Low-level Viremia Research Articles

Association of low-level viremia with mortality among people living with HIV on antiretroviral therapy in Dehong, Southwest China: A retrospective cohort study.

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. 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. 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. 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.

Adverse Effect of Nonalcoholic Fatty Liver Disease on the Therapeutic Response in Patients with Chronic Hepatitis B.

The impact of nonalcoholic fatty liver disease (NAFLD) on the treatment outcome of chronic hepatitis B (CHB) is undefined and deserves an in-depth investigation. Histologically-proven CHB receiving first-line antiviral regimens as initial therapy was enrolled and grouped by the concurrence of NAFLD, and followed up at six monthly intervals. Therapeutic response related data were recorded and compared at multiple time points. Kaplan-Meier and Cox regression analyses were utilized to estimate the impact of NAFLD on complete virological response (CVR). We enrolled 267 patients (CHB: 164; CHB with NAFLD: 103) with comparable follow-up durations. They were also comparable in baseline HBV DNA levels and HBeAg positivity. Patients with concomitant NAFLD showed less significant decline in HBV DNA, qHBsAg, pgRNA, and liver enzyme levels over time; moreover, their cumulative incidences of CVR were significantly lower and that of low-level viremia (LLV) were significantly higher at 6, 12, 18, 24 months. First CVR of CHB was delayed with the presence NAFLD (11.0 vs. 7.0 months, p<0.001) and further prolonged with higher grade of liver steatosis (Grade 2-3 vs. 1: 13.0 vs. 9.0 months). On multivariate analysis, HBeAg positivity (HR: 0.650, p=0.036), grade of steatosis (G2 [HR: 0.447, p=0.004]; G3 [HR: 0.085, p=0.002]) and HBV DNA (log10 IU/mL) (HR: 0.687, p<0.001) were significantly associated with delayed CVR, whereas grade of necroinflammation (HR: 1. 758, p<0.001) accelerated the CVR. In CHB patients receiving initial antiviral therapy, NAFLD was associated with higher levels of HBV DNA, pgRNA, and liver enzymes, and higher incidence of LLV and delayed CVR.

Impact of low-level viremia with drug resistance on CD4 cell counts among people living with HIV on antiretroviral treatment in China

BackgroundMaintaining 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.MethodsWe 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.ResultsAmong 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.ConclusionPersistent 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.

MO979: Influence of BK Virus Plasma Viral Load in Kidney Transplant Outcomes

Abstract BACKGROUND AND AIMS BK virus infection (BKi) is an important cause of kidney transplant (KT) loss. Besides to reducing immunosuppression, the rest of the therapies have not shown a clear benefit. Our purpose is to analyze the risk factors for BKi and the influence of BK plasma viral load on KT outcomes. METHOD Prospective cohort study of KT with BKi, defined by the presence of BK viremia in ≥3 consecutive determinations, from 01 January 2010 to 31 December 2020. BK viremia was determined every 10 days during the first 3 months, at 6th month, 12th month and in case of impaired renal function. In patients with positive viremia, immunosuppressive therapy was changed (reduction/discontinuation of mycophenolate and/or switching to everolimus). Patients with high-level viremia (≥10 000 copies/mL) and low-level viremia (&amp;lt;10 000 copies/mL) were compared. To identify risk factors for BKi, for each KT with BKi, we selected two matched controls and performed a logistic regression analysis. Graft survival was analyzed according to BK viremia (high-level, low-level and negative) using Kaplan–Meier and Cox regression analysis was performed to determine risk factors for graft survival. RESULTS 849 KT were performed, of which 67 (7.9%) presented BKi. Six KT were excluded due to incomplete data. Finally, 61 KT BKi (n = 27, high-level viremia; n = 34 low-level viremia) and 122 controls were analyzed. The median post-KT time to BKi was 2 months. In the multivariable analysis, male recipient, older age and re-KT were risk factors for BKi. Proven BK-associated nephropathy was diagnosed in five KT recipients and nine patients had persistent BK viremia, all of them from the high plasma viral loads group. Only one patient lost the graft due to BK-associated nephropathy. Patients with low-level viremia had worse renal function one month after KT than controls but without differences at the first year. Patients with high-level viremia had worse renal function one year after KT and worse graft survival than recipients with low-level viremia and controls (P = 0.037). In the multivariable analysis, when we analyzed exclusively patients with BKi, high-level viremia was a risk factor for kidney graft survival (HR: 16.31; P = 0.034). CONCLUSION BKi is not an uncommon complication after KT. Only high BK viral load was associated with BK-associated nephropathy, persistent viremia, and poorer graft survival. BK viremia &amp;lt;10 000 copies/mL did not affect KT outcomes. Therefore, monitoring BK plasma viral loads and changes in immunosuppression to reduce viremia are effective strategies to minimize the impact of BK virus on graft survival.

