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We compared CD4 changes and viral load set-point in individuals infected with different human immunodeficiency virus type 1 (HIV-1) subtypes. HIV-1 subtype significantly influences seroconversion CD4 levels and rate of decline but not viral load set point, indicating that viral genetic diversity is associated with disease progression.Background. Human immunodeficiency virus type 1 (HIV-1) subtype may influence disease progression. We compared CD4 lymphocyte cell count levels at seroconversion, decline rates and viral load set point in individuals infected with different HIV-1 subtypes.Methods. We used data from the Concerted Action on SeroConversion to AIDS and Death in Europe (CASCADE) collaboration, restricted to those infected since 1996, aged ≥15 years, and applied mixed effects models for CD4 cell count decline and median regression for viral load set point (mean level 6–24 months from seroconversion).Results. The analysis included 3364 seroconverters with known HIV-1 subtypes. Compared with subtype B, CD4 at seroconversion was significantly higher for subtype CRF01 and lower for subtype C. Subsequent CD4 decline was significantly slower for subtypes A and CRF02 and marginally slower for subtype C compared with B. Mean CD4 loss at 2 years of seroconversion for white men exposed through sex between men, aged 30–39 years, having seroconverted since 2006, enrolled within 6 months of seroconversion, and without acute infection was 88, 142, 100, 130, 103, and 167 cells/µL for subtypes A, B, C, CRF01_AE, CRF02_AG, and G, respectively. In adjusted analysis, median viral load set point and time to clinical AIDS/death did not differ significantly by subtype, although all subtypes, except C, tended to have lower levels compared with B.Conclusions. HIV-1 subtype significantly influences seroconversion CD4 cell levels and decline rates but not viral load set point. These findings may be helpful to HIV-positive individuals and their attending physicians in understanding disease progression. [ABSTRACT FROM PUBLISHER]

Background. Recent updates of human immunodeficiency virus (HIV) treatment guidelines have raised the CD4+ cell count thresholds for antiretroviral therapy initiation from 350 to 500 cells/mm3 in the United States and from 200 to 350 cells/mm3 in mid- and low-income countries. Robust data of time from HIV seroconversion to CD4+ cell counts of 200, 350, and 500 cells/mm3 are lacking but are needed to inform health care planners of the likely impact and cost effectiveness of these and possible future changes in CD4+ cell count initiation threshold. Methods. Using Concerted Action on Seroconversion to AIDS and Death in Europe data from individuals with well-estimated dates of HIV seroconversion, we fitted mixed models on the square root of CD+ cell counts measured before combined antiretroviral therapy (cART) initiation. Restricting analyses to adults (age >16 years), we predicted time between seroconversion and CD4+ cell count <200,<350, and<500 cells/mm3 as well as CD4+ cell count distribution and proportions reaching these thresholds at 1, 2, and 5 years after seroconversion. Results. Median (interquartile range [IQR]) follow-up for the 18 495 eligible individuals from seroconversion while cART-free was 3.7 years (1.5, 7). Most of the subjects were male (78%), had a median age at seroconversion of 30 years (IQR, 25-37 years), and were infected through sex between men (55%). Estimated median times (95% confidence interval [CI]) from seroconversion to CD4+ cell count <500, <350, and <200 cells/mm3 were 1.19 (95% CI, 1.12-1.26), 4.19 (95% CI, 4.09-4.28), and 7.93 (95% CI, 7.76-8.09) years, respectively. Almost half of infected individuals would require treatment within 1 year of seroconversion for guidelines recommending its initiation at 500 cells/mm3, compared with 26% and 9% for guidelines recommending initiation at 350 and 200 cells/mm3, respectively. Conclusions. These data suggest substantial increases in the number of individuals who require treatment and call for early HIV testing. [ABSTRACT FROM AUTHOR]

Objective. This cross-sectional study determines the impact of the pandemic lockdowns on physical activity, and evaluates the factors associated with physical activity cessation on students and personnel of eight Greek Higher Education Institutions. Materials and Methods. A total of 6,380 volunteer participants completed a survey reporting their physical activity levels and perceptions during the COVID-19 pandemic. The survey was made available through an online platform. Results. Both the conduct and intensity of physical activity were significantly reduced from the pre-pandemic era to the second lockdown (P<0.001). Walking was the most frequently selected type of physical activity, in all periods except for the second lockdown. Loss of interest (52.4%) was the main, self-reported factor for cessation of physical activity. Females had a 31% lower probability of ceasing physical activity during lockdowns. Conclusion. The conduct and intensity of physical activity decreased significantly during the pandemic. Female gender, annual checkup attendance, and specific physical activity types during the pre-pandemic era were associated with a reduction in the risk of pausing physical activity during lockdowns. Lockdowns may be implemented in future health crises, hence measures for maintaining the physical activity of the general population, such as online group sessions and support from healthcare professionals, should be prepared. [ABSTRACT FROM AUTHOR]

Joint modeling of longitudinal and time-to-event data, particularly through shared parameter models (SPMs), is a common approach for handling longitudinal marker data with an informative terminal event. A critical but often neglected assumption in this context is that the visiting/observation process is noninformative, depending solely on past marker values and visit times. When this assumption fails, the visiting process becomes informative, resulting potentially to biased SPM estimates. Existing methods generally rely on a conditional independence assumption, positing that the marker model, visiting process, and time-to-event model are independent given shared or correlated random effects. Moreover, they are typically built on an intensity-based visiting process using calendar time. This study introduces a unified approach for jointly modeling a normally distributed marker, the visiting process, and time-to-event data in the form of competing risks. Our model conditions on the history of observed marker values, prior visit times, the marker's random effects, and possibly a frailty term independent of the random effects. While our approach aligns with the shared-parameter framework, it does not presume conditional independence between the processes. Additionally, the visiting process can be defined on either a gap time scale, via proportional hazard models, or a calendar time scale, via proportional intensity models. Through extensive simulation studies, we assess the performance of our proposed methodology. We demonstrate that disregarding an informative visiting process can yield significantly biased marker estimates. However, misspecification of the visiting process can also lead to biased estimates. The gap time formulation exhibits greater robustness compared to the intensity-based model when the visiting process is misspecified. In general, enriching the visiting process with prior visit history enhances performance. We further apply our methodology to real longitudinal data from HIV, where visit frequency varies substantially among individuals., (© The Author(s) 2024. Published by Oxford University Press.)

