Search

Background: About 20% of on-treatment patients with chronic hepatitis B (CHB) experienced low-level viraemia (LLV), which is associated with persistent lowgrade inflammation, fibrosis progression, and increased risk of hepatocellular carcinoma. We aimed to investigate the high-risk factors related to LLV. Methods: In this retrospective study, patients receiving entecavir (ETV) treatment from January 2018 to January 2023 were enrolled, and were divided into a LLV (HBV DNA 20-2000 IU/mL) cohort and a complete virological response (CVR) (HBV DNA < 20 IU/mL) cohort according to the virological response at week 48 posttreatment. Treatment baseline characteristics were retrieved from electronic medical records. Multivariate logistic regression was performed. Results: Totally, 1653 patients were enrolled, male patients accounted for 73.0%; the median age was 44 years; the mean HBV DNA level was 5.9 Log10 IU/ml. Among them, 472 (28.6%) experienced LLV. Multivariate analysis showed that HBeAg positivity (OR = 2.650, 95% CI: 2.000-3.511, p < 0.001), HBV DNA ≥ 6.0 Log10 IU/mL (OR = 1.370, 95% CI: 1.054-1.780, p = 0.019), qHBsAg ≥ 9000 IU/mL (OR = 4.472, 95% CI: 3.410-5.866, p < 0.001), cirrhosis (OR = 1.650, 95% CI: 1.234-2.207, P = 0.001), LSM ≥ 13.0 kPa (OR = 1.644, 95% CI: 1.203-2.246, p = 0.002), and PLT < 100×109/L (OR = 1.450, 95% CI: 1.094-1.922, p = 0.010) at baseline were related to the development of LLV. Conclusions: High HBV DNA/HBsAg quantification/LSM, low PLT, HBeAg positivity, and liver cirrhosis were high-risk factors associated with LLV in patients receiving entecavir treatment. [ABSTRACT FROM AUTHOR]

Jinxian Xu, Yang Zhang, Lujian Zhu, Shiyue Tang, Hanglu Xu, Dehe Zhang, Haijun Chen, Jing Zhou Department of Infectious Diseases, Zhejiang University Medical College Affiliated Jinhua Hospital, Jinhua, People’s Republic of ChinaCorrespondence: Jing Zhou, Department of Infectious Diseases, Zhejiang University Medical College Affiliated Jinhua Hospital, Jinhua, People’s Republic of China, Email zhoujing001011@sina.comBackground: Chronic hepatitis B (CHB) presents a global health challenge due to its potential to cause severe liver conditions such as hepatocellular carcinoma (HCC) and cirrhosis. Prior research has established a correlation between CHB infection with low-level viremia (LLV) and liver disease progression, such as increased HCC incidence. This study aims to investigate whether LLV during treatment with nucleos(t)ide analogs (NAs) contributes to the accelerated progression of liver fibrosis (LF).Methods: This retrospective cohort study at Jinhua Central Hospital focused on CHB patients undergone NA monotherapy for over 96 weeks. Patients were categorized into maintained virological response (MVR) and LLV groups based on hepatitis B virus (HBV) DNA levels. The study assessed LF using various markers and methods, including chitinase 3-like 1 protein (CHI3L1), aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis-4 (FIB-4) score, and transient elastography.Results: Analysis was conducted on 92 CHB patients, categorized into LLV (n=42) and MVR (n=50) groups, following the exclusion of 101 patients for various reasons. Significant findings included lower baseline HBV DNA in MVR (< 20 IU/mL) compared to LLV (67.8 IU/mL, P< 0.001) and different AST/ALT ratios (LLV: 1.1, MVR: 1.36, P=0.011). LF was assessed using CHI3L1, FIB-4, and APRI, with LLV showing a higher baseline CHI3L1 (LLV:83.3 ng/mL vs MVR: 54.5 ng/mL, P=0.016) and scores compared to MVR, indicative of fibrosis. CHI3L1 levels in LLV were higher at baseline and weeks 48, 72, and 96 than MVR, with significance at baseline (P=0.038) and week 48 (P=0.034). Liver stiffness measurement (LSM) showed a time-dependent decline in both groups but no significant intergroup differences.Conclusion: Non-invasive monitoring of CHB patients who have received treatment indicates that LLV contributes to the progression of LF, necessitating proactive adjustment of antiviral treatment strategies.Keywords: chronic hepatitis B, low-level viremia, liver fibrosis, non-invasive methods, treatment strategies

As use of human immunodeficiency virus (HIV) integrase strand transfer inhibitors (INSTI) increases and formulations are being developed for maintenance therapies and chemoprophylaxis, assessing virus suppression under INSTI-based regimens in prevention-relevant biologic compartments, such as the male genital tract, is timely. We used cell-source marker virion immunocapture to examine amplification of particle RNA then assessed the phylogenetic relatedness of seminal and blood viral sequences from men with HIV who were prescribed INSTI-based regimens. Seminal plasma immunocaptures yielded amplifiable virion RNA from 13 of 24 (54%) men, and the sequences were primarily associated with markers indicative of macrophage and resident dendritic cell sources. Genetic distances were greatest (>2%) between seminal virions and circulating proviruses, pointing to ongoing low-level expression from tissue-resident cells. While the low levels in semen predict an improbable likelihood of transmission, viruses with large genetic distances are expressed under potent INSTI therapy and have implications for determining epidemiologic linkages if adherence is suboptimal. [ABSTRACT FROM AUTHOR]

Low-level viremia (LLV) ranging from 50 to 1,000 copies/ml is common in most HIV-1-infected patients receiving antiretroviral therapy (ART). However, the source of LLV and the impact of LLV on the HIV-1 reservoir during ART remain uncertain. We hypothesized that LLV may arise from the HIV reservoir and its occurrence affect the composition of the reservoir after LLV episodes. Accordingly, we investigated the genetic linkage of sequences obtained from plasma at LLV and pre-ART time points and from peripheral blood mononuclear cells (PBMCs) at pre-ART, pre-LLV, LLV, and post-LLV time points. We found that LLV sequences were populated with a predominant viral quasispecies that accounted for 67.29%-100% of all sequences. Two episodes of LLV in subject 1, spaced 6 months apart, appeared to have originated from the stochastic reactivation of latently HIV-1-infected cells. Moreover, 3.77% of pre-ART plasma sequences were identical to 67.29% of LLV-3 plasma sequences in subject 1, suggesting that LLV may have arisen from a subset of cells that were infected before ART was initiated. No direct evidence of sequence linkage was found between LLV viruses and circulating cellular reservoirs in all subjects. The reservoir size, diversity, and divergence of the PBMC DNA did not differ significantly between the pre- and post-LLV sampling points (P > 0.05), but the composition of viral reservoir quasispecies shifted markedly before and after LLV episodes. Indeed, subjects with LLV had a higher total PBMC DNA level, greater viral diversity, a lower proportion of variants with identical sequences detected at two or more time points, and a shorter variant duration during ART compared with subjects without LLV. Overall, our findings suggested that LLV viruses may stem from an unidentified source other than circulating cellular reservoirs. LLV episodes may introduce great complexity into the HIV reservoir, which brings challenges to the development of treatment strategies. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) infection is a dynamic disease where patients progress through several stages defined by HBV e‐antigen (HBeAg) status, HBV‐DNA levels and transaminase elevations, with antiviral therapy indicated only in specific stages. However, some patients cannot be classified into one of the stages and are said to fall into an ‘indeterminate phase’ or ‘grey zone’. Exact definitions of the indeterminate phase vary from guideline to guideline as a result of different cut‐off values for biomarker measurements. Data suggest that as many as 50% of HBV patients may be in an indeterminate phase and may not rapidly transition out of this phase. Clinical data that suggest these patients are at increased risk of hepatocellular carcinoma (HCC) are complemented by molecular evidence of integrations of HBV‐DNA into the host genome, chromosomal translocations and immune activation despite liver enzymes that may suggest lack of inflammation. Antiviral therapy reduces these hepatocarcinogenic mechanisms and is reflected in a reduction of fibrosis and HCC risk. We review key data on patients in the indeterminate phase, with emphasis on HCC as an outcome. We take a holistic approach and link new biological data with clinical observations as well as examine the potential role of antiviral therapy in reducing HCC risk among patients in the indeterminate phase. With the availability of safe and effective oral antivirals, consideration must be given as to how much residual risk of HCC should be tolerated among patients in the indeterminate phase. [ABSTRACT FROM AUTHOR]

Highly effective oral antiviral therapy with low drug resistance can strongly inhibit HBV replication；however, some patients may still have low-level viremia (LLV) after receiving entecavir, tenofovir disoproxil fumarate, tenofovir alafenamide, or tenofovir amibufenamide for 48 weeks or more. Multiple studies in China and globally show that LLV after antiviral therapy is closely associated with the progression of chronic hepatitis B liver fibrosis, the risk of decompensated liver cirrhosis and hepatocellular carcinoma, and the reduction in long-term survival rate. Therefore, this article reviews the development, risk factors, and clinical harm of LLV after first-line treatment with nucleos (t) ide analogues, as well as different treatment regimens, in order to provide a reference for the treatment of LLV in chronic hepatitis B patients in the future. [ABSTRACT FROM AUTHOR]

