The RT M184V resistance mutation clearance in the reservoir is mainly related to CD4 nadir and viral load zenith independently of therapeutic regimen type.

OBJECTIVES: Resistance associated mutations (RAMs) are archived in the HIV reservoir and can re-emerge with an inappropriate ART use limiting treatment options. However, recent studies, using ultra-deep sequencing (UDS), showed a decrease of quasispecies harbouring RAMs, suggesting that recycling some antiretrovirals could be considered. The aim of this study was to characterize, in HIV treated PLWHIV, the M184V mutation decrease kinetics in proviral DNA and associated factors of M184V mutation clearance over time. METHODS: UDS was performed on HIV-DNA from blood cells at different time points to quantify the percentage of M184V positive quasispecies. The sequence reads were analysed with a minimum coverage set at 50 and an ambiguity filter at 5% or 2%. RESULTS: At 2.5 years after the first time point, the M184V lost was observed in 50% of PLWHIV. Moreover, univariate analyses highlight that a higher nadir CD4 count and a lower zenith HIV1 RNA viral load were correlated with a faster clearance of the mutation. In multivariate analysis, a higher zenith was negatively associated with the M184V clearance at the 5% threshold. Interestingly, lamivudine/emtricitabine presence in the ART therapy regiment during the 5 years was not associated with the persistence of the M184V. CONCLUSIONS: Our study provides new information concerning the clearance speed of M184V mutation over time in PLWHIV with fully suppressed viremia, opens the discussion about the duration needed to consider a lamivudine/emtricitabine recycling and reinforces the association of the nadir and zenith values with the M184V mutation clearance.

Epidemiological impact of Neisseria gonorrhoeae and Chlamydia trachomatis screening in men having sex with men: a modelling study.

OBJECTIVES: The impact of the systematic screening of Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) in men having sex with men (MSM) on these pathogens' epidemiology remains unclear. We conducted a modelling study to analyse this impact in French MSM. METHODS: We modelled NG and CT transmission using a site-specific deterministic compartmental model. We calibrated NG and CT prevalence at baseline using results from MSM enrolled in the Dat'AIDS cohort. The baseline scenario was based on 1 million MSM, 40 000 of whom were tested every 90 days and 960 000 every 200 days. Incidence rate ratios (IRRs) at steady state were simulated for NG, CT, NG and/or CT infections, for different combinations of tested sites, testing frequency and numbers of frequently tested patients. RESULTS: The observed prevalence rate was 11.0%, 10.5% and 19.1% for NG, CT and NG and/or CT infections. The baseline incidence rate was estimated at 138.2 per year per 100 individuals (/100PY), 86.8/100PY and 225.0/100PY for NG, CT and NG and/or CT infections. Systematically testing anal, pharyngeal and urethral sites at the same time reduced incidence by 14%, 23% and 18% (IRR: 0.86, 0.77 and 0.82) for NG, CT and NG and/or CT infections. Reducing the screening interval to 60 days in frequently tested patients reduced incidence by 20%, 29% and 24% (IRR: 0.80, 0.71 and 0.76) for NG, CT and NG and/or CT infections. Increasing the number of frequently tested patients to 200 000 reduced incidence by 29%, 40% and 33% (IRR: 0.71, 0.60 and 0.67) for NG, CT and NG and/or CT infections. No realistic scenario could decrease pathogens' incidence by more than 50%. CONCLUSIONS: To curb the epidemic of NG and CT in MSM, it would not only be necessary to drastically increase screening, but also to add other combined interventions.

Epidemiology and characteristics of Paget's disease of bone in a French nationwide HIV cohort.

Paget's disease of bone (PDB) has rarely been reported in people with HIV (PWH). We describe the prevalence and characteristics of patients with PDB in the French multicenter Dat'AIDS cohort. Among 49 698 PWH actively followed in 2022, 9 had a diagnosis of PDB. The overall prevalence of PDB was 0.02% [95% confidence interval (CI) 0.01-0.03]. The prevalence of PDB in PWH is very low and does not appear to differ from the non-HIV population.

Experiences of mpox illness and case management among cis and trans gay, bisexual and other men who have sex with men in England: a qualitative study.

