Low-level Viremia Research Articles

Prevalence and Associated Factors of Low-Level Viremia in Chronic Hepatitis B Patients After Long-Term Therapy with Nucleos(t)ide Analogs.

Low-level viremia is usually defined as a detectable but lower than 2000 IU/mL hepatitis B virus DNA level after 12 months or longer duration of antiviral therapy in chronic hepatitis B patients. In this study, we aimed to clarify the factors associated with lowlevel viremia in patients during long-term monotherapy with tenofovir disoproxil fumarate or entecavir. Chronic hepatitis B patients having received entecavir or tenofovir disoproxil fumarate treatment for 12 months or more were enrolled from October 2019 to October 2021 at a tertiary hospital in Shanghai, China. In accordance with their hepatitis B virus DNA levels, chronic hepatitis B patients were grouped into 3 categories, hepatitis B virus DNA > 2000 IU/mL, low-level viremia, and complete virological response (hepatitis B virus DNA < 10 IU/mL). Compared with complete virological response patients, factors related to lowlevel viremia were evaluated. This study enrolled a total of 160 chronic hepatitis B patients, whose duration of treatment ranged from 12 to 144 months. In total, 107 patients achieved complete virological response, 51 showed low-level viremia, and 2 showed hepatitis B virus DNA > 2000 IU/mL. After multivariate logistic regression analysis, hepatitis e antigen-positivity (odds ratio = 6.479, 95% CI: 2.480-16.922, P = .000), entecavir treatment (odds ratio = 4.742, 95% CI: 1.855-12.118, P = .001), and duration of therapy (odds ratio = 0.168, 95% CI: 0.072-0.388, P = .000) were independently associated with low-level viremia. Having received long-term antiviral treatment, low-level viremia still occurred in 31.9% of patients. Longer duration of therapy was a protective factor, and HBeAg-positivity and entecavir treatment were risk factors for low-level viremia.

The association between low-level viraemia and subsequent viral non-suppression among people living with HIV/AIDS on antiretroviral therapy in Uganda.

Uganda's efforts to end the HIV epidemic by 2030 are threatened by the increasing number of PLHIV with low-level viraemia (LLV). We conducted a study to determine the prevalence of LLV and the association between LLV and subsequent viral non-suppression from 2016 to 2020 among PLHIV on ART in Uganda. This was a retrospective cohort study, using the national viral load (VL) program data from 2016 to 2020. LLV was defined as a VL result of at least 50 copies/ml, but less than 1,000 copies/ml. Multivariable logistic regression was used to determine the factors associated with LLV, and cox proportional hazards regression model was used to determine the association between LLV and viral non-suppression. A cohort of 17,783 PLHIV, of which 1,466 PLHIV (8.2%) had LLV and 16,317 (91.8%) had a non-detectable VL was retrospectively followed from 2016 to 2020. There were increasing numbers of PLHIV with LLV from 2.0% in 2016 to 8.6% in 2020; and LLV was associated with male sex, second line ART regimen and being of lower age. 32.5% of the PLHIV with LLV (476 out of 1,466 PLHIV) became non-suppressed, as compared to 7.7% of the PLHIV (1,254 out of 16,317 PLHIV) with a non-detectable viral load who became non-suppressed during the follow-up period. PLHIV with LLV had 4.1 times the hazard rate of developing viral non-suppression, as compared to PLHIV with a non-detectable VL (adjusted hazard ratio was 4.1, 95% CI: 3.7 to 4.7, p < 0.001). Our study indicated that PLHIV with LLV increased from 2.0% in 2016 to 8.6% in 2020, and PLHIV with LLV had 4.1 times the hazard rate of developing viral non-suppression, as compared to PLHIV with a non-detectable VL. Hence the need to review the VL testing algorithm and also manage LLV in Uganda.

Real world use of dolutegravir two drug regimens.