Introduction: Globally, approximately 40 million people are living with HIV (PWH), with a new HIV infection occurring every 2 minutes. In Türkiye, the number of PWH is increasing, posing challenges to achieving national-level virological suppression goals. Current antiretroviral therapies (ART), tailored to individual people with HIV, have significantly improved viral suppression and maintenance. However, some individuals experience low-level viremia (LLV) despite adherence to consistent drug therapy. This study aims to identify the determinants and implications of LLV and ART management strategies. Methods: The study was conducted through a retrospective analysis of electronic medical records of 830 PWH followed at the Izmir Tepecik Training and Research Hospital of Health Sciences University over a 10-year period. Demographic characteristics, definitions of unsuppressed viremia, and ART regimens of the PWH included in this study were evaluated. Results: Low-level viremia was diagnosed in 17.1% of the 99 PWH with unsuppressed viremia enrolled in the study. The presence of comorbidities was found to have a significant impact on the development of low-level viremia. Additionally, it was observed that individuals with LLV had lower rates of virological suppression compared to other groups. Discussion and Conclusion: This study evaluated the determinants of low-level viremia in people living with HIV and highlighted the presence of comorbidities and the importance of individualized treatment approaches. Further research is needed to effectively manage low-level viremia in PWH. [ABSTRACT FROM AUTHOR]

Background: People living with HIV (PLWH) and receiving antiretroviral therapy (ART) have a goal of achieving and maintaining viral suppression; however, the existence of PLWH that show events of low‐level viremia (LLV) between 50 and 1000 copies/mL and with different virological consequences have been observed. Moreover, some reports indicate that LLV status can lead to residual immune activation and inflammation, leading to a higher occurrence of non‐AIDS‐defining events (nADEs) and other adverse clinical outcomes. Until now, however, published data have shown controversial results that hinder understanding of this phenomenon's actual cause(s) and origin(s). Integrase strand transfer inhibitors (INSTIs)‐based therapies could lead to lower LLV over time and, therefore, more effective virological control. Objectives: This review aims to assess recent findings to provide a view of the clinical significance and management of low‐level HIV viremia in the era of INSTIs. [ABSTRACT FROM AUTHOR]

Objective: Although the tenofovir alafenamide/emtricitabine/bictegravir (TAF/FTC/BIC) regimen is recommended in national and international guidelines for changing treatment in treatment-experienced patients living with HIV (PLwHIV), there are limited real-life data reported in Türkiye. We aimed to evaluate the changes in virological and immunological indicators, renal functions, and lipid profiles in the follow-up of patients who switched to TAF/FTC/BIC. Methods: The study included treatment-experienced PLwHIV aged 18 years or older who were followed at the infectious diseases outpatient clinic between January 2020 and December 2021. Follow-up parameters before and after switching to TAF/FTC/BIC were evaluated retrospectively. Results: A total of 77 PLwHIV were included. Of those, 71 (92.2%) were male, and the median age was 42 years. The 24th and 48th week median HIV RNA values of patients whose viral loads were measured were 35 (27-77) copies/ml and 34 (24-49) copies/ml, respectively, after switching. We did not detected a significant difference in CD4+T lymphocyte count, CD4+ T lymphocyte percentage, and CD4+/CD8+ ratio when compared with pre-treatment values. Virological suppression was not maintained in 24.7% (n=19/77) of PLwHIV. While "incomplete virological response" was not detected in any patients, 2.6% (n=2/77) had virological rebound, 1.3% (n=1/77) were virological non-responders, 10.4% (n=8/77) had low-level viremia, and 20.8% (n=16/77) had virological blip. Glomerular filtration rate (GFR) (101 ml/min./1.73m² vs. 96 ml/min./1.73m², p=0.05) and total cholesterol level (199 mg/dl vs. 185 mg/dl, p=0.05) decreased at 48th week. In switching from tenofovir alafenamide/emtricitabine/elvitegravir/cobicistat (TAF/FTC/EVG/Cob) to TAF/FTC/BIC, significant decreases were detected in GFR (101 ml/min./1.73m² vs. 95 ml/min./1.73m², p=0.016) and total cholesterol levels (205 mg/dl vs. 182 mg/dl, p<0.001). Conclusion: Even if virological suppression is achieved before switching, virological suppression may be impaired in patients after switching to TAF/FTC/BIC. Moreover, renal functions should be closely monitored due to the significant decrease in GFR, especially when switching from TAF/FTC/EVG/Cob to TAF/FTC/BIC. [ABSTRACT FROM AUTHOR]

There is an ongoing debate regarding whether low-level viremia (LLV), in particular persistent LLV, during HIV treatment with optimal adherence originates from low-level viral replication, viral production, or both. We performed an observational study in 30 individuals with LLV who switched to a boosted darunavir (DRV)-based therapy. In-depth virological analyses were used to characterize the viral population and the (activity) of the viral reservoir. Immune activation was examined using cell-bound and soluble markers. The primary outcome was defined as the effect on HIV-RNA and was categorized by responders (<50 cp/mL) or non-responders (>50 cp/mL). At week 24, 53% of the individuals were considered responders, 40% non-responders, and 7% could not be assigned. Sequencing showed no evolution or selection of drug resistance in the non-responders. Production of defective virus with mutations in either the protease (D25N) or RT active site contributed to persistent LLV in two individuals. We show that in about half of the study participants, the switch to a DRV-based regimen resulted in a viral response indicative of ongoing low-level viral replication as the cause of LLV before the switch. Our data confirm that in clinical management, high genetic barrier drugs like DRV are a safe choice, irrespective of the source of LLV. [ABSTRACT FROM AUTHOR]

Background Human immunodeficiency virus low-level viremia (LLV) is associated with subsequent treatment failure at least with non nucleoside reverse transcriptase inhibitor (NNRTI)-containing antiretroviral therapy. Data on implications of LLV occurring under dolutegravir, which has largely replaced NNRTIs in Africa, are scarce, however. Methods We included adults with human immunodeficiency virus in Lesotho who had ≥2 viral loads (VLs) taken after ≥6 months of NNRTI- or dolutegravir-based antiretroviral therapy. Within VL pairs, we assessed the association of viral suppression (<50   copies/mL) and low- and high-range LLV (50–199 and 200–999   copies/mL, respectively) with virological failure (≥1000   copies/mL) using a mixed-effects regression model. Participants could contribute VLs to the NNRTI and the dolutegravir group. Results Among 18 550 participants, 12 216 (65.9%) were female and median age at first VL included was 41.2 years (interquartile range, 33.4–51.5). In both groups, compared with a suppressed VL, odds of subsequent virological failure were higher for low-range LLV (NNRTI: adjusted odds ratio; 95% confidence interval: 1.9; 1.4–2.4 and dolutegravir: 2.1; 1.3–3.6) and high-range LLV (adjusted odds ratio; 95% confidence interval, 4.2; 3.1–5.7 and 4.4; 2.4–7.9). Conclusions In the dolutegravir era, LLV remains associated with virological failure, endorsing the need for close clinical and laboratory monitoring of those with a VL ≥50 copies/mL. [ABSTRACT FROM AUTHOR]

Despite effective antiretroviral therapies (ARTs), a subset of people living with HIV (PLWH) still experience low-level viremia (LLV, i.e., 50–1,000 copies/mL). The present study compared PLWH experiencing LLV with those maintaining virological suppression (VS) and explored the potential impact of preexisting drug resistance and other factors on LLV. We conducted a retrospective, 1:1 matched case–control study within a cohort of drug-experienced VS subjects from the Italian Antiviral Response Cohort Analysis database, followed in the period 2009–2019. Cases were individuals experiencing LLV, while controls were those who maintained VS. Matching was for calendar year of first ART regimen. Preexisting drug resistance was calculated as cumulative genotypic susceptibility score (GSS) according to regimen administered at the observational period start. To explore the effect of cumulative GSS, treated as a binary variable (≥2 and <2) and other factors on LLV, we performed a logistic regression analysis. Within a main population of 3,455 PLWH, 337 cases were selected. Cases were comparable to the controls for both gender and age. However, cases showed that they had experienced a longer time since HIV diagnosis, a higher number of drugs previously administered, lower baseline CD4+ T cell count and a higher zenith viral load (VL). By multivariate analysis, we found that higher zenith VL [adjusted odds ratio (aOR) (95% confidence interval [CI]) 1.30 (1.14–1.48)], a cumulative usage of both PI [aOR (95% CI): 2.03 (1.19–3.48)] and InSTI [aOR (95% CI): 2.23 (1.47–3.38)] and a cumulative GSS <2 [aOR (95% CI) 0.67 (0.46–0.98)], were associated with a higher risk in developing LLV. In current high-efficacy ART era, in drug-experienced PLWH, the predictors of increased risk of LLV were the presence of preexisting drug resistance, higher zenith VL, and previous PI, and InSTI exposure. [ABSTRACT FROM AUTHOR]

Abstract Background Low-level viremia (LLV) has been identified as a potential precursor to virologic failure (VF), yet its clinical implications, particularly within the context of Integrase Strand Transfer Inhibitors (INSTIs)-based regimens, remain insufficiently explored. The study aimed to investigate the relationship between LLV and VF within ART-naïve patients on INSTIs-based regimens in China. Methods A longitudinal cohort study was conducted with ART-naïve patients aged ≥ 18 years at Beijing Ditan Hospital, under the Chinese National Free Antiretroviral Treatment Program (NFATP). The LLV was defined as a viral load (VL) ranging from 50 to 199 copies/mL after six months of ART initiation, and VF as a VL ≥ 200 copies/mL. Sensitive analyses were also performed, defining LLV as 50–999 copies/mL and VF as exceeding 1000 copies/mL. Multivariate logistic regression, Kaplan-Meier (KM) curve, and Generalized Estimating Equation (GEE) models were used to evaluate the risk factors associated with LLV and VF events. Results The study involved 830 ART-naïve patients, comprising 600 in the INSTIs group and 230 in the protease inhibitors (PIs) group. LLV events were observed in 10.4% of patients on PIs-based regimens and and 3.2% on INSTIs-based regimens (P