Background: Systemic lupus erythematosus (SLE) is characterised by increased cardiovascular morbidity and mortality risk. We aimed to examine the prevalence of traditional cardiovascular risk factors and their control in an international survey of patients with systemic lupus erythematosus., Methods: In this multicentre, cross-sectional study, cardiovascular risk factor data from medical files of adult patients (aged ≥18) with SLE followed between Jan 1, 2015, and Jan 1, 2020, were collected from 24 countries, across five continents. We assessed the prevalence and target attainment of cardiovascular risk factors and examined potential differences by country income level and antiphospholipid syndrome coexistence. We used the Systemic Coronary Risk Evaluation algorithm for cardiovascular risk estimation, and the European Society of Cardiology guidelines for assessing cardiovascular risk factor target attainment. People with lived experience were not involved in the research or writing process., Findings: 3401 patients with SLE were included in the study. The median age was 43·0 years (IQR 33-54), 3047 (89·7%) of 3396 patients were women, 349 (10.3%) were men, and 1629 (48·1%) of 3390 were White. 556 (20·7%) of 2681 patients had concomitant antiphospholipid syndrome. We found a high cardiovascular risk factor prevalence (hypertension 1210 [35·6%] of 3398 patients, obesity 751 [23·7%] of 3169 patients, and hyperlipidaemia 650 [19·8%] of 3279 patients), and suboptimal control of modifiable cardiovascular risk factors (blood pressure [target of <130/80 mm Hg], BMI, and lipids) in the entire SLE group. Higher prevalence of cardiovascular risk factors but a better blood pressure (target of <130/80 mm Hg; 54·9% [1170 of 2132 patients] vs 46·8% [519 of 1109 patients]; p<0·0001), and lipid control (75·0% [895 of 1194 patients] vs 51·4% [386 of 751 patients], p<0·0001 for high-density lipoprotein [HDL]; 66·4% [769 of 1158 patients] vs 60·8% [453 of 745 patients], p=0·013 for non-HDL; 80·9% [1017 of 1257 patients] vs 61·4% [486 of 792 patients], p<0·0001 for triglycerides]) was observed in patients from high-income versus those from middle-income countries. Patients with SLE with antiphospholipid syndrome had a higher prevalence of modifiable cardiovascular risk factors, and significantly lower attainment of BMI and lipid targets (for low-density lipoprotein and non-HDL) than patients with SLE without antiphospholipid syndrome., Interpretation: High prevalence and inadequate cardiovascular risk factor control were observed in a large multicentre and multiethnic SLE cohort, especially among patients from middle-income compared with high-income countries and among those with coexistent antiphospholipid syndrome. Increased awareness of cardiovascular disease risk in SLE, especially in the above subgroups, is urgently warranted., Funding: None., Competing Interests: Declaration of interests AGS has received speaker fees from Merck and Schering-Plough, Bristol Myers Squibb, UCB, Pfizer, Novartis, Lilly and Women's College Hospital, Toronto, ON, Canada. AMK has received speaker fees from Boehringer Ingelheim and Sanofi; has participated on advisory boards for Pfizer, Gilead, and Boehringer Ingelheim; and has received congress sponsorship from Pfizer, Celgene, UCB, Mylan, and Roche. GJP-E has received grants from Janssen; consulting fees from GSK, AstraZeneca, Janssen, Novartis, and Bago; speakers fees from GSK, Werfen, Janssen, AstraZeneca, and Novartis; support for attending meetings and travel from GSK, AstraZeneca, and Boehringer Ingelheim; and for participation on a data safety monitoring board or advisory board from RemeGen, AstraZeneca, and Janssen. GAK has received consulting fees from Janssen and Scipher; and for participation on a data safety monitoring board or advisory board from Janssen. MFU-G has received grant support from Janssen and Pfizer; has been a speaker for GSK and AstraZeneca; and has been a member of advisory boards for AstraZeneca and Ferrer. NC-C has received grants from Roche and UCB. EH has received consulting fees and meeting fees from Johnson & Johnson, Boehringer Ingelheim, Bayer, GSK, Roche-Chugai, and Sanofi-Genzyme; speaking fees from Johnson & Johnson, GSK, and Roche-Chugai; and research funding from Commonwealth Serum Laboratories Behring, GSK, Roche-Chugai, and Johnson & Johnson. NP has received grants from Gilead Sciences Hellas and the European Centre for Disease Prevention and Control. OAM has received speaker's fees or payment for advisory boards from AbbVie, APSEN, AstraZeneca, Boehringer Ingelheim, Celltrion, GSK, and Janssen. MS has received research grants and consulting fees, and has participated as a speaker for: AbbVie, Bristol Myers Squibb, GSK, Janssen, Lilly, Pfizer, Roche, and AstraZeneca. ACSM has received speaker fees from GSK and AstraZeneca. All other authors and SURF-SLE and APS Collaborators declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Introduction: Mortality rates for people living with HIV (PLHIV) on antiretroviral therapy (ART) in high-income countries continue to decline. We compared mortality rates among PLHIV on ART in Europe for 2016-2020 with Spectrum's estimates., Methods: The AIDS Impact Module in Spectrum is a compartmental HIV epidemic model coupled with a demographic population projection model. We used national Spectrum projections developed for the 2022 HIV estimates round to calculate mortality rates among PLHIV on ART, adjusting to the age/country distribution of PLHIV starting ART from 1996 to 2020 in the Antiretroviral Therapy Cohort Collaboration (ART-CC)'s European cohorts., Results: In the ART-CC, 11,504 of 162,835 PLHIV died. Between 1996-1999 and 2016-2020, AIDS-related mortality in the ART-CC decreased from 8.8 (95% CI: 7.6 to 10.1) to 1.0 (0.9-1.2) and from 5.9 (4.4-8.1) to 1.1 (0.9-1.4) deaths per 1000 person-years among men and women, respectively. Non-AIDS-related mortality decreased from 9.1 (7.9-10.5) to 6.1 (5.8-6.5) and from 7.0 (5.2-9.3) to 4.8 (4.3-5.2) deaths per 1000 person-years among men and women, respectively. Adjusted all-cause mortality rates in Spectrum among men were near ART-CC estimates for 2016-2020 (Spectrum: 7.02-7.47 deaths per 1000 person-years) but approximately 20% lower in women (Spectrum: 4.66-4.70). Adjusted excess mortality rates in Spectrum were 2.5-fold higher in women and 3.1-3.4-fold higher in men in comparison to the ART-CC's AIDS-specific mortality rates., Discussion: Spectrum's all-cause mortality estimates among PLHIV are consistent with age/country-controlled mortality observed in ART-CC, with some underestimation of mortality among women. Comparing results suggest that 60%-70% of excess deaths among PLHIV on ART in Spectrum are from non-AIDS causes., Competing Interests: R.G.'s institution has received grants from UNAIDS and the Bill and Melinda Gates Foundation. N.P. has received grants unrelated to this study and paid to his institution from Gilead Sciences Hellas and ECDC. R.Z. has not received honoraria in the past 3 years. J.V. has personal fees from Merck/MSD, Gilead, Pfizer, Astellas Pharma, Basilea, German Centre for Infection Research (DZIF), University Hospital Freiburg/Congress and Communication, Academy for Infectious Medicine, University Manchester, German Society for Infectious Diseases (DGI), Ärztekammer Nordrhein, University Hospital Aachen, Back Bay Strategies, and German Society for Internal Medicine (DGIM) and grants from Merck/MSD, Gilead, Pfizer, Astellas Pharma, Basilea, German Centre for Infection Research (DZIF), German Federal Ministry of Education and Research (BMBF), (PJ-T: DLR), University of Bristol, and Rigshospitalet Copenhagen. M.C.'s institution received research grants and expert opinion fees from Gilead, MSD, and Viiv. R.T. has received grant funding from Gilead, Janssen, and ViiV unrelated to this work. J.W.E. reports personal fees from Oxford Policy Management. The remaining authors have no funding or conflicts of interest to disclose., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: More than 300 cities including the city of Amsterdam in the Netherlands have joined the UNAIDS Fast-Track Cities initiative, committing to accelerate their HIV response and end the AIDS epidemic in cities by 2030. To support this commitment, we aimed to estimate the number and proportion of Amsterdam HIV infections that originated within the city, from Amsterdam residents. We also aimed to estimate the proportion of recent HIV infections during the 5-year period 2014-2018 in Amsterdam that remained undiagnosed., Methods: We located diagnosed HIV infections in Amsterdam using postcode data (PC4) at time of registration in the ATHENA observational HIV cohort, and used HIV sequence data to reconstruct phylogeographically distinct, partially observed Amsterdam transmission chains. Individual-level infection times were estimated from biomarker data, and used to date the phylogenetically observed transmission chains as well as to estimate undiagnosed proportions among recent infections. A Bayesian Negative Binomial branching process model was used to estimate the number, size, and growth of the unobserved Amsterdam transmission chains from the partially observed phylogenetic data., Results: Between 1 January 2014 and 1 May 2019, there were 846 HIV diagnoses in Amsterdam residents, of whom 516 (61%) were estimated to have been infected in 2014-2018. The rate of new Amsterdam diagnoses since 2014 (104 per 100,000) remained higher than the national rates excluding Amsterdam (24 per 100,000), and in this sense Amsterdam remained a HIV hotspot in the Netherlands. An estimated 14% [12-16%] of infections in Amsterdan MSM in 2014-2018 remained undiagnosed by 1 May 2019, and 41% [35-48%] in Amsterdam heterosexuals, with variation by region of birth. An estimated 67% [60-74%] of Amsterdam MSM infections in 2014-2018 had an Amsterdam resident as source, and 56% [41-70%] in Amsterdam heterosexuals, with heterogeneity by region of birth. Of the locally acquired infections, an estimated 43% [37-49%] were in foreign-born MSM, 41% [35-47%] in Dutch-born MSM, 10% [6-18%] in foreign-born heterosexuals, and 5% [2-9%] in Dutch-born heterosexuals. We estimate the majority of Amsterdam MSM infections in 2014-2018 originated in transmission chains that pre-existed by 2014., Conclusions: This combined phylogenetic, epidemiologic, and modelling analysis in the UNAIDS Fast-Track City Amsterdam indicates that there remains considerable potential to prevent HIV infections among Amsterdam residents through city-level interventions. The burden of locally acquired infection remains concentrated in MSM, and both Dutch-born and foreign-born MSM would likely benefit most from intensified city-level interventions., Funding: This study received funding as part of the H-TEAM initiative from Aidsfonds (project number P29701). The H-TEAM initiative is being supported by Aidsfonds (grant number: 2013169, P29701, P60803), Stichting Amsterdam Dinner Foundation, Bristol-Myers Squibb International Corp. (study number: AI424-541), Gilead Sciences Europe Ltd (grant number: PA-HIV-PREP-16-0024), Gilead Sciences (protocol numbers: CO-NL-276-4222, CO-US-276-1712, CO-NL-985-6195), and M.A.C AIDS Fund., Competing Interests: AB, MM, DB, EO, Tv, CF, OR No competing interests declared, Av Funding for managing the ATHENA cohort is supported by a grant from the Dutch Ministry of Health, Welfare and Sport through the Centre for Infectious Disease Control of the National Institute for Public Health and the Environment. Received grants unrelated to this study from European Centre for Disease Prevention and Control paid to author's institution, NP Received grants unrelated to this study from ECDC and Gilead Sciences Hellas, paid to author's institution. Received honoraria for presentations unrelated to this study from Gilead Sciences Hellas, MP Received unrestricted research grants and speaker/ advisory fees from Gilead Sciences, Abbvie and MSD; all of which were paid to author's institute and were unrelated to this study, PR Has received grants unrelated to this study from Gilead Sciences, ViiV Healthcare and Merck, paid to author's institution. Received Honoraria for lecture from Merck paid to institution. Received Honoraria from Gilead Sciences, ViiV Healthcare and Merck, paid to institution, Gd Received honoraria to her Institution for scientific advisory board participations for Gilead Sciences and speaker fees from Gilead Sciences (2019), Takeda (2018-2022) and ExeVir (2020-current), (© 2022, Blenkinsop et al.)