Lower Incidence of HIV-1 Blips Observed During Integrase Inhibitor-Based Combination Antiretroviral Therapy.

As the nature of viral blips remains unclear, their occurrence often leads to uncertainty. This study compares blip incidence rates during treatment with different combination antiretroviral therapy anchors. Retrospective cohort study in a tertiary hospital. All antiretroviral regimens between 2010 and 2020 containing 2 nucleos(-t)ide reverse transcriptase inhibitors and 1 anchor in virologically suppressed people living with HIV (PLWH) from our center were evaluated for the occurrence of blips [isolated viral loads (VLs) 50-499 copies/mL between measurements <50 copies/mL]. Factors associated with blips were identified using multivariable generalized estimating equation-based negative binomial models. The relationship between blips and either persistent low-level viremia (consecutive VLs ≥ 50 copies/mL not classified as failure) or virologic failure (consecutive VLs ≥ 200 or 1 VL ≥ 500 copies/mL) was also evaluated. In total, 308 blips occurred during 3405 treatment courses in 1661 PLWH. Compared with a non-nucleoside reverse transcriptase inhibitor anchor, blip incidence was higher for protease inhibitors (incidence rate ratio 1.37; 95% confidence interval 1.05 to 1.78) and lower for integrase inhibitors (INSTIs) (incidence rate ratio 0.64; 95% confidence interval: 0.43 to 0.96). In addition, blips were associated with higher zenith VL, higher VL test frequency, and shorter time since antiretroviral therapy initiation. PLWH experiencing blips were more likely to demonstrate persistent low-level viremia but not virologic failure. Blips led to extra consultations and measurements. INSTI-based regimens display a low number of blips. Although we found no correlation with virologic failure, the occurrence of blips led to an increased clinical burden. Further research is needed to elucidate the implications and underlying mechanisms of these findings.

Predictors and Timing to Viral Suppression in HIV-Infected Pregnant Women in the University of Zimbabwe Birth Cohort Study During the Era of Lifelong Antiretroviral Therapy (Option B+ Treatment Strategy)

BackgroundAchieving 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.MethodsHIV-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.ResultsFrom 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 &amp;gt; 1,000 copies/ml) was observed in 133 (21.9%) women being 76.2, 27.4 and 7.7% in self-reported-ART-naïve, 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 &amp;gt;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.DiscussionLack 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.Clinical Trial Registrationwww.ClinicalTrials.gov, identifier: NCT04087239.

