Performance of a Modified In-House HIV-1 Avidity Assay among a Cohort of Newly Diagnosed HIV-1 Infected Individuals and the Effect of ART on the Maturation of HIV-1 Specific Antibodies

2019 ◽  
Vol 17 (2) ◽  
pp. 134-145 ◽  
Author(s):  
Diviya Alex ◽  
Tennison Inba Raj Williams ◽  
Jaiprasath Sachithanandham ◽  
Swaminathan Prasannakumar ◽  
John Paul Demosthenes ◽  
...  
Keyword(s):  
Virological Failure ◽  
Roc Analysis ◽  
Load Testing ◽  
Viral Kinetics ◽  
Antibody Avidity ◽  
Avidity Assay ◽  
Paired Samples ◽  
Treatment Naïve ◽  
The Impact ◽  
Hiv 1

Background: Viral kinetics impact humoral immune response to HIV; antibody avidity testing helps distinguish recent (<6 months) and long-term HIV infection. This study aims to determine the frequency of recent HIV-1 infection among clients attending ICTC (Integrated Counselling and Testing Centre) using a commercial EIA, to correlate it with a modified in-house avidity assay and to study the impact of ART on anti-HIV-1 antibody maturation. Method: Commercial LAg Avidity EIA was used to detect antibody avidity among 117 treatment naïve HIV-1 infected individuals. A second-generation HIV ELISA was modified for in-house antibody avidity testing and cutoff was set based on Receiver Operating Characteristic (ROC) analysis. Archived paired samples from 25 HIV-1 infected individuals before ART and after successful ART; samples from 7 individuals responding to ART and during virological failure were also tested by LAg Avidity EIA. Results: Six individuals (5.1%) were identified as recently infected by a combination of LAg avidity assay and HIV-1 viral load testing. The modified in-house avidity assay demonstrated sensitivity and specificity of 100% and 98.2%, respectively, at AI=0.69 by ROC analysis. Median ODn values of individuals when responding to ART were significantly lower than pre-ART [4.136 (IQR 3.437– 4.827) vs 4.455 (IQR 3.748–5.120), p=0.006] whereas ODn values were higher during virological failure [4.260 (IQR 3.665 – 4.515) vs 2.868 (IQR 2.247 – 3.921), p=0.16]. Conclusion: This modified in-house antibody avidity assay is an inexpensive method to detect recent HIV-1 infection. ART demonstrated significant effect on HIV-1 antibody avidity owing to changes in viral kinetics.

scholarly journals Evaluation of the limiting antigen avidity EIA (LAg) in people who inject drugs in Greece

2016 ◽  
Vol 145 (2) ◽  
pp. 401-412 ◽  
Author(s):  
G. K. NIKOLOPOULOS ◽  
A. KATSOULIDOU ◽  
M. KANTZANOU ◽  
C. ROKKA ◽  
C. TSIARA ◽  
...  
Keyword(s):  
Optical Density ◽  
People Who Inject Drugs ◽  
Recombinant Form ◽  
Hiv Diagnosis ◽  
Hiv Rna ◽  
Avidity Assay ◽  
Window Period ◽  
Treatment Naïve ◽  
Hiv 1 ◽  
Similar Incidence

SUMMARYThis analysis assessed the utility of the limiting antigen avidity assay (LAg). Samples of people who inject drugs (PWID) in Greece with documented duration of HIV-1 infection were tested by LAg. A LAg-normalized optical density (ODn) ⩽1·5 corresponds to a recency window period of 130 days. The proportion true recent (PTR) and proportion false recent (PFR) were estimated in 28 seroconverters and in 366 samples collected >6 months after HIV diagnosis, respectively. The association between LAg ODn and HIV RNA level was evaluated in 232 persons. The PTR was 85·7%. The PFR was 20·8% but fell to 5·9% in samples from treatment-naive individuals with long-standing infection (>1 year), and to 0 in samples with the circulating recombinant form CRF35 AD. A LAg-based algorithm with a PFR of 3·3% estimated a similar incidence trend to that calculated by analyses based on HIV-1 seroconversions. In recently infected persons indicated by LAg, the median log10 HIV RNA level was high (5·30, interquartile range 4·56–5·90). LAg can help identify highly infectious HIV(+) individuals as it accurately identifies recent infections and is correlated with the HIV RNA level. It can also produce reliable estimates of HIV-1 incidence.