Background: The 2022-2024 global mpox outbreak, occurring primarily in the sexual networks of gay, bisexual and other men who have sex with men (GBMSM), has not been accompanied by a focus on patient perspectives of illness. We explore the experiences of GBMSM diagnosed with mpox in England to understand needs for social and clinical support. Methods: In-depth interviews (March/July 2023) were conducted with 22 GBMSM diagnosed with mpox in 2022, randomly selected from a national mpox surveillance database, and 4 stakeholders from clinical/community-based organisations. Interviews covered experiences of illness, testing, diagnosis, treatment and contact tracing, and were recorded, transcribed and analysed with a thematic framework. Findings: Media coverage drawing on homophobic stereotypes around sex between men contributed to feelings of stigma and shame. GBMSM living with HIV appeared to cope better with mpox stigma, drawing on their experiences of being diagnosed with HIV for resilience. Younger GBMSM with less experience of stigmatising illness found mpox diagnosis more traumatic and sometimes required support beyond what was provided. Accessing testing could be complicated when healthcare professionals did not recognise mpox symptoms. Men felt information on course of illness, isolation and vaccination after recovery was often inconsistent and contradictory. GBMSM described that care from sexual health and infectious disease units usually better met their emotional and medical needs. This was frequently linked by men to these services having skills in working with the GBMSM community and managing infection risk sensitively. General hospital services and centralised contact tracing could increase feelings and experiences of stigma as some staff were perceived to lack skills in supporting GBMSM and, sometimes, clinical knowledge. Long-term impacts described by men included mental health challenges, urethral/rectal symptoms and life-changing disability. Interpretation: In this study stigma was a central feature of mpox illness among GBMSM and could be exacerbated or lessened depending on the clinical and social support provided. Involving communities affected by outbreaks in co-producing, planning and delivering care (including contact-tracing) may help improve support provided. Funding: TCW, AJR, AS and FMB received support from the National Institute for Health and Care Research (NIHR) under its Programme Grants for Applied Research Programme (Ref: NIHR202038). CS and JS receive support from the National Institute for Health and Care Research Health Protection Research Unit (NIHR HPRU) in Blood Borne and Sexually Transmitted Infections at UCL in partnership with UKHSA; RV receives support from the NIHR HPRU in Emerging and Zoonotic Infections and NIHR HPRU in Gastrointestinal Infections. The views expressed are those of the author(s) and not necessarily those of the NIHR, UK Health Security Agency, World Health Organization or the Department of Health and Social Care.

Experiences with health care services and HIV testing after sexual assault in cisgender gay, bisexual and other men who have sex with men and transgender people.

OBJECTIVES: This qualitative sub-study aimed to explore how cisgender gay, bisexual, and other men who have sex with men (cis-GBMSM) and transgender people who reported non-consensual sex (NCS) accessed health care services, what barriers they faced, and how this experience influenced subsequent HIV testing. METHODS: SELPHI is an online randomized controlled trial evaluating both acceptability and efficiency of HIV-self testing among cis-GBMSM and transgender people. Semi-structured interviews were conducted, audio-recorded, transcribed, and analysed through a framework analysis, as a qualitative sub-study. We identified narratives of NCS from interviews and investigated experiences of cis-GBMSM and transgender people accessing health care services following sexual assault. RESULTS: Of 95 participants, 15 (16%) spontaneously reported NCS. Participants reported a broad range of NCS, including partner's coercive behaviours, non-consensual removal of condoms, and rapes. All feared HIV transmission, leading them to test for HIV, underlining a marked lack of awareness of post-exposure prophylaxis (PEP). Most had negative experiences in communicating with reception staff in sexual health clinics following these incidents. A lack of confidentiality and empathy was described in these situations of psychological distress. Clinic visits were primarily focused on testing for HIV and sexually transmitted infection, and generally no specific psychological support was offered. Getting a negative HIV result was a key step in regaining control for people who experienced NCS. CONCLUSIONS: Sexual health care providers should take care to more fully address the issue of NCS with cis-GBMSM and transgender people when it arises. Recognizing and managing the emotional impact of NCS on affected patients would prevent negative experiences and increase confidence in care.

High proportion of post-migration HIV acquisition in migrant men who have sex with men receiving HIV care in the Paris region, and associations with social disadvantage and sexual behaviours: results of the ANRS-MIE GANYMEDE study, France, 2021 to 2022.

