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Objective To systematically evaluate the incidence rate of low-level viremia (LLV) in chronic hepatitis B (CHB) patients and related influencing factors, and to provide evidence-based medicine evidence for effective intervention and prevention of LLV in clinical practice. Methods This study was conducted according to the PRISMA guideline, with a PROSPERO registration number of CRD42023455304. CNKI, Wanfang Data, VIP, SinoMed, PubMed, Embase, Web of Science, and the Cochrane library were searched for observational studies on LLV and related influencing factors in CHB patients published up to July 21, 2023. Stata 16.0 software was used to perform the meta-analysis. Results A total of 12 articles were included, with a total sample size of 3408 cases, among whom there were 1181 patients with LLV. The meta-analysis showed that the incidence rate of LLV was 32.8% (95% confidence interval [CI] : 27.6%-38.3%) in treatment-experienced CHB patients. High HBsAg quantification (odds ratio [OR] =2.107, 95%CI: 1.782-2.491, P<0.001), positive HBeAg (OR=3.258, 95%CI: 2.629-4.038, P<0.001), high HBV DNA level at baseline (OR=1.286, 95%CI: 1.157-1.430, P<0.001), and history of entecavir treatment (OR=3.089, 95%CI: 1.880-5.074, P<0.001) were risk factors for LLV; duration of antiviral therapy ≥3 years (OR=0.175, 95%CI: 0.093-0.331, P<0.001) and high alanine aminotransferase level at baseline (OR=0.985, 95%CI: 0.978-0.992, P<0.001) were protective factors against LLV. The sensitivity analysis showed no significant change in effective value, suggesting that the results of the meta-analysis were relatively stable. The funnel plot of the studies included was basically symmetrical, and the results of the Egger's test and the Begg's test suggested that there was no obvious publication bias in the articles included. Conclusion Clinicians should guide decision making based on the influencing factors for LLV and related clinical evidence, so as to reduce long-term clinical risks and avoid adverse outcomes. [ABSTRACT FROM AUTHOR]

We evaluated subsequent virologic outcomes in individuals experiencing low-level virem ia (LLV) on dolutegravir (DTG)-based first-line antiretroviral therapy (ART) in Botswana. We used a national dataset from 50,742 adults who initiated on DTG-based first-line ART from June 2016–December 2022. Individuals with at least two viral load (VL) measurements post three months on DTG-based first-line ART were evaluated for first and subsequent episodes of LLV (VL:51–999 copies/mL). LLV was sub-categorized as low-LLV (51–200 copies/mL), medium-LLV (201–400 copies/mL) and high-LLV (401–999 copies/mL). The study outcome was virologic failure (VF) (VL ≥ 1000 copies/mL): virologic non-suppression defined as single-VF and confirmed-VF defined as two-consecutive VF measurements after an initial VL < 1000 copies/mL. Cox regression analysis identified predictive factors of subsequent VF. The prevalence of LLV was only statistically different at timepoints >6–12 (2.8%) and >12–24 (3.9%) (p-value < 0.01). LLV was strongly associated with both virologic non-suppression (adjusted hazards ratio [aHR] = 2.6; 95% CI: 2.2–3.3, p-value ≤ 0.001) and confirmed VF (aHR = 2.5; 95% CI: 2.4–2.7, p-value ≤ 0.001) compared to initially virally suppressed PLWH. High-LLV (HR = 3.3; 95% CI: 2.9–3.6) and persistent-LLV (HR = 6.6; 95% CI: 4.9–8.9) were associated with an increased hazard for virologic non-suppression than low-LLV and a single-LLV episode, respectively. In a national cohort of PLWH on DTG-based first-line ART, LLV > 400 copies/mL and persistent-LLV had a stronger association with VF. Frequent VL testing and adherence support are warranted for individuals with VL > 50 copies/mL. [ABSTRACT FROM AUTHOR]