scholarly journals Impact of pretreatment low-abundance HIV-1 drug-resistant variants on virological failure among HIV-1/TB-co-infected individuals

2020 ◽  
Vol 75 (11) ◽  
pp. 3319-3326
Author(s):  
Benjamin Chimukangara ◽  
Jennifer Giandhari ◽  
Richard Lessells ◽  
Nonhlanhla Yende-Zuma ◽  
Benn Sartorius ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Virological Failure ◽  
Statistical Significance ◽  
Drug Resistant ◽  
Resistance Mutations ◽  
Next Generation Sequencing Ngs ◽  
Ngs Data ◽  
The Impact ◽  
Hiv 1 ◽  
Control Study

Abstract Objectives To determine the impact of pretreatment low-abundance HIV-1 drug-resistant variants (LA-DRVs) on virological failure (VF) among HIV-1/TB-co-infected individuals treated with NNRTI first-line ART. Methods We conducted a case–control study of 170 adults with HIV-1/TB co-infection. Cases had at least one viral load (VL) ≥1000 RNA copies/mL after ≥6 months on NNRTI-based ART, and controls had sustained VLs &lt;1000 copies/mL. We sequenced plasma viruses by Sanger and MiSeq next-generation sequencing (NGS). We assessed drug resistance mutations (DRMs) using the Stanford drug resistance database, and analysed NGS data for DRMs at ≥20%, 10%, 5% and 2% thresholds. We assessed the effect of pretreatment drug resistance (PDR) on VF. Results We analysed sequences from 45 cases and 125 controls. Overall prevalence of PDR detected at a ≥20% threshold was 4.7% (8/170) and was higher in cases than in controls (8.9% versus 3.2%), P = 0.210. Participants with PDR at ≥20% had almost 4-fold higher odds of VF (adjusted OR 3.7, 95% CI 0.8–18.3) compared with those without, P = 0.104. PDR prevalence increased to 18.2% (31/170) when LA-DRVs at ≥2% were included. Participants with pretreatment LA-DRVs only had 1.6-fold higher odds of VF (adjusted OR 1.6, 95% CI 0.6–4.3) compared with those without, P = 0.398. Conclusions Pretreatment DRMs and LA-DRVs increased the odds of developing VF on NNRTI-based ART, although without statistical significance. NGS increased detection of DRMs but provided no additional benefit in identifying participants at risk of VF at lower thresholds. More studies assessing mutation thresholds predictive of VF are required to inform use of NGS in treatment decisions.

scholarly journals Evaluation of the HIV-1 drug resistance to elsulfavirine and the effectiveness of it among Russian treatment-naïve patients

2021 ◽  
Vol 12 (5) ◽  
pp. 29-39
Author(s):  
A. A. Kirichenko ◽  
D. E. Kireev ◽  
A. V. Kravchenko ◽  
A. V. Pokrovskaya ◽  
U. A. Kuimova ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Antiretroviral Therapy ◽  
Virological Failure ◽  
Resistance Testing ◽  
Study Group ◽  
Resistance Mutations ◽  
Drug Resistance Testing ◽  
The Third ◽  
Treatment Naïve ◽  
Hiv 1