Abstract Introduction Viral load assessment for people living with HIV is key for monitoring treatment and achieving the 95-95-95. In this study, we aimed to assess the degree of viral suppression at different thresholds and treatment duration after the introduction of dolutegravir-based therapy in ten public hospitals in Sierra Leone. Methods We used a cross-sectional study design to recruits patients aged 18 years or older between August 2022 and January 2023. Statistical analyses were performed using R-software. Logistic regression was used to assess factors independently associated with viral suppression. The level of significance was set at P 12). Viral suppression rates were higher for patients aged 40 or older (40–50 years: aOR 2.05, 95%CI 1.41–3.04, P 60 years: aOR 2.69, 95%CI 1.28–6.63, P = 0.02). Men had 49% lower odds of viral suppression than women (aOR 0.50, 95% CI 0.38–0.67, P

Mortality in children accounts for 15% of all AIDS-related deaths globally, with a higher burden among Cameroonian children (25%), likely driven by poor virological response. We sought to evaluate viral suppression (VS) and its determinants in a nationally representative paediatric and young adult population receiving antiretroviral therapy (ART). A cross-sectional and multicentric study was conducted among Cameroonian children (p < 0.001. VS was 85.1% on a DTG-based regimen versus 80.0% on efavirenz/nevirapine and 65.6% on lopinavir/ritonavir or atazanavir/ritonavir. VS was higher in females versus males (85.8% versus 78.2%, p < 0.001). The VS rate remained stable around 85% at 12 and 24 months but dropped to about 80% at 36 months after ART initiation, p < 0.009. Independent predictors of non-VS were younger age, longer ART duration (>36 months), backbone drug (non-TDF/3TC) and anchor drug (non-DTG based). In this Cameroonian paediatric population with varying levels of transition to DTG, overall VS remains below the 95% targets. Predictors of non-VS are younger age, non-TDF/3TC- and non-DTG-based regimens. Thus, efforts toward eliminating paediatric AIDS should prioritise the transition to a DTG-based regimen in this new ART era.

Background: Low-level viremia (LLV) has been identified as a potential precursor to virologic failure (VF), yet its clinical implications, particularly within the context of Integrase Strand Transfer Inhibitors (INSTIs)-based regimens, remain insufficiently explored. The study aimed to investigate the relationship between LLV and VF within ART-naïve patients on INSTIs-based regimens in China. Methods: A longitudinal cohort study was conducted with ART-naïve patients aged ≥ 18 years at Beijing Ditan Hospital, under the Chinese National Free Antiretroviral Treatment Program (NFATP). The LLV was defined as a viral load (VL) ranging from 50 to 199 copies/mL after six months of ART initiation, and VF as a VL ≥ 200 copies/mL. Sensitive analyses were also performed, defining LLV as 50–999 copies/mL and VF as exceeding 1000 copies/mL. Multivariate logistic regression, Kaplan-Meier (KM) curve, and Generalized Estimating Equation (GEE) models were used to evaluate the risk factors associated with LLV and VF events. Results: The study involved 830 ART-naïve patients, comprising 600 in the INSTIs group and 230 in the protease inhibitors (PIs) group. LLV events were observed in 10.4% of patients on PIs-based regimens and and 3.2% on INSTIs-based regimens (P < 0.001). INSTIs-based regimens demonstrated a protective effect against LLV events (aHR = 0.27, 95% CI 0.137–0.532). VF events occurred in 10.9% of patients on PIs-based regimens and 2.0% on INSTIs-based regimens, respectively (P < 0.001). The occurrence of LLV events significantly increased the risk of VF by 123.5% (95% CI 7.5%-364.4%), while the integrase inhibitors were associated with a 76.9% (95% CI 59.1%-86.9%) reduction in VF risk. Conclusion: Our findings indicate that INSTIs-based regimens are critical protective factors against LLV and subsequent VF. These results underscore the importance of HIV viral load monitoring to ensuring effective treatment outcomes, highlighting the necessity for prompt and precise monitoring to refine HIV treatment methodologies. [ABSTRACT FROM AUTHOR]

Background: Predictors of virologic failure in those receiving long-acting injectable (LAI) cabotegravir/rilpivirine (CAB/RPV) have been evaluated; however, factors associated with low-level viremia, including blips and persistent low-level viremia (pLLV), are not well-described. Methods: A retrospective cohort study was performed using data from April 2021 through December 2022. Inclusion criteria included treatment with CAB/RPV for at least 3 months, availability of pre- and postswitch HIV RNA values, HIV RNA value of <200 copies/mL (cpm) at the time of switch to CAB/RPV, and at least 1 postswitch HIV RNA collected >21 days after the start of CAB/RPV. Outcomes included incidence of HIV RNA ≥20, ≥50, and ≥200 cpm after switch and factors associated with detectable HIV RNA after switch. Results: The median duration of follow-up among 144 participants was 287 days. After switching to CAB/RPV, occurrences of at least 1 HIV RNA ≥20, ≥50, and ≥200 cpm after switch were 34.7%, 15.3%, and 2.8%, respectively. Those with pLLV before switch were significantly more likely to have detectable HIV RNA after switch [hazard ratio 24.39 (8.71–68.34)], and 44.4% of those with pLLV before switch continued with pLLV after switch to LAI CAB/RPV. Body mass index, late injection, and monthly versus every two-month dosing were not associated with detectable viremia after switch. Conclusions: Despite virologic suppression at the time of switch and the perceived adherence benefits, participants still experienced blips or pLLV after switch to LAI CAB/RPV. Having detectable HIV RNA on oral therapy before switch was associated with detectable HIV RNA after switching. [ABSTRACT FROM AUTHOR]

Introduction: Viral load assessment for people living with HIV is key for monitoring treatment and achieving the 95-95-95. In this study, we aimed to assess the degree of viral suppression at different thresholds and treatment duration after the introduction of dolutegravir-based therapy in ten public hospitals in Sierra Leone. Methods: We used a cross-sectional study design to recruits patients aged 18 years or older between August 2022 and January 2023. Statistical analyses were performed using R-software. Logistic regression was used to assess factors independently associated with viral suppression. The level of significance was set at P < 0.05. Results: Of the 2,253 patients recruited, 1,720 (76%) were women and 1,705 (76%) were receiving a fixed dose combination of tenofovir, lamivudine and dolutegravir. The median age and duration of anti-retroviral therapy (ART) was 36.0 (IQR, 28.0–45.0) years and 40.9 (IQR, 14.4–79.6) months, respectively. Using a threshold of HIV RNA < 1000 copies/mL, 1,715 (88.4%) patients on ART for more than 6 months were virally suppressed. Viral suppression rates were higher with dolutegravir-based (1,277, 89.5%) than efavirenz-based (418, 86.2%) ART. HIV RNA was < 200 copies/mL in 1,643 (84.6%) patients or < 50 copies/mL in 1,487 (76.6%) patients or between 50 and 999 copies/mL in 228 (11.7%) patients. Viral suppression rates at different ART durations (months) were as follows: 84.2% (≤ 3), 88.8% (4–6), 90.9% (6–12), and 88.1% (> 12). Viral suppression rates were higher for patients aged 40 or older (40–50 years: aOR 2.05, 95%CI 1.41–3.04, P < 0.01; 50–60 years: aOR 2.51, 95%CI 1.53–4.35, P < 0.01; >60 years: aOR 2.69, 95%CI 1.28–6.63, P = 0.02). Men had 49% lower odds of viral suppression than women (aOR 0.50, 95% CI 0.38–0.67, P < 0.01). Conclusion: We report a viral suppression rate of 88.4% among patients on treatment for at least 6 months, with higher rate of suppression with dolutegravir than efavirenz. Factors associated with virological suppression were age and gender, emphasizing the need for innovative differentiated ART delivery models to optimize viral suppression and achieve the 95% target. [ABSTRACT FROM AUTHOR]

Human immunodeficiency virus (HIV) is a significant infection that attacks immune system cells and integrates its genetic material into host cells. Left untreated, it leads to acquired immunodeficiency syndrome (AIDS). Antiretroviral therapy (ART) is used to control HIV infection. Etravirine (ETR) is an important non-nucleoside reverse transcriptase inhibitor (NNRTI) utilized in the treatment of HIV. Low-level viremia (LLW) is a serious clinical condition, and the underlying mechanisms remain incompletely understood. The aim of our study is to analyze and elucidate the resistance status of Lys104Gln, Lys102Gln, Lys101Arg-Lys104Arg, Ser191Phe, Ile94Leu-Lys104Arg, Lys104Glu-His235Leu, Ala98Ser and Val179Ile mutations using in-silico methods, which are identified as low-level viremic strains, because their resistance status to ETR is unknown.

ABSTRACTBackground & Aims The WHO declared to eliminate hepatitis B virus (HBV) by 2030. However, an increasing number of patients are presenting with low-level viremia (LLV) with the widespread use of antiviral medications. The diagnostic efficiency and coverage area of HBV infection are low. Hence, this study intended to drive the HBV infection detection to effectively adaptable for any small to medium-sized laboratory or field survey.Methods We established, optimized, and evaluated a colloidal gold test strip for detection of HBV DNA based on CRISPR/Cas13a combined with recombinase-aided amplification (RAA) technology. Furthermore, 180 HBV-infected patients (including patients with different viral loads, LLV patients and dynamic plasma samples of patients on antiviral therapy) were enrolled for clinical validation.Results The strip detection of HBV DNA was established based on RAA-CRISPR-Cas13a technology with a sensitivity of 101 copies/μL and a specificity of 100%. HBV DNA gradient concentration plasmids and clinical samples were effectively identified by this approach. The positive coincidence rate for LLV patients was 87%, while the negative coincidence rate was 100%. The positive coincidence rate reached 100% in LLV patients (viral loading >100 IU/mL). The sensitivity, specificity, positive predictive agreement (PPA) and negative predictive agreement (NPA) values of dynamic plasma detection in patients on antiviral therapy were 100%, 92.15%, 93.75%, and 100%, respectively.Conclusions We develop rapid and portable RAA-CRISPR/Cas13a-based strip of HBV DNA detection for LLV patients. This study provides a visual and faster alternative to current PCR-based diagnosis for HBV infection.