Background: To investigate the association between Clostridioides difficile infection (CDI), antibiotic use, and infection control interventions, during an antibiotic stewardship program (ASP) implemented in a tertiary-care hospital in Greece from 2013 to 2018., Methods: Analysis was applied for the following monthly indices: 1. consumption of antibiotics; 2. use of hand hygiene disinfectant solutions; 3. percentage of isolations of patients either with multidrug-resistant (MDR) bacteria, or CDI, or admitted from another hospital; and 4. percentage of patients with CDI divided into two groups: community-acquired CDI (CACDI) and hospital-associated CDI (HACDI) (onset ≤72 h and >72 h after admission, respectively)., Results: During the study, a significant reduction in CACDI rate from 0.3%/admissions [95% CI 0.1-0.6] to 0.1%/admissions [95% CI 0.0-0.3] (p-value = 0.035) was observed in adults ICU, while CDI rates were stable in the rest of the hospital. Antibiotic consumption showed a significant reduction in total hospital, from 91.7 DDDs [95% CI 89.7-93.7] to 80.1 DDDs [95% CI 79.1-81.1] (p-value<0.001), except adults ICU. Non-advanced antibiotics correlated with decreased CDI rates in Adults Clinic Departments and ICU. Isolation of patients one and two months earlier correlated with decreased CACDI rates per 20% [95% CI 0.64-1.00, p-value = 0.046] and HACDI per 23% [95% CI 0.60-1.00, p-value = 0.050] in Adults Clinic Departments. Consumption of disinfectant solutions current month correlated with decreased rate for CACDI per 33% [95% CI 0.49-0.91, p-value = 0.011] and HACDI per 38% [95% CI 0.40-0.98, p-value = 0.040] in total Hospital Clinics., Conclusion: Rational antibiotic prescribing during ASP along with multipronged intervention strategy focusing on hand hygiene and patient isolation measures prevent and control CDI outbreaks in the hospital setting., (Copyright © 2022 Australasian College for Infection Prevention and Control. Published by Elsevier B.V. All rights reserved.)

