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

Abstract 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 2002–2018 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, HRHLLV=5.93, and HRHLB=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/mm3 (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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Factors associated with high-risk low-level viremia leading to virologic failure: 16-year retrospective study of a Chinese antiretroviral therapy cohort

10.21203/rs.2.16492/v2 ◽

2020 ◽

Author(s):

Tong Zhang ◽

Haibo Ding ◽

Minghui An ◽

Xiaonan Wang ◽

Wen Tian ◽

...

Keyword(s):

Antiretroviral Therapy ◽

High Risk ◽

Virologic Failure ◽

Baseline Viral Load ◽

Factors Associated ◽

Low Level ◽

Subtype B ◽

High Level ◽

Hiv 1

Abstract 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 2002–2018 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, HRHLLV=5.93, and HRHLB=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/mm3 (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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Factors associated with high-risk low-level viremia leading to virologic failure: 16-year retrospective study of a Chinese antiretroviral therapy cohort

10.21203/rs.2.16492/v4 ◽

2020 ◽

Author(s):

Tong Zhang ◽

Haibo Ding ◽

Minghui An ◽

Xiaonan Wang ◽

Wen Tian ◽

...

Keyword(s):

Antiretroviral Therapy ◽

High Risk ◽

Virologic Failure ◽

Baseline Viral Load ◽

Factors Associated ◽

Low Level ◽

Subtype B ◽

High Level ◽

Hiv 1

Abstract 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 2002–2018 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, HRHLLV=5.93, and HRHLB=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/mm3 (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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Factors associated with high-risk low-level viremia leading to virologic failure: 16-year retrospective study of a Chinese antiretroviral therapy cohort

BMC Infectious Diseases ◽

10.1186/s12879-020-4837-y ◽

2020 ◽

Vol 20 (1) ◽

Cited By ~ 3

Author(s):

Tong Zhang ◽

Haibo Ding ◽

Minghui An ◽

Xiaonan Wang ◽

Wen Tian ◽

...

Keyword(s):

Retrospective Study ◽

Antiretroviral Therapy ◽

High Risk ◽

Virologic Failure ◽

Factors Associated ◽

Low Level

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Factors Associated With CD8+ T-Cell Activation in HIV-1–Infected Patients on Long-term Antiretroviral Therapy

JAIDS Journal of Acquired Immune Deficiency Syndromes ◽

10.1097/qai.0000000000000286 ◽

2014 ◽

Vol 67 (2) ◽

pp. 153-160 ◽

Cited By ~ 20

Author(s):

Lu Zheng ◽

Babafemi Taiwo ◽

Rajesh T. Gandhi ◽

Peter W. Hunt ◽

Ann C. Collier ◽

...

Keyword(s):

T Cell ◽

Antiretroviral Therapy ◽

T Cell Activation ◽

Cell Activation ◽

Cd8 T Cell ◽

Factors Associated ◽

Hiv 1

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Discordance between Etravirine Phenotype and Genotype-Based Predicted Phenotype for Subtype C HIV-1 from First-Line Antiretroviral Therapy Failures in South Africa

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02101-19 ◽

2020 ◽

Vol 64 (5) ◽

Author(s):

Kevin D. McCormick ◽

Kerri J. Penrose ◽

Chanson J. Brumme ◽

P. Richard Harrigan ◽

Raquel V. Viana ◽

...

Keyword(s):