Copyright of Journal of Modern Laboratory Medicine is the property of Journal of Modern Laboratory Medicine Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background There are conflicting data regarding baseline determinants of virological nonsuppression outcomes in persons with human immunodeficiency virus (HIV) starting antiretroviral treatment (ART). We evaluated the impact of different baseline variables in the RESPOND cohort. Methods We included treatment-naive participants aged ≥18 who initiated 3-drug ART, in 2014–2020. We assessed the odds of virological suppression (VS) at weeks 48 and 96 using logistic regression. Viral blips, low-level viremia (LLV), residual viremia (RV), and virological failure (VF) rates were assessed using Cox regression. Results Of 4310 eligible participants, 72% started integrase strand transfer inhibitor (INSTI)-based regimens. At 48 and 96 weeks, 91.0% and 93.3% achieved VS, respectively. At 48 weeks, Kaplan-Meier estimates of rates were 9.6% for viral blips, 2.1% for LLV, 22.2% for RV, and 2.1% for VF. Baseline HIV-1 RNA levels >100 000 copies/mL and CD4+ T-cell counts ≤200/µL were negatively associated with VS at weeks 48 (adjusted odds ratio, 0.51 [95% confidence interval,.39–.68] and.40 [.27–.58], respectively) and 96 and with significantly higher rates of blips, LLV, and RV. CD4+ T-cell counts ≤200/µL were associated with higher risk of VF (adjusted hazard ratio, 3.12 [95% confidence interval, 2.02–4.83]). Results were consistent in those starting INSTIs versus other regimens and those starting dolutegravir versus other INSTIs. Conclusions Initial high HIV-1 RNA and low CD4+ T-cell counts are associated with lower rates of VS at 48 and 96 weeks and higher rates of viral blips, LLV, and RV. Low baseline CD4+ T-cell counts are associated with higher VF rates. These associations remain with INSTI-based and specifically with dolutegravir-based regimens. These findings suggest that the impact of these baseline determinants is independent of the ART regimen initiated. [ABSTRACT FROM AUTHOR]

In this study, we characterized HIV-1 RNA and HIV-1 DNA genotyping drug resistance detection in patients with low-level viremia (LLV) in Liangshan, China. Whole blood samples were collected from HIV/AIDS patients who had received antiretroviral therapy (ART) for ≥6 months and whose HIV-1 RNA loads were 50–1,000 copies/mL for two consecutive times at least 1-month apart. The patients were enrolled from a county in Liangshan Yi Autonomous Prefecture, Sichuan Province, between May 2021 and May 2022. Plasma and blood cells were separated. Plasma samples were tested for HIV-1 RNA genotyping drug resistance, while blood cell samples were tested for HIV-1 DNA genotyping drug resistance. Then, HIV-1 RNA and HIV-1 DNA genotyping drug resistance outcomes were compared. Among the 32 participants, 16 were males, while 16 were females, with the median age of 34.5 years. The main HIV-1 infection route was heterosexual transmission. The median ART duration was 3.9 years. Two types of nucleoside reverse transcriptase inhibitors (NRTIs) + one non-nucleoside reverse transcriptase inhibitor (NNRTI) were the main antiviral therapeutic options. Pol region genes for 28 HIV-1 DNA samples and 10 HIV-1 RNA samples were successfully amplified. The success rate of pol region gene amplification for HIV-1 DNA was significantly higher than that of HIV-1 RNA (χ2 = 20.988, p < .05). In HIV-1 RNA and HIV-1 DNA samples, M184 (4/8) and K103 (3/8) were the most frequent drug resistance mutation sites. Among the NNRTIs, the rates of drug resistance were highest to efavirenz (EFV) (6/8) and nevirapine (NVP) (6/8), while among the NRTIs, the rates of drug resistance were highest to abacavir (ABC) (4/8), emtricitabine (FTC) (4/8), and lamivudine (3TC) (4/8). In conclusion, detection of HIV-1 RNA genotyping drug resistance combined with HIV-1 DNA genotyping drug resistance can improve the success rate of drug resistance detection in patients with LLV. [ABSTRACT FROM AUTHOR]

Summary: Background: HIV low-level viremia (LLV) (51–999 copies/mL) can progress to treatment failure and increase potential for drug resistance. We analyzed retrospective longitudinal data from people living with HIV (PLHIV) on antiretroviral therapy (ART) in Kenya to understand LLV prevalence and virologic outcomes. Methods: We calculated rates of virologic suppression (≤50 copies/mL), LLV (51–999 copies/mL), virologic non-suppression (≥1000 copies/mL), and virologic failure (≥2 consecutive virologic non-suppression results) among PLHIV aged 15 years and older who received at least 24 weeks of ART during 2015–2021. We analyzed risk for virologic non-suppression and virologic failure using time-dependent models (each viral load (VL)

INTRODUCTION: The initiation of antiviral treatment in patients with chronic hepatitis B with compensated cirrhosis and low-level viremia (LLV; HBV DNA 15–2,000 IU/mL) remains controversial. We sought to compare the long-term outcomes of these untreated patients according to their viremic status. METHODS: Six hundred twenty-seven untreated patients with chronic hepatitis B with compensated cirrhosis were analyzed retrospectively. The risk of hepatocellular carcinoma (HCC) and liver-related clinical events, including hepatic decompensation, were compared between patients with LLV and undetectable HBV DNA. Patients who received antiviral treatment were censored during treatment initiation. RESULTS: Themean age of the patientswas 54.7 years, 64.4% ofwhomweremale.During the study period, 59 patients developed HCC (20 and 39 in the undetectable and LLV groups, respectively) with an annual incidence of 2.44/100 person-years. Multivariable analysis revealed that the LLV group was associated with a significantly higher risk of HCC (adjusted hazard ratio: 2.36, P 5 0.002) than the undetectable group. In the 204 propensity score–matched cohort, the LLV group had a 2.16-fold greater risk of HCC than the undetectable group (P 5 0.014). Liver-related clinical events occurred in 121 patients with an annual incidence of 5.25/ 100 person-years. Despite not reaching statistical significance, the LLV group tended to have a higher risk of liver-related events in the propensity score–matched cohort (hazard ratio: 1.14, P 5 0.50). DISCUSSION: Compared with patients with undetectable HBV DNA, those with compensated cirrhosis and LLV had a significantly higher risk of HCC. Antiviral treatment should be advised for these patients. [ABSTRACT FROM AUTHOR]

Objectives: Real-world experience with coformulated bictegravir, emtricitabine, and tenofovir alafenamide (BIC/FTC/TAF) is sparse as a switch regimen among people living with HIV (PLWH) having achieved viral suppression after previous virologic failures with the emergence of K65N/R. Methods: In this retrospective study, PLWH aged ≥20 years who had previous virologic failures with emergent K65N/R were included for switching to BIC/FTC/TAF after having achieved plasma HIV RNA load (PVL) 50 copies/ml) at week 48 using a modified US Food and Drug Administration snapshot algorithm. Results: A total of 72 PLWH with K65N/R who switched to BIC/FTC/TAF were identified. A total of 42 (59.7%) had concurrent M184V/I, and 9 (12.5%) had ≥1 thymidine analog mutations. The median duration of viral suppression was 4.7 years (interquartile range 2.3-5.8), and 97.2% (n = 70) had PVL

BackgroundThe clinical management of low-level viremia (LLV) remains unclear. The objective of this study was to investigate the association of blips and LLV with virologic failure.MethodsWe enlisted patients who newly enrolled into the HIV Research Network between 2005 and 2015, had HIV-1 RNA more than 200 copies/ml, and were either antiretroviral therapy (ART)-naive or ART-experienced and not on ART. Patients were included who achieved virologic suppression (≤50 on two consecutive viral loads) and had at least two viral loads following suppression. Blips and LLV (≥2 consecutive >51 copies/ml) were categorized separately into three categories: no blips/LLV, 51-200, 201-500. Cox proportional hazards regression was used to assess association between rates of blips/LLV and virologic failure (two consecutive >500).ResultsThe 2795 patients were mostly male (75.4%), black (50.3%), and MSM (52.9%). Median age was 38 years old (interquartile range 29-48). Most patients (88.8%) were ART-naive at study entry. Overall, 283 (10.1%) patients experienced virologic failure. A total of 152 (5.4%) patients experienced LLV to 51-200 and 110 (3.9%) patients experienced LLV to 201-500. Both LLV 51-200 [adjusted hazard ratio (aHR) 1.83 (1.10,3.04)] and LLV 201-500 [aHR 4.26 (2.65,6.86)] were associated with virologic failure. In sensitivity analysis excluding ART-experienced patients, the association between LLV 51 and 200 and virologic failure was not statistically significant.ConclusionLLV between 201 and 500 was associated with virologic failure, as was LLV between 51 and 200, particularly among ART-experienced patients. Patients with LLV below the current Department of Health and Human Services threshold for virologic failure (persistent viremia ≥200) may require more intensive monitoring because of increased risk for virologic failure.

