet. 2014; 10(3):e1004196. PMC: 3945438. DOI: 10.1371/journal.pgen.1004196. View

11.

Betts M, Harari A . Phenotype and function of protective T cell immune responses in HIV. Curr Opin HIV AIDS. 2009; 3(3):349-55. DOI: 10.1097/COH.0b013e3282fbaa81. View

12.

Kollmann T, Crabtree J, Rein-Weston A, Blimkie D, Thommai F, Wang X . Neonatal innate TLR-mediated responses are distinct from those of adults. J Immunol. 2009; 183(11):7150-60. PMC: 4556237. DOI: 10.4049/jimmunol.0901481. View

13.

Tsai M, Muenchhoff M, Adland E, Carlqvist A, Roider J, Cole D . Paediatric non-progression following grandmother-to-child HIV transmission. Retrovirology. 2016; 13(1):65. PMC: 5016918. DOI: 10.1186/s12977-016-0300-y. View

14.

Leitman E, Thobakgale C, Adland E, Ansari M, Raghwani J, Prendergast A . Role of HIV-specific CD8 T cells in pediatric HIV cure strategies after widespread early viral escape. J Exp Med. 2017; 214(11):3239-3261. PMC: 5679167. DOI: 10.1084/jem.20162123. View

15.

Braud V, Allan D, OCallaghan C, Soderstrom K, DAndrea A, Ogg G . HLA-E binds to natural killer cell receptors CD94/NKG2A, B and C. Nature. 1998; 391(6669):795-9. DOI: 10.1038/35869. View

16.

Meditz A, Haas M, Folkvord J, Melander K, Young R, McCarter M . HLA-DR+ CD38+ CD4+ T lymphocytes have elevated CCR5 expression and produce the majority of R5-tropic HIV-1 RNA in vivo. J Virol. 2011; 85(19):10189-200. PMC: 3196402. DOI: 10.1128/JVI.02529-10. View

17.

Ruel T, Zanoni B, Ssewanyana I, Cao H, Havlir D, Kamya M . Sex differences in HIV RNA level and CD4 cell percentage during childhood. Clin Infect Dis. 2011; 53(6):592-9. PMC: 3160805. DOI: 10.1093/cid/cir484. View

18.

Naidoo V, Mann J, Noble C, Adland E, Carlson J, Thomas J . Mother-to-Child HIV Transmission Bottleneck Selects for Consensus Virus with Lower Gag-Protease-Driven Replication Capacity. J Virol. 2017; 91(17). PMC: 5553170. DOI: 10.1128/JVI.00518-17. View

19.

Kane M, Zang T, Rihn S, Zhang F, Kueck T, Alim M . Identification of Interferon-Stimulated Genes with Antiretroviral Activity. Cell Host Microbe. 2016; 20(3):392-405. PMC: 5026698. DOI: 10.1016/j.chom.2016.08.005. View

20.

Pereyra F, Lo J, Triant V, Wei J, Buzon M, Fitch K . Increased coronary atherosclerosis and immune activation in HIV-1 elite controllers. AIDS. 2012; 26(18):2409-12. PMC: 3660105. DOI: 10.1097/QAD.0b013e32835a9950. View