Progressive Multifocal Leukoencephalopathy Presenting as Expressive Aphasia in a Lung Transplant Recipient

IntroductionProgressive multifocal leukoencephalopathy (PML) is a demyelinating brain disease caused by reactivation of JC virus in immunocompromised patients. PML typically manifests with subacute neurologic deficits including altered mental status, motor deficits, limb ataxia, gait ataxia, and visual symptoms. We report an atypical presentation of PML in a lung transplant recipient (LTR).Case ReportA 71-year-old LTR received rituximab induction followed by a combination of mycophenolate mofetil, tacrolimus, and prednisone. He had a single episode of minimal acute cellular rejection early after LT, but never required significantly augmented immunosuppression. Notably, he had mild leukopenia throughout his post-LT course (WBC count 3-4 thousand/µL), and he had no response to 4 doses of the Pfizer SARS-CoV-2 vaccine, suggesting advanced immunosuppression. At 14 months after LT, the patient reported progressive anomia and aphasia, but no other neurologic deficits. MRI showed an abnormal increased T2/FLAIR signal in the left posterior parieto-occipital subcortical white matter, involving subcortical U fibers, characteristic of PML (Figure A, C). Serum JC virus PCR showed low-level viremia, but CSF from 2 lumbar punctures was PCR negative. Thus, he was diagnosed with possible PML, and immunosuppression was narrowed to a combination of tacrolimus (goal trough 4-6) and prednisone, 5 mg daily. Despite reduced immunosuppression, a repeat MRI 2 months after the initial diagnosis showed worsening PML (Figure B, D) and his symptoms progressed to severe anomia, aphasia, and cortical blindness, but still no motor deficits.SummaryPML is a rare, albeit well described, complication of LT, but presentation with only anomia and aphasia is unusual. Without CSF viral isolation, a definitive diagnosis requires brain tissue; however, MRI changes involving subcortical U fibers in the parieto-occipital area are highly characteristic. Early recognition allows for expeditious management. Progressive multifocal leukoencephalopathy (PML) is a demyelinating brain disease caused by reactivation of JC virus in immunocompromised patients. PML typically manifests with subacute neurologic deficits including altered mental status, motor deficits, limb ataxia, gait ataxia, and visual symptoms. We report an atypical presentation of PML in a lung transplant recipient (LTR). A 71-year-old LTR received rituximab induction followed by a combination of mycophenolate mofetil, tacrolimus, and prednisone. He had a single episode of minimal acute cellular rejection early after LT, but never required significantly augmented immunosuppression. Notably, he had mild leukopenia throughout his post-LT course (WBC count 3-4 thousand/µL), and he had no response to 4 doses of the Pfizer SARS-CoV-2 vaccine, suggesting advanced immunosuppression. At 14 months after LT, the patient reported progressive anomia and aphasia, but no other neurologic deficits. MRI showed an abnormal increased T2/FLAIR signal in the left posterior parieto-occipital subcortical white matter, involving subcortical U fibers, characteristic of PML (Figure A, C). Serum JC virus PCR showed low-level viremia, but CSF from 2 lumbar punctures was PCR negative. Thus, he was diagnosed with possible PML, and immunosuppression was narrowed to a combination of tacrolimus (goal trough 4-6) and prednisone, 5 mg daily. Despite reduced immunosuppression, a repeat MRI 2 months after the initial diagnosis showed worsening PML (Figure B, D) and his symptoms progressed to severe anomia, aphasia, and cortical blindness, but still no motor deficits. PML is a rare, albeit well described, complication of LT, but presentation with only anomia and aphasia is unusual. Without CSF viral isolation, a definitive diagnosis requires brain tissue; however, MRI changes involving subcortical U fibers in the parieto-occipital area are highly characteristic. Early recognition allows for expeditious management.

HIV-1 drug resistance mutations among individuals with low-level viraemia while taking combination ART in Botswana.