Ontlametse T Bareng,1,2 Wonderful T Choga,1,2 Segomotso T Maphorisa,3 Sekgabo Seselamarumo,1 Kaelo K Seatla,1 Patrick T Mokgethi,1,4 Dorcas Maruapula,1,4 Mompati L Mogwele,1 Doreen Ditshwanelo,1,5 Natasha O Moraka,1 Irene Gobe,2 Modisa S Motswaledi,2 Joseph M Makhema,1,6 Rosemary Musonda,1 Roger Shapiro,1,6 Max Essex,1,6 Vlad Novitsky,1 Sikhulile Moyo,1,2,6 Simani Gaseitsiwe1,6 1Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana; 2School of Allied Health Professions, Faculty of Health Sciences, University of Botswana, Gaborone, Botswana; 3Ministry of Health and Wellness, Republic of Botswana, Gaborone, Botswana; 4Department of Biological Sciences, Faculty of Science, University of Botswana, Gaborone, Botswana; 5Department of Biological Science and Biotechnology, Botswana International University of Science and Technology, Palapye, Botswana; 6Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USACorrespondence: Simani Gaseitsiwe, Botswana Harvard AIDS Institute Partnership, Private Bag BO320, Bontleng, Gaborone, Botswana, Tel +267 390 2671, Fax +267 390 1284, Email sgaseitsiwe@bhp.org.bwPurpose: Monitoring HIV-1 drug resistance mutations (DRM) in treated patients on combination antiretroviral therapy (cART) with a detectable HIV-1 viral load (VL) is important for the selection of appropriate cART. Currently, there is limited data on HIV DRM at low-level viremia (LLV) (VL 401– 999 copies/mL) due to the use of a threshold of VL ≥ 1000 copies/mL for HIV DRM testing. We here assess the performance of an in-house HIV drug resistance genotyping assay using plasma for the detection of DRM at LLV.Methods: We used a total of 96 HIV plasma samples from the population-based Botswana Combination Prevention Project (BCPP). The samples were stratified by VL groups: 50 samples had LLV, defined as 401– 999 copies/mL, and 46 had ≥ 1000 copies/mL. HIV pol (PR and RT) region was amplified and sequenced using an in-house genotyping assay with BigDye sequencing chemistry. Known HIV DRMs were identified using the Stanford HIV Drug Resistance Database. Genotyping success rate between the two groups was estimated and compared using the comparison of proportions test.Results: The overall genotyping success rate was 79% (76/96). For VL groups, the genotyping success was 72% (36/50) at LLV and 87% (40/46) at VL ≥ 1000 copies/mL. Among generated sequences, the overall prevalence of individuals with at least 1 major or intermediate-associated DRM was 24% (18/76). The proportions of NNRTI-, NRTI- and PI-associated resistance mutations were 28%, 24%, and 0%, respectively. The most predominant mutations detected were K103N (18%) and M184V (12%) in NNRTI- and NRTI-associated mutations, respectively. The prevalence of DRM was 17% (6/36) at LLV and 30% (12/40) at VL ≥ 1000 copies/mL.Conclusion: The in-house HIV genotyping assay successfully genotyped 72% of LLV samples and was able to detect 17% of DRM amongst them. Our results highlight the possibility and clinical significance of genotyping HIV among individuals with LLV.Keywords: in-house genotyping, low-level viremia, samples, HIV-1C drug resistance testing

Qun Li,1,2 Fengting Yu,1,2 Chuan Song,1– 3 Hongxin Zhao,1,2 Qing Xiao,1,2 Xiaojie Lao,1,2 Siyuan Yang,1,2 Yunxia Tang,1,2 Fujie Zhang1,2 1Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Clinical Center for HIV/AIDS, Capital Medical University, Beijing, People’s Republic of China; 3Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, People’s Republic of ChinaCorrespondence: Fujie Zhang, Clinical and Research Center of Infectious Disease, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of China, Tel +86 10 84322581, Email treatment@chinaaids.cnObjective: In this study, we aimed to determine drug-resistance mutations (DRMs) in HIV-1 patients with low-level viremia (LLV) and explored the performance of next-generation sequencing (NGS) in detecting HIV DRMs by using LLV samples.Methods: Overall, 80 samples with LLV were amplified and sequenced using a commercial Sanger sequencing (SS) genotyping kit. Furthermore, 51 samples successfully sequenced using SS were simultaneously subjected to NGS. Genotyping success rates of various viremia categories by two sequencing methods were calculated. Stanford HIV-1 drug-resistance database (HIVdb version 8.9) was used to analyze the DRMs. In the NGS assay, a threshold of 5% was considered for reporting low-frequency variants, and the DRMs detected using SS and NGS were compared.Results: The overall success rate of PR/RT regions was 88.1% (67/80) using SS and 86.3% (44/51) using NGS. Furthermore, a significant linear trend was noted between viral load and the genotyping success rate. A total of 38.8% (26/67) participants harbored at least one mutation, as revealed through SS. Moreover, the prevalence of DRMs in persistent LLV was significantly higher than that in intermittent LLV (62.1% vs. 21.1%; P < 0.05). A total of 69 DRMs were detected using the two sequencing methods at the threshold of 5%. Moreover, 10 DRMs missed by SS were detected using NGS, whereas 8 DRMs missed by NGS were detected by SS.Conclusion: Our data suggested that the genotyping resistance testing is necessary to guide antiretroviral therapy optimization in LLV patients.Keywords: HIV-1, low-level viremia, drug-resistance mutation, next-generation sequencing

Abstract Background Antiviral therapy has been shown to benefit long-term survival after curative hepatectomy in patients with hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) with high levels of HBV-DNA, but the impact of antiviral therapy on patient recurrence in patients with low levels of HBV-DNA remains less clear. Methods This was a retrospective cohort study analyzing 296 patients with HBV-associated HCC with HBV-DNA levels 5 cm, tumor multiplicity was associated with early recurrence, and antiviral treatment was an independent protective factor for early recurrence of HCC (HR, 0.431; 95% CI 0.274–0.679; p 40 IU/ml, ALP levels > 130 IU/L, and the presence of satellite nodules, and subgroup analysis showed that compared to HBeAg-positive patients, antiviral therapy could significantly prolonged the recurrence-free survival of HBeAg-negative patients. Conclusion Antiviral therapy reduces early tumor recurrence after hepatectomy in patients with low levels of HBV-DNA.

Supplemental Digital Content is Available in the Text. Background: Recycling tenofovir and lamivudine/emtricitabine with dolutegravir (TLD) after failure of non-nucleoside transcriptase inhibitor first-line antiretroviral therapy is more tolerable and scalable than dolutegravir plus optimized nucleoside reverse transcriptase inhibitors. Studies have demonstrated TLD's efficacy as second line, but long-term follow-up is limited. Methods: ARTIST is a single arm, prospective, interventional study conducted in Khayelitsha, South Africa, which switched 62 adults with 2 viral loads >1000 copies/mL from tenofovir, lamivudine/emtricitabine, and an non-nucleoside transcriptase inhibitor to TLD. We report efficacy to 72 weeks and, in a post hoc analysis, evaluated viral load trajectories of individuals with viremic episodes. Results: Virologic suppression was 86% [95% confidence interval (CI) 74 to 93], 74% (95% CI: 61 to 84), and 75% (95% CI: 63 to 86) <50 copies/mL and 95%, 84%, and 77% <400 copies/mL at week 24, 48, and 72, respectively, with 89% (50/56) resistant (Stanford score ≥15) to tenofovir and/or lamivudine preswitch. No participants developed integrase-inhibitor resistance. Of the 20 participants not suppressed at week 24 and/or 48, 2 developed virologic failure, 1 switched regimen (adverse event), 2 were lost to follow-up, 1 missed the visit, 1 transferred out, 9 resuppressed <50 copies/mL with enhanced adherence counseling, and 4 remained viremic (3 with <200 copies/mL) at week 72. Conclusions: Recycling NRTIs with dolutegravir was effective for most participants to 72 weeks. Most with viremia did not develop virologic failure and subsequently suppressed with enhanced adherence counseling or continued to have low-level viremia. No integrase-inhibitor resistance was detected despite low-level viremia in a minority of participants. [ABSTRACT FROM AUTHOR]

There is an ongoing debate regarding whether low-level viremia (LLV), in particular persistent LLV, during HIV treatment with optimal adherence originates from low-level viral replication, viral production, or both. We performed an observational study in 30 individuals with LLV who switched to a boosted darunavir (DRV)-based therapy. In-depth virological analyses were used to characterize the viral population and the (activity) of the viral reservoir. Immune activation was examined using cell-bound and soluble markers. The primary outcome was defined as the effect on HIV-RNA and was categorized by responders (50 cp/mL). At week 24, 53% of the individuals were considered responders, 40% non-responders, and 7% could not be assigned. Sequencing showed no evolution or selection of drug resistance in the non-responders. Production of defective virus with mutations in either the protease (D25N) or RT active site contributed to persistent LLV in two individuals. We show that in about half of the study participants, the switch to a DRV-based regimen resulted in a viral response indicative of ongoing low-level viral replication as the cause of LLV before the switch. Our data confirm that in clinical management, high genetic barrier drugs like DRV are a safe choice, irrespective of the source of LLV.

