Time spent with residual viraemia after virological suppression below 50 HIV-RNA copies/mL according to type of first-line antiretroviral regimen

Abstract Background The use of abacavir (ABC) and rilpivirine (RPV) in the first-line regimen for naïve HIV-infected patients with pretreatment HIV RNA >100,000 copies/mL is not recommended due to a high rate of treatment failure. If a model could accurately predict pretreatment HIV RNA levels, it would be a useful tool for the selection ABC or RPV in the first-line regimen. Methods Thai HIV-infected adults enrolled in the TREAT Asia HIV Observational Database (TAHOD) and additional patients of Ramathibodi Hospital were eligible if they had an HIV RNA result at the time of antiretroviral therapy initiation. Factors associated with pretreatment HIV RNA <100,000 copies/mL were determined by logistic regression. Based on the results of the final model, a prediction model was created. Results A total of 1,223 patients were included in the analysis. Among those in the derivation data set, median [interquartile range (IQR)] age was 36.3 (30.5–42.9) years, median (IQR) CD4 count was 122 (39–216) cells/mm3, and pretreatment HIV RNA was 100,000 (32,449–229,777) copies/mL. Factors associated with pretreatment HIV RNA <100,000 copies/mL were anemia [odds ratio (OR) 2.05 vs. no anemia; 95% confidence interval (CI) 1.28–3.27], CD4 count >200 cells/mm3 (OR 3.00 vs. CD4 count <200 cells/mm3; 95% CI 2.08–4.33), and non-heterosexual HIV exposure (OR 1.61 vs. heterosexual HIV exposure; 95% CI 1.07–2.43). No AIDS-defining illness (11.5), no anemia (18.5), age <35 years (11), CD4 count >200 cells/mm3 (27), duration of HIV infection >1 year (9), and weight >50 years (11) were included in the clinical prediction tool scores. A score ≥45 yielded a sensitivity of 45.3%, specificity of 76.7%, positive predictive value of 68.1%, and negative predictive value of 56.1% among patients in the derivation. The area under the receiver-operator characteristic curve was 0.655 (95% CI 0.614- 0.696) and 0.600 (95% CI 0.533–0.667) in the derivation and validation patients, respectively. Conclusion Our final prediction model had poor sensitivity and specificity for predicting HIV RNA <100,000 copies/mL. Further study on a larger population with a greater diversity of data variables available is necessary to improve the model. Pretreatment HIV RNA remains necessary before ABC or RPV initiation for naïve Thai HIV-infected patients. Disclosures All authors: No reported disclosures.

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Very High Baseline HIV viremia impairs efficacy of NNRTI-based ART: A long-term observation in treatment-naïve patients

10.21203/rs.3.rs-21440/v1 ◽

2020 ◽

Author(s):

Shuai Chen ◽

Yang Han ◽

Xiaojing Song ◽

Yanling Li ◽

Ting Zhu ◽

...

Keyword(s):

Virological Failure ◽

Virological Response ◽

Viral Suppression ◽

Virological Suppression ◽

Viral Rebound ◽

High Baseline ◽

Hiv Rna ◽

Increased Risk ◽

Chi Square Analysis ◽

Very High

Abstract Background: High baseline HIV-RNA level (≥100,000 copies/ml) has been proved to be related with weaker virological response to antiretroviral therapy (ART). However, it was not completely clear whether a very high pre-therapy viral load (≥500,000 copies/ml) can further impair the virological response, especially in the long run. Methods: A retrospective study based on data from multicenter cohorts in China was performed. We enlisted untreated HIV infected adults recruited between18 and 65 years old, who received China’s first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen. All patients had baseline HIV-RNA levels over 500 copies/ml, showed good adherence, and were followed for at least 24 weeks. Virological suppression (VS) was defined as the first HIV-RNA <50 copies/ml which lasted for six months. Virological failure was defined as any of incomplete viral suppression (HIV-RNA ≥200 copies/mL with no recorded VS within 24 weeks of treatment) and viral rebound (confirmed HIV-RNA level ≥50 copies/mL after VS). Chi-square analysis was used to compare rates of VS between different HIV-RNA strata. Kaplan–Meier analysis and Cox regression model were used to compare time to virological suppression. Logistic regression was used to evaluate odds to virological failure. Results: 758 treatment-naïve HIV patients in China were enlisted. Median follow-up time (IQR) was 144 (108-276) weeks. Most patients (68.2%) were given tenofovir disoproxil fumarate (TDF) + lamivudine (3TC) + efavirenz (EFV) regimen. By week 48, rates of VS in three groups (<100,000, 100,000-500,000 and ≥500,000 copies/ml) were 94.1%, 85.0%, and 63.8%, respectively ( p <0.001). Very high baseline HIV viremia over 500,000 copies/ml were found to be independently associated with delayed VS [≥500,000 vs. <100,000, adjusted relative hazard (95% CI), 0.455 (0.32-0.65); p <0.001] as well as incomplete viral suppression [≥500,000 vs. <100,000, adjusted odds ratio (aOR) (95% CI), 6.084 (2.761-13.407); p <0.001] and viral rebound [≥500,000 vs. <100,000, aOR (95% CI), 3.671 (1.009-13.355), p =0.048]. Conclusion: Very high levels of pre-treatment HIV-RNA were significantly related with delayed efficacy of NNRTI-based ART and increased risk of treatment failure. More potent initial regimens should be considered for those with very high baseline viremia.

