OBJECTIVES:People with HIV (PWH) are unable to get private disability insurance on a regular basis in contrast with individuals with other chronic diseases. We aimed to estimate the risk of public disability pension and work absence due to sickness for PWH compared with the background population in Denmark. DESIGN:Nationwide, population-based, matched cohort study of employed PWH with favorable disease characteristics. A comparison cohort of employed individuals was matched 10 : 1 to PWH by date of birth and sex from the general population. METHODS:We computed time to first date of 4 weeks of uninterrupted sick leave, 26 weeks of uninterrupted sick leave, and disability pension being granted. We used Cox regression to obtain hazard ratios (HRs) as a measure of relative risk and competing risk analysis to assess absolute risk. RESULTS:After 6 months of observation, PWH had an increased risk of 4-week sick leave, 26-week sick leave and disability pension compared with the comparison cohort (HR of 1.1 [95% CI: 1.0-1.2), 1.4 (95% CI: 1.1-1.6) and 2.0 (95% CI: 1.5-2.6), respectively]. These risks were increased in most patient subgroups. CONCLUSION:PWH have an increased risk of prolonged sick leave and disability pension, and a slightly increased risk of 4-week sick leave. These risks were within the range of what is described for other chronic diseases. PWH with contemporary cART and favorable disease characteristics should not be generally excluded from access to private disability insurance.

BACKGROUND:Mental health has become an area of concern among people with HIV (PWH). We aim to assess whether the risk of schizophrenia spectrum disorders (SSD) is increased among PWH. To examine whether such risks are affected by familial factors we also accessed the risk among their siblings. METHODS:Nationwide, population-based, matched cohort study of PWH with Danish origin (1995-2021), a comparison cohort from the background population, matched on date of birth and gender, and sibling cohorts. We used cumulative incidence function and Cox regression to estimate absolute risk and hazard ratios (HR) with 95% confidence intervals (CI) of study outcomes and stratified the results according to route of HIV transmission. FINDINGS:We observed an increased risk of SSD among PWH [20-year cumulative incidence 3.7% vs. 1.0% and HR 4.6 (95% CI: 3.8-5.6)], especially among individuals with injection drug use (IDU) as route of HIV transmission [HR 11.3 (95% CI: 7.7-16.4)]. Among siblings increased risk of SSD was mainly observed among siblings of PWH with IDU as route of HIV transmission [HR of 2.9 (95% CI: 1.9-4.5)] and with lack of statistical power among siblings of PWH with men who have sex with men and heterosexual contact as routes of HIV transmission [HR 1.3 (95% CI: 0.9-1.7) and HR 1.2 (95% CI: 0.7-1.9)]. INTERPRETATION:Risk of SSD is substantially increased among PWH, especially among those who report IDU as route of HIV transmission. Familial risk factors might partly contribute to this risk.

Objective:The aim of this study was to investigate the use of nonbarrier contraceptives among women with HIV (WWH) compared to women from the general population (WGP) in Denmark.Design:A nationwide, population-based, matched cohort study.Methods:We included WWH aged 16-50 years, treated at an HIV specialized clinic, and included in The Danish HIV Cohort Study between 1995 and 2021 and an age-matched comparison cohort of WGP. We examined use of hormonal contraception, intrauterine devices (IUDs), and sterilization from 10 years before to 20 years after study inclusion. Additionally, we calculated age-standardized proportions and incidences over calendar time.Results:We included 1720 WWH and 17 720 WGP. Median age was 33 years and almost half of WWH had African origin (41%). Nonbarrier contraceptive use was lower among WWH (8.5%) compared to WGP (32.1%) at study inclusion. Before and after inclusion, WWH had nearly half the nonbarrier contraceptive use of WGP, with notably lower hormonal contraception and IUD use. Initially, fewer WWH were sterilized, but 5 years after inclusion, sterilization became the preferred method among WWH. HC use increased among WWH after 2010 but decreased among WGP after 2005. IUD use increased among both groups during 1995-2021 but remained lower among WWH. Incidence of sterilizations remained stable in both groups.Conclusion:Use of nonbarrier contraceptives was lower among WWH compared to WGP. For WWH, sterilization became the preferred nonbarrier method few years after study inclusion. hormonal contraception and IUD use increased among WWH after 2010 but remained lower than for WGP. Improved contraceptive counseling is recommended to support reproductive health among WWH.

