Changes in perceived ageism during the COVID-19 pandemic: impact on quality of life and mental well-being among Dutch adults aged 55 and older.

Objectives: The COVID-19 pandemic brought ageism to the forefront of public discourse. Negative ageism incurs more negative self-perceptions of aging, which affects physical and mental functioning. Whether negative ageism as perceived and experienced by older adults has worsened as the pandemic lingered, and how such changes impact quality of life (QoL) and mental well-being (MWB), remain urgent questions.Method: In a sample of adults aged 55 or older (n = 500), we aimed to address this by administering the Perceived Ageism Questionnaire twice during the pandemic (T1: between October 2020 and May 2021; T2: on average 45 wk after T1).Results: Higher levels of perceived negative ageism were associated with lower QoL and MWB, at least partially through its unfavorable effects on self-perceptions of aging, even after controlling for ageism experiences in the preceding year (at T2, corrected for T1). Furthermore, we found that perceived negative ageism increased from T1 to T2, which had negative implications for QoL/MWB. Opposite effects were found for perceived positive ageism, although less consistently.Conclusion: These patterns reveal that ageism as perceived and experienced by adults of 55 or older became stronger and more negative throughout the COVID-19 pandemic, which had detrimental implications for individuals' QoL and MWB. These disconcerting findings emphasize the importance of combatting negative ageism in our society.

Investigating habits in humans with a symmetrical outcome-revaluation task.

The translation of the outcome-devaluation paradigm to study habit in humans has yielded interesting insights but proven to be challenging. We present a novel, outcome-revaluation task with a symmetrical design, in the sense that half of the available outcomes are always valuable and the other half not-valuable. In the present studies, during the instrumental learning phase, participants learned to respond (Go) to certain stimuli to collect valuable outcomes (and points) while refraining to respond (NoGo) to stimuli signaling not-valuable outcomes. Half of the stimuli were short-trained, while the other half were long-trained. Subsequently, in the test phase, the signaled outcomes were either value-congruent with training (still-valuable and still-not-valuable), or value-incongruent (devalued and upvalued). The change in outcome value on value-incongruent trials meant that participants had to flexibly adjust their behavior. At the end of the training phase, participants completed the self-report behavioral automaticity index - providing an automaticity score for each stimulus-response association. We conducted two experiments using this task, that both provided evidence for stimulus-driven habits as reflected in poorer performance on devalued and upvalued trials relative to still-not-valuable trials and still-valuable trials, respectively. While self-reported automaticity increased with longer training, behavioral flexibility was not affected. After extended training (Experiment 2), higher levels of self-reported automaticity when responding to stimuli signaling valuable outcomes were related to more 'slips of action' when the associated outcome was subsequently devalued. We conclude that the symmetrical outcome-revaluation task provides a promising paradigm for the experimental investigation of habits in humans.

Failure to eradicate Helicobacter pylori infection is more frequent among HIV-positive patients.

OBJECTIVES: Helicobacter pylori is a worldwide infection, but little is known about the efficacy of treatment for H. pylori infection in HIV-positive patients. The goal of this work was to evaluate outcomes after first-line H. pylori treatment and identify risk factors for failure in HIV-positive patients. METHODS: This registry study of unmatched H. pylori-infected HIV-positive patients and HIV-negative obese pre-bariatric surgery controls was performed in a tertiary university hospital. Cases were enrolled from 2006 to 2017, controls from 2007 to 2014, and both received standard of care. An additional 'optimal' subgroup of cases was enrolled prospectively from 2017 to 2019 which was treated only on the basis of antibiogram, drug interaction search and additional support by one referent physician. Helicobacter pylori eradication failure rates were compared according to clinical, microbiological and pathological parameters and treatment. RESULTS: We analysed 258 HIV-positive patients and 204 HIV-negative control patients. Helicobacter pylori eradication failure rates were markedly greater in cases (24.1%) than in controls (8.8%). The proportions of levofloxacin and metronidazole resistance were greater in cases than in controls (P < 0.05). Among cases treated with H. pylori triple therapy (S3T), the 'optimal' subgroup experienced a 9.5% failure rate vs. 28.6% with other strategies (P = 0.01). Risk factors for failure were H. pylori treatment strategy, exposure to antiretroviral treatment, and alcohol status. Overall, positive HIV status was a risk factor for S3T eradication failure. CONCLUSIONS: Patients co-infected with H. pylori and HIV frequently failed to eradicate H. pylori and this was related to treatment strategy, antiretroviral exposure and lifestyle.

Incidence rate, predictors and outcomes of interruption of HIV care: nationwide results from the Belgian HIV cohort.

