Performance of the Maxim and Sedia Limiting Antigen Avidity assays for population-level HIV incidence surveillance

AbstractBackgroundTwo manufacturers, Maxim Biomedical and Sedia Biosciences Corporation, supply US CDC-approved versions of the HIV-1 Limiting Antigen Avidity EIA (LAg assay) for detecting ‘recent’ HIV infection in cross-sectional incidence estimation. This study assesses and compares the performance of the Maxim and Sedia LAg assays for incidence surveillance.MethodsWe ran both assays on a panel of 2,500 well-characterized HIV-1-infected specimens, most with estimated dates of (detectable) infection. We analysed concordance of assay results, assessed reproducibility using repeat testing and estimated the critical performance characteristics of a test for recent infection—mean duration of recent infection (MDRI) and false-recent rate (FRR)—for a range of normalized optical density (ODn) recency discrimination thresholds, alone and in combination with viral load thresholds. We further defined three hypothetical surveillance scenarios and evaluated overall performance for incidence surveillance, defined as the precision of incidence estimates, by estimating context-specific performance characteristics.ResultsThe Maxim assay produced lower ODn values than the Sedia assay on average, largely as a result of higher calibrator readings (mean calibrator OD of 0.749 vs. 0.643). Correlation of non-normalized OD readings was greater (R2 = 0.938) than those of ODn readings (R2 = 0.908), and the slope was closer to unity (1.054 vs. 0.899). Reproducibility of repeat testing of three blinded control specimens (25 replicates each) was slightly better for the Maxim assay (CV 8.9% to 14.8% vs. 13.2% to 15.0%). The MDRI of a Maxim-based algorithm at the ‘standard’ recency discrimination threshold in combination with viral load (ODn ≤1.5 & VL >1,000) was 201 days (95% CI: 180,223) and for Sedia was 171 days (95% CI: 152,191). Commensurately, the Maxim algorithm had a higher FRR in treatment-naive subjects (1.7% vs. 1.1%). We observed statistically significant differences in MDRI using the ODn alone (≤1.5) and in combination with viral load (>1,000). Under three fully-specified hypothetical surveillance scenarios (comparable to South Africa, Kenya and a concentrated epidemic), recent infection testing algorithms based on the two assays produced similar precision of incidence estimates.ConclusionsDifferences in ODn measurements between the Maxim and Sedia LAg assays on the same specimens largely resulted from differences in the reactivity of calibrators supplied by the manufacturers. Performance for surveillance purposes was extremely similar, although different ODn thresholds were optimal and different values of MDRI and FRR were appropriate for use in survey planning and incidence estimation.

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Validation of population‐level HIV‐1 incidence estimation by cross‐sectional incidence assays in the HPTN 071 (PopART) trial

Journal of the International AIDS Society ◽

10.1002/jia2.25830 ◽

2021 ◽

Vol 24 (12) ◽

Author(s):

Ethan Klock ◽

Ethan Wilson ◽

Reinaldo E. Fernandez ◽

Estelle Piwowar‐Manning ◽

Ayana Moore ◽

...

Keyword(s):

Population Level ◽

Cross Sectional ◽

Incidence Estimation ◽

Hiv 1

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Decreased Specificity of an Assay for Recent Infection in HIV-1-Infected Patients on Highly Active Antiretroviral Treatment: Implications for Incidence Estimates

Clinical and Vaccine Immunology ◽

10.1128/cvi.00120-12 ◽

2012 ◽

Vol 19 (8) ◽

pp. 1248-1253 ◽

Cited By ~ 11

Author(s):

Antoine Chaillon ◽

Stéphane Le Vu ◽

Sylvie Brunet ◽

Guillaume Gras ◽

Frédéric Bastides ◽

...

