Saturday, Mar 6, 2021: 12:01 AM
Isabelle Turcotte1, Amélie Pagliuzza2, Stéphane Isnard3, Cezar Iovi3, Rémi Fromentin2, Steven G. Deeks4, Mary Mahony5, Brooke Hayward5, Maryellen Craig5, Jean-Pierre Routy3, Nicolas Chomont1
1Université de Montréal, Montreal, Canada, 2Centre de Recherche du CHUM, Montreal, Canada, 3McGill University Health Centre, Montreal, Canada, 4University of California San Francisco, San Francisco, CA, USA, 5EMD Serono, Rockland, MD, USA
Administration of recombinant human growth hormone (rhGH) in ART-treated individuals has been shown to increase thymic output and CD4+ T cell counts. We hypothesized that the production of naïve T cells induced by rhGH may lead to the clearance of infected memory CD4+ T cells by repopulating the CD4+ T cell niche.
Twelve HIV-1-infected adults (<40 years of age) on stable ART were enrolled in an open-label single-arm study of rhGH therapy. rhGH was administered by subcutaneous injection on an outpatient basis for a total of 48 weeks (3 mg/day for 24 weeks, followed by 1.5 mg/day for 24 weeks). PBMCs were collected at baseline and every 12 weeks. In isolated CD4+ T cells, we measured thymic output [T Cell Receptor Excision Circles (TRECs) quantification by qPCR], as well as the size of the HIV reservoir by HIV DNA qPCR, tat/rev limiting dilution assay (TILDA) and a modified quantitative viral outgrowth assay (mQVOA).
Most of the participants were male (10 males, 2 females), with a median age of 34 years and a median duration of ART of 3.7 years. No serious adverse events were reported. However, nine participants discontinued rhGH therapy before 48 weeks, most commonly due to musculoskeletal pain (n=6), which resolved after drug discontinuation. To assess the effects of rhGH, we compared baseline values to measures performed at the last visit on active drug and at which PBMCs were available (n=10, mean duration of rhGH therapy = 25 weeks). As expected, the frequency of TRECs in CD4+ T cells slightly increased (1.5 mean fold change; p=0.01), reflecting an increase in thymic output. However, absolute CD4 T cell counts remained unchanged. Administration of rhGH led to a modest but significant reduction in the frequency of CD4+ T cells harboring total HIV DNA (0.8 mean fold change; p=0.01). The frequency of CD4+ T cells with the ability to produce Tat/Rev transcripts upon stimulation remained stable. There was a trend for a decrease in the frequency of CD4+ T cells harboring replication competent HIV (mean fold reduction of 0.41 infectious units per million cells, p=0.08).
In this pilot study, administration of rhGH to individuals on ART led to a modest but statistically significant reduction in HIV reservoir markers despite early rhGH discontinuation in most participants. Reservoir reduction approaches based on a "fill to replace" strategy warrant further investigation.
(E) HIV Reservoirs, Latency, and Curative Strategies Including Therapeutic Vaccines and Gene Therapy
Does this abstract include any aspects of research on SARS-CoV-2 or COVID-19?
Prior Presentation or Publication: In general, CROI does not accept work that has been previously published or publicly presented. Abstract text that is under copyright by a publication or another conference should not be submitted verbatim to CROI. Consideration may be given to a previously presented submission if meaningful newer data or different analyses are included or if the prior presentation was to a conference not focused on HIV- or SARS-CoV-2-related topics. Have your study data or abstract information been published, submitted for publication where publication is anticipated on or before the start of the CROI where you will present, or presented at any other major national or international scientific or medical HIV-related conferences (ie, generally 400 or more attendees)?