OBJECTIVES: We aimed to study the incidence rate, predictors and outcomes of HIV care interruption (HCI) in Belgium. METHODS: We analysed data for adult patients with at least two HIV care records in the Belgian HIV cohort between 1 January 2007 and 31 December 2016. An HCI episode was defined as 1 year without an HIV care record. The HCI incidence rate was analysed using Poisson regression, return to HIV care using a cumulative incidence function with death as a competing risk, and viral load (VL) status upon return to HIV care using logistic regression. RESULTS: We included 16 066 patients accounting for 78 625 person-years of follow-up. The incidence rate of HCI was 5.3/100 person-years [95% confidence interval (CI) 5.1-5.4/100 person-years]. The incidence of return to HIV care after HCI was estimated at 77.5% (95% CI 75.7-79.2%). Of those who returned to care, 43.7% had a VL ≤ 200 HIV-1 RNA copies/mL, suggesting care abroad or suboptimal care (without an HIV-related care record) in Belgium during the HCI, and 56.3% returned without controlled VL and were therefore considered as having experienced a real gap in HIV care; they represented 2.3/100 person-years of follow-up. Factors individually associated with HCI were no antiretroviral therapy (ART) uptake, lower age, injecting drug use, non-Belgian nationality, male gender, not being a man who has sex with men, a shorter time since HIV diagnosis, no high blood pressure and CD4 count < 350 cells/µL. CONCLUSIONS: This study highlights the need to investigate return to care and viral status at return, to better understand HCI. Identified predictors can help health care workers to target patients at higher risk of HCI for awareness and support.

Treatment outcomes of integrase inhibitors, boosted protease inhibitors and nonnucleoside reverse transcriptase inhibitors in antiretroviral-naïve persons starting treatment.

OBJECTIVES: Although outcomes of antiretroviral therapy (ART) have been evaluated in randomized controlled trials, experiences from subpopulations defined by age, CD4 count or viral load (VL) in heterogeneous real-world settings are limited. METHODS: The study design was an international multicohort collaboration. Logistic regression was used to compare virological and immunological outcomes at 12 ± 3 months after starting ART with an integrase strand transfer inhibitor (INSTI), contemporary nonnucleoside reverse transcriptase inhibitor (NNRTI) or boosted protease inhibitor (PI/b) with two nucleos(t)ides after 1 January 2012. The composite treatment outcome (cTO) defined success as VL < 200 HIV-1 RNA copies/mL with no regimen change and no AIDS/death events. Immunological success was defined as a CD4 count > 750 cells/µL or a 33% increase where the baseline CD4 count was ≥ 500 cells/µL. Poisson regression compared clinical failures (AIDS/death ≥ 14 days after starting ART). Interactions between ART class and age, CD4 count, and VL were determined for each endpoint. RESULTS: Of 5198 ART-naïve persons in the International Cohort Consortium of Infectious Diseases (RESPOND), 45.4% started INSTIs, 26.0% PI/b and 28.7% NNRTIs; 880 (17.4%) were aged > 50 years, 2539 (49.4%) had CD4 counts < 350 cells/µL and 1891 (36.8%) had VL > 100 000 copies/mL. Differences in virological and immunological success and clinical failure among ART classes were similar across age groups (≤ 40, 40-50 and > 50 years), CD4 count categories (≤ 350 vs. > 350 cells/µL) and VL categories at ART initiation (≤ 100 000 vs. > 100 000 copies/mL), with all investigated interactions being nonsignificant (P > 0.05). CONCLUSIONS: Differences among ART classes in virological, immunological and clinical outcomes in ART-naïve participants were consistent irrespective of age, immune suppression or VL at ART initiation. While confounding by indication cannot be excluded, this provides reassuring evidence that such subpopulations will equally benefit from contemporary ART.

Dynamics of SARS-CoV-2 RT-PCR positivity and seroprevalence among high-risk healthcare workers and hospital staff.

Staff working in units that were highly exposed to coronavirus disease 2019 were invited to participate in a 6-month study on the carriage and seroprevalence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The results from visits on Day 1 and Day 15 show that 41 cases of SARS-CoV-2 infection were confirmed by reverse transcriptase polymerase chain reaction and/or serology in 326 participants (overall infection rate 12.6%). The presence of comorbidities or symptoms at the time of sample collection was a risk factor for infection, but working as a physician/nurse was not a risk factor. Universal screening in high-risk units, irrespective of symptoms, allowed the identification of asymptomatic and potentially contagious infected workers, enabling them to self-isolate for 7 days.