Objectives:To assess whether bipolar disorders are associated with the risk of HIV infection and whether the risk of bipolar disorders is increased among people with HIV (PWH) and their siblings.Design:Nationwide, population-based, combined matched nested case-control and cohort study of PWH of Danish origin (1995-2021), a comparison cohort from the background population, matched on date of birth and sex, and sibling cohorts.Methods:Conditional logistic regression and Cox regression was used to calculate adjusted odds ratios (aORs) for HIV infection and hazard ratios among PWH for bipolar disorder and receipt of lithium.Results:We included 5322 PWH and 53 220 comparison cohort members. In the case-control study, bipolar disorder was associated with an increased risk of HIV infection [aOR: 1.9, 95% confidence interval (CI): 1.2-3.0], especially when injection drug use was the route of infection (aOR: 7.6, 95% CI: 2.0-28.9). In the cohort study, we observed an increased risk of bipolar disorders among PWH, especially in the first 2 years of observation (hazard ratio: 4.2, 95% CI: 2.4-7.4), whereas the risk of receipt of lithium was lower and the CI crossed 1. The 20-year risk of bipolar disorders for PWH was approximately 1%. Siblings of PWH also had an increased risk of bipolar disorder but not to the same degree as PWH and not of receipt of lithium.Conclusion:Bipolar disorders are associated with the risk of HIV infection, and PWH have increased risk of bipolar disorder and receipt of lithium beyond what familial factors could explain.

We aimed to examine pneumocystis pneumonia (PCP) risk and mortality among people with human immunodeficiency virus (HIV), and associations with (1) time after HIV diagnosis, (2) calendar time, and (3) CD4 cell count. From the Danish HIV cohort study, we identified all adult people with HIV (PWH) (1995-2021). We estimated incidence rates (IRs) and mortality rates. We used Poisson regression analysis to compute adjusted incidence ratios (IRRs) and mortality rate ratios. PCP risk was assessed according to time after HIV diagnosis, calendar time, and low CD4 cell count. Among 4882 PWH (53 647 person-years), we observed 336 PCP events (for the time period 2016-2021 compared to 1995-1999, PCP risk decreased by >90% after the first year of HIV diagnosis; aIRR, 0.08 [95% confidence interval {CI}, .02-.29], and by >40% in the first year, if baseline CD4 count was <200 cells/µL [aIRR, 0.57 [95% CI, .36-.90]). However, no statistically significant change in PCP risk was observed after 1995-1999 for the latter group. PCP risk remained high if the CD4 count was 100 to <200 cells/µL (IR, 16.08 [95% CI, 5.19-49.89]) during the first year of combination antiretroviral therapy (cART), despite a suppressed viral load. Major reductions were found after 1 year of cART (CD4 count 100 to <200 cells/µL). Although nonsignificant, the 3- and 12-month mortality rate decreased by 80% from 1995-1999 to 2016-2021. PCP remains a significant problem among late presenters with HIV, emphasizing the importance of early HIV diagnosis. Continuing PCP prophylaxis until the CD4 count is >100 cells/µL, with at least 1 year of cART and viral suppression for >3 months should be considered; however; further studies are needed to confirm these results.