Since 2015, we prescribed dolutegravir (DTG)-based two drug regimens (DTG-2DR) for 620 people [total cohort 3133 (19.8%)]. Clinic database search 1 January 15 to 31 October 21. Demographic, tolerability and HIV related data analysed. In total, 620 people identified; 561 had complete data. 446 male (79.5%); median age 54 years (interquartile range 46, 59). 343 (61.1%) MSM. Nine people who initiated naïvely achieved viral suppression (100%). 546/552 (99.0%) switched or continued and were suppressed at data censor. 460/552 (83.3%) received DTG-lamivudine (DTG/3TC), 74/552 (13.4%) received DTG-rilpivirine (DTG/RPV) and 18/552 (3.3%) received DTG-emtricitabine (DTG/FTC). 70 (12.5%) switched off DTG-2DR (55 DTG/3TC, 13 DTG/RPV, two DTG/FTC) due to side-effects. 41 episodes of blip (1 off >50 copies/ml) occurred in 30 people (5.3%). 11/41 on DTG-RPV [ n = 7 multi-tablet regimen (MTR), n = 4 single tablet regimen (STR)]. 27/41 DTG-3TC, 3/41 DTG/FTC ( n = 26 MTR, n = 4 STR). Six people (1.1%) failed (confirmed viral load >200 copies/ml or persistent low level viraemia) ( n = 4 DTG-3TC STR, n = 1 DTG-3TC MTR, n = 1 DTG-RPV MTR). Four failures due to low level viraemia, one due to non-adherence and one due to high viral load. Resistance tests performed for 5/6 - mutations detected only in latter person with high viral load failure (on DTG-3TC MTR) who developed triple class resistance. Majority of experience is in DTG/3TC stable switch. Minority of patients developed side-effects. Low number of virological failures, one developed integrase inhibitor resistance. Viral failure associated with MTR, commensurate with trial data showing no failure with resistance if DTG/3TC STR used. Overall DTG-2DR demonstrates high efficacy in real-world setting.

Does menopause transition influence viral suppression and adherence in Women living with HIV?

Increasing numbers of women living with HIV transition through menopause. It is unclear if this transition has an impact on treatment adherence, viral suppression, psychiatric comorbidities or drug use. We aimed at examining adherence and viral suppression during the perimenopausal period and explored the influence of psychiatric comorbidities and active injection drug use (IDU). Retrospective Swiss HIV Cohort Study analysis from 01/2010 to 12/2018. We explored peri- and postmenopausal trends of viral blips, low-level viremia, viral failure, adherence, psychiatric comorbidities and IDU using interrupted time series (ITS) models. Rates of depression and psychiatric care increased during perimenopause before decreasing afterwards. Negative treatment outcomes such as viral blips, low-level viremia, viral failure and low adherence steadily declined while transitioning through menopause - this was also true for subgroups of women with depression, psychiatric treatment and active IDU. Increased rates of depression and psychiatric care while transitioning through menopause do not result in lower rates of adherence or viral suppression in women living with HIV in Switzerland.

Inflammatory Cytokines in Persistent Low-Level Viremia in Human Immunodeficiency Virus-1 Patients on Combination Antiretroviral Therapy in Western Kenya

Inflammatory Cytokines in Persistent Low-Level Viremia in Human Immunodeficiency Virus-1 Patients on Combination Antiretroviral Therapy in Western Kenya

HIV Virologic Failure among Patients with Persistent Low-Level Viremia in Nairobi, Kenya: It Is Time to Review the >1000 Virologic Failure Threshold.

