Impact of Pre-Therapy Viral Load on Virological Response to Modern First-Line Haart

Santoro, Maria Mercedes; Armenia, Daniele; Alteri, Claudia; Flandre, Philippe; Calcagno, Andrea; Santoro, Mario; Gori, Caterina; Fabeni, Lavinia; Bellagamba, Rita; Borghi, Vanni; Forbici, Federica; Latini, Alessandra; Palamara, Guido; Libertone, Raffaella; Tozzi, Valerio; Boumis, Evangelo; Tommasi, Chiara; Pinnetti, Carmela; Ammassari, Adriana; Nicastri, Emanuele; Buonomini, Anna Rita; Svicher, Valentina; Andreoni, Massimo; Narciso, Pasquale; Mussini, Cristina; Antinori, Andrea; Ceccherini‐Silberstein, Francesca; Perri, Giovanni Di; Perno, Carlo Federico

doi:10.3851/imp2531

Cited by 39 publications

(57 citation statements)

References 39 publications

(59 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Among the other confounders, very high pre-HAART viremia (>500,000 copies/mL) was significantly associated with poorer virological response, as previously observed [32] (Table S1). Of note, the lowest hazard of virological undetectability was found in patients with pre-HAART viremia >1,000,000 copies/mL.…”

Section: Resultssupporting

confidence: 81%

“…Depending on methodologies available at the different clinical centers participating in this study, plasma viremia was determined using three different assays: the Roche Cobas CA/CTM version 2.0 (Mannheim, Germany), the Abbott RealTime HIV-1 (Chicago, Illinois), and the VERSANT HIV-1 Version 3.0 (Bayer Corporation, Diagnostics Division, Tarrytown, New York) [32], [33]. Previous studies demonstrated that even if there was not a uniform approach regarding the HIV-1 viral load detection, the results obtained by these assays correlated very well, only a few samples having a difference of more than 0.5 log 10 copies/mL [34], [35].…”

Section: Methodsmentioning

confidence: 99%

“…Immunological reconstitution was defined as a CD4 cell count gain from HAART initiation of at least 150 cells/mm 3 [11]–[12]. Virological success was defined as the time of the first HIV-RNA measurement <50 copies/mL from HAART initiation as the most common undetectability cut-off currently considered for HIV-RNA [11]–[12], [32].…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

A Very Low Geno2pheno False Positive Rate Is Associated with Poor Viro-Immunological Response in Drug-Naïve Patients Starting a First-Line HAART

et al. 2014

Self Cite

View full text Add to dashboard Cite

BackgroundWe previously found that a very low geno2pheno false positive rate (FPR ≤2%) defines a viral population associated with low CD4 cell count and the highest amount of X4-quasispecies. In this study, we aimed at evaluating whether FPR ≤2% might impact on the viro-immunological response in HIV-1 infected patients starting a first-line HAART.MethodsThe analysis was performed on 305 HIV-1 B subtype infected drug-naïve patients who started their first-line HAART. Baseline FPR (%) values were stratified according to the following ranges: ≤2; 2–5; 5–10; 10–20; 20–60; >60. The impact of genotypically-inferred tropism on the time to achieve immunological reconstitution (a CD4 cell count gain from HAART initiation ≥150 cells/mm3) and on the time to achieve virological success (the first HIV-RNA measurement <50 copies/mL from HAART initiation) was evaluated by survival analyses.ResultsOverall, at therapy start, 27% of patients had FPR ≤10 (6%, FPR ≤2; 7%, FPR 2–5; 14%, FPR 5–10). By 12 months of therapy the rate of immunological reconstitution was overall 75.5%, and it was significantly lower for FPR ≤2 (54.1%) in comparison to other FPR ranks (78.8%, FPR 2–5; 77.5%, FPR 5–10; 71.7%, FPR 10–20; 81.8%, FPR 20–60; 75.1%, FPR >60; p = 0.008). The overall proportion of patients achieving virological success was 95.5% by 12 months of therapy. Multivariable Cox analyses showed that patients having pre-HAART FPR ≤2% had a significant lower relative adjusted hazard [95% C.I.] both to achieve immunological reconstitution (0.37 [0.20–0.71], p = 0.003) and to achieve virological success (0.50 [0.26–0.94], p = 0.031) than those with pre-HAART FPR >60%.ConclusionsBeyond the genotypically-inferred tropism determination, FPR ≤2% predicts both a poor immunological reconstitution and a lower virological response in drug-naïve patients who started their first-line therapy. This parameter could be useful to identify patients potentially with less chance of achieving adequate immunological reconstitution and virological undetectability.

