1887

Journal of General Virology header logo

Volume 101, Issue 12

Effect of combination antiretroviral therapy on human immunodeficiency virus 1 specific antibody responses in subtype-C infected children Free

Abstract

Protective antibody responses to human immunodeficiency virus (HIV)-1 infection evolve only in a fraction of infected individuals by developing broadly neutralizing antibodies (bnAbs) and/or effector functions such as antibody-dependent cellular cytotoxicity (ADCC). HIV-1 chronically infected adults and children on combination antiretroviral therapy (cART) showed a reduction in ADCC activity and improvement in HIV-1 specific neutralizing antibody (nAb) responses. Early initiation of cART in infected adults is found to be beneficial in reducing the viral load and delaying disease progression. Herein, we longitudinally evaluated the effect of cART on HIV-1 specific plasma ADCC and nAb responses in a cohort of 20 perinatally HIV-1 subtype-C infected infants and children ≤2 years of age, pre-cART and up to 1 year post-cART initiation. Significant reductions in HIV-1 specific plasma ADCC responses to subtype-C and subtype-B viruses and improvement in HIV-1 neutralization were observed in HIV-1 infected children 1 year post-cART initiation. A positive correlation between reduction in viral load and the loss of ADCC response was observed. This study provides information aiding the understanding of the effects of early initiation of cART on antibody effector functions and viral neutralization in HIV-1 infected children, which needs to be further evaluated in large cohorts of HIV-1 infected children on cART to plan future intervention strategies.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): combination antiretroviral therapy , HIV-1 neutralization , HIV-1 specific ADCC and perinatally HIV-1 infected infants and children
Funding
This study was supported by the:
  • All-India Institute of Medical Sciences (Award A-492)
    • Principle Award Recipient: Kalpana Luthra
  • Science and Engineering Research Board (Award EMR/2015/001276)
    • Principle Award Recipient: Kalpana Luthra
© 2020 The Authors
Loading

Article metrics loading...

/content/journal/jgv/10.1099/jgv.0.001480
2020-09-11
2024-04-23
Loading full text...

Full text loading...

/deliver/fulltext/jgv/101/12/1289.html?itemId=/content/journal/jgv/10.1099/jgv.0.001480&mimeType=html&fmt=ahah