Recent research on antiretroviral treatment (ART) for HIV suggests that integrase strand transfer inhibitors (INSTIs) cause faster weight gain compared to other drug classes. Here, we investigated changes in body mass index (BMI) and obesity prevalence after treatment initiation and corresponding differences between drug classes. Data were derived from a large collaborative cohort in Greece. Included individuals were adults who started ART, in or after 2010, while previously ART naïve and achieved virologic response within the first year of ART. Data were analysed using mixed fractional polynomial models. INSTI regimens led to the more pronounced BMI increases, followed by boosted PI and NNRTI based regimens. Individuals with normal initial BMI are expected to gain 6 kg with an INSTI regimen compared to 4 kg with a boosted PI and less than 3 kg with a NNRTI regimen after four years of treatment. Prevalence of obesity was 5.7% at ART initiation and 12.2%, 14.2% and 18.1% after four years of treatment with NNRTIs, PIs, and INSTIs, respectively. Dolutegravir or Raltegravir were associated with marginally faster BMI increase compared to Elvitegravir. INSTIs are associated with faster weight gain. INSTIs' increased risk of treatment emergent obesity and, possibly, weight-related co-morbidities should be judged against their improved efficacy and tolerability but increased clinical attention is required.

Background: Multidrug-resistant (MDR) bacteremia is a serious health care-associated infection with significant morbidity and excess hospitalization costs. Our aim is to study the association between incidences of MDR bacteremia, antibiotic consumption, and infection control measures in a hospital from 2013 to 2018. Methods: We analyzed the following indices: (1) incidence of bacteremia (carbapenem-resistant Acinetobacter baumanii , Pseudomonas aeruginosa , and Klebsiella pneumoniae , methicillin-resistant Staphylococcus aureus , vancomycin-resistant Enterococci ); (2) use of antibiotics; (3) consumption of disinfectant solutions for hand hygiene; and (4) isolation rates of MDR carrier patients. Findings: The use of advanced antibiotics ( p  = 0.001) and carbapenems ( p  = 0.008) decreased significantly in all hospital departments but the incidence of total MDR bacteremia did not change significantly. Increased use of hand disinfectant solutions was statistically associated with decreased incidence of total MDR bacteremia (incidence rate ratio [IRR]: 0.94, confidence interval [95% CI]: 0.90-0.99, p : 0.020) in all hospital. Also, increased isolation rates of MDR carrier patients 2 months before correlated with decreased incidence of bacteremia due to carbapenem-resistant gram-negative pathogens (IRR: 0.35, 95% CI: 0.18-0.66, p : 0.001) in adults intensive care unit. Conclusion: In our hospital, hand hygiene and isolation of MDR carrier patients controlled MDR bacteremia.

Background: Diode-assisted endodontics is nowadays utilized for pulp space disinfection, but little is known on the bonding potential of this lased root dentin when the tooth is restored with an intracanal polymer post. Objectives: to investigate the influence of diode laser irradiation settings, in laser-assisted endodontics, on the intraradicular bonding of composite materials. Methods: Sixteen two-rooted, maxillary first premolars were collected, prepared up to F4 (Protaper Universal. Dentsply-Maillefer, Ballaigues, Switzerland), and randomly assigned in two groups: group A (chopped mode or short pulse), diode irradiated according to protocol, pulse 25 ms, power 2.5 W, and group B (microchopped mode or ultrashort pulse), pulse 25 μs, peak power 12 W (both groups GentleRay. KaVo Dental, Biberach an der Riss, Germany). Buccal canals were irradiated, palatal ones served as controls. Canals were then obturated, post space was created in all canals, and quartz-fiber posts (ICE light Danville. Danville Materials, San Ramon, CA, USA) were cemented by self-etch self-curing cement (Max Cem Elite. Kerr, West Collins Orange, CA, USA) (Max Cem Elite. Kerr, Brea, CA, USA). A week later, teeth were sectioned horizontally in 1 mm increments. Push-out test was conducted in a Zwick testing machine (Zwick Roell, Ulm, Germany) at 1 mm/min speed, and the force required to dislodge the post from each specimen (F-max) was recorded. Weibull regression models were applied for statistical analyses. Results: Differences in F-max by group (control vs. chopped mode vs. microchopped mode) and height (meaning the apical-to-coronal position of each specimen along the root) were statistically significant (p < 0.05 in all cases). Conclusions: Short pulses (or chopped mode) had a profound positive effect on the quality of intraradicular bonding, while Ultrashort pulses (or microchopped mode) affected it negatively. In addition, apically positioned bonding proved weaker compared with more coronally located specimens.

Objective: The aim of this study was to propose a unified continuum-of-care (CoC) analysis combining cross-sectional and longitudinal elements, incorporating time spent between stages., Design: The established 90-90-90 target follows a cross-sectional four-stage CoC analysis, lacking information on timing of diagnosis, antiretroviral therapy (ART) initiation, and viral suppression durability., Methods: Data were derived from the Athens Multicenter AIDS Cohort Study (AMACS). In the cross-sectional CoC, we added stratification of diagnosed people with HIV (PWH) by estimated time from infection to diagnosis; of those who ever initiated ART or achieved viral suppression by corresponding current status (in 2018); and cumulative incidence function (CIF) of ART initiation and viral suppression, treating loss-to-follow-up (LTFU) as competing event. Viral suppression was defined as viral load less than 500 copies/ml. Viral suppression durability was assessed by the CIF of viral load rebound., Findings: About 89.1% of PWH in 2018 were diagnosed (range of diagnoses: 1980-2018). Median time to diagnosis was 3.5 years (IQR: 1.1-7.0). Among diagnosed, 89.1% were ever treated, of whom 86.7% remained on ART. CIF of ART initiation and LTFU before ART initiation were 80.9 and 6.0% at 5 years since diagnosis, respectively. Among treated, 89.4% achieved viral suppression, of whom 87.4% were currently virally suppressed. The CIF of viral load rebound was 24.2% at 5 years since first viral suppression but substantially reduced in more recent years., Interpretation: The proposed analysis highlights time gaps in CoC not evident by the standard cross-sectional approach. Our analysis highlights the need for early diagnosis and identifies late presenters as a key population for interventions that could decrease gaps in the CoC., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Several lines of evidence suggest that binding SARS-CoV-2 antibodies such as anti-SARS-CoV-2 RBD IgG (anti-RBD) and neutralising antibodies (NA) are correlates of protection against SARS-CoV-2, and the correlation of anti-RBD and NA is very high. The effectiveness (VE) of BNT162b2 in preventing SARS-CoV-2 infection wanes over time, and this reduction is mainly associated with waning immunity, suggesting that the kinetics of antibodies reduction might be of interest to predict VE. In a study of 97 health care workers (HCWs) vaccinated with the BNT162b2 vaccine, we assessed the kinetics of anti-RBD 30-250 days after vaccination using 388 individually matched plasma samples. Anti-RBD levels declined by 85%, 92%, and 95% at the 4th, 6th, and 8th month from the peak, respectively. The kinetics were estimated using the trajectories of anti-RBD by various models. The restricted cubic splines model had a better fit to the observed data. The trajectories of anti-RBD declines were statistically significantly lower for risk factors of severe COVID-19 and the absence of vaccination side effects. Moreover, previous SARS-CoV-2 infection was associated with divergent trajectories consistent with a slower anti-RBD decline over time. These results suggest that anti-RBD may serve as a harbinger for vaccine effectiveness (VE), and it should be explored as a predictor of breakthrough infections and VE.