The EuroSIDA study: 25 years of scientific achievements.

The EuroSIDA study was initiated in 1994 and follows adult people living with HIV (PLHIV) in 100 collaborating clinics across 35 countries covering all European regions, Israel and Argentina. The study aims to study the long-term virological, immunological and clinical outcomes of PLHIV and to monitor temporal changes and regional differences in outcomes across Europe. Annually collected data include basic demographic characteristics, information on AIDS- and non-AIDS-related clinical events, and details about antiretroviral therapy (ART), hepatitis C treatment and other medications, in addition to a range of laboratory values. The summer 2016 data set held data from a total of 23 071 individuals contributing 174 481 person-years of follow-up, while EuroSIDA's unique plasma repository held over 160 000 samples. Over the past 25 years, close to 300 articles have been published in peer-reviewed journals (h-index 52), covering a range of scientific focus areas, including monitoring of clinical and virological outcomes, ART uptake, efficacy and adverse events, the influence of hepatitis virus coinfection, variation in the quality of HIV care and management across settings and regions, and biomarker research. Recognizing that there remain unresolved issues in the clinical care and management of PLHIV in Europe, EuroSIDA was one of the cohorts to found The International Cohort Consortium of Infectious Disease (RESPOND) cohort consortium on infectious diseases in 2017. In celebration of the EuroSIDA study's 25th anniversary, this article aims to summarize key scientific findings and outline current and future scientific focus areas.

Conflicted between Goal-Directed and Habitual Control, an fMRI Investigation.

"Slips of action" occur in everyday life when we momentarily lose sight of a goal (for example, when in a rush or distracted). Associative models propose that these habitual responses can be activated via a direct stimulus-response (S-R) mechanism, regardless of the current hedonic value of the outcome. The slips-of-action task (SOAT) has been extensively used in both healthy and pathological populations to measure habit tendencies, the likelihood of making erroneous responses for devalued outcomes. Inspection of behavioral performance does not reveal, however, whether the impairments were due to impaired goal-directed control or aberrantly strong habit formation. In the current study, we used functional MRI while human participants performed both the instrumental training and SOAT test phases, to elucidate the relative contributions of these mechanisms to performance on the SOAT. On trials in which conflict arises between competing goal-directed and habitual responses, we observed increased activation across areas including the anterior cingulate cortex, paracingulate gyrus, lateral orbitofrontal cortex (OFC), insula, and inferior frontal gyrus (IFG). Responding for devalued outcomes was related to increased activation in the premotor cortex and cerebellum, implicating these regions in habitual responding. Increased activation in the caudate, dorsolateral prefrontal cortex (dlPFC), and frontal pole during training was associated with better performance during the test phase, indicative of goal-directed action control. These results endorse interpretation of the SOAT in terms of competing goal-directed and habitual mechanisms and highlight that cognitive control processes present an additional bottleneck for successful performance on this task.

Association between exposure to antiretroviral drugs and the incidence of hypertension in HIV-positive persons: the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study.

OBJECTIVES: Previous studies have suggested that hypertension in HIV-positive individuals is associated primarily with traditional risk factors such as older age, diabetes and dyslipidaemia. However, controversy remains as to whether exposure to antiretroviral (ARV) drugs poses additional risk, and we investigated this question in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) cohort. METHODS: The incidence of hypertension [systolic blood pressure (BP) > 140 and/or diastolic BP > 90 mmHg and/or initiation of antihypertensive treatment] was determined overall and in strata defined by demographic, metabolic and HIV-related factors, including cumulative exposure to each individual ARV drug. Predictors of hypertension were identified using uni- and multivariable Poisson regression models. RESULTS: Of 33 278 included persons, 7636 (22.9%) developed hypertension over 223 149 person-years (PY) [incidence rate: 3.42 (95% confidence interval (CI) 3.35-3.50) per 100 PY]. In univariable analyses, cumulative exposure to most ARV drugs was associated with an increased risk of hypertension. After adjustment for demographic, metabolic and HIV-related factors, only associations for nevirapine [rate ratio 1.07 (95% CI: 1.04-1.13) per 5 years] and indinavir/ritonavir [rate ratio 1.12 (95% CI: 1.04-1.20) per 5 years] remained statistically significant, although effects were small. The strongest independent predictors of hypertension were male gender, older age, black African ethnicity, diabetes, dyslipidaemia, use of lipid-lowering drugs, high body mass index (BMI), renal impairment and a low CD4 count. CONCLUSIONS: We did not find evidence for any strong independent association between exposure to any of the individual ARV drugs and the risk of hypertension. Findings provide reassurance that screening policies and preventative measures for hypertension in HIV-positive persons should follow algorithms used for the general population.