To assess whether a single instance of low-level viraemia (LLV) is associated with the presence of drug resistance mutations (DRMs) and predicts subsequent virological failure (VF) in adults receiving ART in 30 communities participating in the Botswana Combination Prevention Project. A total of 6078 HIV-1 C pol sequences were generated and analysed using the Stanford HIV drug resistance database. LLV was defined as plasma VL = 51-999 copies/mL and VF was defined as plasma VL ≥ 1000 copies/mL. Among 6078 people with HIV (PWH), 4443 (73%) were on ART for at least 6 months. Of the 332 persons on ART with VL > 50 copies/mL, 175 (4%) had VL ≥ 1000 copies/mL and 157 (4%) had LLV at baseline. The prevalence of any DRM was 57 (36%) and 78 (45%) in persons with LLV and VL ≥ 1000 copies/mL, respectively. Major DRMs were found in 31 (20%) with LLV and 53 (30%) with VL ≥ 1000 copies/mL (P = 0.04). Among the 135 PWH with at least one DRM, 17% had NRTI-, 35% NNRTI-, 6% PI- and 3% INSTI-associated mutations. Among the 3596 participants who were followed up, 1709 (48%) were on ART for ≥6 months at entry and had at least one subsequent VL measurement (median 29 months), 43 (3%) of whom had LLV. The OR of experiencing VF in persons with LLV at entry was 36-fold higher than in the virally suppressed group. A single LLV measurement while on ART strongly predicted the risk of future VF, suggesting the use of VL > 50 copies/mL as an indication for more intensive adherence support with more frequent VL monitoring.

Factors associated with human immunodeficiency virus-1 low-level viremia and its impact on virological and immunological outcomes: A retrospective cohort study in Beijing, China.

We evaluated the impact of low-level viremia (LLV) on virological failure and immune reconstitution among people living with human immunodeficiency virus type 1 (HIV-1) treated with different antiretroviral regimens in Beijing, China. Human immunodeficiency virus type 1-positive adults who were registered at an infectious disease hospital in Beijing between January 1, 2005 and January 1, 2020 were administered antiretroviral therapy (ART) and whose viral load and CD4 counts were monitored were included in this retrospective cohort study. Univariate and multivariate logistic regression analyses were performed to identify risk factors associated with LLV in patients on different ART regimens. Cox proportional hazard model was employed to analyze the virological suppression and immune reconstitution cumulative probability in patients with LLV during follow-up. A total of 10124 HIV-1-infected participants was included. LLV occurred in 723 (8.2%), 204 (10.9%), 133 (8.6%), and 53 (14.4%) patients on first-line ART, second-line ART, third-line ART, and simplified regimens, respectively. Virological failure occurred in 514 (5.8%), 289 (15.5%), 86 (5.5%), and 34 (9.2%) patients on first-line ART, second-line ART, third-line ART, and simplified regimens, respectively. Earlier enrollment, lower baseline CD4 count, and higher baseline viral load were risk factors associated with LLV. LLV was related to increased hazards of virological failure compared to viral suppression of ≤50copies/ml for those on first-line ART. The risk of virological failure and poor immune reconstitution increases when LLV occurs. Targeted viral load and CD4 count monitoring are recommended for people living with HIV-1 with LLV to improve health-related outcomes.

Predictors of low-level HIV viraemia and virological failure in the era of integrase inhibitors: A Spanish nationwide cohort.

To pinpoint factors associated with low-level viraemia (LLV) and virological failure (VF) in people living with HIV in the era of high-efficacy antiretroviral treatment (ART) and widespread use of integrase strand transfer inhibitor (INSTIs)-based ART. We included adults aged >18years starting their first ART between 2015 and 2018 in the Spanish HIV/AIDS Research Network National Cohort (CoRIS). Low-level viraemia was defined as plasma viral load (pVL) of 50-199 copies/mL at weeks 48 and 72 and VF was defined as pVL ≥50 copies/mL at week 48 and pVL ≥200 copies/mL at week 72. Multivariable logistic regression models assessed the impact on LLV and VF of baseline CD4 T-cell count, CD4/CD8 T-cell ratio and pVL, initial ART classes, age at ART initiation, time between HIV diagnosis and ART initiation, gender and transmission route. Out of 4186 participants, 3120 (76.0%) started INSTIs, 455 (11.1%) started boosted protease inhibitors (bPIs) and 443 (10.8%) started nonnucleoside reverse transcriptase inhibitors (NNRTIs), either of them with two nucleos(t)ide reverse transcriptase inhibitors (NRTIs). Low-level viraemia was met in 2.5% of participants and VF in 4.3%. There were no significant differences throughout the years for both virological outcomes. Baseline HIV-1 RNA >5log10 copies/mL was the only consistent predictor of higher risk of LLV [adjusted odds ratio (aOR) = 9.8, 95% confidence interval (CI): 2.0-48.3] and VF (aOR = 5.4, 95%CI: 1.9-15.1), even in participants treated with INSTIs. The rates of LLV and VF were low but remained steady throughout the years. Baseline HIV-1 RNA >5log10 copies/mL showed a persistent association with LLV and VF even in participants receiving INSTIs.