Keyword(s):

Viral Load ◽

Highly Active Antiretroviral Therapy ◽

Demographic Data ◽

Undetectable Viral Load ◽

Antiretroviral Drugs ◽

Recent Infection ◽

Cross Sectional ◽

Highly Active ◽

The Impact ◽

Hiv 1

ABSTRACTThe aim of this study was to estimate the rate of misclassification in treated HIV patients who initiated treatment at the chronic stage of HIV infection using an enzyme immunoassay (EIA) that discriminates between recent infection (RI; within 6 months) and established infection. The performance of EIA-RI was evaluated in 96 HIV-1 chronically infected patients on highly active antiretroviral therapy (HAART) with an undetectable viral load (VL) for at least 3 years. Demographic data, HIV-1 viral load, CD4+T-cell count, viral subtype, and treatment duration were collected. The subset of misclassified patients was further analyzed using samples collected annually. The impact on incidence estimates was evaluated by simulation. The specificity in treated patients was significantly lower (70.8 to 77.1%) than that observed in untreated patients (93.3 to 99.3%,P< 0.001). Patients falsely classified as recently infected had been treated for a longer period and had longer-term viral suppression than those correctly classified. The loss of specificity of the test due to treatment may have a dramatic impact on the accuracy of the incidence estimates, with a major impact when HIV prevalence is high. The cross-sectional studies intended to derive HIV incidence must collect information on treatment or, alternatively, should include detection of antiretroviral drugs in blood specimens to rule out treated patients from the calculations.

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Effectiveness, Durability, and Safety of Dolutegravir and Lamivudine Versus Dolutegravir, Lamivudine, and Abacavir in a Real-Life Cohort of HIV-Infected Adults

Annals of Pharmacotherapy ◽

10.1177/10600280211034176 ◽

2021 ◽

pp. 106002802110341

Author(s):

Inés Mendoza ◽

Alicia Lázaro ◽

Miguel Torralba

Keyword(s):

Viral Load ◽

Safety Profile ◽

Real Life ◽

Hazard Ratio ◽

Treatment Discontinuation ◽

Treatment Naïve ◽

Tn 4 ◽

Risk Of Treatment ◽

Hiv 1 ◽

All Treatment

Background: Dolutegravir (DTG) plus lamivudine (2-DR) is suggested as an initial and switch option in HIV-1 treatment. Objective: To analyze the effectiveness, durability, and safety of 2-DR compared with DTG plus abacavir/lamivudine (3-DR). Methods: This was an observational, ambispective study that included all treatment-naïve (TN) and treatment-experienced (TE) patients who started 2-DR or 3-DR between July 1, 2018, and November 30, 2020. The primary end point was noninferiority, at 24 and 48 weeks, of 2-DR versus 3-DR regarding the percentage of patients with viral load (VL)≥50 and 200 copies/mL in TN (4% margin) and VL<50 and 200 copies/mL in TE (margin 12%). Durability of response, and safety were also measured. Results: 242 patients were included (53 TN and 189 TE). Two TN patients on 2-DR had VL≥50 copies/mL and 1 had VL≥200 copies/mL at week 24. In TE patients on 2-DR, 90.2% achieved VL<200 copies/mL at week 24 (difference: 3.8%; 95% CI = −6.3% to 14%) and 91.8% at week 48 (difference: 0.06%; 95% CI = −9% to 10%), meeting noninferiority criteria. Among the 53 TN patients, only 1 VF was observed in 2-DR. In TN patients, the risk of treatment discontinuation was similar between groups (hazard ratio [HR] = 0.37; P = 0.15); similar rates were also found in TE patients (HR = 0.94; P = 0.85). TE patients on 2-DR showed a better safety profile compared with 3-DR patients ( P<0.001). Conclusion and Relevance: Our results did not show noninferiority in terms of virological effectiveness. Nevertheless, all effectiveness measures support the use of 2-DR in a real-life cohort of TN and TE. Additionally, durability and safety of 2-DR were confirmed to be similar to that of 3-DR.

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Iron, Haptoglobin Phenotype, and HIV-1 Viral Load: A Cross-Sectional Study Among Pregnant Zimbabwean Women

JAIDS Journal of Acquired Immune Deficiency Syndromes ◽

10.1097/00126334-200305010-00011 ◽

2003 ◽

Vol 33 (1) ◽

pp. 74-81 ◽

Cited By ~ 26

Author(s):

Henrik Friis ◽

Exnevia Gomo ◽

Norman Nyazema ◽

Patricia Ndhlovu ◽

Henrik Krarup ◽

...

