Low-Level Viremia Is Associated With Clinical Progression in HIV-Infected Patients Receiving Antiretroviral Treatment

Bernal, Enrique; Gómez, José María Pérez; Jarrín, Inma; Cano, Alfredo; Muñoz, Ángeles; Alcaráz, Antonia; Imaz, Arkaitz; Iribarren, José Antonio; Rivero, María; Arazo, Piedad; Gutiérrez, Félix

doi:10.1097/qai.0000000000001678

Cited by 57 publications

(85 citation statements)

References 33 publications

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“…In contrast to previous studies, we focused only on the factors of high-risk LLV subgroup leading to VF, to identify conditions that need prompt treatment during ART. Although we used new definitions of LLV and VF, we found some similar risk factors as several resource-rich cohort studies, including the high zenith VL and low nadir CD4 + T cell counts [3,22,23]. In addition, we found that long-term ART, AZT + 3TC + NVP or DDI + NRTI+NNRTI regimens, Manchu and subtype B′ infection were all risk factors in this study.…”

Section: Discussionsupporting

confidence: 77%

“…Antiretroviral therapy (ART) can limit virus replication to less than 50 copies/ml and effectively prolong the life of HIV-1 infected patients [1]. However, in approximately 10-30% of the patients, depending on the definition, standard ART cannot control viral replication completely [2,3]. The plasma of such patients shows low level of viral replication, which is designated as low level viremia (LLV) [4].…”

Section: Introductionmentioning

confidence: 99%

“…Although most studies suggest that LLV contributes to VF, the potential risk factors of LLV have not been sufficiently investigated. Several HIV cohort studies from developed countries where subtype B was predominant found that the high zenith baseline VL and low nadir baseline CD4 + T cell counts were associated with the risk of LLV [3,[22][23][24][25]. However, the evidence from non-subtype B infected cases and resource-limited regions are still lacking.…”

Section: Introductionmentioning

confidence: 99%

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Factors associated with high-risk low-level viremia leading to virologic failure: 16-year retrospective study of a Chinese antiretroviral therapy cohort

Zhang

Ding

et al. 2020

BMC Infect Dis

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Background: Low level viremia (LLV) often occurs during antiretroviral therapy (ART) against HIV-1. However, whether LLV increases the risk of virologic failure (VF) is controversial because of the non-uniform definitions of LLV and VF. Methods: A long-term first line regimen ART cohort from 2002 to 2018 from Shenyang, northeast China, was retrospectively studied. All participants were followed up every 3 to 6 months to evaluate the treatment effect. The high-risk LLV subgroups leading to VF (with strict standards) were explored with Cox proportional hazards model and linear mixed-effect model. The association factors of high-risk LLV were further explored using multivariate logistic regression analyses. Results: A total of 2155 HIV-1 infected participants were included; of these, 38.7% showed LLV. Both high level LLV (HLLV) and any other level LLV coupled with high level blip (HLB) showed higher risk of VF (hazards ratios, HR HLLV = 5.93, and HR HLB = 2.84, p < 0.05 respectively). Moreover, HR increased with prolonged duration of LLV. Independent factors associated with high-risk LLV included the zenith baseline viral load (VL) above 6 log copies/ml (aOR = 3.49, p = 0.002), nadir baseline CD4 + T cell counts below 200 cells/mm 3 (aOR = 1.78, p = 0.011), Manchu (aOR = 2.03, p = 0.003), ART over 60 months (aOR = 1.81, p = 0.004), AZT + 3TC + NVP (aOR = 2.26, p < 0.001) or DDI-based regimen (aOR = 9.96, p = 0.002), and subtype B′ infection (aOR = 8.22, p = 0.001). Conclusions: In case of VF with strict standards, high-risk LLV leading to VF includes VL above 400 copies/ml, occurring at least once. Serious laboratory indicators or advanced stage of infection, long term ART and subtype B′ infection might also predict the occurrence of high-risk LLV.