show abstract

Section: Resultssupporting

confidence: 81%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

A Very Low Geno2pheno False Positive Rate Is Associated with Poor Viro-Immunological Response in Drug-Naïve Patients Starting a First-Line HAART

et al. 2014

Self Cite

View full text Add to dashboard Cite

show abstract

“…The reasons for these inconsistencies remain unclear [12], but the limited time of follow-up in most studies should be noted. Also, it is well known that the viral load (VL) level at treatment initiation plays a determinative role in the first-line treatment response and the development of DRM [14]. …”

Section: Introductionmentioning

confidence: 99%

“…This was done by analyzing the time to second-line viral failure (VF) and the increase of CD4+ T-cells at 12 and 24 months of second-line ART. Moreover, since the baseline level of VL at initiation of first-line ART is an independent factor associated with decreased virological success [14], the effect of VL level at first-line ART failure on the second line outcome was investigated. For all analysis, patients were included over a period of 15 years, 1999–2014.…”

Section: Introductionmentioning

confidence: 99%

Effect of therapy switch on time to second-line antiretroviral treatment failure in HIV-infected patients

et al. 2017

View full text Add to dashboard Cite

BackgroundSwitch from first line antiretroviral therapy (ART) to second-line ART is common in clinical practice. However, there is limited knowledge of to which extent different reason for therapy switch are associated with differences in long-term consequences and sustainability of the second line ART.Material and methodsData from 869 patients with 14601 clinical visits between 1999–2014 were derived from the national cohort database. Reason for therapy switch and viral load (VL) levels at first-line ART failure were compared with regard to outcome of second line ART. Using the Laplace regression model we analyzed the median, 10th, 20th, 30th and 40th percentile of time to viral failure (VF).ResultsMost patients (n = 495; 57.0%) switched from first-line to second-line ART without VF. Patients switching due to detectable VL with (n = 124; 14.2%) or without drug resistance mutations (DRM) (n = 250; 28.8%) experienced VF to their second line regimen sooner (median time, years: 3.43 (95% CI 2.90–3.96) and 3.20 (95% 2.65–3.75), respectively) compared with those who switched without VF (4.53 years). Furthermore level of VL at first-line ART failure had a significant impact on failure of second-line ART starting after 2.5 years of second-line ART.ConclusionsIn the context of life-long therapy, a median time on second line ART of 4.53 years for these patients is short. To prolong time on second-line ART, further studies are needed on the reasons for therapy changes. Additionally patients with a high VL at first-line VF should be more frequently monitored the period after the therapy switch.

show abstract

The role of baseline HIV-1 RNA, drug resistance, and regimen type as determinants of response to first-line antiretroviral therapy

et al. 2014

View full text Add to dashboard Cite

The factors influencing virological response to first-line combined antiretroviral therapy (cART) in an Italian cohort of HIV-1-infected patients were examined. Eligible patients were those enrolled in a national prospective observational cohort (Antiretroviral Resistance Cohort Analysis), starting first-line cART between 2001 and 2011 and who had at least one follow-up of HIV-1 RNA. The primary endpoint was virological success, defined as the first viral load <50 copies/ml. Time to events were analyzed by Kaplan-Meier analysis and Cox proportional hazard model. One thousand three hundred five patients met the study inclusion criteria. In a multivariable model adjusting for transmission mode, presence of transmitted drug resistance, baseline CD4(+) cell count, viral subtype, and type of NRTI backbone employed, independent predictors of virological success were higher baseline viral load (≥500,000 vs. <100,000 HR 0.52; P < 0.001), a weighted genotypic susceptibility score (wGSS) <3 (HR 0.58; P = 0.003), male sex (HR 0.76 P = 0.001), and type of initial third drug employed (integrase inhibitor vs. boosted protease inhibitors HR 3.23; P < 0.001). In the subset with HIV-1 RNA >100,000 copies/ml, virologic success was only associated with the use of integrase inhibitors in the first cART regimen. Independent predictors of immunological success were baseline CD4(+) cell count and wGSS <3. High baseline HIV-1 RNA, predicted activity of the first-line regimen based on genotypic resistance testing, gender, and use of new agents were found to predict time to achieve virological success. The type of initial nucleoside analog backbone was not found to predict virological response.

show abstract

Impact of Pre-Therapy Viral Load on Virological Response to Modern First-Line Haart

Cited by 39 publications

References 39 publications

A Very Low Geno2pheno False Positive Rate Is Associated with Poor Viro-Immunological Response in Drug-Naïve Patients Starting a First-Line HAART

A Very Low Geno2pheno False Positive Rate Is Associated with Poor Viro-Immunological Response in Drug-Naïve Patients Starting a First-Line HAART

Effect of therapy switch on time to second-line antiretroviral treatment failure in HIV-infected patients

The role of baseline HIV-1 RNA, drug resistance, and regimen type as determinants of response to first-line antiretroviral therapy

Contact Info

Product

Resources

About