A small percentage of people living with HIV (PLHIV) spontaneously regulate viral replication without suppressive antiretroviral treatment (ART) and are categorized into ‘elite controllers’ (EC, HIV-RNA < 50 c/mL) and ‘viremic controllers’ (VC, HIV-RNA between 50-10,000 c/ml). Some EC and VC may lose controller status in time. Here we provide extensive plasma proteomics to identify biomarkers and pathways related to spontaneous viral control and its long-term preservation among 36 EC and 147 VC (discovery) and 14 EC and 5 VC (validation). VC exhibited higher concentrations of CRTAM, LY9, and CD6 and lower concentrations of VAT1 compared to EC in both the discovery and validation cohort. Longitudinal analysis of pre- and post-ART samples (median follow-up: 5.3 years) revealed downregulation of various immune-related proteins in both EC and VC. Over a 17-year follow-up period, loss of viral control occurred in 31

BACKGROUND:People with HIV (PWH) using antiretroviral therapy (ART) remain at increased risk for infections such as community-acquired pneumonia (CAP) and herpes zoster (HZ), for which vaccinations are recommended. However, these recommendations do not consider the combined effects of age, CD4 count, and duration of ART on infection risk. We assessed how these factors influence CAP and HZ incidence to better tailor vaccination strategies. METHODS:We used data from a nationwide cohort study including all PWH aged ≥18 years in care between 2010 and 2023. All documented CAP and HZ episodes were included, and incidence rates were calculated per 1000 person-years of follow-up (PYFU), stratified by age, CD4 count, and ART duration. RESULTS:Community-acquired pneumonia and herpes zoster incidence rates were highest in PWH with CD4 ≤ 200 cells/µL, ranging from 34 to 107/1000 PYFU for CAP and 9 to 63/1000 PYFU for HZ, depending on age. In those with CD4 ≥ 500 cells/µL and ≥1 year on ART, incidence rates ranged from 5 to 20/1000 PYFU for CAP and 4 to 5/1000 PYFU for HZ, depending on age. CONCLUSIONS:Incidence rates are the highest in PWH with CD4 counts ≤200 cells/µL and/or not on ART, whereas PWH with CD4 counts ≥500 and ≥1 year on ART have a risk of CAP and HZ comparable to that of the general population. These findings support aligning vaccine recommendations for PWH on long-term suppressive ART with immune reconstitution with those for the general population, while HIV-specific vaccination strategies may remain most relevant for individuals with virological failure and/or poor immune reconstitution.

Background: Demonstrating durable viral suppression after switching to dolutegravir/lamivudine in clinical practice solidifies its use. Methods: This was a prospective cohort (DUALING) study conducted in 24 Dutch HIV treatment centers. HIV-RNA-suppressed cases undergoing triple-drug antiretroviral therapy without prior virological failure or resistance who switched to dolutegravir/lamivudine (cases) were 1:2 matched to controls, who remained on triple-drug antiretroviral therapy. Matching was stratified by dolutegravir use in the triple-drug antiretroviral therapy, and further by age, sex, HIV acquisition route, CD4+T-cell nadir, and HIV-RNA zenith. The primary endpoint was the treatment failure rate at 2 years, determined using intention-to-treat and on-treatment analyses with a 5% noninferiority margin. Results: The 2040 mostly male (84.3%) participants included 390 cases of dolutegravir-based triple-drug regimens with 680 controls, and 290 cases of non-dolutegravir-based triple-drug regimens with 580 controls. In the dolutegravir-based cases and controls, treatment failure occurred in 12.6% and 23.3% of patients in the intention-to-treat analysis (difference: −10.7%, 95%CI: −15.3% to −6.1%) and 2.6% and 2.4% of patients in the on-treatment analysis (difference: +0.2%, 95%CI −1.9% to +2.3%). The treatment failure risk in non-dolutegravir-based cases and controls was 15.2% and 19.9% in the intention-to-treat analysis (difference: −4.7, 95%CI: −10.0% to +0.6%) and 1.2% and 1.9% in the on-treatment analysis (difference +0.7%, 95%CI −2.6% to +1.1%). Therapy modifications unrelated to virological failure explained the higher treatment failure rate in the intention-to-treat analysis. In dolutegravir/lamivudine cases, a shorter time of prior triple-drug antiretroviral therapy, age < 50 years, and non-Western origin were associated with treatment failure in the multivariable analysis. Viral blips occurred in 6.8% of cases and 5.1% of controls. In the post hoc analysis, discontinuing tenofovir disoproxil fumarate-based triple-drug antiretroviral therapy led to weight gain in people with (+2.7 kg) and without (+2.3 kg) prior dolutegravir use. Conclusions: In this nationwide clinical practice study, switching to dolutegravir/lamivudine was noninferior to continuing triple-drug antiretroviral therapy after 2 years of follow-up.