Persistent low-level viremia (PLLV) of 200-999 copies/ml has been reported as a risk factor for HIV virologic failure (VF). This retrospective study was aimed at characterizing patients with PLLV, determining factors associated with VF, and determining the effect of regimen change. Data were extracted from electronic medical records for HIV care and treatment. Patients' characteristics (N = 705) were as follows: a mean age of 42 years, majority female (55%), and 51% married. A majority (78.7%) had a history of opportunistic infections in their ART lifetime. To determine factors associated with VF, 187 records on patients who maintained PLLV and 12 on deceased patients at the time of data review were eliminated from the analysis, leaving 506 patient records. Out of the 506, 89% (451/506) suppressed VL to nondetectable levels while 11% (55/506) had VF, and the difference was significant (P = 0.0001). Virologic failure was significantly associated with ages 10-30 years (P < 0.05). Baseline VL ≥ 1000 (OR 3.929; P = 0.002) and 200-999 copies/ml (OR 4.062; P = 0.004) were associated with VF. During PLLV, factors associated with VF included the following: PLLV of 200-999 copies/ml (P < 0.05), viral blips (OR 4.545; P = 0.0001), mean maximum VL (P < 0.05), and age (P = 0.043). Married marital status was inversely associated with VF (OR 0.318; P = 0.026). Regimen change was not significantly associated with virologic outcomes. However, patients who switched regimens to the second line had a high risk of VF (P = 0.028; OR 3.203). Regimen change was significantly high (P < 0.05) among adolescents and patients with a start regimen of 2NRTI+1NNRTI. Most of the PLLV patients (89%) achieved nondetectable VL after their continued ART monitoring for at least 12 months. Therefore, PLLV was not an indicator of VF. However, a consistent VL of ≥200-999 copies/ml at baseline and more than 12 months of ART care and treatment were significantly associated with VF. Patients with VL 200-999 copies/ml, adolescents, and young adults require intensive ART monitoring and support.

Humoral Response after Two Doses of BNT162b2 mRNA Vaccine Has a Role in Predicting Response after Three Doses That Is Related to Plasma HIV Viremia and Nadir CD4+ Cell Count in HIV-Positive Patients.

We investigated the spike IgG levels of HIV+ patients on antiretroviral therapy six months after they received their second dose (T2) and six months after the third dose (T3) of the BNT162b2 mRNA vaccine, as well as the influence of different levels of plasma HIV viremia of overall CD4+ cell count and nadir value on the humoral time course. One hundred eighty-four patients were enrolled. The median age was 55 years, the median CD4+ cell count was 639 cells/mm3 and the median nadir value was 258 cells/mm3. On the basis of all tests performed during the study period, persistently undetectable plasma HIV RNA (PUD) was found in 66 patients, low-level viremia (LLV) in 57 and ongoing viremia (OV) in 61. Serum levels of IgG antibodies against a trimeric S-protein antigen were tested with DiaSorin Liaison SARS-CoV-2 TrimericS IgG and the response was classified as optimal (>75th percentile), intermediate (50th−25th percentile) and low (<25th percentile). The frequencies of the three different patterns of plasma HIV viremia (PUD, LLV and OV) were comparable in patients with low, intermediate and optimal IgG response evaluated at T2, with no difference in overall CD4+ cell count or nadir count. At T3, 92.9% of patients achieved an optimal response: T2 response proved to be the most important factor in predicting T3 optimal response in patients with LLV and OV.A nadir value ≤ 330 cells/mm3 had 100% sensitivity in predicting a non-optimal response. In conclusion, we demonstrated the persistence of anti-spike IgG, with high serum levels occurring in most patients six months after the third dose of the BNT162b2 mRNA vaccine and a predictive role of humoral response at T2 in subjects with detectable plasma HIV viremia. Immunological alterations related to past immunodeficiency may persist despite immune reconstitution, and the nadir value could be a useful tool for elaborating personalized vaccine schedules.

Retention on ART and viral suppression among patients in alternative models of differentiated HIV service delivery in KwaZulu-Natal, South Africa.