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Features of application of raltegravir in HIV-infected patients with different somatic pathologies

Journal Infectology ◽

10.22625/2072-6732-2021-13-3-92-100 ◽

2021 ◽

Vol 13 (3) ◽

pp. 92-100

Author(s):

N. V. Sizova ◽

E. S. Obizhaeva ◽

S. O. Mayorova

Keyword(s):

Clinical Practice ◽

Undetectable Viral Load ◽

Virological Suppression ◽

Side Reactions ◽

Main Criterion ◽

Good Tolerance ◽

Hiv Rna ◽

Study Evaluation ◽

High Level ◽

First Time

Purpose of the study. Evaluation of the efficacy, safety and tolerability of raltegravir regimens in HIV-infected patients with concomitant pathology in real clinical practice.Materials and methods. A retrospective analysis was carried out of 277 outpatient records of HIV-infected patients who received raltegravir (RAL) as a third component both in patients without previous experience of antiretroviral therapy (ART) and in patients with experience of treatment with various somatic pathologies. The main criterion for the effectiveness of the scheme was the proportion of patients with undetectable viral load at the start of the analysis. Additional criteria for evaluating the efficacy and safety of the regimen were the dynamics of the number of CD4-lymphocytes, the frequency and nature of undesirable side reactions.Results. On average, patients with no experience of treatment and with experience of treatment received regimens with raltegravir for about 5 years. At the time of the study in 2020, 69.8% of patients on ART for the first time continued to take a regimen containing raltegravir. In this group, the proportion of patients with virological suppression (PCR of HIV RNA less than 50 kopecks / ml) was 97.7%. 75.2% of patients in the second group in 2020 continued to take the RAL regimen. The proportion of patients with virological suppression (VL less than 50 kopecks / ml) in this group was 97.5%. During the treatment, there was no discontinuation of the regimen in both groups due to undesirable side reactions to raltegravir.Conclusion. The results of this study confirm that RAL-based regimens provide a high level of efficacy with a good tolerance and safety profile in routine clinical practice for both naive and experienced patients with various somatic pathologies.

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Comment on: Residual viraemia does not influence 1 year virological rebound in HIV-infected patients with HIV RNA persistently below 50 copies/mL

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dks233 ◽

2012 ◽

Vol 67 (10) ◽

pp. 2540-2541 ◽

Cited By ~ 1

Author(s):

N. Iannotti ◽

G. Masini ◽

C. Bernardini ◽

L. Soavi ◽

G. Cologni ◽

...

Keyword(s):

Hiv Rna ◽

Residual Viraemia

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Impact of first-line antiretroviral therapy regimens on the restoration of the CD4/CD8 ratio in the CNICS cohort

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkaa024 ◽

2020 ◽

Vol 75 (6) ◽

pp. 1604-1610 ◽

Cited By ~ 1

Author(s):

Sabina Herrera ◽

Borja M Fernandez-Felix ◽

Peter W Hunt ◽

Steven G Deeks ◽

Talía Sainz ◽

...