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Section: Discussionsupporting

confidence: 77%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Factors associated with high-risk low-level viremia leading to virologic failure: 16-year retrospective study of a Chinese antiretroviral therapy cohort

Zhang

Ding

et al. 2020

BMC Infect Dis

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“…The potential contribution of LLV to clinical outcomes in PLHIV receiving long‐term ART, as well as the mechanisms involved, remains unclear. Increased mortality for LLV patients has been suggested , but has not been shown in other studies . Regarding cardiovascular risk, Zhang et al .…”

Section: Discussionmentioning

confidence: 88%

“…Although most PLHIV achieve stable suppression of viral replication during ART, persistent low‐level viraemia (LLV) occurs in some individuals. LLV has been associated with subsequent virological failure and emerging drug resistance , but the relationship between LLV and clinical endpoints is controversial . Recently, we reported a trend for increased mortality among Swedish PLHIV with LLV, with the main overall cause of death being CVD .…”

Section: Introductionmentioning

confidence: 96%

Is low‐level HIV‐1 viraemia associated with elevated levels of markers of immune activation, coagulation and cardiovascular disease?

et al. 2019

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Objectives The clinical significance of low‐level viraemia (LLV) during antiretroviral therapy (ART) is debated. We retrospectively investigated longitudinal levels of plasma markers associated with inflammation, altered coagulation and cardiovascular disease in Swedish HIV‐positive adults in relation to LLV or permanent virological suppression during long‐term ART. Methods Plasma levels of C‐reactive protein (CRP), D‐dimer, vascular cell adhesion molecule 1 (VCAM‐1), suppression of tumorigenicity 2 (ST2), growth differentiation factor 15 (GDF‐15), soluble CD14 (sCD14), soluble CD163 (sCD163), interferon‐γ‐induced protein 10 (IP‐10) and β‐2‐microglobulin were measured in 34 individuals with LLV (viral load 50–999 HIV‐1 RNA copies/mL) and in matched controls with persistent virological suppression. Biomarker levels were analysed in samples obtained during episodes of LLV and follow‐up samples obtained 1 year later (with similar timing for controls). All biomarkers were analysed using an independent sample t‐test and analysis of covariance (ANCOVA) after logarithmic transformation. Log‐rank analysis was applied for markers with concentration values out of range. Results Compared with controls, patients with LLV had significantly higher levels of GDF‐15 [geometric mean 3416 (95% confidence interval (CI) 804–14 516) pg/mL versus 2002 (95% CI 355–11 295) pg/mL in controls; P = 0.026] and D‐dimer [mean 1114 (95% CI 125–9917) ng/mL versus 756 (95% CI 157–3626) ng/mL; P = 0.038] after adjustment for age, CD4 count nadir and type of ART. In the unadjusted t‐test, only GDF‐15 was significantly higher and in the log‐rank test, both GDF‐15 and D‐dimer were significantly elevated. No significant differences were observed for the other biomarkers analysed. Conclusions Although levels of inflammation markers were similar in ART recipients with and without LLV, persons with LLV had significantly higher levels of GDF‐15 and D‐dimer. These findings suggest a potential link between LLV and cardiovascular outcomes.

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Learning from Persistent Viremia: Mechanisms and Implications for Clinical Care and HIV-1 Cure

Wu,

Simonetti

2023

Curr HIV/AIDS Rep

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Purpose of Review In this review, we discuss what persistent viremia has taught us about the biology of the HIV-1 reservoir during antiretroviral therapy (ART). We will also discuss the implications of this phenomenon for HIV-1 cure research and its clinical management. Recent Findings While residual viremia (RV, 1–3 HIV-1 RNA copies/ml) can be detected in most of people on ART, some individuals experience non-suppressible viremia (NSV, > 20–50 copies/mL) despite optimal adherence. When issues of drug resistance and pharmacokinetics are ruled out, this persistent virus in plasma is the reflection of virus production from clonally expanded CD4+ T cells carrying proviruses. Recent work has shown that a fraction of the proviruses source of NSV are not infectious, due to defects in the 5′-Leader sequence. However, additional viruses and host determinants of NSV are not fully understood. Summary The study of NSV is of prime importance because it represents a challenge for the clinical care of people on ART, and it sheds light on virus-host interactions that could advance HIV-1 remission research.

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Low-Level Viremia Is Associated With Clinical Progression in HIV-Infected Patients Receiving Antiretroviral Treatment

Abstract: In this cohort, LLV200-499 was strongly associated with AIDS events/death and virological failure, but not with any serious NAE. Therefore, vigorous treatment should be implemented in patients with more than 200 copies per milliliter.

Cited by 57 publications

References 33 publications

Factors associated with high-risk low-level viremia leading to virologic failure: 16-year retrospective study of a Chinese antiretroviral therapy cohort

Factors associated with high-risk low-level viremia leading to virologic failure: 16-year retrospective study of a Chinese antiretroviral therapy cohort

Is low‐level HIV‐1 viraemia associated with elevated levels of markers of immune activation, coagulation and cardiovascular disease?

Learning from Persistent Viremia: Mechanisms and Implications for Clinical Care and HIV-1 Cure

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