Outcomes of persistent low-level viremia among HIV patients on antiretroviral therapy: A prospective cohort study.

We aimed to investigate the relationship between low-level viremia (LLV) and virological failure (VF), death, and non-AIDS events (NAEs). A prospective cohort study of people living with HIV (PLHIV) on antiretroviral therapy (ART) was conducted from 2011-2018 at an HIV clinic in Shenyang, China. The incidence of VF and the mortality and NAEs due to LLV were assessed. Cox proportional hazards regression was performed to investigate risk factors for VF, mortality, and NAEs. In total, 1288 patients, contributing 3915 person-years of follow-up (median follow-up, 2.5years [interquartile range: 2-4years]), were enrolled. Thirty-one patients (2.4%) experienced VF, 5 (0.4%) died, and 38 (3.0%) experienced NAEs. The risk of VF was significantly increased among patients with a viral load (VL) of 200-499 copies/mL (adjusted hazard ratio [aHR]: 14.92, 95% confidence interval [CI]: 5.92-37.60) or 500-999 copies/mL (aHR: 13.68, 95% CI: 3.61-51.87), but not among patients with a VL of 50-199 copies/mL (aHR: 3.10, 95% CI: 0.86-11.09). The risk of NAEs was significantly increased among patients with LLV (aHR: 7.33, 95% CI: 3.73-14.42). Compared to no LLV, a VL of 50-199 copies/mL (aHR: 4.11, 95% CI: 1.73-9.74), 200-499 copies/mL (aHR: 18.31, 95% CI: 6.66-50.33), and 500-999 copies/mL (aHR: 21.34, 95% CI: 5.69-80.01) showed higher risk of NAEs. Low-level viremia was associated with VF and NAEs. Patients with LLV, especially those with a VL ≥200 copies/mL, may need more frequent VL testing and NAE screening.

Low-level Viremia in Treated HIV-1 Infected Patients: Advances and Challenges

Antiretroviral therapy (ART) can effectively suppress HIV-1 replication, improving quality of life and restoring the lifespan of persons living with HIV (PLWH) to near-normal levels. However, after standardized ART, a low level of HIV-1 RNA, i.e., low-level viremia (LLV), may still be identified in 3% to 10% of the patients. LLV is capable of impacting the immunological and clinical outcomes of patients and serves as a risk factor for transmission. The underlying mechanism of LLV is not yet certain, and the effects of LLV on patient outcomes remain under evaluation. Understanding LLV will allow effective prevention and control strategies to be designed for the benefit of PLWH.

HIV viral load non-suppression and associated factors among pregnant and postpartum women in rural northeastern South Africa: a cross-sectional survey

ObjectivesWe aimed to measure the prevalence of maternal HIV viral load (VL) non-suppression and assess associated factors, to evaluate progress towards United Nations-AIDS (UNAIDS) targets.DesignCross-sectional study.SettingThe eight largest community health...