Background: Migrant populations are overrepresented among persons diagnosed with HIV in the European Union and the European Economic Area. Understanding the timing of HIV acquisition (premigration or postmigration) is crucial for developing public health interventions and for producing reliable estimates of HIV incidence and the number of people living with undiagnosed HIV infection. We summarize a recently proposed method for determining the timing of HIV acquisition and apply it to both real and simulated data., Methods: The considered method combines estimates from a mixed model, applied to data from a large seroconverters' cohort, with biomarker measurements and individual characteristics to derive probabilities of premigration HIV acquisition within a Bayesian framework. The method is applied to a subset of data from the European Surveillance System (TESSy) and simulated data., Findings: Simulation study results showed good performance with the probabilities of correctly classifying a premigration case or a postmigration case being 87.4% and 80.4%, respectively. Applying the method to TESSy data, we estimated the proportions of migrants who acquired HIV in the destination country were 31.9%, 37.1%, 45.3%, and 45.2% for those originating from Africa, Europe, Asia, and other regions, respectively., Conclusions: Although the considered method was initially developed for cases with multiple biomarkers' measurements, its performance, when applied to data where only one CD4 count per individual is available, remains satisfactory. Application of the method to TESSy data, estimated that a substantial proportion of HIV acquisition among migrants occurs in destination countries, having important implications for public health policy and programs., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: The continuum of care (CoC) model has been used to describe the main pillars of HIV care. This study aims to systematically review methods and elucidate gaps in the CoC analyses, especially in terms of the timing of the progression through steps, recognized nowadays as a critical parameter for an effective response to the epidemic., Methods: A PubMed and EMBASE databases search up to December 2019 resulted in 1918 articles, of which 209 were included in this review; 84 studies presented in major HIV conferences were also included. Studies that did not provide explicit definitions, modelling studies and those reporting only on metrics for subpopulations or factors affecting a CoC stage were excluded. Included articles reported results on 1 to 6 CoC stages., Results: Percentage treated and virally suppressed was reported in 78%, percentage diagnosed and retained in care in 58%, percentage linked to care in 54% and PLHIV in 36% of the articles. Information for all stages was provided in 23 studies. Only 6 articles use novel CoC estimates: One presents a dynamic CoC based on multistate analysis techniques, two base their time-to-next-stage estimates on a risk estimation method based on the cumulative incidence function, weighted for confounding and censoring and three studies estimated the HIV infection time based on mathematical modelling., Conclusion: A limited number of studies provide elaborated time analyses of the CoC. Although time analyses lack the straightforward interpretation of the cross-sectional CoC, they provide valuable insights for the timely response to the HIV epidemic. A future goal would be to develop a model that retains the simplicity of the cross-sectional CoC but also incorporates timing between stages., (© 2021. The Author(s).)

Introduction: Model-based estimates of key HIV indicators depend on past epidemic trends that are derived based on assumptions about HIV disease progression and mortality in the absence of antiretroviral treatment (ART). Population-based HIV Impact Assessment (PHIA) household surveys conducted between 2015 and 2018 found substantial numbers of respondents living with untreated HIV infection. CD4 cell counts measured in these individuals provide novel information to estimate HIV disease progression and mortality rates off ART., Methods: We used Bayesian multi-parameter evidence synthesis to combine data on (1) cross-sectional CD4 cell counts among untreated adults living with HIV from 10 PHIA surveys, (2) survival after HIV seroconversion in East African seroconverter cohorts, (3) post-seroconversion CD4 counts and (4) mortality rates by CD4 count predominantly from European, North American and Australian seroconverter cohorts. We used incremental mixture importance sampling to estimate HIV natural history and ART uptake parameters used in the Spectrum software. We validated modelled trends in CD4 count at ART initiation against ART initiator cohorts in sub-Saharan Africa., Results: Median untreated HIV survival decreased with increasing age at seroconversion, from 12.5 years [95% credible interval (CrI): 12.1-12.7] at ages 15-24 to 7.2 years (95% CrI: 7.1-7.7) at ages 45-54. Older age was associated with lower initial CD4 counts, faster CD4 count decline and higher HIV-related mortality rates. Our estimates suggested a weaker association between ART uptake and HIV-related mortality rates than previously assumed in Spectrum. Modelled CD4 counts in untreated people living with HIV matched recent household survey data well, though some intercountry variation in frequencies of CD4 counts above 500 cells/mm 3 was not explained. Trends in CD4 counts at ART initiation were comparable to data from ART initiator cohorts. An alternate model that stratified progression and mortality rates by sex did not improve model fit appreciably., Conclusions: Synthesis of multiple data sources results in similar overall survival as previous Spectrum parameter assumptions but implies more rapid progression and longer survival in lower CD4 categories. New natural history parameter values improve consistency of model estimates with recent cross-sectional CD4 data and trends in CD4 counts at ART initiation., (© 2021 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Objective: Combined antiretroviral treatment (cART) results in profound immunologic improvement, but it is unclear whether CD4 cell counts return to levels similar to those of HIV-negative individuals. We explore long-term CD4 cell count evolution post-cART and its association with baseline levels, virologic suppression, pre-cART cumulative viremia and other factors., Design: Data were derived from the AMACS. Included individuals were adults who started cART, at least 2003, while previously ART-naive., Methods: Changes in CD4 cell counts were modeled through piecewise linear mixed models., Results: A total of 3405 individuals were included. The majority was male (86.0%), homosexual (58.8%) with median (IQR) age at cART initiation 36 (31-44) years and a median (IQR) follow-up of 3.9 (2.0-6.9) years. Most persons (57%) starting cART with less than 200 cells/μl did not reach 600 cells/μl after 7 years of treatment. Those starting cART with 200-349 CD4 cells/μl could reach 600 cells/μl within less than 2 years of fully suppressive treatment. Probability of CD4 normalization (i.e. >800 cells/μl) after 7 years of suppressive treatment was 24 and 46% for those starting treatment with less than 200 or 200-349 CD4 cells/μl, respectively. Lower pre-cART cumulative viremia was associated with faster CD4 recovery. CD4 cell count increases after 4 years were either insignificant or very slow, irrespectively of baseline levels., Conclusion: cART initiation before CD4 cell count drops below 350 cells/μl is crucial for achieving normal CD4 levels. These findings underline the importance of timely diagnosis and cART initiation as the risk of both AIDS and non-AIDS-related morbidity/mortality remains increased in patients with incomplete CD4 recovery.