BACKGROUND:Starting antiretroviral treatment (ART) at higher CD4 cell counts is associated with reduced non-AIDS-defining malignancy (NADM) risk. We studied whether starting ART within 1 year after acquiring human immunodeficiency virus type 1 (HIV-1) reduces this risk while also adjusting for socioeconomic status. METHODS:We included individuals (≥18 years) from the Dutch national ATHENA cohort diagnosed with human immunodeficiency virus (HIV) and having started ART between 2000 and 2022 without prior NADM with ≥6 months of follow-up. "Early ART" initiators were defined as starting ART <365 days following a negative HIV test or primary HIV infection, all others as "late-ART" starters. Hazard ratios (HR) for NADM were estimated using Cox regression, adjusted for a priori selected confounders (age, sex at birth, smoking, alcohol use, calendar time, HIV transmission route, region of origin, nadir CD4 cell count, HIV-1 viral copy-years), and socioeconomic status (SES) using data from Statistics Netherlands. RESULTS:Compared to "late-ART" (n = 17 965) participants, "early-ART" participants (n = 1858) were younger (median 34.8 vs 39.0 years), with a higher nadir CD4 count (median 478 vs 260 cells/µL). NADM were diagnosed in 25 "early-ART" and 869 "late-ART" starters resulting in an incidence rate of 2.22/1000 person-years (PY) (95% confidence interval [CI] = 1.50-3.28) and 4.87/1000 PY (95% CI = 4.56-5.21), respectively. "Early-ART" initiation was associated with a reduced risk of any NADM (HR = 0.60 [95% CI = .40-.91]) and infection-unrelated NADM (HR = 0.60 [95% CI = .37-.98]), but not of infection-related NADM (HR = 0.58 [95% CI = .27-1.28]). Additional adjustment for SES only minimally changed the hazard ratios. CONCLUSIONS:Starting ART within 1 year of HIV acquisition is associated with a reduced NADM risk compared to starting ART later.

OBJECTIVE:People with HIV have an increased cardiovascular disease risk. Persistent inflammation and mitochondrial dysfunction are considered important contributors to impaired autonomic cardiovascular control, as evidenced by decreased baroreflex sensitivity (BRS) and heart rate variability (HRV). We assessed differences in cross-correlation BRS (xBRS) and HRV between people with and without HIV and explored associations with HIV-specific characteristics. DESIGN:We included participants with and without HIV from the AGE h IV cohort study, and general population participants from the multiethnic HEalthy LIfe in an Urban Setting (HELIUS) study, all European men aged 50-70 years. METHODS:Using a noninvasive continuous blood pressure measurement, we calculated xBRS and two HRV parameters [successive differences in normal-to-normal intervals (SDNN) and the root mean square of differences between successive normal-to-normal intervals (RMSSD)]. Regression models, adjusted for traditional cardiovascular risk factors, assessed differences in xBRS and HRV between the participant groups and associated HIV-specific characteristics. RESULTS:xBRS, SDNN, and RMSSD were significantly higher in both control groups compared to participants with HIV. Longer time since HIV diagnosis and longer prior use of dideoxynucleosides and thymidine analogues were significantly associated with lower xBRS. Nadir CD4 + cell count was positively associated with SDNN, while longer duration of thymidine analogue use was negatively associated with SDNN and prior use of dideoxynucleosides with lower RMSSD. CONCLUSION:Impaired autonomic cardiovascular control in men with HIV, potentially related to prior antiretroviral drug exposure and prior immunodeficiency, might contribute to HIV-associated cardiovascular disease risk.