Differentiated models of HIV care (DMOC) aim to improve health care efficiency. We describe outcomes of five DMOC in KwaZulu-Natal, South Africa: facility adherence clubs (facility AC) and community adherence clubs (community AC), community antiretroviral treatment (ART) groups (CAG), spaced fast lane appointments (SFLA), and community pick up points (PuP). This retrospective cohort study included 8241 eligible patients enrolled into DMOC between 1/1/2012 and 31/12/2018. We assessed retention in DMOC and on ART, and viral load suppression (<1000 copies/mL). Kaplan-Meier techniques were applied to describe crude retention. Mixed effects parametric survival models with Weibull distribution and clustering on health center and individual levels were used to assess predictors for ART and DMOC attrition, and VL rebound (≥1000 copies/mL). Overall DMOC retention was 85%, 80%, and 76% at 12, 24 and 36 months. ART retention at 12, 24 and 36 months was 96%, 93%, 90%. Overall incidence rate of VL rebound was 1.9 episodes per 100 person-years. VL rebound rate was 4.9 episodes per 100 person-years among those enrolled in 2012-2015, and 0.8 episodes per 100 person-years among those enrolled in 2016-2018 (RR 0.12; 95% CI, 0.09-0.15, p<0.001). Prevalence of confirmed virological failure was 0.6% (38/6113). Predictors of attrition from DMOC and from ART were male gender, younger age, shorter duration on ART before enrollment. Low level viremia (>200-399 copies/mL) was associated with higher hazards of VL rebound and attrition from ART. Concurrent implementation of several DMOC in a large ART program is feasible and can achieve sustained retention on ART and VL suppression.

Absence of transmission of vYF next generation Yellow Fever vaccine in mosquitoes.

One of the most effective vaccines against an arbovirus is the YFV-17D live-attenuated vaccine developed in 1937 against Yellow Fever (YF). This vaccine replicates poorly in mosquitoes and consequently, is not transmitted by vectors. Vaccine shortages, mainly due to constrained productions based on pathogen-free embryonated eggs, led Sanofi to move towards alternative methods based on a state-of-the-art process using continuous cell line cultures in bioreactor. vYF-247 is a next-generation live-attenuated vaccine candidate based on 17D adapted to grow in serum-free Vero cells. For the development of a new vaccine, WHO recommends to document infectivity and replication in mosquitoes. Here we infected Aedes aegypti and Aedes albopictus mosquitoes with vYF-247 vaccine compared first to the YF-17D-204 reference Sanofi vaccines (Stamaril and YF-VAX) and a clinical human isolate S-79, provided in a blood meal at a titer of 6.5 Log ffu/mL and secondly, to the clinical isolate only at an increased titer of 7.5 Log ffu/mL. At different days post-infection, virus replication, dissemination and transmission were evaluated by quantifying viral particles in mosquito abdomen, head and thorax or saliva, respectively. Although comparison of vYF-247 to reference vaccines could not be completed to yield significant results, we showed that vYF-247 was not transmitted by both Aedes species, either laboratory strains or field-collected populations, compared to clinical strain S-79 at the highest inoculation dose. Combined with the undetectable to low level viremia detected in vaccinees, transmission of the vYF-247 vaccine by mosquitoes is highly unlikely.

HIV-1C in-House RNA-Based Genotyping Assay for Detection of Drug Resistance Mutations in Samples with Low-Level Viral Loads.

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. 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. 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. 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.

The influence of low-level viremia on CD4+ cell count in human immunodeficiency virus–infected patients

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. 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. 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. 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.

EE592 Long-Term Health and Economic Benefits of Switching to Tenofovir Alafenamide Versus Continuing on Entecavir in Chronic Hepatitis B Patients With Low-Level Viremia in Saudi Arabia

EE592 Long-Term Health and Economic Benefits of Switching to Tenofovir Alafenamide Versus Continuing on Entecavir in Chronic Hepatitis B Patients With Low-Level Viremia in Saudi Arabia

Influencing factors for low-level viremia and their dynamic changes in patients with chronic hepatitis B treated with nucleos(t)ide analogues for the first time

Influencing factors for low-level viremia and their dynamic changes in patients with chronic hepatitis B treated with nucleos(t)ide analogues for the first time

