Low-Level Viremia Is Associated With Cumulative Adherence to Antiretroviral Therapy in Persons With HIV

Castillo‐Mancilla, José; Morrow, Mary; Coyle, Ryan P; Coleman, Stacey S; Zheng, Jia‐Hua; Ellison, Lucas; Bushman, Lane R.; Kiser, Jennifer J.; Anderson, Peter L.; MaWhinney, Samantha

doi:10.1093/ofid/ofab463

Cited by 20 publications

(10 citation statements)

References 22 publications

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“…However, our observation of emergent DRMs during LLV episodes implies that LLV, even in this low range, could be associated with ongoing replication, at least in some individuals. In this context, suboptimal adherence could act as a confounder for the relationship between LLV and VF [ 32 ], as could pre-ART DRM [ 29 ]; the lack of adherence data is a limitation of our study in this respect. Considering the possibility of confounding, here exemplified by reservoir size, adherence, and pre-ART resistance, a causal relationship between LLV and VF cannot be established from our study.…”

Section: Discussionmentioning

confidence: 99%

Virologic Failure Following Low-level Viremia and Viral Blips During Antiretroviral Therapy: Results From a European Multicenter Cohort

Elvstam

Malmborn

Elén

et al. 2022

Clinical Infectious Diseases

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Background It is unclear whether low-level viremia (LLV), defined as repeatedly detectable viral load (VL) of <200 copies/mL, and/or transient viremic episodes (blips) during antiretroviral therapy (ART), predict future virologic failure. We investigated the association between LLV, blips, and virologic failure (VF) in a multi-center European cohort. Methods People with HIV-1 who started ART 2005 or later were identified from the EuResist Integrated Database. We analyzed the incidence of VF (≥200 copies/mL) depending on viremia exposure, starting 12 months after ART initiation (grouped as suppression [≤50 copies/mL], blips [isolated VL of 51–999 copies/mL], and LLV [repeated VLs of 51–199 copies/mL]) using Cox proportional hazard models adjusted for age, sex, injecting drug use, pre-ART VL, CD4 count, HIV-1 subtype, type of ART, and treatment experience. We queried the database for drug resistance mutations (DRM) related to episodes of LLV and VF and compared those with baseline resistance data. Results During 81,837 person-years of follow-up, we observed 1,424 events of VF in 22,523 participants. Both blips (adjusted subhazard ratio [aHR], 1.7; 95% confidence interval [CI], 1.3−2.2) and LLV (aHR, 2.2; 95% CI, 1.6−3.0) were associated with VF, compared with virologic suppression. These associations remained statistically significant in sub-analyses restricted to people with VL <200 copies/mL and those starting ART 2014 or later. Among people with LLV and genotype data available within 90 days following LLV, 49/140 (35%) had at least one DRM. Conclusions Both blips and LLV during ART are associated with increased risk of subsequent VF.

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Section: Discussionmentioning

confidence: 99%

Virologic Failure Following Low-level Viremia and Viral Blips During Antiretroviral Therapy: Results From a European Multicenter Cohort

Elvstam

Malmborn

Elén

et al. 2022

Clinical Infectious Diseases

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“…Human immunodeficiency virus-associated chronic inflammation and immune activation play a key role, driven in part by ongoing low-level viral replication at reservoir sites despite ART-induced virologic suppression [ 10 , 11 ]. Furthermore, ART-treated PWH may experience intermittent viral nonsuppression [ 12 , 13 , 14 ], which may further heighten the inflammatory state that exists among PWH with controlled HIV, potentially contributing to deleterious end-organ effects [ 11 , 15 ]. At any given HIV-1 ribonucleic acid viral load (VL), women have greater immune activation and higher systemic levels of inflammatory biomarkers than men [ 16 ], possibly impacting differential NACM risk by sex observed in PWH [ 17 ].…”

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confidence: 99%

Cumulative Human Immunodeficiency Virus (HIV)-1 Viremia Is Associated With Increased Risk of Multimorbidity Among US Women With HIV, 1997–2019