Although newborns are generally vaccinated against chronic hepatitis B virus, incidence of HBV infection decreases. However, in 2016, there were still 86 million cases of chronic HBV infection in China. In 2019, there were 296 million cases of chronic HBV infection worldwide, and approximately 820 000 people die from related diseases caused by HBV infection annually, such as liver failure, cirrhosis or HCC. Mostly, the clinical treatment of patients with chronic hepatitis B can achieve therapeutic effects of inhibiting virus replication and delaying disease progression after standar-dized antiviral treatments (such as entecavir, tenofovir, and propofol tenofovir). But with a deeper understanding of the di-sease and the improvement of detection technology, it has been found in clinical practice that some patients, after 48 weeks of standardized treatment, had serum HBV DNA levels below 2 000 IU/mL and continuously or intermittently exceeding the lower limit of detection， which indicates a state of low-level viremia（LLV）. The mechanism of LLV is currently unclear. Related studies have shown that LLV of HBV affects the clinical prognosis of patients, mainly manifesting as promoting liver inflammation, development of liver fibrosis, and an increased risk of decompensated cirrhosis, hepatocellular carcinoma, and drug resistance. In addition, there are no clear recommendations for the treatment of patients with HBV LLV. This article will review the definition, possible mechanisms, clinical significance, and clinical management strategies of HBV LLV, providing reference for clinical physicians.

Abstract Background and Aim Hepatocellular carcinoma development can be decreased by achieving and maintaining complete virological response (CVR) in chronic hepatitis B. However, it is unclear whether switching from entecavir (ETV) to tenofovir alafenamide (TAF) could achieve and maintain CVR in patients with low‐level viremia (LLV; HBV DNA ≤ 3.3 log IU/mL) or occasional detectable HBV DNA during ETV treatment. Therefore, we aimed to examine whether the switching from ETV to TAF is effective in achieving CVR in patients with LLV or occasional detectable HBV DNA. Methods This study comprised 45 patients who switched from ETV to TAF. All patients received ETV and TAF for >2 years, and the HBV DNA levels were measured every 3 months. Maintaining undetectable HBV DNA during 2‐year period is defined as CVR. The primary endpoint is the CVR rate during ETV and TAF treatment. Results The CVR rate for each of the 2 years of ETV and TAF therapy was 33.3% (15/45) and 68.9% (31/45, P

Abstract Introduction Monitoring HIV viral load (HVL) in people living with HIV (PLHIV) on antiretroviral therapy (ART) is recommended by the World Health Organization. Implementation of HVL testing programs have been affected by logistic and organizational challenges. Here we describe the HVL monitoring cascade in a rural setting in Tanzania and compare turnaround times (TAT) between an on-site and a referral laboratory. Methods In a nested study of the prospective Kilombero and Ulanga Antiretroviral Cohort (KIULARCO) we included PLHIV aged ≥ 15 years, on ART for ≥ 6 months after implementation of routine HVL monitoring in 2017. We assessed proportions of PLHIV with a blood sample taken for HVL, whose results came back, and who were virally suppressed (HVL

We evaluated subsequent virologic outcomes in individuals experiencing low-level virem ia (LLV) on dolutegravir (DTG)-based first-line antiretroviral therapy (ART) in Botswana. We used a national dataset from 50,742 adults who initiated on DTG-based first-line ART from June 2016–December 2022. Individuals with at least two viral load (VL) measurements post three months on DTG-based first-line ART were evaluated for first and subsequent episodes of LLV (VL:51–999 copies/mL). LLV was sub-categorized as low-LLV (51–200 copies/mL), medium-LLV (201–400 copies/mL) and high-LLV (401–999 copies/mL). The study outcome was virologic failure (VF) (VL ≥ 1000 copies/mL): virologic non-suppression defined as single-VF and confirmed-VF defined as two-consecutive VF measurements after an initial VL < 1000 copies/mL. Cox regression analysis identified predictive factors of subsequent VF. The prevalence of LLV was only statistically different at timepoints >6–12 (2.8%) and >12–24 (3.9%) (p-value < 0.01). LLV was strongly associated with both virologic non-suppression (adjusted hazards ratio [aHR] = 2.6; 95% CI: 2.2–3.3, p-value ≤ 0.001) and confirmed VF (aHR = 2.5; 95% CI: 2.4–2.7, p-value ≤ 0.001) compared to initially virally suppressed PLWH. High-LLV (HR = 3.3; 95% CI: 2.9–3.6) and persistent-LLV (HR = 6.6; 95% CI: 4.9–8.9) were associated with an increased hazard for virologic non-suppression than low-LLV and a single-LLV episode, respectively. In a national cohort of PLWH on DTG-based first-line ART, LLV > 400 copies/mL and persistent-LLV had a stronger association with VF. Frequent VL testing and adherence support are warranted for individuals with VL > 50 copies/mL.