Hepatitis A virus seroprevalence among children and adolescents in a high-burden HIV setting in urban South Africa

Hepatitis A virus (HAV) infection is one of the most important global causes of viral hepatitis. Recent reviews suggested that HAV endemicity in South Africa could shift from high to intermediate. A hospital-based HAV seroprevalence study was conducted between February 2018 and December 2019 in Pretoria, South Africa. Systematic sampling was performed on children and adolescents (1–15 years) who attended outpatient services. Participants with a known HIV status and valid HAV serology results were included. Of the 1220 participants, the median age was 7 years (IQR: 4–11), with 648 (53.11%) males and 572 (46.89%) females. Of 628 (51.48%) HIV-infected participants, most (329, 71.83%) were both immunologically and virologically controlled or had low-level viremia (74, 16.16%). Almost three-quarters (894, 73.28%) were living in formal dwellings, and just over half (688, 56.39%) had access to clean water sources inside the house. Increasing age was associated with testing HAV IgG-positive (OR 1.25; 95% CI 1.20–1.30, p < 0.001), with 19.8% of participants one year of age compared with 86.7% of participants 15 years of age. This study suggests that South Africa has an intermediate HAV seroprevalence, with rates < 90% by 10 years of age (68.6%). Increased age and informal dwellings are statistically associated with HAV seropositivity, while HIV status does not significantly influence HAV seropositivity.

Comparative sensitivity of automated (Abbott M2000) and manual plasma HIV-1 RNA PCR assays for the detection of persistent viremia after long-term antiretroviral therapy

BackgroundThe 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). MethodsPlasma 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 <40 copies/mL by Abbott. Pooled plasma from each donor was divided and tested. Abbott results were reported as target detected <40 copies/mL but not quantifiable (target detected <40) or target not detected (TND), and SCA results were classified as HIV-1 RNA detected or not detected. ResultsBy Abbott, 17% (51/309) of sample results were target detected <40, whereas 83% (258/309) were TND. Of the samples that were target detected <40 by Abbott, 73% (37/51) had HIV-1 RNA detected by SCA. By contrast, 43% of samples that were TND by Abbott (110/258) had HIV-1 RNA detected by SCA (p < 0.001). ConclusionPlasma samples from PWH with HIV-1 RNA detected but <40 copies/ml by the automated Abbott M2000 assay are likely (73% of 51 samples) to have HIV-1 RNA detected by an optimized manual assay with single copy sensitivity. An Abbott HIV-1 RNA result of target not detected did not exclude low-level viremia: 43% of 258 samples had HIV-1 RNA detected by the single copy assay. These findings indicate that the Abbott M2000 assay cannot exclude the persistence of viremia on ART and thus may have less utility, compared to a manual single copy assay, for assessing the impact of experimental interventions designed to eliminate low-level viremia as a step towards achieving ART-free HIV-1 remission.

A Concentration Method for HIV Drug Resistance Testing in Low-Level Viremia Samples.

Drug resistance testing in HIV-1 low-level viremia (LLV) samples is challenging yet critical. Our study is aimed at assessing the performance of lentivirus concentration reagent (LCR) in combination with a validated Sanger sequencing (SS) for monitoring drug resistance mutations (DRMs) in LLV samples. A series of clinical samples were diluted and amplified for genotypic resistance testing (GRT) to prove the performance of the LCR. The Stanford HIV-1 drug resistance database (HIVdb version 8.9) was used to analyze the mutations. HIV-1 subtypes and CRFs were determined using the COMET online tool. The overall success rate of genotyping was compared with ultracentrifugation combined with SS. Furthermore, the success rates at varied VL of the two concentration methods were evaluated, and the DRMs of diluted samples were compared with those undiluted samples. When LCR was used, the overall success rate was 90% (72/80) in the PR and RT regions and 60% (48/80) in the IN region. In addition, when HIV RNA was 1000 copies/ml, 400 copies/ml, 200 copies/ml, and 100 copies/ml, the success rates of PR and RT regions were 100%, 100%, 95%, and 65%, respectively, while the success rates of IN region were 85%, 60%, 45%, and 50%, respectively. We found that the sample DR-387A2 missed the E138A mutation, and mutations in other samples were consistent with undiluted samples using LCR. LCR will support monitoring DRMs in HIV-1 patients with LLV and can be an effective alternative for small- and medium-sized laboratories that cannot afford an ultracentrifuge.