References

  1. Neogi U, Sood V, Banerjee S, Ghosh N, Verma S et al. Global HIV-1 molecular epidemiology with special reference to genetic analysis of HIV-1 subtypes circulating in North India: functional and pathogenic implications of genetic variation. Indian J Exp Biol 2009; 47:424–431[PubMed]
     [Google Scholar]
  2. Herout S, Mandorfer M, Breitenecker F, Reiberger T, Grabmeier-Pfistershammer K et al. Impact of early initiation of antiretroviral therapy in patients with acute HIV infection in Vienna, Austria. PLoS One 2016; 11:e0152910 [View Article][PubMed]
     [Google Scholar]
  3. Rasmussen TA, Tolstrup M, Søgaard OS. Reversal of latency as part of a cure for HIV-1. Trends Microbiol 2016; 24:90–97 [View Article][PubMed]
     [Google Scholar]
  4. Overbaugh J, Morris L. The antibody response against HIV-1. Cold Spring Harb Perspect Med 2012; 2:a007039 [View Article]
     [Google Scholar]
  5. Pantophlet R, Burton DR. Gp120: target for neutralizing HIV-1 antibodies. Annu Rev Immunol 2006; 24:739–769 [View Article][PubMed]
     [Google Scholar]
  6. Goulder PJ, Lewin SR, Leitman EM. Paediatric HIV infection: the potential for cure. Nat Rev Immunol 2016; 16:259–271 [View Article][PubMed]
     [Google Scholar]
  7. Fouda GG, De Paris K, Levy O, Marchant A, Gray G et al. Immunological mechanisms of inducing HIV immunity in infants. Vaccine 2020; 38:411–415 [View Article][PubMed]
     [Google Scholar]
  8. Kumar S, Kumar R, Khan L, Makhdoomi MA, Thiruvengadam R et al. CD4-binding site directed cross-neutralizing scFv monoclonals from HIV-1 subtype C infected Indian children. Front Immunol 2017; 8:1568 [View Article][PubMed]
     [Google Scholar]
  9. Makhdoomi MA, Khan L, Kumar S, Aggarwal H, Singh R et al. Evolution of cross-neutralizing antibodies and mapping epitope specificity in plasma of chronic HIV-1-infected antiretroviral therapy-naïve children from India. J Gen Virol 2017; 98:1879–1891 [View Article][PubMed]
     [Google Scholar]
  10. Aggarwal H, Khan L, Chaudhary O, Kumar S, Makhdoomi MA et al. Alterations in B cell compartment correlate with poor neutralization response and disease progression in HIV-1 infected children. Front Immunol 2017; 8:1697 [View Article]
     [Google Scholar]
  11. Ljunggren K, Moschese V, Broliden P-A, Giaquinto C, Quinti I et al. Antibodies mediating cellular cytotoxicity and neutralization correlate with a better clinical stage in children born to human immunodeficiency virus-infected mothers. J Infect Dis 1990; 161:198–202 [View Article]
     [Google Scholar]
  12. Goo L, Chohan V, Nduati R, Overbaugh J. Early development of broadly neutralizing antibodies in HIV-1–infected infants. Nat Med 2014; 20:655–658 [View Article]
     [Google Scholar]
  13. Simonich CA, Williams KL, Verkerke HP, Williams JA, Nduati R et al. HIV-1 neutralizing antibodies with limited hypermutation from an infant. Cell 2016; 166:77–87 [View Article]
     [Google Scholar]
  14. Kumar S, Panda H, Makhdoomi MA, Mishra N, Safdari HA et al. An HIV-1 broadly neutralizing antibody from a clade C-infected pediatric elite neutralizer potently neutralizes the contemporaneous and autologous evolving viruses. J Virol 2019; 93:e01495-18 [View Article][PubMed]
     [Google Scholar]
  15. Mishra N, Makhdoomi MA, Sharma S, Kumar S, Dobhal A et al. Viral characteristics associated with maintenance of elite neutralizing activity in chronically HIV-1 clade C-infected monozygotic pediatric twins. J Virol 2019; 93:e00654-19 [View Article][PubMed]
     [Google Scholar]
  16. Ditse Z, Muenchhoff M, Adland E, Jooste P, Goulder P et al. HIV-1 subtype C-infected children with exceptional neutralization breadth exhibit polyclonal responses targeting known epitopes. J Virol 2018; 92:e00878-18 [View Article][PubMed]
     [Google Scholar]
  17. Muenchhoff M, Adland E, Karimanzira O, Crowther C, Pace M et al. Nonprogressing HIV-infected children share fundamental immunological features of nonpathogenic SIV infection. Sci Transl Med 2016; 8:358ra125 [View Article]
     [Google Scholar]
  18. WHO Consolidated Guidelines on the Use of Antiretroviral Drugs for Treating and Preventing HIV Infection: Recommendations for a Public Health Approach, 2nd ed. Geneva: World Health Organization; 2016
     [Google Scholar]
  19. Casazza JP, Betts MR, Picker LJ, Koup RA. Decay kinetics of human immunodeficiency virus-specific CD8+ T cells in peripheral blood after initiation of highly active antiretroviral therapy. J Virol 2001; 75:6508–6516 [View Article]
     [Google Scholar]
  20. Lisco A, Wong C-S, Lage SL, Levy I, Brophy J et al. Identification of rare HIV-1–infected patients with extreme CD4+ T cell decline despite ART-mediated viral suppression. JCI Insight 2019; 4:e127113 [View Article]
     [Google Scholar]
  21. Madhavi V, Ana-Sosa-Batiz FE, Jegaskanda S, Center RJ, Winnall WR et al. Antibody-dependent effector functions against HIV decline in subjects receiving antiretroviral therapy. J Infect Dis 2015; 211:529–538 [View Article]
     [Google Scholar]
  22. Madhavi V, Kulkarni A, Shete A, Lee WS, Mclean MR et al. Effect of combination antiretroviral therapy on HIV-1-specific antibody-dependent cellular cytotoxicity responses in subtype B- and subtype C-infected cohorts. J Acquir Immune Defic Syndr 2017; 75:345–353 [View Article]
     [Google Scholar]
  23. Prakash SS, Chaudhary AK, Lodha R, Kabra SK, Vajpayee M et al. Efficient neutralization of primary isolates by the plasma from HIV-1 infected Indian children. Viral Immunol 2011; 24:409–413 [View Article]
     [Google Scholar]
