Persistent low-Level viremia in persons living with HIV undertreatment: An unresolved status

Abstract

Antiretroviral therapy (ART) allows suppressed viremia to reach less than 50 copies/mL in most treated persons living with HIV (PLWH). However, the existence of PLWH that show events of persistent low-level viremia (pLLV) between 50 and 1000 copies/mL and with different virological consequences have been observed. PLLV has been associated with higher virological failure (VF), viral genotype resistance, adherence difficulties and AIDS events. Moreover, some reports show that pLLV status can lead to residual immune activation and inflammation, with an increased risk of immunovirological failure and a pro-inflammatory cytokine level which can lead to a higher occurrence of non-AIDS defining events (NADEs) and other adverse clinical outcomes. Until now, however, published data have shown controversial results that hinder understanding of the true cause(s) and origin(s) of this phenomenon. Molecular mechanisms related to viral reservoir size and clonal expansion have been suggested as the possible origin of pLLV. This review aims to assess recent findings to provide a global view of the role of pLLV in PLWH and the impact this status may cause on the clinical progression of these patients.

HIV Virologic Failure among Patients with Persistent Low‐Level Viremia in Nairobi, Kenya: It Is Time to Review the >1000 Virologic Failure Threshold

“…In addition, those whose VL measurements were all consistently ≥200-999 copies/ml while at PLLV were 14 times more likely to experience VF compared to those with viral blips (five times) and those whose viral load measurements were consistently ≤199 copies/ml. This observation adds to the evidence that VL above 200 copies/ml at PLLV is a risk factor for VF, as reported by previous studies [ 1 , 8 , 26 , 32 , 33 ]. For instance, an LLV of 200–999 copies/ml was a risk factor for VF (OR 3.14), unlike an LLV of 50–199 copies/ml (OR 1.01) [ 4 ].…”

Factors associated with low-level viraemia in people with HIV starting antiretroviral therapy: A Swedish observational study

“…Although most people with HIV (PWH) receiving antiretroviral therapy (ART) achieve persistent viral suppression, some individuals have low but detectable plasma levels of HIV RNA without meeting criteria for virologic failure, a phenomenon commonly referred to as low-level viraemia (LLV) [ 1 ]. LLV could arise from two separate mechanisms: either passive release of viral particles from latently infected cells or as a consequence of ongoing replication [ 2 – 4 ].…”

Reaching HIV epidemic control in Nigeria using a lower HIV viral load suppression cut-off

“…Given the increased risk of virologic nonsuppression, virologic failure, HIV drug resistance, immune activation, inflammation, noncommunicable diseases, and serious non-AIDS events [10] associated with low-level viremia, monitoring virologic suppression at lower viral load cut-off values is important for understanding progress towards HIV epidemic control. As of 2022, the Nigeria program has not only achieved the third 95 of 95–95–95 at the less than 1000 copies/ml cut off value but has also achieved rates of virologic suppression at even lower cut off values of less than 50 copies/ml in 87% of PWH on ART with potential implications toward reduced morbidity, mortality, and transmission.…”