Background and Aim: Hepatocellular carcinoma development can be decreased by achieving and maintaining complete virological response (CVR) in chronic hepatitis B. However, it is unclear whether switching from entecavir (ETV) to tenofovir alafenamide (TAF) could achieve and maintain CVR in patients with low‐level viremia (LLV; HBV DNA ≤ 3.3 log IU/mL) or occasional detectable HBV DNA during ETV treatment. Therefore, we aimed to examine whether the switching from ETV to TAF is effective in achieving CVR in patients with LLV or occasional detectable HBV DNA. Methods: This study comprised 45 patients who switched from ETV to TAF. All patients received ETV and TAF for >2 years, and the HBV DNA levels were measured every 3 months. Maintaining undetectable HBV DNA during 2‐year period is defined as CVR. The primary endpoint is the CVR rate during ETV and TAF treatment. Results: The CVR rate for each of the 2 years of ETV and TAF therapy was 33.3% (15/45) and 68.9% (31/45, P < 0.01), respectively, and the CVR rate increased by switching from ETV to TAF. In patients with occasional detectable HBV DNA during ETV treatment (22 patients), 15 achieved CVR and 7 maintained occasional detectable HBV DNA. In patients with LLV during ETV treatment (eight patients), three achieved CVR and five had occasional detectable HBV DNA. Conclusion: Switching from ETV to TAF increases the CVR rate in patients with LLV or occasional detectable HBV DNA and could be an alternative treatment option. [ABSTRACT FROM AUTHOR]

Introduction: Monitoring HIV viral load (HVL) in people living with HIV (PLHIV) on antiretroviral therapy (ART) is recommended by the World Health Organization. Implementation of HVL testing programs have been affected by logistic and organizational challenges. Here we describe the HVL monitoring cascade in a rural setting in Tanzania and compare turnaround times (TAT) between an on-site and a referral laboratory. Methods: In a nested study of the prospective Kilombero and Ulanga Antiretroviral Cohort (KIULARCO) we included PLHIV aged ≥ 15 years, on ART for ≥ 6 months after implementation of routine HVL monitoring in 2017. We assessed proportions of PLHIV with a blood sample taken for HVL, whose results came back, and who were virally suppressed (HVL < 1000 copies/mL) or unsuppressed (HVL ≥ 1000 copies/mL). We described the proportion of PLHIV with unsuppressed HVL and adequate measures taken as per national guidelines and outcomes among those with low-level viremia (LLV; 100–999 copies/mL). We compare TAT between on-site and referral laboratories by Wilcoxon rank sum tests. Results: From 2017 to 2020, among 4,454 PLHIV, 4,238 (95%) had a blood sample taken and 4,177 (99%) of those had a result. Of those, 3,683 (88%) were virally suppressed. In the 494 (12%) unsuppressed PLHIV, 425 (86%) had a follow-up HVL (102 (24%) within 4 months and 158 (37%) had virologic failure. Of these, 103 (65%) were already on second-line ART and 32/55 (58%) switched from first- to second-line ART after a median of 7.7 months (IQR 4.7–12.7). In the 371 (9%) PLHIV with LLV, 327 (88%) had a follow-up HVL. Of these, 267 (82%) resuppressed to < 100 copies/ml, 41 (13%) had persistent LLV and 19 (6%) had unsuppressed HVL. The median TAT for return of HVL results was 21 days (IQR 13–39) at the on-site versus 59 days (IQR 27–99) at the referral laboratory (p < 0.001) with PLHIV receiving the HVL results after a median of 91 days (IQR 36–94; similar for both laboratories). Conclusion: Robust HVL monitoring is achievable in remote resource-limited settings. More focus is needed on care models for PLHIV with high viral loads to timely address results from routine HVL monitoring. [ABSTRACT FROM AUTHOR]