Prevalence and risk factors of measles seronegativity in a cohort of HIV-positive subjects: a retrospective study.

OBJECTIVES: Measles infection is a vaccine-preventable disease currently resurging in Europe. HIV-infected subjects are at higher risk of complications following measles infection. We investigated the risk factors associated with being seronegative in a cohort of HIV-infected subjects. METHODS: All HIV-infected subjects in our cohort who had a measles serological test performed between December 2005 and May 2017 were retrospectively identified. A measles immunoglobulin G (IgG) titre > 275 mIU/mL was considered protective. Risk factors were analysed using logistic regression. RESULTS: Measles serology was available in 273 of 3124 subjects in active follow-up (8.7%). The prevalence of measles seronegativity was 21.6% (59 of 273). In the univariate analysis, being born after 1970 and HIV infection by vertical transmission were both associated with a higher risk of measles seronegativity, while a nadir CD4 T-cell count < 200 cells/µL was associated with a lower risk of measles seronegativity. In the multivariate analysis, only being born after 1970 [odds ratio (OR) 4.9; 95% confidence interval (CI) 1.3-18.7] and vertical transmission (OR 7.7; 95% CI 3.3-18.3) were significantly associated with seronegativity. Among the vertically infected subjects with measles-mumps-rubella (MMR) immunization documentation, the median number of doses of vaccine received before testing was 2 (range 1-3). CONCLUSIONS: HIV-infected subjects born after 1970 and vertically infected subjects should be screened for measles seropositivity.

Long-term effectiveness of recommended boosted protease inhibitor-based antiretroviral therapy in Europe.

OBJECTIVES: The aim of the study was to evaluate the long-term response to antiretroviral treatment (ART) based on atazanavir/ritonavir (ATZ/r)-, darunavir/ritonavir (DRV/r)-, and lopinavir/ritonavir (LPV/r)-containing regimens. METHODS: Data were analysed for 5678 EuroSIDA-enrolled patients starting a DRV/r-, ATZ/r- or LPV/r-containing regimen between 1 January 2000 and 30 June 2013. Separate analyses were performed for the following subgroups of patients: (1) ART-naïve subjects (8%) at ritonavir-boosted protease inhibitor (PI/r) initiation; (2) ART-experienced individuals (44%) initiating the new PI/r with a viral load (VL) ≤500 HIV-1 RNA copies/mL; and (3) ART-experienced patients (48%) initiating the new PI/r with a VL >500 copies/mL. Virological failure (VF) was defined as two consecutive VL measurements >200 copies/mL ≥24 weeks after PI/r initiation. Kaplan-Meier and multivariable Cox models were used to compare risks of failure by PI/r-based regimen. The main analysis was performed with intention-to-treat (ITT) ignoring treatment switches. RESULTS: The time to VF favoured DRV/r over ATZ/r, and both were superior to LPV/r (log-rank test; P < 0.02) in all analyses. Nevertheless, the risk of VF in ART-naïve patients was similar regardless of the PI/r initiated after controlling for potential confounders. The risk of VF in both treatment-experienced groups was lower for DRV/r than for ATZ/r, which, in turn, was lower than for LPV/r-based ART. CONCLUSIONS: Although confounding by indication and calendar year cannot be completely ruled out, in ART-experienced subjects the long-term effectiveness of DRV/r-containing regimens appears to be greater than that of ATZ/r and LPV/r.

Meropenem-clavulanate for drug-resistant tuberculosis: a follow-up of relapse-free cases.

BACKGROUND: Extensively drug-resistant tuberculosis (XDR-TB), defined as TB caused by a Mycobacterium strain resistant to at least rifampicin, isoniazid, any fluoroquinolone and one of the injectable anti-tuberculosis drugs, remains a worldwide public health threat. Among repurposed drugs empirically used for XDR-TB cases, carbapenems have been studied in vitro and in animal models, with encouraging results. However, only short-term follow-up data from clinical studies are currently available. OBJECTIVES: To study the long-term follow-up of XDR-TB cases treated with a regimen containing meropenem-clavulanate (M/Clav). DESIGN: Retrospective observational case series study at a single hospital. METHODS: All hospitalised drug-resistant TB patients who received M/Clav as part of their treatment from 2009 to 2016 were included. Demographic and clinical data were extracted from medical records. RESULTS: Eighteen XDR-TB patients were included in the analysis. The successful outcome and mortality rates were respectively 83.3% and 11.1%. No relapses were observed in cured patients after a median follow-up of 4 years. No specific adverse events were attributed to treatment with M/Clav. CONCLUSION: The rate of sustained successful treatment outcome observed here is far higher than the 26% observed in the 2014 World Health Organization XDR-TB cohort, suggesting that carbapenems may be beneficial for the treatment of difficult-to-treat TB cases.