Abstract Background Maintaining plasma HIV RNA suppression below the limit of quantification is the goal of antiretroviral therapy (ART). When viral loads (VL) remain in low-level viremia (LLV), or between 201 and 999 copies/mL, the clinical consequences are still not clear. We investigated the occurrence of LLV with drug resistance and its effect on CD4 cell counts in a large Chinese cohort. Methods We analysed data of 6,530 ART-experienced patients (42.1 ± 10.9 years; 37.3% female) from the China’s national HIV drug resistance (HIVDR) surveillance database. Participants were followed up for 32.9 (IQR 16.7–50.5) months. LLV was defined as the occurrence of at least one viral load (VL) measurement of 50–200 copies/mL during ART. Outcomes were drug resistance associated mutations (DRAM) and CD4 cell counts levels. Results Among 6530 patients, 58.0% patients achieved VL less than 50 copies/mL, 27.8% with VL between 50 and 999 copies/mL (8.6% experienced LLV), and 14.2% had a VL ≥ 1000 copies/mL. Of 1818 patients with VL 50–999 copies/mL, 182 (10.0%) experienced HIVDR, the most common DRAM were M184I/V 28.6%, K103N 19.2%, and V181C/I/V 10.4% (multidrug resistance: 27.5%), and patients with HIVDR had a higher risk of CD4 cell counts

Antiretroviral therapy (ART) aims to inhibit HIV replication, decrease CD4 T cell loss, and immune function recovery in order to reduce the morbidity and mortality associated with the infection. Treatment should also, improve quality of life and control HIV spread. However, incomplete viral suppression still occurs during ART. Viral suppression and virological failure (VF) thresholds vary between studies in terms of virological rebound (VR) states using different detection thresholds. Further understanding of influencing factors and adverse outcomes in various VR states should provide important guidance for HIV treatment.

Objectives: To investigate the association of low‐level viremia (LLV) with mortality among people living with HIV (PLHIV) on antiretroviral therapy (ART) in Dehong, Southwest China. Methods: We analysed data collected from a cohort of PLHIV on ART in Dehong. PLHIV were enrolled in this cohort after they started ART, with viral load (VL) tested once a year afterwards. Each VL level was then categorized into one of the four groups: <50, 50–199, 200–999 and ≥1000 copies/ml. VL levels of 50–199 and 200–999 copies/ml were defined as LLV. The VL level for each participant was re‐categorized and fitted into an extended Cox regression model as a time‐varying covariate to examine the associations of VL level with all‐cause and AIDS‐related deaths. Results: Among the included 7273 of 8762 PLHIV in this study, median age (interquartile range, IQR) was 36 (30–43) years and 59.9% were male. The patients were followed up for a median duration (IQR) of 6.2 (4.3–8.2) years. Compared with VL <50 copies/ml, LLV 200–999 copies/ml (adjusted hazard ratio [aHR] and 95% confidence interval [95% CI]: 1.56 [1.04, 2.32]) were associated with elevated risk of all‐cause mortality and LLV50‐199 (aHR [95% CI]: 1.00 [0.68, 1.45]) were not. Similarly, only LLV200‐999 copies/ml (aHR [95% CI]: 2.37 [1.36, 4.14]) corresponded to higher risk of AIDS‐related mortality. Conclusions: This study suggests that PLHIV on ART may have elevated death risks even though the viremia is suppressed at a low level. Interventions targeting PLHIV with LLV should be developed to reduce their mortality. [ABSTRACT FROM AUTHOR]

• Reverse-transcriptase mutation K65N/R reduces the HIV susceptibility to tenofovir. • Bictegravir, emtricitabine, and tenofovir alafenamide were effective as maintenance therapy in people living with HIV with archived K65N/R. • The rate of experiencing viral rebound was 2.8% at week 48 of the stable switch. • The presence of M184V/I plus K65N/R was not associated with viral rebound. Real-world experience with coformulated bictegravir, emtricitabine, and tenofovir alafenamide (BIC/FTC/TAF) is sparse as a switch regimen among people living with HIV (PLWH) having achieved viral suppression after previous virologic failures with the emergence of K65N/R. In this retrospective study, PLWH aged ≥20 years who had previous virologic failures with emergent K65N/R were included for switching to BIC/FTC/TAF after having achieved plasma HIV RNA load (PVL) <200 copies/ml for ≥3 months. PLWH were excluded if integrase inhibitor resistance-associated mutations were detected. The primary end point was losing virologic control (PVL >50 copies/ml) at week 48 using a modified US Food and Drug Administration snapshot algorithm. A total of 72 PLWH with K65N/R who switched to BIC/FTC/TAF were identified. A total of 42 (59.7%) had concurrent M184V/I, and 9 (12.5%) had ≥1 thymidine analog mutations. The median duration of viral suppression was 4.7 years (interquartile range 2.3-5.8), and 97.2% (n = 70) had PVL <50 copies/ml before switching. After a median observation of 98.6 weeks (interquartile range 77.9-120.3), 94.4% (n = 68) continued BIC/FTC/TAF. At week 48, the rate of losing virologic control was 2.8% (2/72). M184V/I was not associated with viral rebound. Despite the emergence of K65N/R +/- M184V/I after virologic failures, BIC/FTC/TAF could be an option for simplification after viral suppression. [ABSTRACT FROM AUTHOR]

Background It is unclear whether low-level viremia (LLV), defined as repeatedly detectable viral load (VL) of <200 copies/mL, and/or transient viremic episodes (blips) during antiretroviral therapy (ART), predict future virologic failure. We investigated the association between LLV, blips, and virologic failure (VF) in a multicenter European cohort. Methods People with HIV-1 who started ART in 2005 or later were identified from the EuResist Integrated Database. We analyzed the incidence of VF (≥200 copies/mL) depending on viremia exposure, starting 12 months after ART initiation (grouped as suppression [≤50 copies/mL], blips [isolated VL of 51–999 copies/mL], and LLV [repeated VLs of 51–199 copies/mL]) using Cox proportional hazard models adjusted for age, sex, injecting drug use, pre-ART VL, CD4 count, HIV-1 subtype, type of ART, and treatment experience. We queried the database for drug-resistance mutations (DRM) related to episodes of LLV and VF and compared those with baseline resistance data. Results During 81 837 person-years of follow-up, we observed 1424 events of VF in 22 523 participants. Both blips (adjusted subhazard ratio [aHR], 1.7; 95% confidence interval [CI], 1.3–2.2) and LLV (aHR, 2.2; 95% CI, 1.6–3.0) were associated with VF, compared with virologic suppression. These associations remained statistically significant in subanalyses restricted to people with VL <200 copies/mL and those starting ART 2014 or later. Among people with LLV and genotype data available within 90 days following LLV, 49/140 (35%) had at least 1 DRM. Conclusions Both blips and LLV during ART are associated with increased risk of subsequent VF. [ABSTRACT FROM AUTHOR]

Objective To investigate the influencing factors for low-level viremia (LLV) and their dynamic changes in chronic hepatitis B (CHB) patients treated with nucleos (t) ide analogues (NAs) for the first time. Methods A retrospective analysis was performed for 78 CHB patients who attended Department of Infectious Diseases, The First Affiliated Hospital of Nanchang University, from November 2020 to March 2022 and received antiviral therapy with NAs for at least 12 months, and according to HBV DNA level during treatment, they were divided into sustained virologic response (SVR) group with 58 patients and LLV group with 20 patients. The independent samples t-test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. The multivariate Logistic regression analysis was used to investigate the independent influencing factors for LLV and establish a predictive model, and the receiver operating characteristic (ROC) curve was used to evaluate the predictive value of this model. The Kaplan-Meier method was used to analyze cumulative HBV DNA negative conversion rate, and the Log-rank test was used for comparison. The analysis of variance with repeated measures was used to analyze the differences in HBV DNA and HBsAg between the two groups or within each group at weeks 0, 12, 24, 36, and 48. Results Compare with the SVR group, the LLV group had significantly higher HBeAg positive rate (90.0% vs 48.3%, χ²=10.701, P=0.001), log (HBV DNA) value (7.26±1.46 vs 5.65±1.70, t=-4.178, P<0.001), and log (HBsAg) value (4.53±0.86 vs 3.44±0.93, t=-4.813, P<0.001) and significantly lower age [29 (26-34) vs 33 (30-43), Z=-2.751, P=0.009], alanine aminotransferase (ALT) [67.0 (54.0-122.0) U/L vs 111.0 (47.0-406.0) U/L, Z=-2.203, P=0.028], aspartate aminotransferase [43.5 (32.8-62.8) U/L vs 77.5 (35.0-213.0) U/L, Z=-2.466, P=0.014], and liver stiffness measurement [7.7 (6.3-8.5) kPa vs 8.9 (7.2-11.4) kPa, Z=-2.022, P=0.043]. The multivariate logistic regression analysis showed that baseline HBV DNA (odds ratio [OR]=2.365, 95% confidence interval [CI]: 1.220-4.587, P=0.011), HBsAg (OR=4.229, 95% CI: 1.098-16.287, P=0.036), and ALT (OR=0.965, 95% CI: 0.937-0.994, P=0.018) were independent influencing factors for LLV in CHB patients, and the predictive model of Logit (MLLV) =-8.668+1.441×lgHBsAg+0.598×lgHBV DNA-0.016×ALT was established based on these factors, which had a larger area under the ROC curve than HBV DNA, HBsAg, and ALT (0.931 vs 0.774/0.856/0.666), with a sensitivity of 85.00% and a specificity of 93.10% at the optimal cut-off value of 0.44. The CHB patients with baseline HBV DNA >7.29 lgIU/mL or HBsAg >4.38 lgIU/mL had a significantly lower DNA negative conversion rate than those with DNA ≤7.29 lgIU/mL or HBsAg ≤4.38 lgIU/mL (χ²=22.52 and 26.35, both P<0.001). In the CHB patients, the highest reduction rates of HBV DNA and HBsAg were observed at weeks 12 and 24, respectively, and the LLV group had significantly higher levels of HBV DNA and HBsAg than the SVR group at weeks 0, 12, 24, 36, and 48 (HBV DNA: t=-4.084, -4.526, -5.688, -7.123, and-6.266, all P<0.001; HBsAg: t=-4.652, -4.691, -4.952, -4.804, and-4.407, all P<0.001). Conclusion For the CHB patients treated with NAs for the first time, those with high HBV DNA load, high HBsAg quantification, and low ALT level at baseline are more likely to develop LLV, and dynamic monitoring of these indices is of great significance to observe the onset of LLV. [ABSTRACT FROM AUTHOR]

