Virological Outcome and Management of Persistent Low-Level Viraemia in HIV-1-Infected Patients: 11 Years of the Swiss HIV Cohort Study

Boillat‐Blanco, Noémie; Darling, Katharine E A; Schöni‐Affolter, Franziska; Vuichard, Danielle; Rougemont, Mathieu; Fulchini, Rosamaria; Bernasconi, Enos; Aouri, Manel; Clerc, Olivier; Furrer, Hansjakob; Günthard, Huldrych F.; Cavassini, Matthias

doi:10.3851/imp2815

Cited by 45 publications

(38 citation statements)

References 37 publications

(48 reference statements)

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“…In analogy, an increased risk of virological failure in patients with LLV has been reported, but methodological differences make comparisons between studies difficult, e.g. regarding the definitions of LLV and virological failure [15–17, 20, 21]. Few studies have investigated patients with LLV between 50 and 200 copies/mL [18, 19, 37].…”

Section: Discussionmentioning

confidence: 99%

“…Although LLV has been associated with an increased risk of drug resistance by some researchers, other studies suggest that this risk is low for patients with HIV RNA <50 copies/mL[10–14]. Consequently, patients with LLV may be at increased risk of virological failure [15–21]. However, other investigators have failed to identify such an association [22, 23], and the level of viremia at which the risk of virological failure becomes significant remains controversial.…”

Section: Introductionmentioning

confidence: 99%

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Virological failure and all-cause mortality in HIV-positive adults with low-level viremia during antiretroviral treatment

et al. 2017

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ObjectiveAlthough most HIV-infected individuals achieve undetectable viremia during antiretroviral therapy (ART), a subset have low-level viremia (LLV) of varying duration and magnitude. The impact of LLV on treatment outcomes is unclear. We investigated the association between LLV and virological failure and/or all-cause mortality among Swedish patients receiving ART.MethodsHIV-infected patients from two Swedish HIV centers were identified from the nationwide register InfCare HIV. Subjects aged ≥15 years with triple agent ART were included at 12 months after treatment initiation if ≥2 following viral load measurements were available. Patients with 2 consecutive HIV RNA values ≥1000 copies/mL at this time point were excluded. Participants were stratified into four categories depending on viremia profiles: permanently suppressed viremia (<50 copies/mL), LLV 50–199 copies/mL, LLV 200–999 copies/mL and viremia ≥1000 copies/mL. Association between all four viremia categories and all-cause death was calculated using survival analysis with viremia as a time-varying covariate, so that patients could change viremia category during follow-up. Association between the three lower categories and virological failure (≥2 consecutive measurements ≥1000 copies/mL) was calculated in a similar manner.ResultsLLV 50–199 copies/mL was recorded in 70/1015 patients (6.9%) and LLV 200–999 copies/mL in 89 (8.8%) during 7812 person-years of follow-up (median 6.5 years). LLV 200–999 copies/mL was associated with virological failure (adjusted hazard ratio 3.14 [95% confidence interval 1.41–7.03, p<0.01]), whereas LLV 50–199 copies/mL was not (1.01 [0.34–4.31, p = 0.99]; median follow-up 4.5 years). LLV 200–999 copies/mL had an adjusted mortality hazard ratio of 2.29 (0.98–5.32, p = 0.05) and LLV 50–199 copies/mL of 2.19 (0.90–5.37, p = 0.09).ConclusionsIn this Swedish cohort followed during ART for a median of 4.5 years, LLV 200–999 copies/mL was independently associated with virological failure. Patients with LLV had higher rates of all-cause mortality, although not statistically significant in multivariate analysis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Virological failure and all-cause mortality in HIV-positive adults with low-level viremia during antiretroviral treatment

et al. 2017

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“…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%

