Plasma Human Immunodeficiency Virus 1 RNA and CD4+T-Cell Counts Are Determinants of Virological Nonsuppression Outcomes with Initial Integrase Inhibitor-Based Regimens: A Prospective RESPOND Cohort Study

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  • Hortensia Álvarez
  • Amanda Mocroft
  • Bastian Neesgaard
  • Simon Edwards
  • Veronica Svedhem
  • Huldrych F. Günthard
  • Robert Zangerle
  • Colette Smith
  • Antonella Castagna
  • Antonella D'Arminio Monforte
  • Ferdinand Wit
  • Melanie Stecher
  • Clara Lehman
  • Cristina Mussini
  • Eric Fontas
  • Eva González
  • Jan Christian Wasmuth
  • Anders Sönnerborg
  • Stephane De Wit
  • Nikoloz Chkhartishvili
  • Christoph Stephan
  • Kathy Petoumenos
  • Nadine Jaschinski
  • Vani Vannappagari
  • Joel Gallant
  • Lital Young
  • Alain Volny Anne
  • Lauren Greenberg
  • Raquel Martín-Iguacel
  • Eva Poveda
  • Josep M. Llibre
Background
There are conflicting data regarding baseline determinants of virological nonsuppression outcomes in persons with human immunodeficiency virus (HIV) starting antiretroviral treatment (ART). We evaluated the impact of different baseline variables in the RESPOND cohort.

Methods
We included treatment-naive participants aged ≥18 who initiated 3-drug ART, in 2014–2020. We assessed the odds of virological suppression (VS) at weeks 48 and 96 using logistic regression. Viral blips, low-level viremia (LLV), residual viremia (RV), and virological failure (VF) rates were assessed using Cox regression.

Results
Of 4310 eligible participants, 72% started integrase strand transfer inhibitor (INSTI)-based regimens. At 48 and 96 weeks, 91.0% and 93.3% achieved VS, respectively. At 48 weeks, Kaplan-Meier estimates of rates were 9.6% for viral blips, 2.1% for LLV, 22.2% for RV, and 2.1% for VF. Baseline HIV-1 RNA levels >100 000 copies/mL and CD4+ T-cell counts ≤200/µL were negatively associated with VS at weeks 48 (adjusted odds ratio, 0.51 [95% confidence interval, .39–.68] and .40 [.27–.58], respectively) and 96 and with significantly higher rates of blips, LLV, and RV. CD4+ T-cell counts ≤200/µL were associated with higher risk of VF (adjusted hazard ratio, 3.12 [95% confidence interval, 2.02–4.83]). Results were consistent in those starting INSTIs versus other regimens and those starting dolutegravir versus other INSTIs.

Conclusions
Initial high HIV-1 RNA and low CD4+ T-cell counts are associated with lower rates of VS at 48 and 96 weeks and higher rates of viral blips, LLV, and RV. Low baseline CD4+ T-cell counts are associated with higher VF rates. These associations remain with INSTI-based and specifically with dolutegravir-based regimens. These findings suggest that the impact of these baseline determinants is independent of the ART regimen initiated.
OriginalsprogEngelsk
TidsskriftClinical Infectious Diseases
Vol/bind77
Udgave nummer4
Sider (fra-til)593-605
Antal sider13
ISSN1058-4838
DOI
StatusUdgivet - 2023
Eksternt udgivetJa

Bibliografisk note

Publisher Copyright:
© 2023 The Author(s).

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