Expanding antiviral therapy for chronic hepatitis B: scale up screening and treatment

The Chinese Society of Hepatology, Chinese Medical Association published "Expert Opinions on Expanding Antiviral Therapy for Chronic Hepatitis B" in 2022, with a focus on "active screening of the existing patients, paying attention to the potential risk of disease progression, and active intervening of the low level viremia," and recommended that specific actions be taken to further optimize the expanding screening, widening the antiviral indications, and scale up the diagnosis and treatment of low level viremia.

Low-level viraemia among people living with HIV in Nigeria: a retrospective longitudinal cohort study

HIV transmission can occur with a viral load of at least 200 copies per mL of blood and low-level viraemia can lead to virological failure; the threshold level at which risk for virological failure is conferred is uncertain. To better understand low-level viraemia prevalence and outcomes, we analysed retrospective longitudinal data from a large cohort of people living with HIV on antiretroviral therapy (ART) in Nigeria. In this retrospective cohort study using previously collected longitudinal patient data, we estimated rates of virological suppression (≤50 copies per mL), low-level viraemia (51-999 copies per mL), virological non-suppression (≥1000 copies per mL), and virological failure (≥2 consecutive virological non-suppression results) among people living with HIV aged 18 years and older who initiated and received at least 24 weeks of ART at 1005 facilities in 18 Nigerian states. We analysed risk for low-level viraemia, virological non-suppression, and virological failure using log-binomial regression and mixed-effects logistic regression. At first viral load for 402 668 patients during 2016-21, low-level viraemia was present in 64 480 (16·0%) individuals and virological non-suppression occurred in 46 051 (11·4%) individuals. Patients with low-level viraemia had increased risk of virological failure (adjusted relative risk 2·20, 95% CI 1·98-2·43; p<0·0001). Compared with patients with virological suppression, patients with low-level viraemia, even at 51-199 copies per mL, had increased odds of low-level viraemia and virological non-suppression at next viral load; patients on optimised ART (ie, integrase strand transfer inhibitors) had lower odds than those on non-integrase strand transfer inhibitors for the same low-level viraemia range (eg, viral load ≥1000 copies per mL following viral load 400-999 copies per mL, integrase strand transfer inhibitor: odds ratio 1·96, 95% CI 1·79-2·13; p<0·0001; non-integrase strand transfer inhibitor: 3·21, 2·90-3·55; p<0·0001). Patients with low-level viraemia had increased risk of virological non-suppression and failure. Programmes should revise monitoring benchmarks and targets from less than 1000 copies per mL to less than 50 copies per mL to strengthen clinical outcomes and track progress to epidemic control. None.

The virological consequences of low-level viraemia

With highly active antiretroviral therapy (ART), people living with HIV can achieve and maintain viral suppression below a detectable level, preventing transmission of HIV and AIDS-related mortality.1,2 However, persistent low-level viraemia (usually defined as plasma HIV-RNA between 50 copies per mL to below the threshold for virological failure) occurs among some people living with HIV receiving ART.3–5 Despite its occurrence, the clinical significance and management of low-level viraemia remains unclear,3,5,6 particularly with dolutegravir-based ART regimen.

HIV-1 Genotypic Resistance Testing Using Sanger and Next-Generation Sequencing in Adults with Low-Level Viremia in China

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. 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. 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 onemutation, 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. Our data suggested that the genotyping resistance testing is necessary to guide antiretroviral therapy optimization in LLV patients.