Virologic Failure ◽

Transcriptase Inhibitor ◽

Subtype C ◽

Genotypic Resistance ◽

Low Level ◽

Nnrti Resistance ◽

Subtype B ◽

Treatment Naïve ◽

Hiv 1 ◽

Interpretation Systems

ABSTRACT Etravirine (ETR) is a nonnucleoside reverse transcriptase inhibitor (NNRTI) used in treatment-experienced individuals. Genotypic resistance test-interpretation systems can predict ETR resistance; however, genotype-based algorithms are derived primarily from HIV-1 subtype B and may not accurately predict resistance in non-B subtypes. The frequency of ETR resistance among recombinant subtype C HIV-1 and the accuracy of genotypic interpretation systems were investigated. HIV-1LAI containing full-length RT from HIV-1 subtype C-positive individuals experiencing virologic failure (>10,000 copies/ml and >1 NNRTI resistance-associated mutation) were phenotyped for ETR susceptibility. Fold change (FC) was calculated against a composite 50% effective concentration (EC50) from treatment-naive individuals and three classifications were assigned: (i) <2.9-FC, susceptible; (ii) ≥2.9- to 10-FC, partially resistant; and (iii) >10-FC, fully resistant. The Stanford HIVdb-v8.4 was used for genotype predictions merging the susceptible/potential low-level and low-level/intermediate groups for 3 × 3 comparison. Fifty-four of a hundred samples had reduced ETR susceptibility (≥2.9-FC). The FC correlated with HIVdb-v8.4 (Spearman’s rho = 0.62; P < 0.0001); however, 44% of samples were partially (1 resistance classification difference) and 4% completely discordant (2 resistance classification differences). Of the 34 samples with an FC of >10, 26 were HIVdb-v8.4 classified as low-intermediate resistant. Mutations L100I, Y181C, or M230L were present in 27/34 (79%) of samples with an FC of >10 but only in 2/46 (4%) of samples with an FC of <2.9. No other mutations were associated with ETR resistance. Viruses containing the mutation K65R were associated with reduced ETR susceptibility, but 65R reversions did not increase ETR susceptibility. Therefore, genotypic interpretation systems were found to misclassify ETR susceptibility in HIV-1 subtype C samples. Modifications to genotypic algorithms are needed to improve the prediction of ETR resistance for the HIV-1 subtype C.

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Long-term CD4+ T-Cell Response in HIV-1-Infected Patients Continuing Combination Antiretroviral Therapy Despite High-Level Viremia and Drug Resistance

European Journal of Clinical Microbiology & Infectious Diseases ◽

10.1007/s10096-002-0845-7 ◽

2003 ◽

Vol 22 (1) ◽

pp. 69-71

Author(s):

D. Dionisio ◽

A. Vivarelli ◽

M. Zazzi ◽

F. Esperti ◽

C. Fabbri ◽

...

Keyword(s):

Drug Resistance ◽

T Cell ◽

Antiretroviral Therapy ◽

Cell Response ◽

T Cell Response ◽

Cd4 T Cell ◽

Combination Antiretroviral Therapy ◽

High Level ◽

Hiv 1

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Stopping, starting, and sustaining HIV antiretroviral therapy: a mixed-methods exploration among African American/Black and Latino long-term survivors of HIV in an urban context

BMC Public Health ◽

10.1186/s12889-021-10464-x ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Marya Gwadz ◽

Charles M. Cleland ◽

Robert Freeman ◽

Leo Wilton ◽

Linda M. Collins ◽

...

Keyword(s):

African American ◽

Mixed Methods ◽

Antiretroviral Therapy ◽

High Risk ◽

Risk Levels ◽

Factors Associated ◽

American Black ◽

Hiv Antiretroviral Therapy ◽

Black And Latino

AbstractBackgroundAlthough periods of HIV antiretroviral therapy (ART) discontinuation have deleterious health effects, ART is not always sustained. Yet, little is known about factors that contribute to such ART non-persistence among long-term HIV survivors. The present study applied a convergent parallel mixed-methods design to explore the phenomena of stopping/starting and sustaining ART, focusing on low-socioeconomic status African American or Black and Latino persons living with HIV (PLWH) who face the greatest challenges.MethodsParticipants (N = 512) had poor engagement in HIV care and detectable HIV viral load. All received structured assessments andN = 48 were randomly selected for in-depth interviews. Quantitative analysis using negative binomial regression uncovered associations among multi-level factors and the number of times ART was stopped/started and the longest duration of sustained ART. Qualitative data were analyzed using a directed content analysis approach and results were integrated.ResultsParticipants were diagnosed 18.2 years ago on average (SD = 8.6), started ART a median five times (Q1 = 3, Q3 = 10), and the median longest duration of sustained ART was 18 months (Q1 = 6, Q3 = 36). Factors associated with higher rates of stops/starts were male sex, transgender identity, cannabis use at moderate-to-high-risk levels, and ART- and care-related stigma. Factors associated with lower rates of stops/starts were older age, more years since diagnosis, motivation for care, and lifetime injection drug use (IDU). Factors associated with longer durations of sustained ART were Latino/Hispanic ethnicity, motivation for ART and care, and recent IDU. Factors associated with a shorter duration were African American/Black race, alcohol use at moderate-to-high-risk levels, and social support. Qualitative results uncovered a convergence of intersecting risk factors for stopping/starting ART and challenges inherent in managing HIV over decades in the context of poverty. These included unstable housing, which contributed to social isolation, mental health distress, and substance use concerns, the latter prompting selling (“diverting”) ART. Primarily complementary quantitative and qualitative findings described mechanisms by which risk/protective factors operated and ways PLWH successfully restart and/or sustain ART.ConclusionsThe field focuses substantially on ART adherence, but greater attention to reducing the frequency of ART non-persistence is needed, along with creating social/structural conditions favorable for sustained ART.