BACKGROUND:Definitions of virological failure and treatment discontinuation for long-acting injectable (LAI) cabotegravir and rilpivirine antiretroviral therapy are inconsistent in clinical practice and observational studies, which complicates interpretation and implementation of findings. The CONSENSUS-LAI study aimed to establish consistent definitions of virological failure and treatment discontinuation to enhance evidence transferability and support optimal clinical outcomes. METHODS:The study had two phases. Phase 1 was an international online survey exploring existing definitions of virological and treatment discontinuation, conducted between April 25 and July 1, 2024. Eligible participants were health-care professionals working in infectious disease or sexual health services who had provided care to at least ten people living with HIV in the past 6 months, had prescribed LAI cabotegravir and rilpivirine in clinical trials or clinical practice, and were able to give informed consent. Participants were recruited via social media and mailing lists of medical specialist societies. Phase 2 was a Delphi process, in which a panel of experts, selected to ensure representation from all six WHO regions, scored leading definitions from phase 1 on a 9-point Likert scale. The proposed definitions were scored according to four validity criteria: clarity, usability in the expert's setting, appropriateness across clinical purposes, and applicability across relevant population groups. Revisions were suggested in iterative rounds until consensus was reached. Consensus was predefined as at least 75% of experts agreeing or strongly agreeing (scores 7-9) with the validity criteria. FINDINGS:386 LAI cabotegravir and rilpivirine prescribers across 28 countries completed the survey, revealing 15 definitions for virological failure on LAI cabotegravir and rilpivirine and nine for treatment discontinuation. 52 experts participated in the Delphi process. Consensus agreement on both definitions was reached after two rounds for all validity criteria. For virological failure, the consensus definition was as follows: (a) viral load 200 copies or more per mL or more on two occasions 2-4 weeks apart, or (b) a single viral load of more than 1000 copies per mL, and/or (c) emergent resistance, in the context of timely injections and prior suppression of less than 200 copies per mL, OR (d) unable to suppress viral load to less than 200 copies per mL on continuous therapy. For treatment discontinuation the consensus definition was as follows: people on LAI cabotegravir and rilpivirine who have missed two consecutive injections and have not taken oral bridging in the interim, irrespective of reason for discontinuation. INTERPRETATION:The consensus definitions provide a foundation for aligning practice and evaluating patient outcomes. Further validation of the viral load threshold for virological failure and the optimal viral load retesting window is required. FUNDING:ViiV Healthcare.

BACKGROUND:Tuberculosis (TB) remains the leading cause of death among people with HIV. The aim of this study was to describe the incidence of TB, to explore risk factors and to calculate their population attributable fractions (PAFs) in people with HIV across Europe, stratified by region. METHODS:This was a longitudinal study of people with HIV aged ≥18 years with follow-up from either 1 January 2012 or cohort enrolment until date of a TB diagnosis, date of last visit, death or 31 December 2022. Factors associated with TB, in particular antiretroviral therapy status and smoking, were analysed using multivariable Poisson regression. RESULTS:A total of 38 837 participants with HIV had a median (interquartile range) follow-up of 7.7 (4.3-10.4) years. Overall, 306 TB cases were diagnosed during 275 811 person-years of follow-up (PYFU) (incidence rate 1.03 (95% CI 0.91-1.11) per 1000 PYFU). 3.3% (81/2428) of participants had incident TB in Eastern Europe (incidence rate 6.13 (95% CI 4.93-7.62) per 1000 PYFU). Overall, the incidence rate decreased from 2.03 (95% CI 1.53-2.68) per 1000 PYFU in 2012 to 0.44 (95% CI 0.20-0.97) per 1000 PYFU in 2022. Modifiable risk factors were smoking (adjusted incidence rate ratio (aIRR) 2.94, 95% CI 1.62-5.34) and not receiving antiretroviral therapy (versus on; aIRR 3.29, 95% CI 2.36-4.58). A history of TB pre-baseline increased the risk of recurrence (aIRR 7.77, 95% CI 4.09-14.74). The PAF for not receiving antiretroviral therapy was 34.6% in non-Eastern Europe and 31.2% in Eastern Europe. CONCLUSIONS:TB incidence has been decreasing among people with HIV, but remains more frequent in Eastern Europe. Improvement of antiretroviral therapy coverage and adherence and a focus on non-communicable disease risk factors such as smoking could reduce the incidence of TB.