Background:We aimed to examine pneumocystis pneumonia (PCP) risk and mortality among people with human immunodeficiency virus (HIV), and associations with (1) time after HIV diagnosis, (2) calendar time, and (3) CD4 cell count. Methods:From the Danish HIV cohort study, we identified all adult people with HIV (PWH) (1995-2021). We estimated incidence rates (IRs) and mortality rates. We used Poisson regression analysis to compute adjusted incidence ratios (IRRs) and mortality rate ratios. PCP risk was assessed according to time after HIV diagnosis, calendar time, and low CD4 cell count. Results:Among 4882 PWH (53 647 person-years), we observed 336 PCP events (for the time period 2016-2021 compared to 1995-1999, PCP risk decreased by >90% after the first year of HIV diagnosis; aIRR, 0.08 [95% confidence interval {CI}, .02-.29], and by >40% in the first year, if baseline CD4 count was <200 cells/µL [aIRR, 0.57 [95% CI, .36-.90]). However, no statistically significant change in PCP risk was observed after 1995-1999 for the latter group. PCP risk remained high if the CD4 count was 100 to <200 cells/µL (IR, 16.08 [95% CI, 5.19-49.89]) during the first year of combination antiretroviral therapy (cART), despite a suppressed viral load. Major reductions were found after 1 year of cART (CD4 count 100 to <200 cells/µL). Although nonsignificant, the 3- and 12-month mortality rate decreased by 80% from 1995-1999 to 2016-2021. Conclusions:PCP remains a significant problem among late presenters with HIV, emphasizing the importance of early HIV diagnosis. Continuing PCP prophylaxis until the CD4 count is >100 cells/µL, with at least 1 year of cART and viral suppression for >3 months should be considered; however; further studies are needed to confirm these results.

BACKGROUND:The long-term cancer risk following tuberculosis disease in people with human immunodeficiency virus (HIV) remains unclear. We aimed to assess cancer risk following tuberculosis in a nationwide cohort of people with HIV in Denmark. METHODS:We conducted a population-based cohort study including all individuals enrolled in the Danish HIV Cohort Study from 1995 to 2020. Tuberculosis and cancer diagnoses were identified through nationwide registries. Incidence rates (IRs) and adjusted incidence rate ratios (aIRRs) were calculated using Poisson regression, adjusting for time-varying CD4 count, age, sex, and Charlson Comorbidity Index (CCI). Additionally, we calculated aIRRs stratified by age group, sex, CCI, and CD4 count. RESULTS:Among 6135 people with HIV (median age, 37.1 years; 74.1% male), 319 had a tuberculosis diagnosis. During 62 878 person-years of follow-up (PYFU), 451 cancers were observed, including 55 lung cancers. The overall cancer IR among people with HIV without previous tuberculosis disease was 18.6 per 1000 PYFU (95% confidence interval [CI], 16.9-20.4), and 19.0 per 1000 PYFU (95% CI, 10.4-25.6) among people with HIV following tuberculosis (aIRR, 1.1; 95% CI, .7-1.8). For lung cancer, the aIRR after tuberculosis was 1.7 (95% CI, .5-5.5). In stratified analyses, aIRRs were slightly higher among women (1.3; 95% CI, .6-2.9) and those aged ≥50 years (1.4; 95% CI, .8-2.4). CONCLUSIONS:In this nationwide cohort of more than 6000 people with HIV followed for up to 25 years, we observed no increased risk of cancer following tuberculosis disease. These findings do not support changes to continued standardized cancer surveillance in people with HIV and tuberculosis.

Antiretroviral therapy (ART) in people with HIV (PWH) can lead to weight gain, but the effects of nucleoside reverse transcriptase inhibitors such as abacavir (ABC) are not well understood. In this study, we investigated whether discontinuing ABC would mitigate weight changes and metabolic complications in PWH. In a randomized controlled trial including PWH on dolutegravir, ABC, and lamivudine (DTG/ABC/3TC), participants were randomized 2:1 to either switch to DTG/3TC or continue DTG/ABC/3TC. Data was collected at baseline, week 24, and week 48. This study was powered to detect a difference of 2 kg in weight between groups. Secondary outcomes included body composition, fat and muscle distribution, and metabolic parameters. Weight and metabolic changes were analyzed by linear mixed modeling. Eighty-one participants were randomized. Switching from DTG/ABC/3TC to DTG/3TC was not associated with a significant change in weight at 48 weeks in the intention to treat (ITT) analysis (mean difference − 0.5 kg, 95