The aim of the study: to analyze the prevalence of resistance mutations to elsulfavirine and to evaluate the effectiveness of it among HIV-infected treatment-naïve patients in real clinical practice.Materials and methods. The study included 578 patients with HIV infection, which divided into 3 groups. The first group is 354 HIV-infected treatment-naïve patients for whom HIV-1 nucleotide sequences were obtained as part of routine drug resistance testing. The second study group included 111 HIV-infected treatment-naïve patients, tested for drug resistance before the antiretroviral therapy containing elsulfavirine. The third study group included 113 HIV-infected treatment-naïve patients, each of whom was assigned a treatment regimen containing elsulfavirine without prior drug resistance testing. The observation period for patients of the second and third groups who received treatment was 24 weeks. To assess the effectiveness of antiretroviral therapy in patients, viral load, CD4+ T-cell counts, and adherence to therapy were assessed. HIV-1 subtypes and drug resistance mutations were determined using the Stanford HIV Resistance Database (v. 8.9-1). To clarify the results of subtyping, phylogenetic analysis of nucleotide sequences was carried out using the MEGA program (v. 6.0).Results. The prevalence of mutations associated with decreased susceptibility to elsulfavirine among HIV-infected treatment-naïve patients was 1.7% and 4.5% for the first and second groups of patients, respectively. All of the patients have only single resistance mutations which, according to the results of preclinical studies, cannot cause drug resistance. The use of elsulfavirine in real clinical practice among treatment-naïve patients has demonstrated good virological and immunological efficacy of the drug. As a result of 24 weeks of therapy in patients of the second group, no treatment ineffectiveness, and the development of drug resistance were observed. Among the patients of the third group, 6 patients (5.3%) have the virological failure of therapy associated with the resistance to the used drugs. All patients with virological failure had a resistance mutation profile associated with a high level of drug resistance to one of the drugs in the treatment regimen, lamivudine. Additionally, 1 patient had a combination of mutations that reduce susceptibility to elsulfavirine, and 4 patients had mutations that can reduce susceptibility to elsulfavirine in combination with other mutations.Conclusion. The low prevalence of mutations associated with a decrease in susceptibility to elsulfavirine and the absence of combinations of mutations make it possible to predict the successful use of this drug for Russian treatment-naïve patients. Reported cases of virological failure of antiretroviral therapy are difficult to interpret in the context of elsulfavirine due to the lack of an exact list of mutations and their combinations, and associations with the degree of resistance to it. This study describes for the first time the mutation profiles in patients with virological failure of therapy containing elsulfavirine and demonstrates the necessity of the further study of drug resistance profile to drug in vitro and in vivo.

scholarly journals Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains

2020 ◽  
Author(s):  
Yongjian Liu ◽  
Yu Zhang ◽  
Hanping Li ◽  
Xiaolin Wang ◽  
Lei Jia ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Geographic Distance ◽  
Sequence Database ◽  
Genotypic Resistance ◽  
Nonnucleoside Reverse Transcriptase Inhibitors ◽  
Treatment Naïve ◽  
Relationship Of ◽  
The Impact ◽  
Search Program ◽  
Hiv 1

Abstract Background: There is increasing evidence that HIV-1 genetic diversity can have an impact on drug resistance. The aim of this study is to investigate the epidemiological situation of CRF65_cpx and the impact of natural polymorphisms of this variant on genotypic resistance. Methods: We used the BLAST search program followed by phylogenetic analysis to identify additional CRF65_cpx pol sequences from the Los Alamos HIV Sequence Database. Maximum likelihood phylogeny was estimated to clarify the epidemiological relationship of CRF65_cpx strains. Genotypic resistance was determined by submitting sequences to the Stanford HIV Drug Resistance Database. Results: A total of 32 CRF65_cpx pol sequences were obtained. The CRF65_cpx strains were detected in seven provinces with large geographic distance. Yunnan CRF65_cpx sequences were mainly derived from a heterosexual risk group, whereas the CRF65_cpx sequences in other provinces were almost exclusively derived from an MSM population. With one exception of V179E, the other 31 strains harbored V179D mutation. The combination of V179D and K103R, conferring intermediate resistance to EFV and NVP, was detected in seven treatment-naive MSM patients. Conclusions: This study confirmed the expansion CRF65_cpx in China. Furthermore, we found the natural presence of the V179D and K103R/V179D mutations associated with resistance to NNRTIs in HIV-1 CRF65_cpx. Our findings highlight the contribution of polymorphic mutations to drug resistance and underscore the challenges in treating patients harboring CRF65_cpx strains.

Low level of the K103N HIV-1 above a threshold is associated with virological failure in treatment-naive individuals undergoing efavirenz-containing therapy

AIDS ◽  
2011 ◽  
Vol 25 (3) ◽  
pp. 325-333 ◽  
Author(s):  
Derrick D Goodman ◽  
Yun Zhou ◽  
Nicolas A Margot ◽  
Damian J McColl ◽  
Lijie Zhong ◽  
...  
Keyword(s):  
Virological Failure ◽  
Low Level ◽  
Treatment Naïve ◽  
Hiv 1

scholarly journals TOP-Plus is a Versatile Biosensor Platform for Monitoring SARS-CoV-2 Antibody Durability