Background Real-world data showing the long-term effectiveness of long-acting injectable cabotegravir and rilpivirine are scarce. We assessed the effectiveness of cabotegravir and rilpivirine in all individuals who switched to cabotegravir and rilpivirine in the Netherlands. Methods We used data from the ATHENA cohort, an ongoing observational nationwide HIV cohort in the Netherlands. In the primary analysis, we matched individuals who commenced cabotegravir and rilpivirine and had no history of virological failure (ie, one or more measurements of a plasma HIV RNA >= 1000 copies per mL; hereafter referred to as exposed) 1:2 with individuals using oral antiretroviral therapy (ART; hereafter referred to as unexposed). We assessed the effectiveness of cabotegravir and rilpivirine using restricted mean survival time (RMST) until loss of virological control (one or more measurements of plasma HIV RNA >= 200 copies per mL). In the secondary analysis, we assessed loss of virological control in individuals who commenced cabotegravir and rilpivirine with previous virological failure or unsuppressed HIV-1 RNA at cabotegravir and rilpivirine initiation, or both. Findings In primary analysis, 585 exposed and 1170 unexposed individuals were included between Feb 27, 2018, and Aug 17, 2023. Median follow-up was 13 years (IQR 09 to 17). 14 exposed (2%) and 29 unexposed (2%) individuals had a loss of virological control, with no difference in RMST (difference=0026, 95% CI -0029 to -0080). Seven (50%) exposed individuals re-suppressed without a regimen change. Seven (50%) switched ART, and six (43%) of 14 had documented integrase strand transfer inhibitor (INSTI) or non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance. No unexposed individuals switched ART after loss of virological control. In the secondary analysis, 105 individuals were included between July 1, 2016, and Aug 17, 2023. During a median follow up of 14 years (IQR 08 to 18), nine (9%) had a loss of virological control, of which five (56%) had INSTI or NNRTI resistance. Interpretation Switching to cabotegravir and rilpivirine was not associated with a higher risk of loss of virological control among individuals without previous virological failure compared with oral ART. The high risk of loss of virological control among individuals with previous virological failure or an unsuppressed HIV-1 RNA at cabotegravir and rilpivirine initiation warrants more careful monitoring. Copyright (c) 2025 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.

Introduction Oral pre-exposure prophylaxis (PrEP) prevents Human Immunodeficiency Virus (HIV) acquisition. In the Netherlands, PrEP is accessible through the national PrEP program (NPP) or general practitioners (GP). Still, some men who have sex with men (MSM) entering HIV care indicated having PrEP experience prior to diagnosis. We aimed to identify barriers and missed opportunities in PrEP uptake, care and use among MSM with HIV and previous PrEP experience. Methods Between March 2022-March 2023, we conducted semi-structured in-depth interviews on PrEP among MSM diagnosed with HIV from 2019 onwards with previous PrEP experience. Interviewees were recruited through their HIV treatment centers and social media. Results Of the 11 included MSM, most reported significant PrEP-uptake delay because of the limited NPP capacity and high threshold of accessing PrEP from GPs (e.g. stigma, lack of sexual health expertise). Additional uptake or use barriers included anticipated/experienced side-effects, burden of daily pill-taking or event-driven regimen complexity, the latter leading to PrEP discontinuation. Missed opportunities in counseling on adherence and safer sex alternatives after discontinuation were reported. Most interviewees considered informal PrEP unsuitable. Conclusion PrEP uptake delay played a crucial role in context of HIV infection among MSM with HIV and previous PrEP experience. HIV diagnoses at or shortly after PrEP initiation emphasize the importance of ensuring rapid and timely PrEP access. Uptake barriers at GPs, stigma on sexuality, lack of expertise, and missed care opportunities need to be addressed. Early detection of PrEP protocol/user-mismatch and counseling on safer sex alternatives after discontinuation are pivotal for sustainable HIV prevention.

Background:HIV viremia has been considered a cardiovascular disease (CVD) risk factor, but many studies have had insufficient data on potential confounders. We explored the association between viremia and CVD after adjusting for established risk factors and analyzed whether consideration of viremia would improve CVD prediction. Methods:Adults from RESPOND were followed from the first date with available data until the first of rigorously defined CVD, loss to follow-up, death, or administrative censoring. We first analyzed the associations between 6 measures of viremia (time-updated, before antiretroviral therapy [ART], viremia category, and measures of cumulative viremia) and CVD after adjusting for the variables in the D:A:D CVD score (age, sex/gender, smoking, family history, diabetes, recent abacavir, CD4 count, blood pressure, cholesterol, high-density lipoprotein, cumulative use of stavudine, didanosine, indinavir, lopinavir, and darunavir). We subsequently compared predictive performance with and without viremia in 5-fold internal cross-validation. Results:A total of 547 events were observed in 17 497 persons (median follow-up, 6.8 years). Although some viremia variables were associated with CVD in univariable analyses, there were no statistically significant associations after adjusting for potential confounders, neither for measures of current viral load, pre-ART viral load, highest viremia category during ART, nor cumulative viremia (modeled both as total cumulative viremia, cumulative viremia during ART, and recent cumulative viremia). Consistently, none of the viremia variables improved prediction capacity. Conclusions:In this large international cohort, HIV viremia was not associated with CVD when adjusting for established risk factors. Our results did not show viremia to be predictive of CVD among people with HIV.