People with HIV (PWH) have a high risk of coronary artery disease (CAD). Cytomegalovirus (CMV) co-infection is very common in PWH, but little is known about its association with CAD. We aimed to investigate if CMV IgG serostatus and concentrations are associated with CAD in PWH. From the Copenhagen Comorbidity in HIV Infection (COCOMO) Study we included PWH with coronary CT angiography (CCTA) and quantitative CMV IgG concentration measurements. We measured the stenosis grades and plaque volumes in the coronary vessels. Using multivariable regressions adjusted for traditional CAD risk factors, we investigated if CMV IgG serostatus and concentrations were associated with any atherosclerosis, obstructive CAD, or plaque volumes. We included 620 PWH of whom 586 had positive CMV serostatus, which was not associated with any atherosclerosis, obstructive CAD, or plaque volumes. A doubling of CMV IgG concentrations was associated with any atherosclerosis (OR 1.21 [95% CI: 1.06–1.39]), obstructive CAD (OR 1.31 [95% CI: 1.07–1.59]), and higher total plaque volume (1.56 [95% CI: 1.21–2.01] fold increase), but the association did not remain significant after adjustment for traditional CAD risk factors. This indicates that CMV IgG serostatus and concentrations are not independently associated with prevalent CAD in PWH.

BACKGROUND:Although people with HIV might be at risk of severe outcomes from infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; coronavirus 2019 [COVID-19]), regional and temporal differences in SARS-CoV-2 testing in people with HIV across Europe have not been previously described. METHODS:We described the proportions of testing, positive test results, and hospitalizations due to COVID-19 between 1 January 2020 and 31 December 2021 in the EuroSIDA cohort and the factors associated with being tested for SARS-CoV-2 and with ever testing positive. RESULTS:Of 9012 participants, 2270 (25.2%, 95% confidence interval [CI] 24.3-26.1) had a SARS-CoV-2 polymerase chain reaction test during the study period (range: 38.3% in Northern to 14.6% in Central-Eastern Europe). People from Northern Europe, women, those aged <40 years, those with CD4 cell count <350 cells/mm3, and those with previous cardiovascular disease or malignancy were significantly more likely to have been tested, as were people with HIV in 2021 compared with those in 2020. Overall, 390 people with HIV (4.3%, 95% CI 3.9-4.8) tested positive (range: 2.6% in Northern to 7.1% in Southern Europe), and the odds of testing positive were higher in all regions than in Northern Europe and in 2021 than in 2020. In total, 64 people with HIV (0.7%, 95% CI 0.6-0.9) were hospitalized, of whom 12 died. Compared with 2020, the odds of positive testing decreased in all regions in 2021, and the associations with cardiovascular disease, malignancy, and use of tenofovir disoproxil fumarate disappeared in 2021. Among study participants, 58.9% received a COVID-19 vaccine (range: 72.0% in Southern to 14.8% in Eastern Europe). CONCLUSIONS:We observed large heterogeneity in SARS-CoV-2 testing and positivity and a low proportion of hospital admissions and deaths across the regions of Europe.