2021 ◽  
Author(s):  
Sabrina E Racine-Brzostek ◽  
Mohsen Karbaschi ◽  
Christian Gaebler ◽  
P J Klasse ◽  
Jim Yee ◽  
...  
Keyword(s):  
Post Infection ◽  
Neutralizing Antibody ◽  
Antibody Avidity ◽  
Avidity Assay ◽  
Paired Samples ◽  
The Status ◽  
Antibody Titers ◽  
Antigen Interaction ◽  
Antibody Levels

Abstract Background Low initial SARS-CoV-2 antibody titers dropping to undetectable levels within months after infection have raised concerns over long term immunity. Both the antibody levels and avidity of the antibody-antigen interaction should be examined to understand the quality of the antibody response. Methods A testing-on-a-probe “plus” panel (TOP-Plus) was developed, which included a newly developed avidity assay built into the previously described SARS-CoV-2 TOP assays that measured total antibody (TAb), surrogate neutralizing antibody (SNAb), IgM and IgG on a versatile biosensor platform. TAb and SNAb levels were compared with avidity in previously infected individuals at 1.3 and 6.2 months post-infection in paired samples from 80 COVID-19 patients. Sera from SARS-CoV-2 vaccinated individuals were also evaluated for antibody avidity. Results The newly designed avidity assay in this TOP panel correlated well with a reference Bio-Layer Interferometry avidity assay (r=0.88). The imprecision of the TOP avidity assay was less than 10%. Although TAb and neutralization activity (by SNAb) decreased between 1.3 and 6.2 months post-infection, the antibody avidity increased significantly (P &lt; 0.0001). Antibody avidity in 10 SARS-CoV-2 vaccinated individuals (median 28 days post-vaccination) was comparable to the measured antibody avidity in infected individuals (median 26 days post-infection). Conclusion This highly precise and versatile TOP-Plus panel with the ability to measure SARS-CoV-2 TAb, SNAb, IgG and IgM antibody levels and avidity of individual sera on one sensor can become a valuable asset in monitoring not only SARS-CoV-2-infected patients, but also the status of individuals’ COVID-19 vaccination response.

scholarly journals Cirrhosis and Rapid Virological Response to Peginterferon Plus Ribavirin Determine Treatment Outcome in HCV-1 IL28B rs12979860 CC Patients

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Alessio Aghemo ◽  
Elisabetta Degasperi ◽  
Maria Grazia Rumi ◽  
Enrico Galmozzi ◽  
Luca Valenti ◽  
...  
Keyword(s):  
Treatment Outcome ◽  
Treatment Failure ◽  
Virological Response ◽  
Hcv Rna ◽  
Rapid Virological Response ◽  
Virus Genotype ◽  
Viral Kinetics ◽  
Treatment Naïve ◽  
Baseline Predictor ◽  
The Impact

Background. The rs12979860 CC genotype of the interleukin 28B (IL28B) polymorphism is associated with high rates of sustained virological response (SVR) to peginterferon (PegIFN) and ribavirin (Rbv) in hepatitis C virus genotype-1 (HCV-1) patients. The impact of baseline predictors of treatment outcome and their interplay with viral kinetics in HCV-1 CC patients has not been fully evaluated.Aim. To identify baseline and on-therapy predictors of treatment failure in HCV-1 IL28B CC patients.Methods. Treatment-naïve HCV-1 patients, compliant to PegIFN and Rbv who did not discontinue treatment for nonvirological reasons, were analyzed.Results. 109 HCV-1 IL28B CC were studied. Sixty were males, 39 with BMI >25, 69 with >600,000 IU/mL HCV RNA, 15 with HCV1a, and 30 with cirrhosis. Overall, 75 (69%) achieved an SVR; cirrhosis was the only baseline predictor of treatment failure (OR: 2.58, 95% CI: 1.07–6.21) as SVR rates were 53% in cirrhotics versus 75% in noncirrhotics (P=0.03). HCV RNA undetectability (<50 IU/mL) at week 4 (RVR) was achieved by 58 patients (53%). The SVR rates were independent of RVR in noncirrhotics, 76% (34/45) RVR (+) and 74% (25/34) RVR (−) (P=0.9). In cirrhotic patients, SVR rates were significantly higher in RVR (+) compared to RVR (−) (10/13 (77%) versus 6/17 (35%)P=0.03).Conclusions. In HCV-1 IL28B CC patients, cirrhosis is the only clinical baseline predictor of PegIFN and Rbv treatment failure. However, in IL28B CC cirrhotics, the achievement of RVR identifies those patients who still have high rates of SVR to Peg-IFN/Rbv therapy.

