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

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.

Keywords: ART; HIV-1 DNA; HIV-1 residual viremia; HIV-1 tropism; Virological suppression.