The replication-competent HIV reservoir is detectable in circulating monocytes and is increased in ART-suppressed chronic HIV-infected individuals with cognitive impairment

Abstract

Abstract Background Measuring replication-competent HIV (rcHIV) in monocytes (MO) in the setting of antiretroviral therapy (ART)-suppression, remains a topic of intense interest, particularly due to the continued presence of cognitive (cog.) decline, as well as in our pursuit for an HIV cure. Methods PBMCs from ART-suppressed chronic HIV-infected donors, whom had available cog. performance scores, were cell sorted using flow cytometry to obtain ultra pure MO and CD4 T cells confirmed by subsequent flow analyses. Using a novel modified TZM-bl co-culture assay, frequencies of cells producing rcHIV (IUPM) were calculated. Total p24 associated with rcHIV produced by MO or CD4 T cells was quantified using a relative light unit to rcHIV-associated p24 standard curve. The infectious potential (IP) was calculated as a ratio of total rcHIV-associated p24 and IUPM. Non-parametric tests assessed group comparisons. Results All HIV-infected donors in cog. impaired (n=7) and cog. normal (n=9) groups were male, on ART > 3 months, and virally-suppressed. IUPMs in MO were detectable in 11 of 16 donors (median IUPM=1.32). IUPMs in CD4 T cells were detectable in 13 of 16 donors (median IUPM=7.22) and were higher as compared to MO (p=0.004). Median IP was slightly higher in MO as compared to CD4 T cells (0.443 vs. 0.104, p=0.271). Cog. impaired donors had higher IUPMs in MO as compared to cog. normal donors (4.43 vs. 0.31, p=0.015). IP between cog. groups were similar for both cellular compartments. Conclusions Despite ART-suppression, circulating MO are capable of producing rcHIV and may contribute to cog. impairment, as well as pose a challenge for HIV remission efforts. Monitoring and targeting HIV persistence in MO during ART-suppression are warranted.