Objective To understand the liver function and the occurrence of complications in patients with hepati⁃ tis B virus (HBV）-related compensated cirrhosis with serum hepatitis B virus (HBV) DNA ≤ 2 000 IU/mL and to pro⁃ vide a basis for subsequent clinical management. Methods Information on liver function evaluation indexes and com⁃ plications was collected from 220 HBV-related compensated cirrhosis patients with serum HBV DNA ≤ 2 000 IU/mL. Results Among the biochemical indexes of liver function in 220 patients, serum alpha-fetoprotein was 4. 80 (2. 12, 8. 35) ng/mL, total bilirubin was 18. 90 (14. 10，28. 76）µmol/L, albumin was 39. 35 (34. 60，43. 90) g/L, creatinine was 64 (56，73. 52）µmol/L, alanine aminotransferase was 31. 73 (21. 12，52. 17) U/L, aspartate aminotransferase was 30. 35 (23. 85，48. 85) U/L，γ-glutamyl transpeptidase was 42. 70 (24，66. 08) U/L, alkaline phosphatase was 82. 05 (63. 38，113) U/L, platelets were 105 (57. 25，158）×109 /L, prothrombin activity was 81. 03% (66%，93. 97%), and international normalized ratio was 1. 09 (1. 02，1. 21). CTP classification of liver function was predominantly grade A. The model score for end-stage liver disease was 8. 91±3. 78, the aspartate transferase and platelet ratio index was 1. 63± 2. 83, and the 4-factor-based liver fibrosis index score was 4. 84±5. 28. Complications in 220 patients were splenomegaly in 103, hypersplenism in 110, esophagogastric fundic varices in 74, portal vein thrombosis in 6, and HCC in 6. The incidence of splenomegaly was higher in HBV-related compensated cirrhosis patients aged <40 years in comparison with other ages (χ2 =6. 864，P<0. 05). Conclusions Although liver function was essentially normal in HBV-related compensated cirrhosis patients with serum HBV DNA ≤ 2 000 IU/mL, some indicators were in the low end of the normal range. HBVrelated compensated cirrhosis patients with serum HBV DNA ≤ 2 000 IU/mL have a higher incidence of complications such as splenomegaly and hypersplenism. [ABSTRACT FROM AUTHOR]

Expanding antiviral therapy is currently the new trend for the diagnosis and treatment of chronic hepatitis B, and related research evidence should be studied and discussed. Reducing the threshold of alanine aminotransferase (ALT) for initiating antiviral therapy is one of the most important changes during the expansion of antiviral therapy. Chronic hepatitis B patients with a low - level increase in ALT or a high normal level of ALT still have a higher risk of liver cancer and thus require further intervention. At present, nucleos(t)ide analogues show a certain clinical effect in some patients in terms of virological inhibition and improvement in fibrosis, while reducing ALT threshold places higher requirements for biochemical response after treatment. In addition, although the mechanism and definition of low - level viremia (LLV)after treatment remain unclear, further intervention of LLV is an important strategy for optimizing patient management in clinical practice. Switch to another potent nucleos(t) ide analogue may improve the virologic response rate of patients with LLV, and nucleos(t)ide analogues combined with interferon or other new targeted drugs will be an important research direction for the treatment of LLV in the future. [ABSTRACT FROM AUTHOR]

Background: Achieving and maintaining viral suppression (VS) in people living with HIV/AIDS on antiretroviral therapy (ART) remains a crucial clinical goal, more so in pregnancy to prevent mother-to-child-transmission (MTCT). There is a need to understand VS kinetics and barriers to achieving it in order to meet the target of eliminating HIV-MTCT by 2030. Methods: HIV-infected pregnant women =20 weeks of gestation with different durations of Tenofovir/Lamivudine/Efavirenz exposures seeking antenatal care services at four primary health centres in high-density residential areas in Harare, Zimbabwe were enrolled in the University of Zimbabwe Birth Cohort Study. Plasma viral load (VL) was quantified by reverse transcriptase-polymerase chain reaction. Demographic, clinical, socio-economic and HIV- and ART-related factors were tested in multivariable logistic regression analyses as potential predictors for VS and undetectable VL. Results: From March 2016 to June 2019, 608 HIV-infected pregnant women were enrolled. 63 (10.4%) were self-reported-ART-naïve; 324 (53.3%) and 221 (36.3%) initiated ART pre- and post-conception, respectively. Time from ART initiation to VS (VL = 1,000 copies/ml) in 95%of the women was 126 days. Overall lack of VS (VL > 1,000 copies/ml) was observed in 133 (21.9%) women being 76.2, 27.4 and 7.7% in self-reported-ARTnaïve, post-conception and pre-conception groups, respectively. Undetectable VL (=50 copies/ml) was observed in 371 (61.2%) and low-level viremia (51-1,000 copies/ml) in 102 (16.8%) women. In multivariable models for all participants regardless of ART exposure, being on ART was the strongest predictor for both VS and undetectable VL (odds ratio 95% confidence interval, OR (CI): 8.9(4.2-19.5) and 8.1(3.2-24.4), respectively). For women on ART, duration of ART use >126 days was the strongest predictor with OR (CI): 6.7(3.3-14.0) for VS and 8.5(5.6-13.1) for undetectable VL. Other relevant predictors for favourable virological outcomes were older maternal age, HIV-status disclosure, absence of ART side effects and self-reported depression. Having a spouse/intimate partner on ART predicted a 4 times higher likelihood for VS. Discussion: Lack of VS was frequently observed in this Harare cohort of pregnant women, mainly due to new HIV diagnosis, hence not being on ART and suboptimal duration of ART exposure. Since VS for 95% of women needed about 4 months of ART exposure, eliminating HIV-MTCT will require timely screening and commencing women together with their spouses/intimate partners on ART before pregnancy or early after conception. [ABSTRACT FROM AUTHOR]