Background: Following initiation of combined antiretroviral therapy, the majority of human immunodeficiency virus-infected patients experience immune reconstitution indicated by virologic suppression and an increase in peripheral CD4+ T-cell counts. Some patients may suffer from low-level viremia, which was reported to be significantly associated with acquired immunodeficiency syndrome cases, virologic failure, and death. We aimed to further investigate the influence of low-level viremia on CD4+ T-cell count. Methods: In our study, we included human immunodeficiency virus-seropositive patients on combined antiretroviral therapy, for at least 6 months, who received at least one assessment of human immunodeficiency virus plasma viral load and CD4+ cell count every 6 months, from January 2009 to January 2019. The copy-year viremia was determined by calculating the area under the curve of the plasma human immunodeficiency virus viral load. Results: When comparing patients with a mean CD4+ cell count <200 cells/μL, there was no significant difference between patients with a mean viral load <1000 copies/mL and patients with a mean viral load ≥1000 copies/mL (p = 0.219). Among those with a mean viral load <1000 copies/mL, a higher proportion of patients had a mean CD4+ cell count ≥500 cells/µL (p < 0.001). The mean CD4+ cell count of patients with copy-years viremia (log10) <4 (577.7, interquartile range 429.2-736.7) was significantly higher than that of patients with copy-years viremia (log10) ≥4 (443.3, interquartile range 319.0-558.4) (p < 0.001). In multivariate logistic regression analysis, we observed that malignancy without history, lower copy-years viremia, and high nadir CD4+ cell count were independent predictors of mean CD4+ cell count ≥500 cells/µL. Conclusion: Human immunodeficiency virus-infected patients with a history of malignancy, high copy-year viremia, and lower nadir CD4+ cell counts should be monitored carefully in clinical settings. [ABSTRACT FROM AUTHOR]

Background: Antiviral therapy has been shown to benefit long-term survival after curative hepatectomy in patients with hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) with high levels of HBV-DNA, but the impact of antiviral therapy on patient recurrence in patients with low levels of HBV-DNA remains less clear. Methods: This was a retrospective cohort study analyzing 296 patients with HBV-associated HCC with HBV-DNA levels < 2000 IU/mL who underwent hepatectomy at Zhongnan Hospital of Wuhan University between March 2013 and December 2017, of whom 157 patients received antiviral therapy (antiviral group) and 139 patients did not receive antiviral therapy (non-antiviral group), propensity score matching was used for survival analysis of patients in both groups, and subgroup analysis of major risk factors was performed. Results: The baseline characteristics of the two groups were comparable. At a median follow-up of 54 months, the 1-, 3-, and 5-year overall survival rates after propensity score matching (PSM) were 94.9%, 80.8%, 66.5%, and 90.9%, 64.6%, 49.4% for the antiviral and non-antiviral groups, respectively, p = 0.009, and the corresponding 1-, 3-, and 5-year RFS for the two groups were 81.8%, 76.8%, 76.8%, and 67.7%, 55.6%, 55.6%, respectively. p = 0.001, and the overall survival and recurrence-free survival were significantly better in the antiviral group than in the non-antiviral group. Multi-factor COX regression analysis showed that prothrombin time ≥ 13 s, methemoglobin level ≥ 20 ng/ml, platelet count ≥ 100 × 109/L, tumor size > 5 cm, tumor multiplicity was associated with early recurrence, and antiviral treatment was an independent protective factor for early recurrence of HCC (HR, 0.431; 95% CI 0.274–0.679; p < 0.001), but not associated with a low risk of late relapse (HR, 0.822; 95% CI 0.526–1.284; p = 0.389), and the main risk factors for late relapse included AST levels > 40 IU/ml, ALP levels > 130 IU/L, and the presence of satellite nodules, and subgroup analysis showed that compared to HBeAg-positive patients, antiviral therapy could significantly prolonged the recurrence-free survival of HBeAg-negative patients. Conclusion: Antiviral therapy reduces early tumor recurrence after hepatectomy in patients with low levels of HBV-DNA. [ABSTRACT FROM AUTHOR]

Background: The ability of automated, FDA-cleared plasma HIV-1 RNA assays to detect low-level viremia, compared to manual, highly sensitive research-only methods, is not well-defined. We therefore tested paired plasma samples from people with HIV-1 (PWH) on long-term antiretroviral therapy (ART) with both the Abbott M2000 RealTime HIV-1 Viral Load assay (Abbott) and a quantitative reverse transcriptase (RT)-initiated PCR assay that has a reported 95% detection limit of 1 HIV-1 RNA copy/ml (single copy assay, SCA). Methods: Plasma samples from 309 participants in the AIDS Clinical Trials Group study A5321 were tested by both Abbott and SCA. Participants were mostly men (82%). All were on stable ART for a median of 7 years with HIV-1 RNA

Background: This study aimed to investigate factors contributing to non-sustained viral suppression, including intermittent viremia and persistent low-level viremia, during cabotegravir (CAB) plus rilpivirine (RPV) long-acting (LA) injectable therapy, with a focus on pharmacokinetics (PK)., Methods: A prospective cohort study was conducted on people with HIV (PWH) transitioning from stable oral antiretroviral therapy (ART) to bimonthly CAB+RPV LA. Standardized follow-up included close monitoring through blood sampling for plasma HIV-1 viral load (VL) and multiple plasma drug concentrations measurements to analyze the connection between PK parameters and virologic outcomes., Results: Among 173 patients with a median (IQR) follow-up of 11.1(7.1-13.2) months and 789 pre-dose measurements, 38.7% experienced VL≥20 copies/mL, and 16.2% had levels ≥50 copies/mL. Intermittent viremia occurred in 34.7% of patients, and persistent low-level viremia in 4%. Virological failure developed in two cases. Predictors of non-sustained viral suppression included VL at HIV diagnosis [AHR: 1.49 per log10 VL, 95% CI: 1.04-2.12, P =.027], detectable viremia on oral ART [AHR: 2.45, 95% CI: 1.29-4.65, P =.006], and the level of viral suppression at transition [AHR: 0.38, 95% CI: 0.19-0.75, P =.004]. We found a significant association between low trough concentrations of CAB and RPV and episodes of detectable viremia exceeding 50 copies/mL. However, none of the assessed PK covariates predicted non-sustained viral suppression in multivariable models., Conclusion: Non-sustained viral suppression in PWH transitioning from stable oral ART to CAB+RPV LA was linked to pre-existing factors before transition. Higher VL pre-ART and incomplete suppression on oral therapy increased the risk, independent of PK parameters., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Mortality in children accounts for 15% of all AIDS-related deaths globally, with a higher burden among Cameroonian children (25%), likely driven by poor virological response. We sought to evaluate viral suppression (VS) and its determinants in a nationally representative paediatric and young adult population receiving antiretroviral therapy (ART). A cross-sectional and multicentric study was conducted among Cameroonian children (<10 years), adolescents (10-19 years) and young adults (20-24 years). Data were collected from the databases of nine reference laboratories from December 2023 to March 2024. A conditional backward stepwise regression model was built to assess the predictors of VS, defined as a viral load (VL) <1000 HIV-RNA copies/mL. Overall, 7558 individuals (females: 73.2%) were analysed. Regarding the ART regimen, 17% of children, 80% of adolescents and 83% of young adults transitioned to dolutegravir (DTG)-based regimens. Overall VS was 82.3%, with 67.3% (<10 years), 80.5% (10-19 years) and 86.5% (20-24 years), and p < 0.001. VS was 85.1% on a DTG-based regimen versus 80.0% on efavirenz/nevirapine and 65.6% on lopinavir/ritonavir or atazanavir/ritonavir. VS was higher in females versus males (85.8% versus 78.2%, p < 0.001). The VS rate remained stable around 85% at 12 and 24 months but dropped to about 80% at 36 months after ART initiation, p < 0.009. Independent predictors of non-VS were younger age, longer ART duration (>36 months), backbone drug (non-TDF/3TC) and anchor drug (non-DTG based). In this Cameroonian paediatric population with varying levels of transition to DTG, overall VS remains below the 95% targets. Predictors of non-VS are younger age, non-TDF/3TC- and non-DTG-based regimens. Thus, efforts toward eliminating paediatric AIDS should prioritise the transition to a DTG-based regimen in this new ART era.