Background Pre-exposure prophylaxis (PrEP) effectively prevents HIV, but its association with sexually transmitted infections (STIs) has raised concerns about risk compensation, potentially impacting the expansion of PrEP programmes. Aim We examined the relationship between PrEP and the incidence of chlamydia, gonorrhoea and syphilis. Methods In this prospective cohort study, we compared STI rates before and after PrEP initiation among users in the capital region of Denmark (2019–2022), calculating incidence rate ratios adjusted for age and testing frequency (aIRR). To pinpoint when increases began, we plotted weekly STI rates, adjusting the timeline to correspond with PrEP initiation. Results The study included 1,326 PrEP users with a median age of 35 years. The STI incidence rate per 100,000 person-years rose from 35.3 before to 81.2 after PrEP start, with an aIRR of 1.35 (95% CI: 1.18–1.56). Notably, this increase preceded PrEP initiation by 10–20 weeks. Specific aIRR for chlamydia, gonorrhoea and syphilis were 1.23 (95% CI: 1.03–1.48), 1.24 (95% CI: 1.04–1.47) and 1.15 (95% CI: 0.76–1.72), respectively. In subanalyses for anatomical sites aIRR was 1.26 (95% CI: 1.01–1.56) for rectal chlamydia and 0.66 (95% CI: 0.45–0.96) for genital gonorrhoea. Conclusion We found a 35% increase in STI incidence associated with PrEP use. It started before PrEP initiation, challenging the assumption that PrEP leads to risk compensation. Instead, the data suggest that individuals seek PrEP during periods of heightened sexual risk-taking. Consequently, PrEP programmes should include sexual health consultations, STI testing, treatment and prevention strategies to prevent HIV and improve sexual health.

People with HIV (PWH) and people with diabetes mellitus have increased risk of severe COVID-19, but little is known about humoral response to COVID-19 vaccines in PWH with DM. We investigated SARS-CoV-2 antireceptor-binding domain (anti-RBD) immunoglobulin G (IgG) geometrical concentrations and neutralizing antibody capacity (nAB) in PWH with and without diabetes mellitus. Anti-RBD IgG and nAB in COVID-19-vaccinated PWH were not associated with diabetes mellitus-status or HbA1c 24 months after the initial COVID-19 vaccination.

Background All-cause and AIDS-mortality in Europe has been decreasing between 1996 and 2020. However, regional differences as well as their drivers remain unclear. This study investigates mortality differences and their drivers, including usage of and response to antiretroviral therapy (ART) and active tuberculosis (TB), among people with HIV across Europe. Methods People with HIV enrolled in EuroSIDA were followed from 2001 through 2020. Immunologic-virologic status (IVS) was categorized as poor (CD4-cell count <= 350 cells/mm(3) and viral load (VL) > 200 copies/ml), good (CD4 >= 500 and VL < 200), or intermediate (remaining combinations). Participants missing either CD4-cell count or VL were categorized as unknown. Regional differences in mortality were analyzed using multivariable Poisson regression with interaction analyses between regions of Europe and IVS, ART, or TB status. Findings 20,364 people with HIV were included: 13,715/20,346 (67.3%) from Western, 3020/20,364 (14.8%) from Central Eastern, and 3629/20,364 (17.8%) from Eastern Europe. At enrolment, median age was 40 years (inter-quartile range (IQR): 33-48), median CD4-cell count 449 cells/mm(3) (IQR: 291-638), and most were male 14,993/20,346 (73.3%). A total of 2639 died during 192,591 person-years of follow-up (crude mortality rate 13.7/1000 person-years, 95% CI: 13.2-14.2), 519/2639 (19.7%) from AIDS (2.7/1000 person-years, 2.5-2.9). All-cause and AIDS-mortality rates decreased over time but remained higher in Eastern Europe after adjusting for confounders. Being off ART (aIRR 2.42; 95% CI 2.14-2.74), poor IVS (aIRR 4.2; 95% CI 3.39-5.20) and prior TB (aIRR 3.33; 95% CI 2.75-4.03) were associated with higher all-cause mortality. For all-cause mortality the effect of ART (test for interaction: p < 0.001) and IVS (p = 0.02), but not TB (p = 0.5) varied across regions. Interpretation Overall mortality and AIDS-mortality rates decreased over time, but remained higher in Eastern Europe. A poor IVS, being off ART and prior active TB were related to higher mortality. Eastern Europe had the highest proportion of people with poor or unknown IVS, emphasizing the continued need to improve HIV care with a focus on early diagnosis, ART initiation, and adherence.