BACKGROUND:The impact of long-term virological suppression (VS) and CD4 count recovery on non-AIDS-defining cancers (NADCs) is unclear. We determined whether poor immune recovery was associated with incident cancer risk in people with human immunodeficiency virus (HIV) with VS. METHODS:Participants from the Data-Collection on Adverse Effects of Anti-HIV Drugs (D:A:D) and International Cohort Consortium of Infectious Disease (RESPOND) collaborations in Europe and Australia who achieved ≥2 years of VS on antiretroviral therapy (ART) between December 1999 and December 2022 were included. Follow-up was from baseline (date of VS for 2 years) until the earliest of a first cancer event, virological failure, final follow-up, or administrative censoring date. Multivariable Poisson regression was used to assess associations between cancer incidence (overall, AIDS-defining cancer, NADC, infection-related cancer, infection-unrelated cancer) and time-updated CD4 count stratified by pre-ART nadir CD4 counts. RESULTS:Overall, 48 343 people with VS were included (median [interquartile range] baseline age, 43 years [37-50]; CD4 count, 540 cells/µL [380-730]; nadir CD4 count, 245 cells/µL [121-394]; 74% male). There were 1933 incident cancers (median follow-up, 6.2 years [2.9-9.5]; incidence rate [IR], 6.43; 95% confidence interval [CI]: 6.15-6.73/1000 person-years). Higher time-updated CD4 count was associated with a reduced risk of overall cancer (adjusted incidence rate ratio for time-updated CD4 count 350-499 cells/µL: 0.45 [95% CI: 0.39-0.51]; 500-749 cells/µL: 0.30 [95% CI: 0.27-0.34]; and ≥750 cells/µL: 0.26 [95% CI: 0.23-0.30] vs <350 cells/µL; P < .0001). There was a significant reduction in all cancer risk by higher time-updated CD4 count, regardless of nadir CD4 count, with higher pre-ART nadir CD4 count exhibiting lower risk. CONCLUSIONS:Despite VS on ART for more than 2 years, people with poorer immune recovery experienced a significantly higher incidence of cancer. This highlights the importance of early HIV diagnosis and ART initiation, and appropriate cancer screening strategies for those with poor immune recovery.

Objective: This study investigated the association of plasma microRNAs before and during antiretroviral therapy (ART) with poor CD4+ T-cell recovery during the first year of ART. Design: MicroRNAs were retrospectively measured in stored plasma samples from people with HIV (PWH) in sub-Saharan Africa who were enrolled in a longitudinal multicountry cohort and who had plasma viral-load less than 50 copies/ml after 12 months of ART. Methods: First, the levels of 179 microRNAs were screened in a subset of participants from the lowest and highest tertiles of CD4+ T-cell recovery (ΔCD4) (N = 12 each). Next, 11 discordant microRNAs, were validated in 113 participants (lowest tertile ΔCD4: n = 61, highest tertile ΔCD4: n = 52). For discordant microRNAs in the validation, a pathway analysis was conducted. Lastly, we compared microRNA levels of PWH to HIV-negative controls. Results: Poor CD4+ T-cell recovery was associated with higher levels of hsa-miR-199a-3p and hsa-miR-200c-3p before ART, and of hsa-miR-17-5p and hsa-miR-501-3p during ART. Signaling by VEGF and MET, and RNA polymerase II transcription pathways were identified as possible targets of hsa-miR-199a-3p, hsa-200c-3p, and hsa-miR-17-5p. Compared with HIV-negative controls, we observed lower hsa-miR-326, hsa-miR-497-5p, and hsa-miR-501-3p levels before and during ART in all PWH, and higher hsa-miR-199a-3p and hsa-miR-200c-3p levels before ART in all PWH, and during ART in PWH with poor CD4+ T-cell recovery only. Conclusion: These findings add to the understanding of pathways involved in persistent HIV-induced immune dysregulation during suppressive ART.

