Impact of antiretroviral therapy during primary HIV infection on T‐cell immunity after treatment interruption

Author:

Tipoe Timothy1,Ogbe Ane1,Lee Ming12,Brown Helen1,Robinson Nicola1,Hall Rebecca3,Petersen Claire3,Lewis Heather3,Thornhill John4,Ryan Fiona5,Fox Julie56,Fidler Sarah27,Frater John18

Affiliation:

1. Peter Medawar Building for Pathogen Research, Nuffield Dept of Medicine University of Oxford Oxford UK

2. Department of HIV Medicine St Mary's Hospital Imperial College Healthcare NHS Trust London UK

3. Department of Infectious Disease Imperial College London London UK

4. Barts Health NHS Trust London UK

5. Guy's and St Thomas' NHS Foundation Trust London UK

6. NIHR Clinical Research Facility Guys and St Thomas' NHS Trust London UK

7. NIHR Imperial College Biomedical Research Centre London UK

8. NIHR Oxford Biomedical Research Centre Oxford UK

Abstract

AbstractThis study aims to understand the impact of early antiretroviral therapy (ART) on HIV‐specific T‐cell responses measured after treatment interruption, which may inform strategies to deliver ART‐free immune‐mediated viral suppression. HIV‐specific T‐cell immunity was analysed using gamma interferon enzyme‐linked immunospot assays in two studies. SPARTAC included individuals with primary HIV infection randomised to 48 weeks of ART (n = 24) or no immediate therapy (n = 37). The PITCH (n = 7) cohort started antiretroviral therapy in primary infection for at least one year, followed by TI. In SPARTAC, participants treated in PHI for 48 weeks followed by TI for 12 weeks, and those who remained untreated for 60 weeks made similar HIV Gag‐directed responses (both magnitude and breadth) at week 60. However, the treated group made a greater proportion of novel HIV Gag‐directed responses by Week 60, suggestive of a greater reserve to produce new potentially protective responses. In the more intensively followed PITCH study, 6/7 participants showed dominant Gag and/or Pol‐specific responses post‐TI compared with pre‐TI. Although early ART in PHI was not associated with major differences in HIV‐specific immunity following TI compared with untreated participants, the potential to make more new Gag‐directed responses warrants further investigation as this may inform strategies to achieve ART‐free control.

Publisher

Wiley

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