Study Identifies Possible New Patient Phenotype in HIV Space

Previously associated with elite controller status, having an inherent low viral reservoir is now possibly linked to individuals with chronic HIV infection who initiate treatment with antiretrovirals more than 6 months after becoming infected, according to study results published recently in EBioMedicine.

“Ours is the first study to assess the kinetics of reservoirs in chronically HIV-1-infected individuals harbouring low levels of total HIV-1 DNA,” the authors noted.

A group of 451 individuals with HIV were enrolled in and retrospectively screened for the study. Seventy-one percent (n = 319) were regularly treated at Hospital Germans Trias i Pujol, with the remaining 29% (n = 132) receiving care at Hospital Clinic, both in Barcelona, Spain. Most (83.6%) patients were male, from Spain (81%), and men who had sex with other men (58%), with a median (interquartile range [IQR]) age of 31 (27-37) years when their HIV was diagnosed.

All study participants had plasma viral loads that had been suppressed for at least 3 years, along with cryopreserved peripheral blood mononuclear cells (PBMCs). The low viral reservoir treated (LoViReT) cohort (n = 42; 9.3%) was on combination antiretroviral therapy (cART) with a viral level of less than 50 HIV-DNA copies/10⁶ PBMCs vs greater than 50 HIV-DNA copies/10⁶ PBMCs in the control group.

Study results show that 66% of the LoViReT cohort began cART in the chronic phase (cp-LoViReT), or more than 6 months after they were infected. And yet, their data demonstrate that their HIV-DNA levels were already at lower-than-expected levels compared with the control group (P = .002). Their HIV-specific antibodies were significantly fewer in number, and with much less avidity, following cART initiation.

These individuals also were shown to have faster decay of their viral latency, a less impaired CD8⁺ T-cell compartment, and fewer circulating antigens by the time they reached their 5-year mark on treatment. The decay speed of the HIV viral reservoir was deemed significant in the cp-LoViRetT cohort compared with the control group: 16- vs 5-fold, respectively (P <.001).

“HIV-1 infection disrupts T-cell subset homeostasis, with a dramatic decrease in the frequency of CD8⁺ T_N cells and massive expansion of CD8⁺ T_TM cells in infected individuals treated during both the acute phase and the chronic phase. A naturally low level of cell-associated HIV-1 DNA could result in a more preserved immune system,” the authors concluded. “Further studies on the host and viral parameters of these individuals are warranted to identify factors that are potentially involved in these phenomena.”

The authors suggest that these further studies encompass the following:

• HIV remission strategies
• Quantification of the inducible reservoir at the RNA level
• Analyzing if individuals with an intrinsic low viral reservoir share any molecular mechanisms of action that does not let HIV “establish latency”
• Larger patient cohorts, with fresher samples of PBMCs

An important study limitation is that HIV-1 DNA was only measured using PBMCs. Due to the retrospective nature of the study, additional tissue samples were not available, such as from lymph nodes and gut-associated lymphoid tissues, both known locations of larger HIV-1 reservoirs.

Reference

Galvez C, Urrea V, Dalmau J, et al. Extremely low viral reservoir in treated chronically HIV-1-infected individuals. EBioMedicine. Published online June 21, 2020. doi:10.1016/j.ebiom.2020.102830