BACKGROUND:The two main objectives were to evaluate the COVID-19 point prevalence and the test performance of the WHO case definition to diagnose COVID-19 clinically in people with HIV in West Ukraine. METHODS:Multicenter cross-sectional study in Lviv, Ukraine, from October 2020-November 2021. COVID-19 unvaccinated people with HIV were included regardless of COVID-19 symptoms at routine clinical visits and had standardized medical, quality of life (EQ(5D)) and SARS-CoV-2 serology assessments. Reported symptoms indicating potential COVID-19 events at inclusion or between March 2020 and inclusion were classified by the WHO case definition as suspected, probable or confirmed. A clinical COVID-19 case was defined as being SARS-CoV-2 seropositive with at least a suspected COVID-19 according to the WHO case definition. The primary endpoints were the clinical COVID-19 prevalence and the test characteristics of the WHO case definition with SARS-CoV-2 serology as reference. (Clinicaltrials.gov:NCT04711954). RESULTS:The 971 included people with HIV were median 40 years, 38.8% women, 44.8% had prior AIDS, and 55.6% had comorbidities. SARS-CoV-2 seroprevalence was 40.1% (95%CI:37.0-43.1) and 20.5% (95%CI:18.0-23.1) had clinical COVID-19 median 4 months (IQR:2-7) before inclusion. Clinical COVID-19 occurred less frequently in people with HIV with tuberculosis history, injecting drug use, CD4+ T-cells <200/mL and unemployment. The quality of life was not impacted after COVID-19. An at least probable COVID-19 classification by the WHO case definition had 44.1% sensitivity (95%CI:38.7-49.7), 85.2% specificity (95%CI:81.5-88.4), 66.6% positive predictive value (95%CI:59.8-73.0) and 69.5% negative predictive value (95%CI:65.5-73.3) to diagnose COVID-19. CONCLUSIONS:COVID-19 unvaccinated people with HIV from Ukraine had a significant COVID-19 rate and using the WHO case definition had insufficient diagnostic accuracy to diagnose these cases. The lower burden in vulnerable people with HIV was unexpected but might reflect a shielding effect.

Background:Confirming the efficacy of dolutegravir/lamivudine in clinical practice solidifies recommendations on its use.Methods:Prospective cohort study (DUALING) in 24 human immunodeficiency virus (HIV) treatment centers in the Netherlands. HIV RNA-suppressed cases were on triple-drug antiretroviral regimens without prior virological failure or resistance and started dolutegravir/lamivudine. Cases were 1:2 matched to controls on triple-drug antiretroviral regimens by the use of dolutegravir-based regimens, age, sex, transmission route, CD4+ T-cell nadir, and HIV RNA zenith. The primary endpoint was the treatment failure rate in cases versus controls at 1 year by intention-to-treat and on-treatment analyses with 5% noninferiority margin.Results:The 2040 participants were 680 cases and 1380 controls. Treatment failure in the 390 dolutegravir-based cases versus controls occurred in 8.72% and 12.50% (difference: -3.78% [95% confidence interval {CI}, -7.49% to .08%]) by intention-to-treat and 1.39% and 0.80% (difference: 0.59% [95% CI, -.80% to 1.98%]) by on-treatment analyses. The treatment failure risk in 290 non-dolutegravir-based cases was also noninferior to controls. Antiretroviral regimen modifications unrelated to virological failure explained the higher treatment failure rate by intention-to-treat. A shorter time on triple-drug antiretroviral therapy and being of non-Western origin was associated with treatment failure. Treatment failure, defined as 2 consecutive HIV RNA >50 copies/mL, occurred in 4 cases and 5 controls but without genotypic resistance detected. Viral blips occured comparable in cases and controls but cases gained more weight, especially when tenofovir-based regimens were discontinued.Conclusions:In routine care, dolutegravir/lamivudine was noninferior to continuing triple-drug antiretroviral regimens after 1 year, supporting the use of dolutegravir/lamivudine in clinical practice.Clinical Trials Registration:NCT04707326.