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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“…As in other studies (10,11), our results may be underpowered by the sample size, which we consider the main limitation of our study. Thus, we were not able to reproduce previous results when a confirmed virological rebound to Ͼ400 copies/ml was investigated.…”

mentioning

confidence: 62%

“…During the last years of the past decade, commercial assays for measuring viral loads reduced their detection limits (3-6), which shifted from 50 to 40 to 20 copies/ml, depending on the assay (7). Recently, a number of reports (8)(9)(10)(11)(12) have focused on the clinical significance of very low-level viremia (e.g., viral-load levels below 20 or between 20 and 50 copies/ml). The use of different assays or a different sample size, and even different baseline characteristics of the studies, may partially explain some of the contradictory findings of the studies.…”

mentioning

confidence: 99%

Quantification of Viral Loads Lower than 50 Copies per Milliliter by Use of the Cobas AmpliPrep/Cobas TaqMan HIV-1 Test, Version 2.0, Can Predict the Likelihood of Subsequent Virological Rebound to >50 Copies per Milliliter

et al. 2013

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b After 1 year of follow-up, patients on HAART with a baseline viral load (VL) of <20 copies/ml showed significantly lower odds of virological rebound to two consecutive VLs of >50 copies/ml than those with baseline VLs of 20 to 39 and 40 to 49 (P < 0.001). The time to virological rebound was also significantly shorter (P < 0.001) for the groups with baseline VLs of 20 to 39 and 40 to 49. T he number of patients failing antiretroviral treatment with low-level viremia (e.g., a viral load [VL] ranging from 40 to 1,000 copies/ml) is increasing (1, 2), and special interest has been shown in the clinical significance of this finding. During the last years of the past decade, commercial assays for measuring viral loads reduced their detection limits (3-6), which shifted from 50 to 40 to 20 copies/ml, depending on the assay (7). Recently, a number of reports (8-12) have focused on the clinical significance of very low-level viremia (e.g., viral-load levels below 20 or between 20 and 50 copies/ml). The use of different assays or a different sample size, and even different baseline characteristics of the studies, may partially explain some of the contradictory findings of the studies. In addition, high variability of the Cobas Ampliprep/Cobas TaqMan v2.0 assay at levels of 20 and 40 HIV copies/ml has been described (13).Since the introduction in our institution of Cobas TaqMan v2.0 (Roche Diagnostics) in June 2009, the lower detection cutoff of 50 copies/ml was shifted to 20 copies/ml, and this new threshold was reported to physicians treating HIV and thus used for making clinical decisions.In this retrospective cohort study, we have investigated the clinical significance of having a viral load between 20 and 50 copies/ml in terms of the odds for a viral-load rebound to more than 50 copies/ml or 400 copies/ml 1 year after testing. When possible, the emergence of resistance was also investigated.All adult HIV patients (Ͼ18 years old) who were on highly active antiretroviral therapy (HAART) with an available follow-up 12 months (median, 12.42 months; interquartile range [IQR], 11.73 to 13.80 months) after a viral-load test result below 50 copies/ml (time zero [T 0 ]) using the Cobas TaqMan v2.0 assay were included. When needed, resistance testing of very low-level viral loads was performed using a concentration step (14) prior to following the standard procedure of the Trugene HIV genotyping kit (Siemens NAD). Two hundred ninety patients met the inclusion criteria, and the pre-T 0 CD4 count, time (in years) with a VL of Ͻ50 before T 0 , number of years on HAART, and type of HAART regimen were retrieved from their medical records. Virological rebound was considered when two consecutive viral loads were recorded. Two definitions of virological rebound were evaluated: (i) rebound to more than 50 copies/ml, confirmed in two consecutive samples, and (ii) rebound to more than 400 copies/ ml, also confirmed in two consecutive samples. The time to virological rebound in months was also recorded. The baseline characteristics were ...

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Virological Outcome and Management of Persistent Low-Level Viraemia in HIV-1-Infected Patients: 11 Years of the Swiss HIV Cohort Study

Abstract: Among patients with pLLV, VF was predicted by previous VF, cART regimen and VL≥200. Most patients who changed cART had undetectable VLs 48 weeks later. These findings support cART modification for pLLV>200 copies/ml.

Cited by 45 publications

References 37 publications

Virological failure and all-cause mortality in HIV-positive adults with low-level viremia during antiretroviral treatment

Virological failure and all-cause mortality in HIV-positive adults with low-level viremia during antiretroviral treatment

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

Quantification of Viral Loads Lower than 50 Copies per Milliliter by Use of the Cobas AmpliPrep/Cobas TaqMan HIV-1 Test, Version 2.0, Can Predict the Likelihood of Subsequent Virological Rebound to >50 Copies per Milliliter

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