Keyword(s):

Viral Load ◽

Cross Sectional Study ◽

Sectional Study ◽

Cross Sectional ◽

Haptoglobin Phenotype ◽

Hiv 1

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Evaluation of multi-assay algorithms for identifying individuals with recent HIV infection: HPTN 071 (PopART)

PLoS ONE ◽

10.1371/journal.pone.0258644 ◽

2021 ◽

Vol 16 (12) ◽

pp. e0258644

Author(s):

Wendy Grant-McAuley ◽

Ethan Klock ◽

Oliver Laeyendecker ◽

Estelle Piwowar-Manning ◽

Ethan Wilson ◽

...

Keyword(s):

Viral Suppression ◽

Point Of Care ◽

Population Level ◽

Hiv Viral Load ◽

Cross Sectional ◽

Individual Level ◽

Viral Loads ◽

Incidence Estimation ◽

Duration Of Infection ◽

Recent Hiv Infection

Background Assays and multi-assay algorithms (MAAs) have been developed for population-level cross-sectional HIV incidence estimation. These algorithms use a combination of serologic and/or non-serologic biomarkers to assess the duration of infection. We evaluated the performance of four MAAs for individual-level recency assessments. Methods Samples were obtained from 220 seroconverters (infected <1 year) and 4,396 non-seroconverters (infected >1 year) enrolled in an HIV prevention trial (HPTN 071 [PopART]); 28.6% of the seroconverters and 73.4% of the non-seroconverters had HIV viral loads ≤400 copies/mL. Samples were tested with two laboratory-based assays (LAg-Avidity, JHU BioRad-Avidity) and a point-of-care assay (rapid LAg). The four MAAs included different combinations of these assays and HIV viral load. Seroconverters on antiretroviral treatment (ART) were identified using a qualitative multi-drug assay. Results The MAAs identified between 54 and 100 (25% to 46%) of the seroconverters as recently-infected. The false recent rate of the MAAs for infections >2 years duration ranged from 0.2%-1.3%. The MAAs classified different overlapping groups of individuals as recent vs. non-recent. Only 32 (15%) of the 220 seroconverters were classified as recent by all four MAAs. Viral suppression impacted the performance of the two LAg-based assays. LAg-Avidity assay values were also lower for seroconverters who were virally suppressed on ART compared to those with natural viral suppression. Conclusions The four MAAs evaluated varied in sensitivity and specificity for identifying persons infected <1 year as recently infected and classified different groups of seroconverters as recently infected. Sensitivity was low for all four MAAs. These performance issues should be considered if these methods are used for individual-level recency assessments.

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541. Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in HIV-1 Treatment Naïve Patients: Week 48 Results in Subgroups Based on Baseline Viral Load, CD4+ Count, and WHO Clinical Staging

Open Forum Infectious Diseases ◽

10.1093/ofid/ofy210.550 ◽

2018 ◽

Vol 5 (suppl_1) ◽

pp. S201-S201 ◽

Cited By ~ 1

Author(s):

Christoph D Spinner ◽

Bruce Rashbaum ◽

Cheryl Mcdonald ◽

Cristina Mussini ◽

Donghan Luo ◽

...

Keyword(s):

Viral Load ◽

Cd4 Count ◽

Baseline Viral Load ◽

Clinical Staging ◽

Treatment Naïve ◽

Tenofovir Alafenamide ◽

Hiv 1

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Insulin Resistance in Patients with Chronic Hepatitis C

Macedonian Medical Review ◽

10.1515/mmr-2016-0018 ◽

2016 ◽

Vol 70 (2) ◽

pp. 93-98

Author(s):

Beti Todorovska ◽

Viktorija Caloska-Ivanova ◽

Magdalena Dimitrova-Genadieva ◽

Elena Curakova ◽

Nenad Joksimovic

Keyword(s):