BackgroundSome migrant men who have sex with men (MSM) acquire HIV in France.AimsWe investigated, in migrant MSM receiving HIV care in France, the (i) rate of post-migration-HIV acquisition in France, (ii) delay between arrival and HIV acquisition and (iii) factors affecting HIV acquisition within 1 year after migration.MethodsThis cross-sectional study focused on ≥ 18-year-old MSM born outside France, receiving HIV care in the Paris region. Information on migration history, socioeconomic condition, sexual activity, and health was collected in May 2021-June 2022 through self-administered questionnaires and medical records. Post-migration-HIV-acquisition rate and delay between arrival in France and HIV acquisition were estimated from biographical data and CD4+ T-cell counts. Predictors of HIV acquisition within 1 year after migration were determined using logistic regression.ResultsOverall post-migration HIV-acquisition rate was 61.7% (715/1,159; 95%CI: 61.2-62.2), ranging from 40.5% (95%CI: 39.6-41.6) to 85.4% (95%CI: 83.9-86.0) in participants from Latin America and North Africa. Among post-migration-HIV acquisitions, those within 1 year after migration represented 13.1% overall (95%CI: 11.6-14.6), being highest in participants from sub-Saharan Africa (25%; 95%CI: 21.5-28.3). Participants ≥ 15-years old at migration, with post-migration-acquired HIV, had a 7.5-year median interval from arrival in France to HIV acquisition (interquartile range (IQR): 3.50-14.75). Older age at arrival, region of origin (sub-Saharan Africa and Asia), degree of social disadvantage and numbers of sexual partners were independently associated with acquiring HIV within 1 year in France.ConclusionOur findings may guide HIV prevention policies for most vulnerable migrants to Europe.

MOSAIC: A cohort study of human mpox virus disease.

Background: Human mpox is a viral disease caused by an Orthopoxvirus, human mpox virus (hMPXV), typically causing fever and a rash. Mpox has historically been endemic to parts of Central and West Africa, with small numbers of imported cases reported elsewhere, but starting May 2022 an unprecedented global outbreak caused by clade IIb hMPXV was reported outside traditionally endemic countries. This prompted the initiation of MOSAIC, a cohort study implemented in Europe and Asia that aims to describe clinical and virologic outcomes of PCR-confirmed hMPXV disease, including those who receive antiviral therapy. The focus of this article, however, is on describing the study protocol itself with implementation process and operational challenges. Methods: MOSAIC recruits participants of any age with laboratory-confirmed mpox disease who provide informed consent. Participants enrol in the cohort for a total of six months. Blood, lesion and throat samples are collected at several timepoints from the day of diagnosis or the first day of treatment (Day 1) until Day 28 for PCR detection of hMPXV. Clinical data are collected by clinicians and participants (via a self-completion questionnaire) for six months to characterize the signs and symptoms associated with the illness, as well as short- and more long-term outcomes. Discussion: The design and prompt implementation of clinical research response is key in addressing emerging outbreaks. MOSAIC began enrolment within two months of the start of the international mpox epidemic. Enrolment has been stopped and the last follow-up visits are expected in January 2024. ICTRP registration: EU CT number: 2022-501132-42-00 (22/06/2022).

Country of birth is associated with discrepancies in the prescription of two-drug regimens in successfully treated people with HIV in France.

OBJECTIVES: We aimed to examine the association of the country of birth and the other patients' characteristics with the prescription of two-drug regimens (2DRs) in virally suppressed people with HIV (PWH) in France. DESIGN: Observational study conducted from the national Dat'AIDS prospectively collected database. METHODS: We included all adults who were actively in care on 31 December 2020 in 26 French centers, with an HIV plasma viral load (pVL) <50 copies/ml for at least 6 months while on antiretroviral therapy (ART). Patients with chronic hepatitis B were excluded because they are not eligible to 2DRs. Univariate and multivariate logistic regressions were built to analyze relationships between patients' characteristics and receiving a 2DR. RESULTS: We analyzed data from 28 395 PWH: 41.7% men who have sex with men, 31.7% women and 26.5% heterosexual men; 35% born abroad. Median age was 53 years [interquartile range (IQR) 44-60]; ART duration 14 years (8-23); duration of virological suppression 87 months (42-142). 2DRs (mainly dolutegravir/rilpivirine, 53.8%, or dolutegravir/lamivudine, 41.7%) were prescribed in 16.3% of the patients and were less common in the 'born abroad' group (18.9% versus 11.5%). The multivariate model showed that individuals born in France were more likely to receive a 2DR [adjusted odds ratio (aOR): 1.62 [1.50-1.74]], independently of other characteristics. Older PLWH and those with higher CD4 + T-cell counts were also more likely to receive a 2DR. CONCLUSION: Despite unrestricted access to ART in France, independently from HIV disease parameters, PWH born abroad were less likely to receive 2DRs as a maintenance regimen than those born in France. Qualitative data are needed to better understand physicians' prescribing practices.