Background: Knowledge of HIV-1 molecular transmission clusters (MTCs) is important, especially in large-scale datasets, for designing prevention programmes and public health intervention strategies. We used a large-scale HIV-1 sequence dataset from nine European HIV cohorts and one Canadian, to identify MTCs and investigate factors associated with the probability of belonging to MTCs., Methods: To identify MTCs, we applied maximum likelihood inferences on partial pol sequences from 8955 HIV-positive individuals linked to demographic and clinical data. MTCs were defined using two different criteria: clusters with bootstrap support >75% (phylogenetic confidence criterion) and clusters consisting of sequences from a specific region at a proportion of >75% (geographic criterion) compared to the total number of sequences within the network. Multivariable logistic regression analysis was used to assess factors associated with MTC clustering., Results: Although 3700 (41%) sequences belonged to MTCs, proportions differed substantially by country and subtype, ranging from 7% among UK subtype C sequences to 63% among German subtype B sequences. The probability of belonging to an MTC was independently less likely for women than men (OR = 0.66; P < 0.001), older individuals (OR = 0.79 per 10-year increase in age; P < 0.001) and people of non-white ethnicity (OR = 0.44; P < 0.001 and OR = 0.70; P = 0.002 for black and 'other' versus white, respectively). It was also more likely among men who have sex with men (MSM) than other risk groups (OR = 0.62; P < 0.001 and OR = 0.69; P = 0.002 for people who inject drugs, and sex between men and women, respectively), subtype B (ORs 0.36-0.70 for A, C, CRF01 and CRF02 versus B; all P < 0.05), having a well-estimated date of seroconversion (OR = 1.44; P < 0.001), a later calendar year of sampling (ORs 2.01-2.61 for all post-2002 periods versus pre-2002; all P < 0.01), and being naïve to antiretroviral therapy at sampling (OR = 1.19; P = 0.010)., Conclusions: A high proportion (>40%) of individuals belonged to MTCs. Notably, the HIV epidemic dispersal appears to be driven by subtype B viruses spread within MSM networks. Expansion of regional epidemics seems mainly associated with recent MTCs, rather than the growth of older, established ones. This information is important for designing prevention and public health intervention strategies.

Accurate case-based surveillance data remain the key data source for estimating HIV burden and monitoring prevention efforts in Europe. We carried out a literature review and exploratory analysis of surveillance data regarding two crucial issues affecting European surveillance for HIV: missing data and reporting delay. Initial screening showed substantial variability of these data issues, both in time and across countries. In terms of missing data, the CD4+ cell count is the most problematic variable because of the high proportion of missing values. In 20 of 31 countries of the European Union/European Economic Area (EU/EEA), CD4+ counts are systematically missing for all or some years. One of the key challenges related to reporting delays is that countries undertake specific one-off actions in effort to capture previously unreported cases, and that these cases are subsequently reported with excessive delays. Slightly different underlying assumptions and effectively different models may be required for individual countries to adjust for missing data and reporting delays. However, using a similar methodology is recommended to foster harmonisation and to improve the accuracy and usability of HIV surveillance data at national and EU/EEA levels.

Background: Clinical guidelines recommend immediate initiation of combined antiretroviral therapy for all HIV-positive individuals. However, those guidelines are based on trials of relatively young participants., Methods: We included HIV-positive antiretroviral therapy-naive, AIDS-free individuals aged 50-70 years after 2004 in the HIV-CAUSAL Collaboration. We used the parametric g-formula to estimate the 5-year risk of all-cause and non-AIDS mortality under (1) immediate initiation at baseline and initiation at CD4 count, (2) <500 cells/mm, and (3) <350 cells/mm. Results were presented separately for the general HIV population and for a US Veterans cohort with high mortality., Results: The study included 9596 individuals (28% US Veterans) with median (interquantile range) age of 55 (52-60) years and CD4 count of 336 (182-513) at baseline. The 5-year risk of all-cause mortality was 0.40% (95% confidence interval (CI): 0.10 to 0.71) lower for the general HIV population and 1.61% (95% CI: 0.79 to 2.67) lower for US Veterans when comparing immediate initiation vs initiation at CD4 <350 cells/mm. The 5-year risk of non-AIDS mortality was 0.17% (95% CI: -0.07 to 0.43) lower for the general HIV population and 1% (95% CI: 0.31 to 2.00) lower for US Veterans when comparing immediate initiation vs initiation at CD4 <350 cells/mm., Conclusions: Immediate initiation seems to reduce all-cause and non-AIDS mortality in patients aged 50-70 years.

Objective: We aimed to estimate the proportion of postmigration HIV acquisition among HIV-positive migrants in Europe., Design: To reach HIV-positive migrants, we designed a cross-sectional study performed in HIV clinics., Methods: The study was conducted from July 2013 to July 2015 in 57 clinics (nine European countries), targeting individuals over 18 years diagnosed in the preceding 5 years and born abroad. Electronic questionnaires supplemented with clinical data were completed in any of 15 languages. Postmigration HIV acquisition was estimated through Bayesian approaches combining extensive information on migration and patients' characteristics. CD4 cell counts and HIV-RNA trajectories from seroconversion were estimated by bivariate linear mixed models fitted to natural history data. Postmigration acquisition risk factors were investigated with weighted logistic regression., Results: Of 2009 participants, 46% were MSM and a third originated from sub-Saharan Africa and Latin America & Caribbean, respectively. Median time in host countries was 8 years. Postmigration HIV acquisition was 63% (95% confidence interval: 57-67%); 72% among MSM, 58 and 51% in heterosexual men and women, respectively. Postmigration HIV acquisition was 71% for Latin America and Caribbean migrants and 45% for people from sub-Saharan Africa. Factors associated with postmigration HIV acquisition among heterosexual women and MSM were age at migration, length of stay in host country and HIV diagnosis year and among heterosexual men, length of stay in host country and HIV diagnosis year., Conclusion: A substantial proportion of HIV-positive migrants living in Europe acquired HIV postmigration. This has important implications for European public health policies.