  24. Andrabi R, Makhdoomi MA, Kumar R, Bala M, Parray H et al. Highly efficient neutralization by plasma antibodies from human immunodeficiency virus type-1 infected individuals on antiretroviral drug therapy. J Clin Immunol 2014; 34:504–513 [View Article]
     [Google Scholar]
  25. Kimura T, Yoshimura K, Nishihara K, Maeda Y, Matsumi S et al. Reconstitution of spontaneous neutralizing antibody response against autologous human immunodeficiency virus during highly active antiretroviral therapy. J Infect Dis 2002; 185:53–60 [View Article]
     [Google Scholar]
  26. Binley JM, Trkola A, Ketas T, Schiller D, Clas B et al. The effect of highly active antiretroviral therapy on binding and neutralizing antibody responses to human immunodeficiency virus type 1 infection. J Infect Dis 2000; 182:945–949 [View Article]
     [Google Scholar]
  27. Choudhary AK, Andrabi R, Prakash SS, Kumar R, Choudhury SD et al. Neutralization potential of the plasma of HIV-1 infected Indian patients in the context of anti-V3 antibody content and antiretroviral therapy. J Microbiol 2012; 50:149–154 [View Article]
     [Google Scholar]
  28. Kulkarni A, Kurle S, Shete A, Ghate M, Godbole S et al. Indian long-term non-progressors show broad ADCC responses with preferential recognition of V3 region of envelope and a region from Tat protein. Front Immunol 2017; 8:5 [View Article]
     [Google Scholar]
  29. Alpert MD, Heyer LN, Williams DEJ, Harvey JD, Greenough T et al. A novel assay for antibody-dependent cell-mediated cytotoxicity against HIV-1- or SIV-infected cells reveals incomplete overlap with antibodies measured by neutralization and binding assays. J Virol 2012; 86:12039–12052 [View Article]
     [Google Scholar]
  30. Montefiori DC. Measuring HIV neutralization in a luciferase reporter gene assay. Methods Mol Biol 2009; 485:395–405 [View Article][PubMed]
     [Google Scholar]
  31. Khan L, Makhdoomi MA, Kumar S, Nair A, Andrabi R et al. Identification of CD4-binding site dependent plasma neutralizing antibodies in an HIV-1 infected Indian individual. PLoS One 2015; 10:e0125575 [View Article]
     [Google Scholar]
  32. Khan L, Kumar R, Thiruvengadam R, Parray HA, Makhdoomi MA et al. Cross-neutralizing anti-HIV-1 human single chain variable fragments(scFvs) against CD4 binding site and N332 glycan identified from a recombinant phage library. Sci Rep 2017; 7:45163 [View Article]
     [Google Scholar]
  33. deCamp A, Hraber P, Bailer RT, Seaman MS, Ochsenbauer C et al. Global panel of HIV-1 Env reference strains for standardized assessments of vaccine-elicited neutralizing antibodies. J Virol 2014; 88:2489–2507 [View Article]
     [Google Scholar]
  34. Lole KS, Bollinger RC, Paranjape RS, Gadkari D, Kulkarni SS et al. Full-length human immunodeficiency virus type 1 genomes from subtype C-infected seroconverters in India, with evidence of intersubtype recombination. J Virol 1999; 73:152–160 [View Article]
     [Google Scholar]
  35. Koyanagi Y, Miles S, Mitsuyasu RT, Merrill JE, Vinters HV et al. Dual infection of the central nervous system by AIDS viruses with distinct cellular tropisms. Science 1987; 236:819–822 [View Article]
     [Google Scholar]
  36. Brooks DG, Zack JA. Effect of latent human immunodeficiency virus infection on cell surface phenotype. J Virol 2002; 76:1673–1681 [View Article]
     [Google Scholar]
  37. Lee WS, Kristensen AB, Rasmussen TA, Tolstrup M, Østergaard L et al. Anti-Hiv-1 ADCC antibodies following latency reversal and treatment interruption. J Virol 2017; 91:e00603-17 [View Article]
     [Google Scholar]
  38. Gupta RK, Peppa D, Hill AL, Gálvez C, Salgado M et al. Evidence for HIV-1 cure after CCR5Δ32/Δ32 allogeneic haemopoietic stem-cell transplantation 30 months post analytical treatment interruption: a case report. Lancet HIV 2020; 7:e340–e347 [View Article]
     [Google Scholar]
  39. Allers K, Hütter G, Hofmann J, Loddenkemper C, Rieger K et al. Evidence for the cure of HIV infection by CCR5Δ32/Δ32 stem cell transplantation. Blood 2011; 117:2791–2799 [View Article]
     [Google Scholar]
  40. Hütter G, Thiel E. Allogeneic transplantation of CCR5-deficient progenitor cells in a patient with HIV infection: an update after 3 years and the search for patient no. 2. AIDS 2011; 25:273–274 [View Article]
     [Google Scholar]
  41. Hütter G, Nowak D, Mossner M, Ganepola S, Müßig A et al. Long-term control of HIV by CCR5 delta32/delta32 stem-cell transplantation. N Engl J Med 2009; 360:692–698 [View Article]
     [Google Scholar]
  42. Lopez-Galindez C, Pernas M, Casado C, Olivares I, Lorenzo-Redondo R. Elite controllers and lessons learned for HIV-1 cure. Curr Opin Virol 2019; 38:31–36 [View Article]
     [Google Scholar]
  43. Palermo E, Acchioni C, Di Carlo D, Zevini A, Muscolini M et al. Activation of latent HIV-1 T cell reservoirs with a combination of innate immune and epigenetic regulators. J Virol 2019; 93:e01194-19 [View Article]
     [Google Scholar]
  44. Tuyishime M, Garrido C, Jha S, Moeser M, Mielke D et al. Improved killing of HIV-infected cells using three neutralizing and non-neutralizing antibodies. J Clin Invest 2020; 7:JCI135557 [View Article]
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/jgv.0.001480
Loading
Effect of combination antiretroviral therapy on human immunodeficiency virus 1 specific antibody responses in subtype-C infected children
J. Gen. Virol. 101, 1289 (2020); https://doi.org/10.1099/jgv.0.001480
/content/journal/jgv/10.1099/jgv.0.001480
/content/journal/jgv/10.1099/jgv.0.001480
Loading

Data & Media loading...

Supplements

Supplementary material 1

EXCEL

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error