Optimal management of patients experiencing persistent low-level viremia (LLV) remains challenging and poorly understood. This study aimed to assess the association between poor antiretroviral treatment (ARV) adherence and persistent LLV. ADHELOW is a sub-study of the ECHEC cohort comprising HIV-infected adults with virological failure (viral load>50 copies/mL). Patients were recruited in 2013–2015 from 4 French university hospitals. Those with LLV (i.e., ≥2 viral load measurements between 50 and 500 copies/mL) were selected and matched on age and sex to 3 controls with virological suppression. The adherence rate was estimated using pharmacy-delivered prescription refills over one year. Overall, 60 patients were included (15 LLV and 45 controls). Mean age was 50.20 years, M/F sex ratio was 14 and mean EPICES (social deprivation) score was 42.90. In univariable analyses, LLV patients had significantly lower adherence (<80%: 53.30% vs. 6.67%, p < 0.01) and were more likely to have an EPICES score >40.2 (60.00% vs. 24.44%, p < 0.01). In multivariable analysis, these two variables remained significantly associated with LLV (OR 31.49, CI 95% [4.54–218.70]) and OR 11.00 (CI 95% [1.87–218.70], respectively). Poor long-term treatment adherence, estimated by prescription refills, was strongly associated with LLV. This reinforces the message that adherence counseling should be the primary intervention to overcome LLV. [ABSTRACT FROM AUTHOR]

To understand the pathogenesis of low level viraemia (LLV) in HIV-infected patients on boosted protease inhibitors (PI/b), we enrolled 34 subjects with a median HIV-RNA 79 copies/mL and followed them for 15 months. Samples for next generation sequencing were collected at three time-points. Two showed resistance-associated mutations (RAMs) in the protease gene, while 95–100% had RAMs in the gag gene, which evolved in approximately a quarter of subjects, suggesting a potential clinical role of these kind of mutations.

To understand the pathogenesis of low level viraemia (LLV) in HIV-infected patients on boosted protease inhibitors (PI/b), we enrolled 34 subjects with a median HIV-RNA 79 copies/mL and followed them for 15months. Samples for next generation sequencing were collected at three time-points. Two showed resistance- associated mutations (RAMs) in the protease gene, while 95-100% had RAMs in the gag gene, which evolved in approximately a quarter of subjects, suggesting a potential clinical role of these kind of mutations. [ABSTRACT FROM AUTHOR]

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The high potency and tolerability of the currently available antiretroviral drugs has modifi ed HIV-1 infection from a life-threatening disease to a chronic illness. Nevertheless, some issues still remain open to optimize the management of HIV-1 infected patients in term of maintenance of virological suppression over time, identifying patients that could benefi t from simplifi cation therapy, and reducing co-mordibities driven by chronic infl ammation. The availability of robust and affordable virological and immunological markers can help in solving these issues by providing information on the burden of HIV-1 reservoir in all the anatomical compartments in which the virus replicates as well as on persistent infl ammation, immune activation and senescence despite successful virological suppression. In this light, this review is aimed at providing new insights (arising from a two-day Italian expert meeting hold in Rome in March 2016) in evaluation and monitoring of HIV-1 infection from a virological, immunological and clinical perspective. Particular attention has been focused on role of novel parameters (such as total HIV-1 DNA, residual viremia, and immunological markers) in optimizing treatment strategies, enhancing medical adherence, and individualizing monitoring. [ABSTRACT FROM AUTHOR]