Keyword(s):

Baseline Viral Load ◽

Strand Transfer ◽

First Line ◽

Hiv Rna ◽

Art Initiation ◽

Primary Endpoints ◽

Secondary Endpoints ◽

Transfer Inhibitor ◽

Integrase Strand Transfer Inhibitor

Abstract Background The CD4/CD8 ratio is an indicator of immunosenescence and a predictor of all-cause mortality in HIV-infected patients. The effects of different ART regimens on CD4/CD8 ratio recovery remain unclear. Methods Clinical cohort study of ART-treated patients from the CFAR Network of Integrated Clinical Systems (CNICS). We included ART-naive adults with HIV infection who achieved undetectable HIV RNA during the first 48 weeks of treatment and had additional follow-up 48 weeks after virological suppression (VS). Primary endpoints included increase in CD4/CD8 ratio at both timepoints and secondary endpoints were CD4/CD8 ratio recovery at cut-offs of ≥0.5 or ≥1.0. Results Of 3971 subjects who met the study criteria, 1876 started ART with an NNRTI, 1804 with a PI and 291 with an integrase strand transfer inhibitor (INSTI). After adjusting for age, sex, race, year of entry, risk group, HCV serostatus, baseline viral load and baseline CD4/CD8 ratio, subjects on an NNRTI showed a significantly greater CD4/CD8 ratio gain compared with those on a PI, either 48 weeks after ART initiation or after 48 weeks of HIV RNA VS. The greater CD4/CD8 ratio improvement in the NNRTI arm was driven by a higher decline in CD8 counts. The INSTI group showed increased rates of CD4/CD8 ratio normalization at the ≥1.0 cut-off compared with the PI group. Conclusions NNRTI therapy was associated with a greater increase in the CD4/CD8 ratio compared with PIs. NNRTI- and INSTI-based first-line ART were associated with higher rates of CD4/CD8 ratio normalization at a cut-off of 1.0 than a PI-based regimen, which might have clinical implications.

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Very High Baseline HIV viremia impairs efficacy of NNRTI-based ART: A long-term observation in treatment-naïve patients

10.21203/rs.3.rs-21440/v2 ◽

2020 ◽

Author(s):

Shuai Chen ◽

Yang Han ◽

Xiaojing Song ◽

Yanling Li ◽

Ting Zhu ◽

...

Keyword(s):

Virological Failure ◽

Virological Response ◽

Viral Suppression ◽

Virological Suppression ◽

Viral Rebound ◽

High Baseline ◽

Hiv Rna ◽

Increased Risk ◽

Chi Square Analysis ◽

Very High

Abstract Background: High baseline HIV-RNA level (≥100,000 copies/ml) has been proved to be related with weaker virological response to antiretroviral therapy (ART). However, it was not completely clear whether a very high pre-therapy viral load (≥500,000 copies/ml) can further impair the virological response, especially in the long run. Methods: A retrospective study based on data from multicenter cohorts in China was performed. We enlisted untreated HIV infected adults recruited between18 and 65 years old, who received China’s first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen. All patients had baseline HIV-RNA levels over 500 copies/ml, showed good adherence, and were followed for at least 24 weeks. Virological suppression (VS) was defined as the first HIV-RNA <50 copies/ml. Virological failure was defined as any of incomplete viral suppression (HIV-RNA ≥200 copies/mL with no recorded VS within 24 weeks of treatment) and viral rebound (confirmed HIV-RNA level ≥50 copies/mL after VS). Chi-square analysis was used to compare rates of VS between different HIV-RNA strata. Kaplan–Meier analysis and Cox regression model were used to compare time to virological suppression. Logistic regression was used to evaluate odds to virological failure.Results: 758 treatment-naïve HIV patients in China were enlisted. Median follow-up time (IQR) was 144 (108-276) weeks. Most patients (68.2%) were given tenofovir disoproxil fumarate (TDF) + lamivudine (3TC) + efavirenz (EFV) regimen. By week 48, rates of VS in three groups (<100,000, 100,000-500,000 and ≥500,000 copies/ml) were 94.1%, 85.0%, and 63.8%, respectively (p<0.001). Very high baseline HIV viremia over 500,000 copies/ml were found to be independently associated with delayed VS [≥500,000 vs. <100,000, adjusted relative hazard (95% CI), 0.455 (0.32-0.65); p <0.001] as well as incomplete viral suppression [≥500,000 vs. <100,000, adjusted odds ratio (aOR) (95% CI), 6.084 (2.761-13.407); p <0.001] and viral rebound [≥500,000 vs. <100,000, aOR (95% CI), 3.671 (1.009-13.355), p =0.048].Conclusion: Very high levels of pre-treatment HIV-RNA were significantly related with delayed efficacy of NNRTI-based ART and increased risk of treatment failure. More potent initial regimens should be considered for those with very high baseline viremia.

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