Evaluation of HIV-DNA and residual viremia levels through week 96 in HIV-infected individuals who continue a two-drug or switch to a three-drug integrase strand transfer inhibitor-based regimen

Rossana Scutari; Laura Galli; Claudia Alteri; Andrea Poli; Lorenzo Piermatteo; Alba Bigoloni; Carlo Federico Perno; Adriano Lazzarin; Francesca Ceccherini-Silberstein; Antonella Castagna; Maria Mercedes Santoro; Nicola Gianotti

doi:10.1016/j.ijantimicag.2023.106771

Evaluation of HIV-DNA and residual viremia levels through week 96 in HIV-infected individuals who continue a two-drug or switch to a three-drug integrase strand transfer inhibitor-based regimen

Int J Antimicrob Agents. 2023 May;61(5):106771. doi: 10.1016/j.ijantimicag.2023.106771. Epub 2023 Mar 3.

Affiliations

¹ Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy; Multimodal Laboratory Research Department, Children Hospital Bambino Gesù, IRCCS, Rome, Italy.
² Infectious Diseases, IRCCS San Raffaele, Milan, Italy.
³ Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.
⁴ Department of Experimental Medicine, University of Rome "Tor Vergata", Rome, Italy.
⁵ Multimodal Laboratory Research Department, Children Hospital Bambino Gesù, IRCCS, Rome, Italy.
⁶ Infectious Diseases, IRCCS San Raffaele, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy.
⁷ Department of Experimental Medicine, University of Rome "Tor Vergata", Rome, Italy. Electronic address: santormaria@gmail.com.

PMID: 36870403
DOI: 10.1016/j.ijantimicag.2023.106771

Abstract

Objectives: To investigate HIV-DNA and residual viremia (RV) levels over 96 weeks (W96) in virologically-suppressed HIV-1-infected individuals enrolled in the Be-OnE Study. Individuals were randomised to continue a two-drug regimen with dolutegravir (DTG) plus one reverse transcriptase inhibitor (RTI) or to switch to elvitegravir/cobicistat/emtricitabine/tenofovir-alafenamide (E/C/F/TAF).

Study design: Total HIV-DNA and RV were evaluated at baseline, W48 and W96 using droplet digital polymerase chain reaction (ddPCR) technique. Potential relationships between viro-immunological parameters and between/within arms were also assessed.

Results: Median (interquartile range [IQR]) HIV-DNA was 2247 (767-4268), 1587 (556-3543) and 1076 (512-2345) copies/10⁶ CD4+T-cells at baseline, W48 and at W96, respectively; RV was 3 (1-5), 4 (1-9) and 2 (2-4) copies/mL, respectively, with no significant differences between arms. A significant reduction in HIV-DNA and RV from baseline to W96 was observed in the E/C/F/TAF arm (HIV-DNA: -285 [-2257; -45], P=0.010; RV: -1 [-3;0], P=0.007). In the DTG + 1 RTI arm, HIV-DNA and RV levels remained stable (HIV-DNA: -549 [-2269;+307], P=0.182; RV: -1 [-3;+1], P=0.280). For both HIV-DNA and RV, there were no significant changes over time between the arms. A positive correlation was found between baseline HIV-DNA and HIV-DNA at W96 (E/C/F/TAF: Spearman correlation coefficient (r_s)=0.726, P=0.0004; DTG + 1 RTI: r_s=0.589, P=0.010). In general, no significant correlations were found between HIV-DNA, RV and immunological parameters over time.

Conclusions: In virologically-suppressed individuals, there was a small reduction in HIV-DNA and HIV-RNA levels from baseline to W96 in individuals who switched to the E/C/F/TAF arm compared with those who remained on DTG + 1 RTI. However, there were no significant differences between the two arms in the changes in HIV-DNA and HIV-RNA over time.

Keywords: Droplet digital PCR; Dual-regimen; HIV reservoir; Residual viremia; Single-tablet regimen; Total HIV-DNA.

Publication types

Randomized Controlled Trial

MeSH terms

Adenine / therapeutic use
Anti-HIV Agents* / pharmacology
Anti-HIV Agents* / therapeutic use
Emtricitabine / therapeutic use
HIV Infections* / drug therapy
Humans
Integrases
RNA / therapeutic use
Reverse Transcriptase Inhibitors / therapeutic use
Tenofovir / therapeutic use
Viremia / drug therapy

Substances

Tenofovir
Emtricitabine
Adenine
Anti-HIV Agents
Reverse Transcriptase Inhibitors
RNA
Integrases