Background: Progressively sensitive assays for plasma HIV RNA have led to increased detection of plasma HIV RNA between 20 and 200 copies/ml, known as low level viremia (LLV) when recurrent or persistent, in HIV-infected patients on antiretroviral therapy (ART). The aim of this study was to determine outcomes following initial detection of LLV in an Australian cohort.Methods: A retrospective study using the HIV Service Database (Alfred Hospital) included all patients on ART who recorded plasma HIV RNA 20-200 copies/mL following prior virological suppression (viral load (VL) HIV RNA <20 copies/mL) over 2 years (2010 to 2012), with follow-up to June 2013. Factors associated with subsequent virological outcome were assessed via univariate and multivariate analysis.Results: Of 919 patients managed by The Alfred HIV service, 207 (22.5%) met inclusion criteria. Mean age was 48.8 years, 91.3% were male. During follow-up, 54% patients recorded no further HIV RNA 20-200 copies/mL (viral blip); 39% had recurrent or persistent VL 20-200 copies/mL (LLV); and 7% progressed to virological failure with VL >200 copies/mL. Factors associated with LLV included co-morbid type 2 diabetes, shorter prior virological suppression and lower nadir CD4 cell count. Clinician management of VL 20-200 copies/mL was generally conservative, with infrequent requests for genotypic analysis (3.3% cases) or change in ART (<1% cases).Conclusions: LLV following virological suppression is common, and occurred as an isolated viral blip in half the patients. Those patients with persistent or recurrent LLV had higher rates of type 2 diabetes, shorter prior virological suppression and lower nadir CD4 cell count. [ABSTRACT FROM AUTHOR]

In HIV-1 patients with low viral burden, sequencing is often problematic, yet important. This study presents a sensitive, sub-type independent system for sequencing of low level viremia. Sequencing data from 32 HIV-1 infected patients with low level viremia were collected longitudinally. A combination of ViroSeq® HIV-1 Genotyping System and an in-house nesting protocol was used. Eight sub-types were represented. The success-rate of amplification of both PR and RT in the same sample was 100% in samples with viral loads above 100 copies/ml. Below 100 copies/ml, this study managed to amplify both regions in 7/13 (54%) samples. The assays were able to amplify either PR or RT in all sub-types included but one sub-type A specimen. In conclusion, this study presents a promising, simple assay to increase the ability to perform HIV-1 resistance testing at low level viremia. This is a prototype assay and the method needs further testing to evaluate clinical performance. [ABSTRACT FROM PUBLISHER]

Low-level viremia (LLV) is a hot and difficult topic that has gradually attracted attention in the field of chronic hepatitis B for evaluating antiviral therapy response in recent years. The presence of LLV may increase drug-resistant mutations, the progression of liver fibrosis, and potentially the development of liver cancer following antiviral therapy. Natural history of chronic HBV infection patients also have LLV, but it is unclear whether these patients are also at risk of disease progression, what the risk is, and whether early antiviral therapy is necessary and beneficial. Therefore, this article provides a reference for the all-encompassing management of this group of patients by reviewing the prevalence and impact of LLV in chronically HBV-infected patients' natural histories.

Abstract: Background: HIV-1 viral load assays are critical tools to monitor antiretroviral therapy efficacy in HIV-infected patients. Two assays based on real-time PCR are available, the Abbott Real-Time HIV-1 assay (Abbott assay) and the new Roche COBAS® AmpliPrep/COBAS® TaqMan® HIV-1 test, v. 2.0 (TaqMan® test v2.0). Objectives: We have compared the performance of the two assays in 546 clinical plasma specimens of group M strains from Luxembourg and Rwanda. Study design: Our analyses focused on subtype inclusivity and platforms accuracy for 328 low level viremia samples. Results: Strong agreement and linear correlation were observed between the two assays (R 2 =0.95) over a wide dynamic range. Bland–Altman analysis showed a mean difference of 0.04log10 indicating minimal overall viral load quantification differences between both platforms. One subtype C was severely underquantified by TaqMan® test v2.0 for which sequence analysis revealed multiple mismatches between the viral sequence and the primer/probe regions. A non significant lower quantification of the Abbott assay was shown for subtype A1 with a mean log10 difference of 0.24. For specimens under 200cp/mL, the overall agreement was 90% at the cut-off of 50cp/mL and 67% at assay''s lower limit of detection of 20 and 40cp/mL. 309 samples were retested by the COBAS® AMPLICOR® HIV-1 MONITOR Test, v. 1.5 and a lack of agreement between the three assays around their lower limit of quantification was revealed. Conclusions: Both real-time tests were closely comparable in the quantification of viral load specimens of ten HIV-1 subtypes and recombinant forms. [Copyright &y& Elsevier]