Background Survival among people with HIV (PWH) has vastly improved globally over the last few decades but remains lower than among the general population. We aimed to estimate time trends of survival among PWH and their families from 1995 to 2021. Methods We conducted a registry-based, nationwide, population-based, matched cohort study. We included all Danish-born PWH from 1995 to 2021 who had been on antiretroviral therapy for 90 days, did not report intravenous drug use, and were not co-infected with hepatitis C (n = 4168). We matched population controls from the general population 10:1 to PWH by date of birth and sex (n = 41,680). For family cohorts, we identified siblings, mothers, and fathers of PWH and population controls. From Kaplan-Meier tables with age as time scale, we estimated survival from age 25. We compared PWH with population controls and families of PWH with families of population controls to calculate mortality rate ratios adjusted for sex, age, comorbidities, and education (aMRR). Findings The median age of death among PWH increased from 27.5 years in 1995-1997 to 73.9 years (2010-2014), but thereafter survival increased only marginally. From 2015 to 2021, mortality was increased among PWH (aMRR 1.87 (95% CI: 1.65-2.11)) and siblings (aMRR: 1.25 (95% CI: 1.07-1.47)), mothers (aMRR: 1.30 (95% CI: 1.17-1.43)), and fathers (aMRR: 1.15 (95% CI: 1.03-1.29)) of PWH compared to their respective control cohorts. Mortality among siblings of PWH who reported heterosexual route of HIV transmission (aMRR: 1.51 (95% CI: 1.16-1.96)) was higher than for siblings of PWH who reported men who have sex with men as route of HIV transmission (aMRR 1.19 (95% CI: 0.98-1.46)). Interpretation Survival among PWH improved substantially until 2010, after which it increased only marginally. This may partly be due to social and behavioural factors as PWH families also had higher mortality.

aDivision of Allergy and Infectious Diseases, University of Washington, Seattle, WA bDepartment of Medicine, Georgetown University, Washington, DC, USA cDepartment of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. Correspondence to Brian R. Wood, MD, Harborview 2W Clinic, 325 9th Ave, Seattle, WA 98104, USA. E-mail: [email protected] Received 19 December, 2022 Accepted 26 December, 2022

IntroductionWith longer life expectancy in people living with HIV (PLWH) on antiretroviral therapy, cardiovascular disease (CVD) has become a common cause of mortality among them. Abacavir has been associated with an increased risk of myocardial infarction, but the mechanism is unknown. Additionally, abacavir may be obesogenic which could mediate an additional risk factor of CVD. We aim to investigate if discontinuation of abacavir will have a favourable impact on body weight and cardiac parameters in PLWH.Methods and analysisRandomised, controlled, superiority trial of virologically suppressed PLWH on dolutegravir, abacavir and lamivudine (DTG/ABC/3TC) for ≥6 months. In total, 70 PLWH will be randomised 1:2 to either continue DTG/ABC/3TC or to switch to dolutegravir and lamivudine (DTG/3TC) providing the power of 80% at alpha 5% to detect a mean difference in weight change of 2 kg (Δ) given an SD of 2.7 kg. Follow-up will be 48 weeks. Data will be collected at baseline and week 48. Primary outcome will be change in mean body weight from baseline to week 24 and 48 evaluated in a linear mixed model. Secondary outcomes will be changes in cardiac, inflammatory and metabolic parameters, fat distribution, coagulation, endothelial, platelet function, quality of life and virological control from baseline to week 48. Measurements include CT of thorax and abdomen, external carotid artery ultrasound, liver elastography and dual energy X-ray absorptiometry and blood analysis. Plasma HIV RNA will be measured at baseline, week 4, 24 and 48. Forty participants (20 from each arm) will be included in a substudy involving cardiac MRI at baseline and week 48. Twenty non-HIV-infected controls will be included with a single scan to compare with baseline scan data.Ethics and disseminationResult from this study will lead to a better understanding of the association between antiretroviral therapy and the impact on weight and risk of CVD. Findings will be useful for both clinicians and PLWH in the guidance of a more individualised HIV treatment. Results from the main study and the substudies will be submitted for publication in a peer-reviewed journal(s). The AVERTAS study is approved by the Ethics Committee of the Capital Region, Denmark (H-20011433), Danish Medicines Agency (EudraCT no. 2019-004999-19) and Regional Data Protection Centre (P-2020–207).Trial registration numberPre-results registration at ClinicalTrials.gov Identifier:NCT04904406, registered 27 May 2021. Protocol version: Protocol version 9.0, 4 April 2023, approved 10-05-2023 by Ethics Committee of the Capital Region, Denmark (H-20011433). Danish Medicines Agency (EudraCT no. 2019-004999-19). Regional Data Protection Centre (P-2020–207) ClinicalTrials.gov.

