TY - JOUR
T1 - Integrated analysis of viral blips, residual viremia, and associated factors in people with HIV
T2 - Results from a retrospective cohort study
AU - Oomen, Patrick G.A.
AU - Dijkstra, Suzan
AU - Hofstra, L. Marije
AU - Nijhuis, Monique M.
AU - Verbon, Annelies
AU - Mudrikova, Tania
AU - Wensing, Annemarie M.J.
AU - Hoepelman, Andy I.M.
AU - Van Welzen, Berend J.
N1 - Publisher Copyright:
© 2023 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.
PY - 2023/10
Y1 - 2023/10
N2 - 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.
AB - 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.
KW - combination antiretroviral therapy
KW - HIV
KW - integrase strand transfer inhibitors
KW - non-nucleoside reverse transcriptase inhibitors
KW - protease inhibitors
KW - residual viremia
KW - viral blips
UR - http://www.scopus.com/inward/record.url?scp=85174816504&partnerID=8YFLogxK
U2 - 10.1002/jmv.29178
DO - 10.1002/jmv.29178
M3 - Article
C2 - 37861450
AN - SCOPUS:85174816504
SN - 0146-6615
VL - 95
JO - Journal of Medical Virology
JF - Journal of Medical Virology
IS - 10
M1 - e29178
ER -