Acquisition du virus de l'immunodéficience humaine et parcours de vie d'hommes ayant des rapports sexuels avec d'autres hommes et ayant émigré en France : une enquête exploratoire.

INTRODUCTION: The ANRS 14058 Ganymede study aims to determine the proportion post-migration HIV-seroconversion in a sample of HIV-positive men having sex with men (MSM) born outside of France and receiving medical care in Paris region (Île-de-France). The study, based on a self-questionnaire, is also focused on the life course of these MSM before, during and after the migration process. PURPOSE OF RESEARCH: The paper refers to a qualitative exploratory study, taking place as a prerequisite for the Ganymede study, in order to refine its questionnaire. The purpose of these interviews was also to explore the migratory motivations and experiences, the sexual biography, and the health history, of a sample of seropositive MSM born outside of France, and to illustrate the diversity of this epidemiological category. RESULTS: Forteen respondents participated in the interview study. Nine of them have learned of their HIV-positive status after having emigrated to France. None of the respondents mentioned a major barrier to medical care access and HIV follow-up. The obstacles they reported were related to the coverage of medical expenses, due to their possible precarious legal and social situation. These men were exposed to the effects of power relations, leading to discrimination and violence, whose wider impacts on health were weakly evoked. CONCLUSIONS: Although the findings of the exploratory study are not to be generalized, they illustrate the health issues of the interviewees, and the wide diversity of their biographies and life courses, emphasizing the impact of gender and class power relations as a source of social and health inequalities, and precariousness. They invite therefore to describe this epidemiological category of "MSM born outside of France" in a more heterogeneous way.

Le 190 a treize ans : l'expérience du premier centre de santé sexuelle français.

Le 190 is a sexual health center in Paris founded in 2010. Its initial objective is to reduce the HIV/AIDS epidemic locally among men who have sex with men (MSM) through multidisciplinary support rooted in the reality of the sexuality and affective life of HIV-positive and HIV-negative MSM. Because of its constant concern for overall gay health and its community character, its activity has diversified and has enabled it to be a forerunner in both care and care pathways, on both the medical and regulatory aspects. Mental health and the complications of chemsex are taking an increasingly important place in the demand for care and the support has been adapted and perfected with the patients. Today, Le 190 is considered a model by many community actors and health professionals and is celebrating its 13th anniversary, an opportunity to share its experience and reaffirm its demonstrated benefit for public health and universal care. The major innovations of the center as well as the limitations and difficulties it has encountered will allow for a better understanding of community health in practice and more specifically gay health.

Doravirine plus lamivudine two-drug regimen as maintenance antiretroviral therapy in people living with HIV: a French observational study.

BACKGROUND: Two-drug regimens based on integrase strand transfer inhibitors (INSTIs) and boosted PIs have entered recommended ART. However, INSTIs and boosted PIs may not be suitable for all patients. We aimed to report our experience with doravirine/lamivudine as maintenance therapy in people living with HIV (PLWH) followed in French HIV settings. METHODS: This observational study enrolled all adults who initiated doravirine/lamivudine between 1 September 2019 and 31 October 2021, in French HIV centres participating in the Dat'AIDS cohort. The primary outcome was the rate of virological success (plasma HIV-RNA < 50 copies/mL) at Week (W)48. Secondary outcomes included: rate of treatment discontinuation for non-virological reasons, evolution of CD4 count and CD4/CD8 ratio over follow-up. RESULTS: Fifty patients were included, with 34 (68%) men; median age: 58 years (IQR 51-62), ART duration: 20 years (13-23), duration of virological suppression: 14 years (8-19), CD4 count: 784 cells/mm3 (636-889). Prior to switching, all had plasma HIV-RNA < 50 copies/mL. All but three were naive to doravirine, and 36 (72%) came from a three-drug regimen. Median follow-up was 79 weeks (IQR 60-96). Virological success rate at W48 was 98.0% (95% CI 89.4-99.9). One virological failure occurred at W18 (HIV-RNA = 101 copies/mL) in a patient who briefly discontinued doravirine/lamivudine due to intense nightmares; there was no resistance at baseline and no resistance emergence. There were three strategy discontinuations for adverse events (digestive disorders: n = 2; insomnia: n = 1). There was no significant change in CD4/CD8 ratio, while CD4 T cell count significantly increased. CONCLUSIONS: These preliminary findings suggest that doravirine/lamivudine regimens can maintain high levels of viral suppression in highly ART-experienced PLWH with long-term viral suppression, and good CD4+ T cell count.