Risk factors for very low-level viremia in patients with chronic hepatitis B virus infection: A single-center retrospective study

Background and aimSeveral effective antiviral drugs are now available; however, the risk of liver-related complications is still present. Low-level viremia (LLV), defined as a hepatitis B virus (HBV) deoxyribonucleic acid (DNA) load lower than 2000 IU/mL, is one of the major factors responsible for these complications. It has been reported that 22.7–43.1% of patients with HBV experience LLV. Herein, we aimed to explore the risk factors for very LLV (VLLV) during antiviral treatment. MethodsWe collected data of patients with chronic hepatitis B (CHB) who received nucleos(t)ide analog treatment from October 2016 to April 2021. VLLV was defined as an HBV DNA load of 9–20 IU/mL. A total of 139 patients with LLV were matched with 139 patients with a sustained virological response at a 1:1 ratio according to age and gender. ResultsSeropositivity rates for hepatitis B e antigen (HBeAg) (45.3% vs. 17.3%, P < 0.001) and hepatitis B surface antigen (HBsAg, 3.11 ± 0.68 lg IU/mL vs. 2.54 ± 1.04 lg IU/mL, P < 0.001) and alanine aminotransferase levels (30.34 ± 15.08 U/L vs. 26.15 ± 16.66 U/L, P = 0.040) in the two groups were significantly different. The multivariate analysis showed that both HBeAg seropositivity (adjusted odd ratio (aOR), 3.63; 95% confidence interval (CI): 1.98–6.64; P < 0.001) and HBsAg levels (aOR, 2.21; 95% CI: 1.53–3.20; P < 0.001) are independent risk factors for VLLV. During the multivariate analysis in the subgroup of HBeAg-positive patients, male gender (aOR, 3.68; 95% CI: 1.23–10.76; P = 0.017) and high HBsAg (aOR, 4.86; 95% CI: 1.73–13.64; P = 0.003) levels were significantly correlated with VLLV. However, this was not the case in HBeAg-negative patients (P > 0.050). HBeAg seropositivity (aOR, 5.08; 95% CI: 2.15–12.02; P < 0.001 vs. aOR, 2.78; 95% CI: 1.16–7.00; P = 0.022) and HBsAg levels (aOR, 2.75; 95% CI: 1.41–5.37; P = 0.003 vs. aOR, 2.10; 95% CI: 1.27–3.46; P = 0.004) significantly increased the risk of VLLV, irrespective of the age group. Both HBsAg (area under the receiver operating characteristic curve (AUC), 0.681; 95% CI: 0.623–0.736; P < 0.001) and HBeAg (AUC, 0.640; 95% CI: 0.581–0.697; P < 0.001) had certain predictive value for VLLV. ConclusionHBeAg seropositivity and higher HBsAg levels were not only risk factors for VLLV but also predicted its occurrence. When a patient with CHB remains HBeAg seropositive with high HBsAg levels after antiviral treatment for 48 weeks, emphasis should be placed on the potential occurrence of VLLV, warranting the use of highly sensitive HBV DNA detection methods.

Incidence of low-level viremia and its impact on virologic failure among people living with HIV-1 who switched to elvitegravir-based antiretroviral therapy

We aimed to investigate the incidence of low-level viremia (LLV) and its impact on virologic failure (VF) in people living with HIV (PLWH) on stable antiretroviral therapy (ART) who switched to co-formulated elvitegravir, cobicistat, emtricitabine and tenofovir alafenamide (EVG/c/FTC/TAF). PLWH aged 18 years or older who had received ART with plasma HIV RNA load (PVL) <50 copies/mL for 6 months or longer and switched to EVG/c/FTC/TAF between March and October 2018 were retrospectively included. The incidence of LLV (defined as PVL of 50-999 copies/mL) and VF (PVL ≥1000 copies/mL) was calculated and represented by Kaplan-Meier plots. The generalised estimating equation model was constructed to identify factors associated with LLV and VF. Resistance-associated mutations were determined using population sequencing. A total of 1078 PLWH were included. The incidence rates of LLV and VF after the switch to EVG/c/FTC/TAF were 3.5 and 0.8 events per 100 person-years of follow-up, respectively, whereas the respective cumulative incidence of LLV and VF reached 11.7% and 2.9% within 3 years of follow-up. LLV was associated with any LLV episode before or after the switch and prior exposure to integrase strand transfer inhibitor-based ART. VF was associated with any LLV before or after the switch and prior exposure to raltegravir, but not the level or frequency of LLV. The risks of LLV and VF were low in PLWH who had achieved virologic suppression and switched to EVG/c/FTC/TAF, and the presence of LLV and prior exposure to raltegravir increased the risk of VF.