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High level of HIV-1 resistance in patients failing long-term first-line antiretroviral therapy in Mali

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dku153 ◽

2014 ◽

Vol 69 (9) ◽

pp. 2531-2535 ◽

Cited By ~ 16

Author(s):

D. B. Fofana ◽

C. Soulie ◽

A. Balde ◽

S. Lambert-Niclot ◽

M. Sylla ◽

...

Keyword(s):

Antiretroviral Therapy ◽

First Line ◽

High Level ◽

Hiv 1

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Long-term safety, tolerability and antiviral activity of rilpivirine in antiretroviral-naïve adolescents living with HIV-1, aged 12 to less than 18 years: Week 240 findings of a phase 2, open-label study, PAINT

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00916-21 ◽

2021 ◽

Author(s):

Johan Lombaard ◽

Francis Ssali ◽

Puthanakit Thanyawee ◽

Jan Fourie ◽

Simon Vanveggel ◽

...

Keyword(s):

Viral Load ◽

Virologic Failure ◽

Virologic Response ◽

Baseline Viral Load ◽

Phase 2 ◽

Adequate Treatment ◽

Living With Hiv ◽

Hiv 1 ◽

Extension Period

Introduction: This Phase-2 study investigated long-term safety and efficacy of rilpivirine (RPV)+two investigator-selected nucleos(t)ide reverse-transcriptase inhibitors (NRTIs), in HIV-1-infected antiviral therapy-naïve adolescents. Methods: Participants (≥12to <18 years) were treated with RPV 25mg qd+2 NRTIs who entered treatment extension period for up to 240 weeks with visits every 3 months. Long-term safety (analysis of adverse events [AEs], laboratory results), efficacy (virologic-response and outcome for patients with viral load <50 and <400 by time to loss of virologic-response (TLOVR) and FDA Snapshot methods, and CD4+ cell count), and adherence (by pill-count) for up to 240 weeks are presented. Results: 24 of 36 entered treatment extension period and 21 completed week 240. At week 240, viral load <50 copies/mL was achieved by 14/32 (43.8%) participants; virologic-response by TLOVR was higher in participants with baseline viral load≤100,000 copies/mL (48.0%) versus viral load >100,000 copies/mL (28.6%). By FDA Snapshot, viral load < 50 copies/mL at week 240 was 53.1% (17/32) in participants with baseline viral load ≤100,000 copies/mL. Higher response was observed in participants with adherence >95% and baseline viral load ≤100,000 copies/mL. Through week 240, 16/32 participants (50.0%) experienced virologic-failure, including seven who developed treatment-emergent RPV resistance-associated mutations (RAMs; frequently E138K); all 7 had ≥1 treatment-emergent NRTI RAM. No serious AEs after week 48, no discontinuations due to AEs between week 48 and week 240 and no new safety signals were observed. RPV did not affect pubertal development/adolescent growth. Conclusions: At the 5-year follow-up, efficacy was low in adolescents, particularly those with poor adherence and/or high baseline viral load >100,000 copies/mL. To limit the risk of virologic failure, Edurant is restricted to patients with a baseline VL ≤100,000 copies/mL in most countries. In addition, adequate treatment adherence to RPV treatment is imperative for long-term viral suppression and should be emphasized in the management of adolescents living with HIV. RPV exhibited favorable long-term safety profile for adolescents living with HIV-1 with adequate adherence. Clinical Trial Number: NCT00799864

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