Insulin Resistance ◽

Chronic Hepatitis ◽

Viral Load ◽

Hepatitis C ◽

Chronic Hepatitis C ◽

Liver Steatosis ◽

Chronic Viral Hepatitis ◽

Cross Sectional ◽

Viral Hepatitis C ◽

Treatment Naïve

Abstract Introduction. Insulin resistance is the most common extrahepatic manifestation associated with hepatitis C virus, which leads to developing more pronounced fibrosis and liver steatosis. The aim of the study was to assess the prevalence of insulin resistance in non-diabetic, treatment naive patients with chronic hepatitis C and to analyze the relation of insulin resistance with genotype, viral load, gender, age, laboratory parameters, inflammatory and fibrotic changes in the liver, body mass index (BMI) and the presence of steatosis. Methods. In this cross sectional study, 224 patients with hepatitis C viral infection were included. The patients were divided into two groups. The first group was with no insulin resistance and the second one with present insulin resistance. They were compared in terms of genotype, viral load, gender, age, inflammatory and fibrotic changes in the liver, BMI and liver steatosis. Results. Insulin resistance was present in 45.5% of patients. The following factors were associated with insulin resistance: age (p=0.0022), inflammatory and fibrotic changes in the liver (p=0.001, p=0.006, respectively), steatosis (p=0.015) and transaminase activities (for AST, p=0,002, for ALT, p=0.001). Conclusion. In the Republic of Macedonia, a high percent of 45.5% among non-diabetic and treatment naïve patients with chronic viral hepatitis C, had insulin resistance. Insulin resistance was more prevalent in older patients, in those with more pronounced inflammatory and fibrotic changes in the liver, in patients with steatosis and in those with higher transaminase activity.

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Detection of HIV-1 viral load in tears of HIV/AIDS patients

Infection ◽

10.1007/s15010-020-01508-2 ◽

2020 ◽

Vol 48 (6) ◽

pp. 929-933

Author(s):

Yujing Qian ◽

Zunyou Wu ◽

Chao Chen ◽

Kuifang Du ◽

Wenbin Wei

Keyword(s):

Viral Load ◽

T Cell ◽

Cell Count ◽

Highly Active Antiretroviral Therapy ◽

Plasma Viral Load ◽

Aids Patients ◽

Cross Sectional ◽

Laboratory Test Results ◽

Hiv 1 ◽

Hiv Aids

Abstract Objectives The tear, as an important bodily secretion, plays a crucial role in preventing infection and maintaining homeostasis of ocular surfaces. Although accumulating studies have reported on the HIV-1 viral load profile among varying bodily fluids and secretions, little was known concerning HIV-1 dynamics in tears. Therefore, the objectives of this study were to investigate the HIV-1 viral load in tears of HIV/AIDS patients and study factors influencing their tear viral load. Methods A cross-sectional study was conducted. 67 patients with a confirmed HIV-1 infection or AIDS were recruited from the Beijing You’an Hospital, China between April 2018 and September 2018. Socio-demographic information and laboratory test results were collected. At the same time, ophthalmic examinations were carried out and tear samples were tested. Results Of 30 highly active antiretroviral therapy (HAART)-naïve patients, 53.3% had detectable HIV-1 RNA in tears. Of 37 patients on HAART, HIV-1 RNA was undetectable in their tears, regardless of treatment duration and blood viral load. Tear viral load ranged from TND (target not detected) to 13,096 copies/mL. Viral load was lower in tears than in blood plasma (p < 0.001), and was significantly correlated with plasma viral load (Rho = 0.566, p < 0.001) and AIDS stage (Rho = 0.312, p = 0.01), but negatively correlated with CD4 + T cell count, CD4 +/CD8 + T cell count, and duration of HIV infection (Rho = -0.450, Rho = − 0.464, Rho = − 0.565; p < 0.001). Conclusions HIV-1 RNA is present in tears of more than half of the HAART-naïve patients, whereas absent in tears of patients on HAART. Tear viral load is positively associated with plasma viral load while it is negatively correlated with CD4 cell count. This study provides novel insights into the area with limited understanding–HIV-1 viral load in tears.

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