Introduction: The incidence and prevalence of HIV infection are important measures of HIV trends; however, they are difficult to estimate because of the long incubation period between infection and symptom development and the relative infrequency of HIV screening. A new method is introduced to estimate HIV incidence, prevalence, and the number of undiagnosed infections in the United States using data from the HIV case surveillance system and CD4 test results., Methods: Persons with HIV diagnosed during 2006-2013 and their CD4 test results were used to estimate the distribution of diagnosis delay from HIV infection to diagnosis based on a well-characterized CD4 depletion model. This distribution was then used to estimate HIV incidence, prevalence, and the number of undiagnosed infections., Results: Applying this method, we estimated that the annual number of new HIV infections decreased after 2007, from 48,300 (95% confidence interval [CI]: 47,300 to 49,400) to 39,000 (95% CI: 36,600 to 41,400) in 2013. Prevalence increased from 923,200 (95% CI: 914,500 to 931,800) in 2006 to 1,104,600 (95% CI: 1,084,300 to 1,124,900) in 2013, whereas the proportion of undiagnosed infections decreased from 21.0% in 2006 (95% CI: 20.2% to 21.7%) to 16.4% (95% CI: 15.7% to 17.2%) in 2013., Conclusions: HIV incidence, prevalence, and undiagnosed infections can be estimated using HIV case surveillance data and information on first CD4 test result after diagnosis. Similar to earlier findings, the decreases in incidence and undiagnosed infections are encouraging but intensified efforts for HIV testing and treatment are needed to meet the goals of the National HIV/AIDS Strategy.

Objective: Effects of transient combination antiretroviral treatment (cART) initiated during early HIV infection (EHI) remain unclear. We investigate whether this intervention affects viral suppression and CD4 cell count increase following its reinitiation in chronic infection (CHI)., Design: Longitudinal observational study., Methods: We identified adult patients from Concerted Action of Seroconversion to AIDS and Death in Europe who seroconverted after 1/1/2000, had a 12 months or less HIV test interval and initiated cART from naive. We classified individuals as 'pretreated in EHI' if treated within 6 months of seroconversion, interrupted for at least 12 weeks, and reinitiated during CHI. Statistical analysis was performed using survival analysis methods and mixed models., Results: Pretreated and initiated in CHI groups comprised 202 and 4263 individuals, with median follow-up after CHI treatment 4.5 and 3 years, respectively. Both groups had similar virologic response and relapse rates (P = 0.585 and P = 0.206) but pretreated individuals restarted treatment with higher baseline CD4 cell count (∼80 cells/μl; P < 0.001) and retained significantly higher CD4 cell count for more than 3 years after treatment (re)initiation. Assuming common baseline CD4 cell count, differences in CD4 cell count slopes were nonsignificant. Immunovirologic response to CHI treatment was not associated with timing or duration of the transient treatment., Conclusion: Although treatment interruptions are not recommended, stopping cART initiated in EHI does not seem to reduce the chance of a successful outcome of treatment in CHI.

It is important not only to collect epidemiologic data on HIV but to also fully utilize such information to understand the epidemic over time and to help inform and monitor the impact of policies and interventions. We describe and apply a novel method to estimate the size and characteristics of HIV-positive populations. The method was applied to data on men who have sex with men living in the UK and to a pseudo dataset to assess performance for different data availability. The individual-based simulation model was calibrated using an approximate Bayesian computation-based approach. In 2013, 48,310 (90% plausibility range: 39,900-45,560) men who have sex with men were estimated to be living with HIV in the UK, of whom 10,400 (6,160-17,350) were undiagnosed. There were an estimated 3,210 (1,730-5,350) infections per year on average between 2010 and 2013. Sixty-two percent of the total HIV-positive population are thought to have viral load <500 copies/ml. In the pseudo-epidemic example, HIV estimates have narrower plausibility ranges and are closer to the true number, the greater the data availability to calibrate the model. We demonstrate that our method can be applied to settings with less data, however plausibility ranges for estimates will be wider to reflect greater uncertainty of the data used to fit the model.

Background: Recommendations have differed nationally and internationally with respect to the best time to start antiretroviral therapy (ART). We compared effectiveness of three strategies for initiation of ART in high-income countries for HIV-positive individuals who do not have AIDS: immediate initiation, initiation at a CD4 count less than 500 cells per μL, and initiation at a CD4 count less than 350 cells per μL., Methods: We used data from the HIV-CAUSAL Collaboration of cohort studies in Europe and the USA. We included 55,826 individuals aged 18 years or older who were diagnosed with HIV-1 infection between January, 2000, and September, 2013, had not started ART, did not have AIDS, and had CD4 count and HIV-RNA viral load measurements within 6 months of HIV diagnosis. We estimated relative risks of death and of death or AIDS-defining illness, mean survival time, the proportion of individuals in need of ART, and the proportion of individuals with HIV-RNA viral load less than 50 copies per mL, as would have been recorded under each ART initiation strategy after 7 years of HIV diagnosis. We used the parametric g-formula to adjust for baseline and time-varying confounders., Findings: Median CD4 count at diagnosis of HIV infection was 376 cells per μL (IQR 222-551). Compared with immediate initiation, the estimated relative risk of death was 1·02 (95% CI 1·01-1·02) when ART was started at a CD4 count less than 500 cells per μL, and 1·06 (1·04-1·08) with initiation at a CD4 count less than 350 cells per μL. Corresponding estimates for death or AIDS-defining illness were 1·06 (1·06-1·07) and 1·20 (1·17-1·23), respectively. Compared with immediate initiation, the mean survival time at 7 years with a strategy of initiation at a CD4 count less than 500 cells per μL was 2 days shorter (95% CI 1-2) and at a CD4 count less than 350 cells per μL was 5 days shorter (4-6). 7 years after diagnosis of HIV, 100%, 98·7% (95% CI 98·6-98·7), and 92·6% (92·2-92·9) of individuals would have been in need of ART with immediate initiation, initiation at a CD4 count less than 500 cells per μL, and initiation at a CD4 count less than 350 cells per μL, respectively. Corresponding proportions of individuals with HIV-RNA viral load less than 50 copies per mL at 7 years were 87·3% (87·3-88·6), 87·4% (87·4-88·6), and 83·8% (83·6-84·9)., Interpretation: The benefits of immediate initiation of ART, such as prolonged survival and AIDS-free survival and increased virological suppression, were small in this high-income setting with relatively low CD4 count at HIV diagnosis. The estimated beneficial effect on AIDS is less than in recently reported randomised trials. Increasing rates of HIV testing might be as important as a policy of early initiation of ART., Funding: National Institutes of Health., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Measures of CD4 T-cell count and HIV-1 plasma viral load before antiretroviral therapy are proxies for virulence. Whether these proxies are changing over time has implications for prevention and treatment. The aim of this study was to investigate those trends., Methods: Data were derived from the Concerted Action on SeroConversion to AIDS and Death in Europe (CASCADE) collaboration of mainly European seroconverter cohorts. Longitudinal CD4 cell counts and plasma viral load measurements before the initiation of antiretroviral therapy or AIDS onset were analysed by use of linear or fractional polynomials mixed models adjusting for all available potential confounders. Calendar time effects were modelled through natural cubic splines., Findings: 15 875 individuals seroconverting from 1979 to 2008 fulfilled the inclusion criteria; 3215 (20·3%) were women; median follow-up was 31 months (IQR 14-62); dropout before starting antiretroviral therapy or AIDS onset was 8·1%. Estimated CD4 counts at seroconversion for a typical individual declined from about 770 cells per μL (95% CI 750-800) in the early 1980s to a plateau of about 570 cells per μL (555-585) after 2002. CD4 cell rate of loss increased up to 2002. Estimated set-point plasma viral loads increased from 4·05 log10 copies per mL (95% CI 3·98-4·12) in 1980 to 4·50 log10 copies per mL (4·45-4·54) in 2002 with a tendency of returning to lower loads thereafter. Results were similar when we restricted analyses to various subsets, including adjusting for plasma viral load assay, censored follow-up at 3 years, or used variations of the main statistical approach., Interpretation: Our results provide strong indications of increased HIV-1 virulence and transmissibility during the course of the epidemic and a potential plateau effect after about 2002., Funding: European Union Seventh Framework Programme., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: We examined differences by geographical origin (GO) in time from HIV seroconversion (SC) to AIDS, death, and initiation of antiretroviral therapy (cART)., Methods: Data from HIV seroconverter cohorts in Europe, Australia and Canada (CASCADE) was used; GO was classified as: western countries (WE), North Africa and Middle East (NAME), sub-Saharan Africa (SSA), Latin America (LA), and Asia (ASIA). Differences by GO were assessed using Cox models. Administrative censoring date was 30 June 2008., Results: Of 16 941 seroconverters, 15 548 were from WE, 158 NAME, 762 SSA, 349 LA, and 124 ASIA. We found no differences by GO in risks of AIDS (P = .99) and death (P = .12), although seroconverters from NAME (adjusted hazard ratio [aHR]: 0.57; 95% CI: 0.33-.94) and SSA (aHR: 0.74; 95% CI: 0.50-1.10) appeared to have lower mortality than WE. Chances of initiating cART differed by GO (P < .001): seroconverters from SSA were more likely to initiate cART than WE (aHR: 1.48; 95% CI: 1.26-1.74), but not after adjustment for CD4 at SC (aHR: 1.11; 95% CI: 0.88-1.40)., Conclusions: In settings with universal access to healthcare, GO does not play a major role in HIV disease progression.