Background:While use of some older antiretroviral drugs (ARVs) is associated with chronic liver enzyme elevation (cLEE), the impact of newer ARVs remains unknown. Methods:People with HIV enrolled in the RESPOND cohort who started an ARV after January 1, 2012 were included (baseline). The primary outcome was first cLEE individuals were censored at first of cLEE, last visit, death, or December 31, 2021. Incidence rates (IRs; events/1000 person-years) were calculated for each ARV overall and by ARV exposure (6-12 months, 1-2 years, and 2+ years). Poisson regression was used to estimate the incidence rate ratio (IRR) of cLEE and its association with individual ARVs and ARV class. Results:Of 17 106 individuals included contributing 87 924 person-years of follow-up, 1932 (11.3%) experienced cLEE (incidence rate [IR], 22.0; 95% CI, 21.0-23.0). There was no evidence of a cumulative ARV effect on cLEE incidence, (6-12 months: IR, 45.8; 95% CI, 41.4-50.19; 1-2 years: IR, 34.3; 95% CI, 31.5-37.4; and 2+ years: IR, 18.5; 95% CI, 17.4-19.7). Any use (vs no prior use) of non-nucleoside reverse transcriptase inhibitors (NNRTIs) as a class and tenofovir disoproxil fumarate (TDF) was independently associated with an increased IRR of cLEE, and any use of darunavir (DRV) was associated with a decreased risk of cLEE. Conclusions:cLEE is common and more frequent during the first year after initiating new ARVs. With a >5-year median follow-up, we found no short-term liver safety concerns with the use of INSTIs. Use of NNRTIs and TDF was associated with an increased cLEE risk, while DRV was associated with lower risk.

Objective: To determine the yield of screening for latent tuberculosis infection (LTBI) among people with HIV (PWH) in low tuberculosis (TB) incidence countries (<10 TB cases per 100 000 persons). Design: A systematic review and meta-analysis were performed to assess prevalence and predictive factors of LTBI, rate of TB progression, effect of TB preventive treatment (TPT), and numbers needed to screen (NNS). Methods: PubMed and Cochrane Library were searched for studies reporting primary data, excluding studies on active or paediatric TB. We extracted LTBI cases, odds ratios, and TB incidences; pooled estimates using a random-effects model; and used the Newcastle–Ottawa scale for bias. Results: In 51 studies with 65 930 PWH, 12% [95% confidence interval (CI) 10–14] had a positive LTBI test, which was strongly associated with origin from a TB-endemic country [odds ratio (OR) 4.7] and exposure to TB (OR 2.9). Without TPT (10 629 PWH), TB incidence was 28/1000 person-years (PY; 95% CI 12–45) for LTBI-test positive versus 4/1000 PY (95% CI 0–7) for LTBI-test-negative individuals. Among 625 PWH (1644 PY) receiving TPT, 15 developed TB (6/1000 PY). An estimated 20 LTBI-positive individuals would need TPT to prevent one case of TB, and numbers NNS to detect LTBI or prevent active TB varied according to a-priori risk of LTBI. Conclusion: The relatively high prevalence of LTBI among PWH and the strong correlation with origin from a TB-endemic country support risk-stratified LTBI screening strategies for PWH in low-incidence countries and treating those who test positive.

Background. With integrase strand transfer inhibitor (INSTI) use associated with increased body mass index (BMI) and BMI increases associated with higher diabetes mellitus (DM) risk, we explored the relationships between INSTI/non-INSTI regimens, BMI changes, and DM risk. Methods. RESPOND participants were included if they had CD4, human immunodeficiency virus (HIV) RNA, and >= 2 BMI measurements during follow-up. Those with prior DM were excluded. DM was defined as a random blood glucose >= 11.1 mmol/L, hemoglobin A1c >= 6.5%/48 mmol/mol, use of antidiabetic medication, or site-reported clinical diagnosis. Poisson regression was used to assess the association between natural log (ln) of time-updated BMI and current INSTI/non-INSTI and their interactions on DM risk. Results. Among 20 865 people with HIV included, most were male (74%) and White (73%). Baseline median age was 45 years (interquartile range [IQR], 37-52), with a median BMI of 24 kg/m(2) (IQR, 22-26). There were 785 DM diagnoses with a crude rate of 0.73 (95% confidence interval [CI], .68-.78)/100 person-years of follow-up. ln(BMI) was strongly associated with DM (adjusted incidence rate ratio [aIRR], 16.54 per log increase; 95% CI, 11.33-24.13; P < .001). Current INSTI use was associated with increased DM risk (IRR, 1.58; 95% CI, 1.37-1.82; P < .001) in univariate analyses and only partially attenuated when adjusted for variables including ln(BMI) (aIRR, 1.48; 95% CI, 1.29-1.71; P < .001). There were no interactions between ln(BMI), INSTI, and non-INSTI use and DM (P = .130). Conclusions. In RESPOND, compared with non-INSTIs, current use of INSTIs was associated with an increased DM risk, which partially attenuated when adjusted for BMI changes and other variables.