Abstract: Background: Numerous studies investigating clinical significance of HIV-1 minimal residual viremia (MRV) suggest potential utility of assays more sensitive than those routinely used to monitor viral suppression. However currently available methods, based on different technologies, show great variation in detection limit and input plasma volume, and generally suffer from lack of standardization. Objectives: In order to establish new tools suitable for routine quantification of minimal residual viremia in patients under virological suppression, some modifications were introduced into standard procedure of the Abbott RealTime HIV-1 assay leading to a “modified” and an “ultrasensitive” protocols. Study design: The following modifications were introduced: calibration curve extended towards low HIV-1 RNA concentration; 4 fold increased sample volume by concentrating starting material; reduced volume of internal control; adoption of “open-mode” software for quantification. Analytical performances were evaluated using the HIV-1 RNA Working Reagent 1 for NAT assays (NIBSC). Both tests were applied to clinical samples from virologically suppressed patients. Results: The “modified” and the “ultrasensitive” configurations of the assay reached a limit of detection of 18.8 (95% CI: 11.1–51.0cp/mL) and 4.8cp/mL (95% CI: 2.6–9.1cp/mL), respectively, with high precision and accuracy. In clinical samples from virologically suppressed patients, “modified” and “ultrasensitive” protocols allowed to detect and quantify HIV RNA in 12.7% and 46.6%, respectively, of samples resulted “not-detectable”, and in 70.0% and 69.5%, respectively, of samples “detected <40cp/mL” in the standard assay. Conclusions: The “modified” and “ultrasensitive” assays are precise and accurate, and easily adoptable in routine diagnostic laboratories for measuring MRV. [Copyright &y& Elsevier]

Abstract: Background: The recent introduction of highly sensitive viral load assays resulted in a significant increase in number of treated HIV-infected patients with a detectable viral load. The significance of a viral load between 20 and 50copies/mL remains unclear. Objectives: To compare the performance of three viral load assays, with special attention for specificity and sensitivity at the lowest level of quantification. Study design: Samples (n =181) were selected from 62 HIV-positive individuals that experience viral blips or episodes of low but detectable viremia under antiretroviral treatment, and from 216 HIV-negative individuals. Each sample was tested in at least two of three assays: the Cobas Amplicor HIV-1 Monitor (CAP/CA), the Cobas Ampliprep/Cobas TaqMan HIV-1 version 1 (CAP/CTM1) and the Cobas Ampliprep/Cobas TaqMan HIV-1 version 2 (CAP/CTM2). Results: No false positive results were recorded. Kappa statistics revealed fair to moderate agreement between the results of the three assays, but important differences in sensitivity were observed, with the highest sensitivity reported for CAP/CTM2 followed by CAP/CTM1 and CAP/CA. The differences in sensitivity remained after equalization of the detection limit for all assays at 50copies/mL. Analysis of samples collected over time showed that patients with single blips in CAP/CA present with recurrent blips in CAP/CTM1 and persistent detectable viremia in CAP/CTM2. Conclusions: Viral load results between 20 and 50copies/mL in either CAP/CTM1 or CAP/CTM2, indicate true viremia. The availability of highly sensitive assays force reconsideration of the terms ‘undetectable’ viral load and ‘virological success’ of antiretroviral treatment. [Copyright &y& Elsevier]

The first-line nucleos(t)ide analogs (NAs) based antiviral drugs can effectively inhibit HBV replication and slow down the progression of chronic hepatitis B. However, about 20% of patients receiving standard NAs antiviral therapy will still develop low-level viremia (LLV). Therefore, understanding the occurrence mechanism of LLV will help to optimize antiviral treatment regimens and improve the prognosis of patients with chronic hepatitis B. This article systematically summarizes the possible mechanisms of LLV occurrence, and the important factor of NAs failure. Taking into account the unique limitations of NAs competitive inhibition of virus replication, weakening host's immune response is not enough to directly eliminate infected hepatocytes. This makes it difficult to achieve a complete virological response in some patients with the active compensatory proliferation of residual infected hepatocytes and the accompanying effective removal or dilution of covalent, closed, circular DNA (cccDNA) pools. Therefore, it is speculated that activating host immunity can eliminate infected liver cells and may be more conducive to address LLV.