Morton

Mehta

Wang

et al. 2022

Open Forum Infectious Diseases

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Background To evaluate the effect of cumulative HIV-1 viremia on aging-related multimorbidity among women living with HIV (WLWH), we analyzed data collected prospectively among women who achieved viral suppression after antiretroviral therapy (ART) initiation (1997—2019). Methods We included WLWH with ≥2 plasma HIV-1 viral loads (VL) < 200 copies/ml within a two-year period (baseline) following self-reported ART use. Primary outcome was multimorbidity (≥2 non-AIDS comorbidities (NACM) of 5 total assessed). The trapezoidal rule calculated viremia copy-years (VCY) as area-under-the-VL-curve. Cox proportional hazard models estimated the association of time-updated cumulative VCY with incident multimorbidity and with incidence of each NACM, adjusting for important covariates (e.g., age, CD4 count, etc). Results 806 WLWH contributed 6,368 women-years, with median 12 (Q1-Q3 7-23) VL per participant. At baseline, median age was 39 years, 56% were Black, and median CD4 was 534 cells/mm3. Median time-updated cumulative VCY was 5.4 (Q1-Q3 4.7-6.9) log10 copy-years/ml. Of 211 (26%) WLWH who developed multimorbidity, 162 (77%) had incident hypertension, 133 (63%) dyslipidemia, 60 (28%) diabetes, 52 (25%) cardiovascular and 32 (15%) kidney disease. Compared with WLWH who had time-updated cumulative VCY <5 log10, the adjusted hazard ratio of multimorbidity was 1.99 (95%CI 1.29-3.08) and 3.78 (95%CI 2.17-6.58) for those with VCY 5-6.9 and ≥7 log10 copy-years/ml, respectively (p < 0.0001). Higher time-updated cumulative VCY increased the risk of each NACM. Conclusions Among ART-treated WLWH, greater cumulative viremia increased the risk of multimorbidity and of developing each NACM, and hence may be a prognostically useful biomarker for NACM risk-assessment in this population.

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“…These findings were compatible with those of Castillo-Mancilla et al, showing a possible relationship between treatment adherence and LLV. 22 We found that the integrase inhibitor was not a predictor of a mean CD4 + cell count ≥500 cells/μL. Changing the ART regimen might not be helpful in the setting of LLV.…”

Section: Discussionmentioning

confidence: 60%

“…These findings were compatible with those of Castillo-Mancilla et al, showing a possible relationship between treatment adherence and LLV. 22…”

Section: Discussionmentioning

confidence: 99%

The influence of low-level viremia on CD4+ cell count in human immunodeficiency virus–infected patients

Lee

Chen

Lin

et al. 2022

Journal of the Chinese Medical Association

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Background: Following initiation of combined antiretroviral therapy, the majority of human immunodeficiency virus–infected patients experience immune reconstitution indicated by virologic suppression and an increase in peripheral CD4+ T-cell counts. Some patients may suffer from low-level viremia, which was reported to be significantly associated with acquired immunodeficiency syndrome cases, virologic failure, and death. We aimed to further investigate the influence of low-level viremia on CD4+ T-cell count. Methods: In our study, we included human immunodeficiency virus-seropositive patients on combined antiretroviral therapy, for at least 6 months, who received at least one assessment of human immunodeficiency virus plasma viral load and CD4+ cell count every 6 months, from January 2009 to January 2019. The copy-year viremia was determined by calculating the area under the curve of the plasma human immunodeficiency virus viral load. Results: When comparing patients with a mean CD4+ cell count <200 cells/μL, there was no significant difference between patients with a mean viral load <1000 copies/mL and patients with a mean viral load ≥1000 copies/mL (p = 0.219). Among those with a mean viral load <1000 copies/mL, a higher proportion of patients had a mean CD4+ cell count ≥500 cells/µL (p < 0.001). The mean CD4+ cell count of patients with copy-years viremia (log10) <4 (577.7, interquartile range 429.2-736.7) was significantly higher than that of patients with copy-years viremia (log10) ≥4 (443.3, interquartile range 319.0-558.4) (p < 0.001). In multivariate logistic regression analysis, we observed that malignancy without history, lower copy-years viremia, and high nadir CD4+ cell count were independent predictors of mean CD4+ cell count ≥500 cells/µL. Conclusion: Human immunodeficiency virus–infected patients with a history of malignancy, high copy-year viremia, and lower nadir CD4+ cell counts should be monitored carefully in clinical settings.

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Low-Level Viremia Is Associated With Cumulative Adherence to Antiretroviral Therapy in Persons With HIV

Cited by 20 publications

References 22 publications

Virologic Failure Following Low-level Viremia and Viral Blips During Antiretroviral Therapy: Results From a European Multicenter Cohort

Virologic Failure Following Low-level Viremia and Viral Blips During Antiretroviral Therapy: Results From a European Multicenter Cohort

Cumulative Human Immunodeficiency Virus (HIV)-1 Viremia Is Associated With Increased Risk of Multimorbidity Among US Women With HIV, 1997–2019

The influence of low-level viremia on CD4+ cell count in human immunodeficiency virus–infected patients

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