BACKGROUND:Women with HIV are globally underrepresented in clinical research. Existing studies often focus on reproductive outcomes, seldom focus on older women, and are often underpowered to assess sex/gender differences. We describe CD4, HIV viral load (VL), clinical characteristics, comorbidity burden, and use of antiretroviral therapy (ART) among women with HIV in the RESPOND study and compare them with those of the men in RESPOND. METHODS:RESPOND is a prospective, multi-cohort collaboration including over 34 000 people with HIV from across Europe and Australia. Demographic and clinical characteristics, including CD4/VL, comorbidity burden, and ART are presented at baseline, defined as the latter of 1 January 2012 or enrolment into the local cohort, stratified by age and sex/gender. We further stratify men by reported mode of HIV acquisition, men who have sex with men (MSM) and non-MSM. RESULTS:Women account for 26.0% (n = 9019) of the cohort, with a median age of 42.2 years (interquartile range [IQR] 34.7-49.1). The majority (59.3%) of women were white, followed by 30.3% Black. Most women (75.8%) had acquired HIV heterosexually and 15.9% via injecting drug use. Nearly half (44.8%) were receiving a boosted protease inhibitor, 31.4% a non-nucleoside reverse transcriptase inhibitor, and 7.8% an integrase strand transfer inhibitor. The baseline year was 2012 for 73.2% of women and >2019 for 4.2%. Median CD4 was 523 (IQR 350-722) cells/μl, and 73.6% of women had a VL <200 copies/mL. Among the ART-naïve population, women were more likely than MSM but less likely than non-MSM (p < 0.001) to have CD4 <200 cells/μL and less likely than both MSM and non-MSM (p < 0.001) to have VL ≥100 000 copies/mL. Women were also more likely to be free of comorbidity than were both MSM and non-MSM (p < 0.0001). CONCLUSION:RESPOND women are diverse in age, ethnicity/race, CD4/VL, and comorbidity burden, with important differences relative to men. This work highlights the importance of stratification by sex/gender for future research that may help improve screening and management guidelines specifically for women with HIV.

BACKGROUND:Currently, real-world data on doravirine are scarce. In a national prospective cohort, we assessed the effectiveness and tolerability of switching to doravirine-based antiretroviral therapy (ART) in people with HIV. METHODS:We did a nationwide, matched, prospective cohort study of people with HIV without previous virological failure and stable for at least 12 months on non-doravirine-containing triple or dual ART switching to doravirine before Sept 1, 2020 (exposed group). Participants in the exposed group were matched 1:2 to individuals continuing stable non-doravirine-containing ART, on age, sex, HIV acquisition category, time since ART initiation, calendar time, pre-ART CD4-count, pre-ART plasma viral load (PVL) and anchor drug class before switching. The primary outcome was protocol-defined virological failure (PDVF; PVL of ≥200 copies per mL) in the intention-to-treat (ITT) population at week 104, with participants modifying their regimen or becoming lost to follow-up considered as PDVF (non-inferiority margin +5%). In contrast, in the on-treatment population, those who modified their regimen or became lost to follow-up were censored from that moment onwards. Tolerability was a secondary outcome. FINDINGS:In total, 590 participants in the exposed group and 1180 participants in the unexposed group (of whom 55·3% used integrase strand transfer inhibitor-based regimens) were included. In the ITT analysis, PDVF occurred in 135 (22·9%) exposed participants and in 295 (25·0%) unexposed participants (risk difference -2·12%, upper limit of the one-sided 95% CI +1·40%). In the on-treatment analysis, 10 (2·2%) of 455 non-censored exposed participants and 26 (2·9%) of 885 non-censored unexposed participants had PDVF (risk difference -0·70%, upper limit of the one-sided 95% CI +0·73%). All exposed participants with a PVL of 200 copies or more per mL resuppressed without regimen modification: no confirmed virological failure (two consecutive PVLs of ≥200 copies per mL) was observed. 104 (17·6%) exposed participants and 211 (17·9%) unexposed participants modified their regimen. 73 (12.4%) exposed participants discontinued doravirine due to adverse events: abnormal dreams (1·7%) and insomnia (1·5%) were most common. INTERPRETATION:Switching to doravirine in well suppressed people with HIV without previous virological failure was non-inferior compared with continuing non-doravirine-containing regimens after 2 years in a real-world setting. FUNDING:None.