Intermittent doravirine/lamivudine/tenofovir disoproxil fumarate (DOR/3TC/TDF) maintains a high level of viral suppression in virologically suppressed people living with HIV.

INTRODUCTION: We aimed to determine whether doravirine/lamivudine/tenofovir disoproxil fumarate (DOR/3TC/TDF) given 5 or 4 days a week was able to maintain viral suppression in people living with HIV (PLHIV). METHODS: In this observational, retrospective study, we included all PLHIVs who had received intermittent DOR/3TC/TDF between 10/01/2019 and 01/31/2021, in two French hospitals. RESULTS: Forty-three PLHIVs were included, median (IQR) age: 52 years (48-58), ART duration: 15 years (8-23), duration of virological suppression: 6 years (2-10). Median follow-up was 78 weeks (IQR 62-97). One virological failure (VF) occurred at W38 (HIV-RNA = 61 and 76 copies/mL), in a patient with no viral resistance at baseline or at time of VF, and during the study period five individuals discontinued DOR/3TC/TDF due to adverse events. There were no significant changes during follow-up in the CD4 count, CD4/CD8 ratio, body weight or residual viremia rate. CONCLUSION: These findings suggest the potential for intermittent DOR/3TC/TDF to maintain virological control.

Complement-dependent mpox-virus-neutralizing antibodies in infected and vaccinated individuals.

Mpox virus (MPXV) caused a multi-country outbreak in non-endemic areas in 2022. Following historic success of smallpox vaccination with vaccinia virus (VACV)-based vaccines, the third generation modified vaccinia Ankara (MVA)-based vaccine was used as prophylaxis for MPXV, but its effectiveness remains poorly characterized. Here, we applied two assays to quantify neutralizing antibodies (NAbs) in sera from control, MPXV-infected, or MVA-vaccinated individuals. Various levels of MVA NAbs were detected after infection, historic smallpox, or recent MVA vaccination. MPXV was minimally sensitive to neutralization. However, addition of complement enhanced detection of responsive individuals and NAb levels. Anti-MVA and -MPXV NAbs were observed in 94% and 82% of infected individuals, respectively, and 92% and 56% of MVA vaccinees, respectively. NAb titers were higher in individuals born before 1980, highlighting the impact of historic smallpox vaccination on humoral immunity. Altogether, our results indicate that MPXV neutralization is complement dependent and uncover mechanisms underlying vaccine effectiveness.

Intermittent Bictegravir/Emtricitabine/Tenofovir Alafenamide Treatment Maintains High Level of Viral Suppression in Virally Suppressed People Living with HIV.

In this observational study, we aimed to evaluate whether bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) administered 5 or 4 days a week is able to maintain viral suppression in people living with HIV (PLHIV). We enrolled 85 patients who initiated intermittent B/F/TAF between 28 November 2018 and 30 July 2020: median (IQR) age 52 years (46-59), duration of virological suppression 9 years (3-13), CD4 633/mm3 (461-781). Median follow-up was 101 weeks (82-111). The virological success rate (no virological failure [VF]: confirmed plasma viral load [pVL] ≥ 50 copies/mL, or single pVL ≥ 200 copies/mL, or ≥50 copies/mL with ART change) was 100% (95%CI 95.8-100) and the strategy success rate (pVL < 50 copies/mL with no ART regimen change) was 92.9% (95%CI 85.3-97.4) at W48. Two VF occurred at W49 and W70, in 2 patients self-reporting poor compliance. No resistance mutation emerged at time of VF. Eight patients presented strategy discontinuation for adverse events. There was no significant change in the CD4 count, residual viraemia rate, neither body weight during follow-up, but a slight increase in CD4/CD8 ratio (p = 0.02). In conclusion, our findings suggest that B/F/TAF administered 5 or 4 days a week could maintain the control of HIV replication in virologically suppressed PLHIV while reducing cumulative exposition of ART.

Country of birth is associated with antiretroviral therapy choice in treatment-naive persons with HIV in France.