Scheduled administration of virus-specific T cells for viral prophylaxis after pediatric allogeneic stem cell transplant

AbstractInfections with double-stranded DNA viruses are a significant cause of morbidity and mortality in pediatric patients following allogeneic hematopoietic stem cell transplantation (HSCT). Virus-specific T-cell therapies (VSTs) have been shown to be an effective treatment for infections with adenovirus, BK virus, cytomegalovirus (CMV), and Epstein-Barr virus (EBV). To date, prophylactic regimens to prevent or mitigate these infections using conventional antiviral medications provide suboptimal response rates. Here we report on a clinical trial (NCT03883906) performed to assess the feasibility of rapid manufacturing and early infusion of quadrivalent VSTs generated from stem cell donors (“donor-derived VSTs”) into allogeneic HSCT recipients with minimal or absent viremia. Patients were eligible to receive scheduled VSTs as early as 21 days after stem cell infusion. Twenty-three patients received scheduled VSTs. Twenty of 23 patients had no viremia at the time of infusion, while 3 patients had very low-level BK viremia. Two developed clinically significant graft-versus-host disease (GVHD), although this incidence was not outside of expected incidence early after HSCT, and both were successfully treated with systemic corticosteroids (n = 2). Five patients were deemed treatment failures. Three developed subsequent significant viremia/viral disease (n = 3). Eighteen patients did not fail treatment, 7 of whom did not develop any viremia, while 11 developed low-level, self-limited viremia that resolved without further intervention. No infusion reactions occurred. In conclusion, scheduled VSTs appear to be safe and potentially effective at limiting serious complications from viral infections after allogeneic transplantation. A randomized study comparing this scheduled approach to the use of VSTs to treat active viremia is ongoing.

HIV: how to manage low-level viraemia in people living with HIV.

BackgroundPeople living with HIV (PLWH) and receiving antiretroviral therapy (ART) have a goal of achieving and maintaining viral suppression; however, low-level viraemia (LLV) (HIV-RNA viral load levels of 50–999 copies/mL) persists in certain patients despite consistent medication adherence, lack of drug interactions and no genotypic resistance. This is a narrative review of the growing evidence of LLV in PLWH to determine risk factors and ART management strategies and to discuss the implications of LLV on the development of future virological failure.MethodsA systematic, comprehensive literature search was completed in the English language using PubMed, Google Scholar and bibliography review to gather information about LLV in PLWH between July 2014 and June 2021. The following keywords were used as search terms: “low-level viremia”, “HIV”, “viral blip”, “intensification”, “genotyping”, “adherence” and “resistance.”ResultsOf 66 studies examined, 39 were analysed and included in this review. All trials included were published between 2014 and 2021. Eleven studies assessed risk factors for LLV. Identified risk factors were low CD4+ T cell nadir counts at baseline, higher baseline viral load measurements, medication non-adherence, non-nucleoside reverse transcriptase inhibitor use and others. Three studies assessed genotyping and concluded that the interpretation of both historical RNA genotype resistance testing and current proviral DNA genotype resistance testing in patients with LLV is appropriate. Seven studies were evaluated and determined that modifying or intensifying ART regimens resulted in decreased incidence of virological failure.ConclusionThis compilation of reviewed data gives a framework for the management of PLWH with LLV. Currently, there are no clear or definitive treatment directions for LLV provided in guidelines. Complicating this topic further is the unclear and varying definitions of LLV. Future research is needed on this topic but patients presenting with LLV should have their medication adherence assessed, drug interactions checked and ART intensified, where appropriate.