Background: About 20% of on-treatment patients with chronic hepatitis B (CHB) experienced low-level viraemia (LLV), which is associated with persistent low-grade inflammation, fibrosis progression, and increased risk of hepatocellular carcinoma. We aimed to investigate the high-risk factors related to LLV., Methods: In this retrospective study, patients receiving entecavir (ETV) treatment from January 2018 to January 2023 were enrolled, and were divided into a LLV (HBV DNA 20-2000 IU/mL) cohort and a complete virological response (CVR) (HBV DNA < 20 IU/mL) cohort according to the virological response at week 48 posttreatment. Treatment baseline characteristics were retrieved from electronic medical records. Multivariate logistic regression was performed., Results: Totally, 1653 patients were enrolled, male patients accounted for 73.0%; the median age was 44 years; the mean HBV DNA level was 5.9 Log 10 IU/ml. Among them, 472 (28.6%) experienced LLV. Multivariate analysis showed that HBeAg positivity (OR = 2.650, 95% CI: 2.000-3.511, p < 0.001), HBV DNA ≥ 6.0 Log 10 IU/mL (OR = 1.370, 95% CI: 1.054-1.780, p = 0.019), qHBsAg ≥ 9000 IU/mL (OR = 4.472, 95% CI: 3.410-5.866, p < 0.001), cirrhosis (OR = 1.650, 95% CI: 1.234-2.207, P = 0.001), LSM ≥ 13.0 kPa (OR = 1.644, 95% CI: 1.203-2.246, p = 0.002), and PLT < 100×10 9 /L (OR = 1.450, 95% CI: 1.094-1.922, p = 0.010) at baseline were related to the development of LLV., Conclusions: High HBV DNA/HBsAg quantification/LSM, low PLT, HBeAg positivity, and liver cirrhosis were high-risk factors associated with LLV in patients receiving entecavir treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Chen, Jia, He, Cui, Du, Kang, Feng, He, Jin, Chen, Wang, Ji, Lau and Wu.)

Abstract Background Low-level viremia generally refers to detectable HBV DNA levels lower than 2000 IU/mL. Studies show that low-level viremia is a risk factor for hepatocellular carcinoma. The aim of this study was to explore the characteristics of low-level viremia patients with hepatitis B-related hepatocellular carcinoma and identify prognostic factors after curative hepatectomy. Methods Data from chronic hepatitis B patients with hepatocellular carcinoma receiving curative hepatectomy for the first time in the first hospital of China Medical University were studied. Patients were divided into two groups based on preoperative HBV DNA levels: group 1 (low-level viremia group, HBV DNA 250 IU/mL (the upper limit of detection in our laboratory) in group 1 than in group 2 (71.2% vs. 86.1%, P

Xinhui Wang, Xiaoli Liu, Peng Wang, Lihua Yu, Fengna Yan, Huiwen Yan, Dongdong Zhou, Zhiyun Yang Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of ChinaCorrespondence: Zhiyun YangCenter of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of ChinaTel/Fax +86-10-84322148Email yangzhiyun2016@163.comBackground and Aims: Although antiviral treatment has been shown to reduce mortality in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients with high HBV-DNA levels, it is still unclear whether it is useful in reducing mortality in patients with low HBV-DNA levels.Methods: A retrospective analysis of 756 HBV-associated HCC patients at the Beijing Ditan Hospital with HBV-DNA levels < 500 IU/mL was conducted between January 2008 and June 2017. Patients were divided into antiviral and non-antiviral groups based on whether they received nucleos(t)ide analogue (NA) treatment when they were diagnosed with HCC in our hospital for the first time. We used 1:4 frequency matching by age, gender, tumor size, Barcelona Clinic Liver Cancer (BCLC) staging, anti-tumor therapy, cirrhosis, diabetes, and hyperlipoidemia to compare the antiviral (n = 366) and non-antiviral (n = 100) groups. A Cox multivariate regression analysis was employed to evaluate the effects of NA therapy on the hazard ratio (HR), and the Kaplan–Meier survival curve was used to determine the mortality risk in patients with HCC. A Log rank test was performed to analyze the effects of NA therapy on the survival rate of patients with HCC.Results: After propensity score matching, the 1-, 3-, and 5-year overall survival (OS) rates for the antiviral and non-antiviral groups were 82.5%, 68.6%, and 52.2%, and 61.0%, 51.0%, and 38.0%, respectively. The l-year progression-free survival (PFS) rates for the two groups were 68.0% and 47.0%, respectively. The OS of the antiviral group was significantly higher than that of the control group (P < 0.001, P = 0.001, and P = 0.013, respectively). The 1-year PFS for the antiviral group was also significantly better than that for the non-antiviral groups (P = 0.005). After adjusting for confounding prognostic factors in the Cox model, the HR of 5-year death after antiviral treatment was 0.721 (95% confidence interval [CI], 0.530– 0.980, P = 0.037). Antiviral therapy is an independent protective factor for 5-year mortality in patients with HCC and low-level viremia.Conclusion: Antiviral therapy significantly reduced mortality in HCC patients with low HBV-DNA levels.Keywords: antiviral therapy, hepatitis B virus, low-level viremia, hepatocellular carcinoma, prognosis, nucleos(t)ide analog

Background: Maintaining plasma HIV RNA suppression below the limit of quantification is the goal of antiretroviral therapy (ART). When viral loads (VL) remain in low-level viremia (LLV), or between 201 and 999 copies/mL, the clinical consequences are still not clear. We investigated the occurrence of LLV with drug resistance and its effect on CD4 cell counts in a large Chinese cohort.Methods: We analysed data of 6,530 ART-experienced patients (42.1 ± 10.9 years; 37.3% female) from the China's national HIV drug resistance (HIVDR) surveillance database. Participants were followed up for 32.9 (IQR 16.7-50.5) months. LLV was defined as the occurrence of at least one viral load (VL) measurement of 50-200 copies/mL during ART. Outcomes were drug resistance associated mutations (DRAM) and CD4 cell counts levels.Results: Among 6530 patients, 58.0% patients achieved VL less than 50 copies/mL, 27.8% with VL between 50 and 999 copies/mL (8.6% experienced LLV), and 14.2% had a VL ≥ 1000 copies/mL. Of 1818 patients with VL 50-999 copies/mL, 182 (10.0%) experienced HIVDR, the most common DRAM were M184I/V 28.6%, K103N 19.2%, and V181C/I/V 10.4% (multidrug resistance: 27.5%), and patients with HIVDR had a higher risk of CD4 cell counts < 200 cells/μL (AOR 3.8, 95% CI 2.6-5.5, p < 0.01) comparing with those without HIVDR. Of 925 patients with VL ≥ 1000 copies/mL, 495 (53.5%) acquired HIVDR, the most common DRAM were K103N 43.8%, M184I/V 43.2%, M41L 19.0%, D67N/G 16.4%, V181C/I/V 14.5%, G190A/S 13.9% and K101E 13.7% (multidrug resistance: 75.8%), and patients with HIVDR had a higher risk of CD4 cell counts < 200 cells/μL (AOR 5.8, 95% CI 4.6-7.4, p < 0.01) comparing with those without HIVDR.Conclusion: Persistent with VL 50-999 copies/mL on ART is associated with emerging DRAM for all drug classes, and patients in this setting were at increased risk of CD4 cell counts < 200 cells/μL, which suggest resistance monitoring and ART optimization be earlier considered. [ABSTRACT FROM AUTHOR]

ObjectivesEvaluating the drug resistance (DR) profiles of LLV patients and the influencing factors of treatment effects in Jiangsu Province.MethodThe Pol gene (Reverse transcriptase and protease) was amplified and sequenced to identify the genotypes and DR profiles among LLV patients in 2021. Questionnaire survey was conducted among HIV/AIDS patients to investigate the potential influence factors of treatment effects.Results242 Pol genes were amplified from 345 specimens, and ten genotypes were detected. The DR rate was 40.5%, with 66, 86, and 14 being resistant to NRTIs, NNRTIs, and PIs, respectively. Patients treated with the 2NRTIs+PIs regimen were detected with more DR; and drug resistance was less detected in married or cohabiting patients than unmarried patients. Non-smokers were less likely to develop LLV at follow-up than smokers; patients with stage II clinical stage at diagnosis and using 2NRTIs+PIs regimen were also more likely to develop LLV at follow-up.ConclusionDrug resistance profiles in LLV patients are severe and differ in treatment regimens and marital statuses. Meanwhile, smoking history, clinical stage, and treatment regimen may influence the therapeutic effect. It is necessary to include LLV people in the free drug resistance testing program.

Background: Due to stringent reimbursement criteria, significant numbers of patients with compensated cirrhosis (CC) and low-level viremia [LLV; serum hepatitis B virus (HBV)–DNA levels of 20–2000 IU/mL] remain untreated especially in the East Asian countries, despite potential risk of disease progression. We analyzed cost-effectiveness to assess rationales for antiviral therapy (AVT) for this population. Methods: We compared cost and effectiveness (quality-adjusted life years, QALYs) in a virtual cohort including 10,000 54-year-old CC-LLV patients receiving AVT (Scenario I) versus no treatment (Scenario II). A Markov model, including seven HBV-related conditions, was used. Values for transition probabilities and costs were mostly obtained from recent real-world South Korean data. Results: As per a simulation of a base-case analysis, AVT reduced costs by $639 USD and yielded 0.108 QALYs per patient for 5 years among CC-LLV patients compared to no treatment. Thus, AVT is a cost-saving option with lower costs and better effectiveness than no treatment. If 10,000 patients received AVT, 815 incident cases of hepatocellular carcinoma (HCC) and 630 HBV-related deaths could be averted in 5 years compared to no treatment. In case of 10-year observation, AVT was consistently dominant. Even when the transition probabilities from CC-LLV vs. maintained virological response to HCC were same, fluctuation of results also lied within willingness-to-pay in South Korea. In the probabilistic sensitivity analysis with the willingness-to-pay threshold, the probability of AVT cost-effectiveness was 100%. Conclusion: The extended application of AVT in CC-LLV patients may contribute positively to individual clinical benefits and national healthcare budgets. [ABSTRACT FROM AUTHOR]