Integrated analysis of viral blips, residual viremia, and associated factors in people with HIV: Results from a retrospective cohort study

Abstract

The etiology of viral blips is not yet fully elucidated. One of the hypotheses is that blips reflect variations in residual viremia (RV) near the detectability threshold. In this study, we evaluated whether RV is associated with viral blips and which factors are associated with RV. All treatment regimens in 2010–2020 consisting of two nucleos(‐t)ide reverse transcriptase inhibitors and one anchor (integrase strand transfer inhibitor [INSTI], non‐nucleoside reverse transcriptase inhibitor [NNRTI], or protease inhibitor [PI]) in people with HIV (PWH) were evaluated for RV (detectable viremia <50 cp/mL) and blips (isolated viral loads [VLs] 50–499 cp/mL between measurements <50 cp/mL). All medical records were reviewed and regimens in which a VL ≥ 50 cp/mL was deemed to result from non‐adherence (based on the documented conclusion by the treating physician) were excluded. Factors associated with blips and RV were identified using generalized linear mixed models. In total, 24 518 VLs from 1658 PWH were analyzed. VLs were measured during INSTI‐ (n = 5119; 20.9%), PI‐ (n = 8935; 36.4%), and NNRTI‐use (n = 10 464; 42.7%). VLs were categorized as blips in 1.4% (n = 332). The 24,186 non‐blip VLs were RNAneg (no RV) (n = 15 326; 63.4%), 1–19 cp/mL (n = 6318; 26.1%), 20–49 cp/mL (n = 1620; 6.7%), or <50 cp/mL with an unknown RV level (n = 922; 3.8%). In 193/1658 PWH (11.6%), the RV level was RNAneg in all VLs assessed. RV 1–19 cp/mL and 20–49 cp/mL (vs. RNAneg) were significantly associated with subsequent viral blips (respective odds ratio 2.66 and 4.90 [95% confidence intervals: 1.98–3.58 and 3.41–7.04]). Zenith VL and use of PIs (vs. INSTIs/NNRTIs) were associated with higher RV and blip odds. This large cohort study showed that blips were associated with higher preceding RV. Both the anchor type and factors previously linked to the latent viral reservoir were associated with RV, suggesting blips having a multifactorial origin.

HIV-1 Remission: Accelerating the Path to Permanent HIV-1 Silencing

“…While these methods may obviate the use of ART, the main limitations to further advancing these approaches include challenges in inducing robust expression of the entire HIV-1 latent reservoir; toxicity of first-generation latency-reversing agents; risk of T-cell activation with potential for cytokine release, leading to an immune reactivation inflammatory syndrome; and adverse effects of reactivating agents on cytotoxic T cell and natural killer cell functions. Additionally, although antiretroviral therapy effectively lowers plasma HIV RNA to levels below the detection limits of commonly used clinical tests (less than 20 RNA copies/mL), low levels of HIV RNA may persist within tissues, suggesting that ongoing viral transcription occurs within reservoir cells [2][3][4][5]. New and radically different approaches are clearly needed to achieve an HIV-1 cure.…”