Low Level Viremia Among People Living with HIV-1 in Nigeria

Low Level Viremia Among People Living with HIV-1 in Nigeria

Severe Hepatic Steatosis Is Associated With Low-Level Viremia and Advanced Fibrosis in Patients With Chronic Hepatitis B in North America.

The obesity epidemic has increased the risk of nonalcoholic fatty liver disease (NAFLD) in both the general and chronic hepatitis B (CHB) populations. Our study aims to determine the prevalence of NAFLD in patients with CHB based on controlled attenuation parameter (CAP) and the epidemiological, clinical, and virological factors associated with severe hepatic steatosis. The Canadian Hepatitis B Network cohort was utilized to provide a cross-sectional description of demographics, comorbidities, antiviral treatment, and hepatits B virus (HBV) tests. Liver fibrosis and steatosis were measured by transient elastography and CAP, respectively. Any grade and severe steatosis were defined as CAP >248 and>280 dB/m, respectively. Advanced liver fibrosis was defined as transient elastography measurement >10.7 kPa. In 1178 patients with CHB (median age: 47.4%, 57.7% males, 75.7% Asian, 13% African, 6.5% White, 86% HBV e antigen negative, median HBV DNA of 2.44 log10IU/mL, 42.7% receiving treatment), the prevalence of any grade and severe steatosis was 53% and 36%, respectively. In the multivariate analysis, obesity was a significant predictor for severe steatosis (adjusted odds ratio: 5.046, 95% confidence interval: 1.22-20.93). Severe steatosis was a determinant associated with viral load (adjusted odds ratio: 0.385, 95% confidence interval: 0.20-0.75, P<.01; r=-0.096, P=.007) regardless of antiviral therapy, age, and alanine aminotransferase levels. In this large multiethnic CHB population, hepatic steatosis is common. Severe steatosis is independently associated with higher fibrosis, but negatively with HBV DNA, regardless of antiviral therapy history.

Study of the Factors that Influence Low-Level Viremias in Human Immunodeficiency Virus Patients in a Tertiary Hospital

Background Low-level viremias (LLVs) can be associated with age, suboptimal adherence, antiretroviral therapy (ART), and local epidemiology. The objective of the study was to analyze the influence of adherence and ART on the LLVs of human immunodeficiency virus patients in a tertiary hospital. Methods A descriptive, multidisciplinary, observational, and retrospective study of human immunodeficiency virus–naive patients who started ART between 2013 and 2018, who have not undergone changes in their ART, and who have been on treatment for at least 1 year was conducted. The following are the variables of the study: age, sex, ART, treatment start date, degree of adherence, and existence of LLVs. Results The sample included 153 patients (83.7% men) with a median age of 40 years (12–82 years). Of the patients who started with a nonnucleotide analog reverse-transcriptase inhibitor as the third drug, 26.8% (n = 56) presented with LLVs, 62.5% (n = 16) with an enhanced protease inhibitor (PI), and 42.7% (n = 75) with an integrase inhibitor. Fifty-seven patients (37.3%) presented with LLVs, with 48 (84.2%) having high adherence (≥90%). Statistically significant differences were observed in the presence of LLVs in patients who started with nonnucleotide analog reverse-transcriptase inhibitor as the third drug (P = 0.025) and in those patients with PI as the third drug (P = 0.047). In patients with LLVs, statistically significant differences were observed in the adherence of patients with PI (P = 0.041). Conclusions A relationship was observed between low adherence, PI as the third drug, and LLVs. In patients with possible poor adherence to ART, a third drug with a high genetic barrier was used, but this did not prevent the presence of LLVs, making it necessary to use other strategies and closely monitor these patients.