Introduction: It is unknown whether HIV treatment guidelines, based on resource-rich country cohorts, are applicable to African populations., Methods: We estimated CD4 cell loss in ART-naïve, AIDS-free individuals using mixed models allowing for random intercept and slope, and time from seroconversion to clinical AIDS, death and antiretroviral therapy (ART) initiation by survival methods. Using CASCADE data from 20 European and 3 sub-Saharan African (SSA) cohorts of heterosexually-infected individuals, aged ≥15 years, infected ≥2000, we compared estimates between non-African Europeans, Africans in Europe, and Africans in SSA., Results: Of 1,959 (913 non-Africans, 302 Europeans-African origin, 744 SSA), two-thirds were female; median age at seroconversion was 31 years. Individuals in SSA progressed faster to clinical AIDS but not to death or non-TB AIDS. They also initiated ART later than Europeans and at lower CD4 cell counts. In adjusted models, Africans (especially from Europe) had lower CD4 counts at seroconversion and slower CD4 decline than non-African Europeans. Median (95% CI) CD4 count at seroconversion for a 15-29 year old woman was 607 (588-627) (non-African European), 469 (442-497) (European-African origin) and 570 (551-589) (SSA) cells/µL with respective CD4 decline during the first 4 years of 259 (228-289), 155 (110-200), and 199 (174-224) cells/µL (p<0.01)., Discussion: Despite differences in CD4 cell count evolution, death and non-TB AIDS rates were similar across study groups. It is therefore prudent to apply current ART guidelines from resource-rich countries to African populations.

Objective: To describe CD4 and HIV RNA changes during treatment resumption (TR) after treatment interruption (TI) compared with response to first highly active antiretroviral therapy (HAART) and to investigate predictors., Methods: Using Concerted Action on SeroConversion to AIDS and Death in Europe (CASCADE) data, we identified subjects who interrupted first HAART, not initiated during primary infection. We estimated rate of CD4 change during TR and time from TR to HIV RNA<500 copies per milliliter and subsequent rebound and factors associated with these outcomes., Results: Of 281 persons treated for median 18.4 months before interrupting, 259 resumed HAART. CD4 increases in the first 3 months on HAART were similar pre-TI and post-TI but after 3 months were significantly higher during pre-TI HAART, with median +106 and +172 cells per microliter at 3 and 18 months, respectively, during initial HAART compared with +99 and +142 cells per microliter during post-TI HAART, respectively. Subjects with lower CD4 counts at TI, aged older than 40 years, and those resuming the same HAART as their pre-TI regimen had lower CD4 increases during the first 3 months of TR. The majority (86%) of individuals reinitiating therapy achieved HIV RNA<500 copies per milliliter., Conclusions: Immune reconstitution after TI is generally poorer than after first HAART, particularly for patients aged older than 40 years at TI and those with poorer immunological responses to pre-TI HAART. Reinitiation of the same HAART regimen as pre-TI also seems to have unfavorable outcomes.

Objective: To provide information on responses to combination antiretroviral therapy in children, adolescents and older HIV-infected persons., Design and Setting: Multicohort collaboration of 33 European cohorts., Subjects: : Forty-nine thousand nine hundred and twenty-one antiretroviral-naive individuals starting combination antiretroviral therapy from 1998 to 2006., Outcome Measures: Time from combination antiretroviral therapy initiation to HIV RNA less than 50 copies/ml (virological response), CD4 increase of more than 100 cells/microl (immunological response) and new AIDS/death were analysed using survival methods. Ten age strata were chosen: less than 2, 2-5, 6-12, 13-17, 18-29, 30-39 (reference group), 40-49, 50-54, 55-59 and 60 years or older; those aged 6 years or more were included in multivariable analyses., Results: The four youngest age groups had 223, 184, 219 and 201 individuals and the three oldest age groups had 2693, 1656 and 1613 individuals. Precombination antiretroviral therapy CD4 cell counts were highest in young children and declined with age. By 12 months, 53.7% (95% confidence interval: 53.2-54.1%) and 59.2% (58.7-59.6%) had experienced a virological and immunological response. The probability of virological response was lower in those aged 6-12 (adjusted hazard ratio: 0.87) and 13-17 (0.78) years, but was higher in those aged 50-54 (1.24), 55-59 (1.24) and at least 60 (1.18) years. The probability of immunological response was higher in children and younger adults and reduced in those 60 years or older. Those aged 55-59 and 60 years or older had poorer clinical outcomes after adjusting for the latest CD4 cell count., Conclusion: Better virological responses but poorer immunological responses in older individuals, together with low precombination antiretroviral therapy CD4 cell counts, may place this group at increased clinical risk. The poorer virological responses in children may increase the likelihood of emergence of resistance.