scholarly journals Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains

2019 ◽  
Author(s):  
Yongjian Liu ◽  
Yu Zhang ◽  
Hanping Li ◽  
Xiaolin Wang ◽  
Lei Jia ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Geographic Distance ◽  
Genotypic Resistance ◽  
Nonnucleoside Reverse Transcriptase Inhibitors ◽  
Treatment Naïve ◽  
Geographic Expansion ◽  
Relationship Of ◽  
The Impact ◽  
Search Program ◽  
Hiv 1

Abstract Background There is increasing evidence that HIV-1 genetic diversity can have an impact on drug resistance. The aim of this study is to investigate the epidemiological situation of CRF65_cpx and the impact of natural polymorphisms of this variant on genotypic resistance. Methods We used the BLAST search program followed by phylogenetic analysis to identify additional CRF65_cpx pol sequences from the Los Alamos HIV Sequence Database. Maximum likelihood phylogeny was estimated to clarify the epidemiological relationship of CRF65_cpx strains. Genotypic resistance was determined by submitting sequences to the Stanford HIV Drug Resistance Database. Results A total of 32 CRF65_cpx pol sequences were obtained. The CRF65_cpx strains were detected in seven provinces with large geographic distance. Yunnan CRF65_cpx sequences were mainly derived from a heterosexual risk group, whereas the CRF65_cpx sequences in other provinces were almost exclusively derived from an MSM population. With one exception of V179E, the other 31 strains harbored V179D mutation. The combination of V179D and K103R, conferring intermediate resistance to EFV and NVP, was detected in seven treatment-naive MSM patients. Conclusions The active transmission of CRF65_cpx among MSM was responsible for the geographic expansion of CRF65_cpx in China. Surprisingly, we found the natural presence of the V179D and K103R/V179D mutations associated with resistance to NNRTIs in HIV-1 CRF65_cpx. Our findings highlight the contribution of polymorphic mutations to drug resistance and underscore the challenges in treating patients harboring CRF65_cpx strains.

scholarly journals Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains

2020 ◽  
Author(s):  
Yongjian Liu ◽  
Yu Zhang ◽  
Hanping Li ◽  
Xiaolin Wang ◽  
Lei Jia ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Geographic Distance ◽  
Sequence Database ◽  
Genotypic Resistance ◽  
Nonnucleoside Reverse Transcriptase Inhibitors ◽  
Treatment Naïve ◽  
Relationship Of ◽  
The Impact ◽  
Search Program ◽  
Hiv 1

Abstract Background: There is increasing evidence that HIV-1 genetic diversity can have an impact on drug resistance. The aim of this study is to investigate the epidemiological situation of CRF65_cpx and the impact of natural polymorphisms of this variant on genotypic resistance. Methods: We used the BLAST search program followed by phylogenetic analysis to identify additional CRF65_cpx pol sequences from the Los Alamos HIV Sequence Database. Maximum likelihood phylogeny was estimated to clarify the epidemiological relationship of CRF65_cpx strains. Genotypic resistance was determined by submitting sequences to the Stanford HIV Drug Resistance Database. Results: A total of 32 CRF65_cpx pol sequences were obtained. The CRF65_cpx strains were detected in seven provinces with large geographic distance. Yunnan CRF65_cpx sequences were mainly derived from a heterosexual risk group, whereas the CRF65_cpx sequences in other provinces were almost exclusively derived from an MSM population. With one exception of V179E, the other 31 strains harbored V179D mutation. The combination of V179D and K103R, conferring intermediate resistance to EFV and NVP, was detected in seven treatment-naive MSM patients. Conclusions: This study confirmed the expansion CRF65_cpx in China. Furthermore, we found the natural presence of the V179D and K103R/V179D mutations associated with resistance to NNRTIs in HIV-1 CRF65_cpx. Our findings highlight the contribution of polymorphic mutations to drug resistance and underscore the challenges in treating patients harboring CRF65_cpx strains.

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