BACKGROUND For people with HIV and CD4+ counts >500 cells/mm3, early initiation of antiretroviral therapy (ART) reduces serious AIDS and serious non-AIDS (SNA) risk compared with deferral of treatment until CD4+ counts are <350 cells/mm3. Whether excess risk of AIDS and SNA persists once ART is initiated for those who defer treatment is uncertain. METHODS The Strategic Timing of AntiRetroviral Treatment (START) trial, as previously reported, randomly assigned 4684 ART-naive HIV-positive adults with CD4+ counts .500 cells/mm3 to immediate treatment initiation after random assignment (n = 2325) or deferred treatment (n= 2359). In 2015, a 57% lower risk of the primary end point (AIDS, SNA, or death) for the immediate group was reported, and the deferred group was offered ART. This article reports the follow-up that continued to December 31, 2021. Cox proportional-hazards models were used to compare hazard ratios for the primary end point from randomization through December 31, 2015, versus January 1, 2016, through December 31, 2021. RESULTS Through December 31, 2015, approximately 7 months after the cutoff date from the previous report, the median CD4+ count was 648 and 460 cells/mm3 in the immediate and deferred groups, respectively, at treatment initiation. The percentage of follow-up time spent taking ART was 95% and 36% for the immediate and deferred groups, respectively, and the time-averaged CD4+ difference was 199 cells/mm3. After January 1, 2016, the percentage of follow-up time on treatment was 97.2% and 94.1% for the immediate and deferred groups, respectively, and the CD4+ count difference was 155 cells/mm3. After January 1, 2016, a total of 89 immediate and 113 deferred group participants experienced a primary end point (hazard ratio of 0.79 [95% confidence interval, 0.60 to 1.04] versus hazard ratio of 0.47 [95% confidence interval, 0.34 to 0.65; P<0.001]) before 2016 (P=0.02 for hazard ratio difference). CONCLUSIONS Among adults with CD4+ counts >500 cells/mm3, excess risk of AIDS and SNA associated with delaying treatment initiation was diminished after ART initiation, but persistent excess risk remained. (Funded by the National Institute of Allergy and Infectious Diseases and others.).

Inducing antiretroviral therapy (ART)-free virological control is a critical step toward a human immunodeficiency virus type 1 (HIV-1) cure. In this phase 2a, placebo-controlled, double-blinded trial, 43 people (85% males) with HIV-1 on ART were randomized to (1) placebo/placebo, (2) lefitolimod (TLR9 agonist)/placebo, (3) placebo/broadly neutralizing anti-HIV-1 antibodies (bNAbs) or (4) lefitolimod/bNAb. ART interruption (ATI) started at week 3. Lefitolimod was administered once weekly for the first 8 weeks, and bNAbs were administered twice, 1 d before and 3 weeks after ATI. The primary endpoint was time to loss of virologic control after ATI. The median delay in time to loss of virologic control compared to the placebo/placebo group was 0.5 weeks ( P = 0.49), 12.5 weeks ( P = 0.003) and 9.5 weeks ( P = 0.004) in the lefitolimod/placebo, placebo/bNAb and lefitolimod/bNAb groups, respectively. Among secondary endpoints, viral doubling time was slower for bNAb groups compared to non-bNAb groups, and the interventions were overall safe. We observed no added benefit of lefitolimod. Despite subtherapeutic plasma bNAb levels, 36% (4/11) in the placebo/bNAb group compared to 0% (0/10) in the placebo/placebo group maintained virologic control after the 25-week ATI. Although immunotherapy with lefitolimod did not lead to ART-free HIV-1 control, bNAbs may be important components in future HIV-1 curative strategies. ClinicalTrials.gov identifier: NCT03837756 .