OBJECTIVES: We aimed to describe factors associated with the choice of first antiretroviral therapy (ART) in persons with HIV (PWH) in France, included the country of birth, as well as the time to undetectable viral load and treatment discontinuation. DESIGN: Observational study conducted from the national Dat'AIDS prospectively collected database. METHODS: We included all adults who started their first ART between 01 January 2014 and 31 December 2020, with a pretherapeutic plasma viral load (pVL) at least 400 copies/ml. Univariable and multivariable logistic regressions were used to analyze PWH characteristics driving to an integrase strand transfer inhibitors (INSTI)-based first prescribed regimen. We also analyzed time to first line discontinuation, and to a first undetectable pVL, using Kaplan-Meier model. RESULTS: We analyzed data from 9094 PWH: 45% MSM, 27% women and 27% heterosexual men; 48% born abroad; 4.7 and 2.8% with concomitant hepatitis B and tuberculosis, respectively. INSTIs were prescribed as first-line therapy in 50% of PWH, which increased over time. Native French PWH were more likely to receive an INSTI-based regimen than PWH born abroad [adjusted prevalence ratio 1.47, 95% confidence interval (CI) 1.33-1.60], as were high pVL at diagnosis, hepatitis B or concomitant tuberculosis. Time before discontinuation of the first ART and reaching a first undetectable pVL was not different according to the place of birth. CONCLUSION: Despite unrestricted access to INSTIs in France, independently from HIV disease parameters, PWH born abroad received INSTIs less frequently as a first regimen than those born in France. Qualitative data are needed to better understand physicians' prescribing practices.

Four days/week antiretroviral maintenance strategy (ANRS 170 QUATUOR): substudies of reservoirs and ultrasensitive drug resistance.

BACKGROUND: In a 4 days/week (4/7 days) maintenance strategy (ANRS-170 QUATUOR trial), the virological impact of an intermittent strategy was assessed by ultrasensitive virological analyses of reservoirs and resistance. METHODS: HIV-1 total DNA, ultra-sensitive plasma viral load (USpVL) and semen VL were measured in the first 121 participants. Sanger and ultra-deep sequencing (UDS) were performed on the HIV-1 genome (Illumina technology) according to the ANRS consensus. A generalized estimation equation with a Poisson distribution was used to compare changes in the proportion of residual viraemia, detectable semen HIV RNA and HIV DNA within and between the two groups over time. RESULTS: The proportion of participants with residual viraemia at Day 0 (D0) and Week 48 (W48) was 16.7% and 25.0% in the 4/7 days group and 22.4% and 29.7% in the 7/7 days group, respectively (+8.3% versus +7.3%, P = 0.971). The proportion of detectable DNA (>40 copies/106 cells) at D0 and W48 was 53.7% and 57.4% in the 4/7 days group and 56.1% and 51.8% in the 7/7 days group, respectively (+3.7% versus -4.3%, P = 0.358). Semen HIV RNA was detectable (≥100 copies/mL) in 2.2% of participants at D0 and 4.5% at W48 in the 4/7 days group versus 6.1% and 9.1% in the 7/7 days group, respectively (+2.3% versus +3.0%, P = 0.743). Emerging resistance at failure was more frequent in the 4/7 days group detected by Sanger sequencing: 3/6 participants versus 1/4 in the 7/7 days group, and similar with the UDS assay: 5/6 versus 4/4, respectively. CONCLUSIONS: These findings support the potency of a 4/7 days maintenance strategy on virological suppression at the reservoirs and emergent resistance level, including minority variants.

Low-level viral loads and virological failure in the integrase strand transfer era.

OBJECTIVES: To analyse the occurrence of virological failure (VF) in patients starting ART with an integrase strand transfer inhibitor (INSTI)-based regimen in recent years, in relation with previous episodes of low-level viral load (LLVL). PATIENTS AND METHODS: Patients starting a first ART between 1 January 2015 and 31 December 2020 based on two NRTIs and one INSTI were included if after virological control (two measures of VL < 50 copies/mL) they had a minimum of two additional VL measurements. Cox models adjusted for sex, age, acquisition group, hepatitis B or C coinfection, place of birth, year of ART initiation, CD4+ T cells and VL at ART initiation, duration of known HIV infection and of ART regimen were used to assess the association between the time to VF and the occurrence of LLVL. ART regimen was evaluated as time-varying covariate. RESULTS: LLVL was described in 13.7% and VF in 11% of the 3302 patients. LLVL was associated with VF [adjusted HR (aHR) 1.76, 95% CI 1.28-2.41], as well as age (aHR 0.97/year, 95% CI 0.96-0.98), CD4+ T cell count at ART initiation (aHR 0.93, 95% CI 0.87-0.98), heterosexual transmission (aHR 1.76, 95% CI 1.30-2.37) and being born abroad (aHR 1.50, 95% CI 1.17-1.93). CONCLUSIONS: LLVL was related to VF. Even in the absence of subsequent failure, LLV episodes have a cost. Thus any VL value above 50 copies/mL should lead to enhanced adherence counselling.