Background:
The HIV-1 host interaction exhibits remarkable diversity, resulting in various clinical profiles and virological traits, including coreceptor tropism. The 2000HIV study, which is a multi-omics study including 1895 people living with HIV-1 (PLWH) (NTC03994835), reflects this notable variability by including different clinical phenotypes, such as elite controllers (EC), viremic controllers (VC), transient controllers (TC), immunological non-responders (INR), rapid progressors (RP) and normal HIV-1 progressors (NP).
Methods:
We quantified the total and intact HIV-1 reservoir by using the Rainbow proviral HIV-1 DNA digital PCR assay in CD4 T cells from blood in a subset of PLWH from the 2000HIV cohort (n = 863). In this study, we identified two distinct groups of PLWH, LoViReT-like and HiViReT-like, based on their total HIV-1 DNA levels (10% cut-off). Coreceptor tropism was determined by sequencing the viral env region and using the Geno2pheno algorithm (10% false positive rate).
Results:
Quantification by the Rainbow HIV-1 DNA assay resulted in a median of 456.1 (CI95%: 410.2-521.4) total HIV-1 DNA copies/10^6 CD4+ T cells (n = 863) and 8.7 (CI95%: 6.7-10.6) intact HIV-1 DNA copies/10^6 CD4+ T cells (n = 565). Total HIV-1 DNA levels in EC and VC were significantly lower than the NP (P <0.0001), whereas total HIV-1 DNA levels in INR were higher than NP (P = 0.0097). Intactness levels were significantly lower in the different controller groups versus NP (P <0.05) (Figure1). The selected samples for the LoViReT-like PLWH and HiViReT-like PLWH harbor total HIV-1 DNA levels of <50 copies/10^6 CD4 T cells and >2170 copies/10^6 CD4 T cells, respectively. Clinical parameters associated with infection (CD4 nadir, latest CD4 count, plasma viral load before ART and viral zenith) were significantly different between both groups (Mann Whitney U test). In addition, PLWH infected by X4-tropic viruses (n = 144) harbor significantly higher levels of total and intact HIV-1 DNA compared to PLWH infected by R5-tropic viruses (n = 561) (P = 0.003 and P = 0.04).
Conclusions:
Intactness levels differ significantly among controller groups and NP, highlighting the importance of intact HIV-1 DNA as a relevant virological parameter. Additionally, the study highlights the role of coreceptor tropism in influencing the reservoir size. This study marks a significant milestone in HIV research, as it represents a pioneering effort to comprehensively characterize the viral reservoir in a substantial number of PLWH.