Objective: To compare the risk of a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test and coronavirus disease 2019 (COVID-19) outcomes in people with HIV (PWH) with the general population, and estimate the association with vaccination status. Design: A nationwide, population based, matched cohort study Methods: We included all Danish PWH ≥18 years (n = 5276) and an age and sex-matched general population cohort (n = 42 308). We used Cox regression analyses to calculate (adjusted) incidence rate ratios [(a)IRR] and further stratified and restricted the analyses. Results: We observed no major difference in risk of first positive SARS-CoV-2 test [aIRR: 0.8 (95% confidence interval (CI): 0.8–0.9)], but a higher risk of first hospital contact with COVID-19 and hospitalization with severe COVID-19 for PWH vs. controls [IRR: 2.0; (1.6–2.5), 1.8 (1.4–2.3)]. Risk of first hospitalization decreased substantially in PWH with calendar time [first half of year 2022 vs. 2020 IRR: 0.3; (0.2–0.6)], whereas the risk compared to population controls remained almost twofold increased. We did not observe increased risk of death after SARS-CoV-2 infection [aIRR: 0.7 (95% CI: 0.3–2.0)]. Compared to PWH who had received two vaccines PWH who receiving a third vaccine had reduced risk of first positive SARS-CoV-2 test, death (individuals ≥60years) and hospitalization [aIRR: 0.9 (0.7–1.0); 0.2 (0.1–0.7); 0.6 (0.2–1.2)]. Conclusion: PWH have almost the same risk of a positive SARS-CoV-2 test as the general population. Although risk of hospital contacts and severe outcomes following SARS-CoV-2 infection is increased, the risk of death does not seem to be substantially increased. Importantly, a third vaccine is associated with reduced risk of infection, and death.

Background Human immunodeficiency virus (HIV) infection is associated with depression. However, previous studies have not addressed familial factors. Methods Nationwide, population-based, matched cohort study of people with HIV (PWH) in Denmark between 1995 and 2021 who were matched on sex and date of birth with a comparison cohort randomly selected from the Danish population. Family-related factors were examined by inclusion of siblings of those in the cohorts. We calculated hazard ratios (HRs) for depression, receipt of antidepressants, electroconvulsive therapy (ECT), and suicide, as well as the yearly proportions of study cohorts with psychiatric hospital contact due to depression and receipt of antidepressants from 10 years before to 10 years after study inclusion. Results We included 5943 PWH and 59 430 comparison cohort members. Median age was 38 years, and 25% were women. We observed an increased risk of depression, receipt of antidepressants, ECT, and suicide among PWH in the 2 first years of observation (HR, 3.3; 95% confidence interval [CI]: 2.5-4.4), HR, 3.0 (95% CI: 2.7-3.4), HR, 2.8 (95% CI: .9-8.6), and HR, 10.7 (95% CI: 5.2-22.2), thereafter the risk subsided but remained increased. The proportions of PWH with psychiatric hospital contact due to depression and receipt of antidepressants were increased prior to and especially after HIV diagnosis. Risk of all outcomes was substantially lower among siblings of PWH than among PWH (HR for receipt of antidepressants, 1.1; 95% CI: 1.0-1.2). Conclusions PWH have an increased risk of depression. Family-related factors are unlikely to explain this risk. In this nationwide, population-based, matched cohort study, we demonstrated an increased risk of depression, receipt of antidepressants, treatment with electroconvulsive therapy, and suicide among people with human immunodeficiency virus compared with date of birth- and sex-matched comparison cohort members.