HIV-1 non-R5 tropism correlates with a larger size of the cellular viral reservoir and a detectable residual viremia in patients under suppressive ART

Simona Di Giambenedetto, Francesca Lombardi, Arturo Ciccullo, Gianmaria Baldin, Davide Moschese, Arianna Emiliozzi, Barbara Rossetti, Andrea De Luca, Francesca Montagnani

Risultato della ricerca: Contributo in rivistaArticolo in rivista

Abstract

Background: The influence of HIV-1 co-receptor usage on the course of therapy in subjects fully responding to ART has been poorly investigated. Objectives: To explore the relationship between co-receptor tropism and cellular reservoir size, residual viremia and subsequent virological outcome in ART-treated patients with HIV-1 RNA stable <50 copies/mL. Study design: Viral co-receptor usage was predicted by viral env DNA sequencing with geno2pheno interpretation (FPR20%) and classified as R5 and non-R5. Total blood-associated HIV-1 DNA levels (log10 copies/106 leukocytes) were measured by qRT-PCR (5′LTR). Residual plasma viremia was categorized as detectable (1–49 cps/mL) or undetectable (<1 copy/mL). Virological rebounds (any HIV-1 RNA >50 copies/mL) were evaluated over 96 weeks. Results: The study included 116 subjects. Patients with R5 virus (n = 59) and non-R5 virus (n = 57) were homogeneous for the main characteristics except for the lower nadir CD4 cell count in the non-R5 group. Patients with non-R5 variants showed higher levels of HIV-1 DNA as compared to patients with R5 virus: mean 2.47 (95% CI 2.37–2.56) vs 2.17 (2.08–2.26) (p < 0.001). Moreover, a higher proportion of patients in the non-R5 group displayed detectable residual viremia with respect to the R5-group (54.4% vs 32.2%, p =.016). Detectable residual viremia was found to be significantly associated with viral rebounds. Conclusion: The presence of non-R5 viral DNA variants is related to a higher probability of residual viremia and to a larger size of the cellular viral reservoir in this setting. These data highlight a potential role of viral tropism in the monitoring of HIV-1 infection in virologically controlled subject.
Lingua originaleEnglish
pagine (da-a)57-62
Numero di pagine6
RivistaJournal of Clinical Virology
Volume103
DOI
Stato di pubblicazionePubblicato - 2018

Keywords

  • ART
  • HIV-1 DNA
  • HIV-1 residual viremia
  • HIV-1 tropism
  • Infectious Diseases
  • Virological suppression
  • Virology

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