European AIDS Clinical Society Second Standard of Care Meeting, Brussels 16-17 November 2016: a summary.

The European AIDS Clinical Society (EACS) organized a second meeting on Standard of Care in Europe on November 16-17 th, 2016. The aims of the meeting were to discuss and propose actions on three topics, namely: Adherence to guidelines for treatment initiation, treatment monitoring and outcomes, Retention in care and HIV and tuberculosis co-infection. Several actions need to be implemented in order to further improve quality of care and treatment of HIV in Europe. A common ground for standard of care, based on the EACS Guidelines should be established throughout Europe. EACS plans to interact with policy makers and other stakeholders to insure this common minimal level of standard of care, in particular for initiating of ART, accessibility of drugs and monitoring of ART with viral load. Progress should be made to monitor retention in care, prevent lost to follow and insure return to care. Improving integration of services and accessibility to care play a major role. Integration is also key for optimizing care of HIV-tuberculosis co-infection, as well as diagnosis and prevention of tuberculosis in population at risk. The Standard of Care meeting organized every other year by EACS provides a unique opportunity to monitor progresses and pitfalls in HIV patient care throughout Europe. It is also a forum for advocacy towards policy makers and other stakeholders to constantly improve HIV patient global management, aiming to provide the same level of quality on the whole continent.

Hepatitis E virus (HEV): seroprevalence and HEV RNA detection in subjects attending a sexually transmitted infection clinic in Brussels, Belgium.

Men who have sex with men (MSM) have an increased incidence of pathogens transmitted by the oro-fecal route. Hepatitis E virus (HEV) is an emerging cause of acute hepatitis and fecal shedding is observed during primary infection. We investigated whether MSM are at increased risk of HEV infection. Subjects who attended a sexually transmitted infection clinic in Brussels and had an HIV test performed between 1 June 2014 and 15 January 2016 were identified. A total of 576 samples were retrospectively screened for both total HEV IgG and HEV RNA. Samples positive for IgG were tested for IgM. MSM proportion was 31·1% (179/576). Overall HEV IgG prevalence was 9·03% (52/576) and was identical in MSM and heterosexual subjects. Among the IgG positive samples, 2/52 (3·84%) samples (both women) were positive for anti-HEV IgM. No sample was positive for HEV RNA. Age over 35 was the only risk factor significantly associated with HEV seropositivity (OR 2·07; 95% CI 1·16-3·67). In conclusion, MSM were not found to have an increased prevalence of HEV as previously reported in other European countries suggesting distinct dynamics of HEV infection in this group across Europe and increased age was associated with a higher risk of seropositivity.

Effectiveness of various cleaning and disinfectant products on Clostridium difficile spores of PCR ribotypes 010, 014 and 027.

BACKGROUND: In healthcare facilities, Clostridium difficile infections spread by transmission of bacterial spores. Appropriate sporicidal disinfectants are needed to prevent development of clusters and outbreaks. In this study different cleaning/disinfecting wipes and sprays were tested for their efficacy against spores of distinctive C. difficile PCR ribotypes. METHODS: Four different products were tested; 1) hydrogen peroxide 1.5%; 2) glucoprotamin 1.5%; 3) a mixture of ethanol, propane and N-alkyl amino propyl glycine; and 4) a mixture of didecyldimonium chloride, benzalkonium chloride, polyaminopropyl, biguanide and dimenthicone as active ingredients. Tiles were contaminated with a test solution containing a concentration of 5x106CFU/ml spores of C. difficile strains belonging to PCR ribotypes 010, 014 or 027. The tiles were left to dry for an hour and then wiped or sprayed with one of the sprays or wipes as intended by the manufacturers. When products neutralized after 5 min, microbiological cultures and ATP measures were performed. RESULTS: Irrespective of the disinfection method, the microbial count log10 reduction of C. difficile PCR ribotype 010 was highest, followed by the reduction of C. difficile 014 and C. difficile 027. Overall, the wipes performed better than the sprays with the same active ingredient. On average, although not significantly, a difference in relative light units (RLU) reduction between the wipes and sprays was found. The wipes had a higher RLU log10 reduction, but no significant difference for RLU reduction was observed between the different C. difficile strains (p = 0.16). CONCLUSION: C. difficile spores of PCR ribotypes 014 and 027 strains are more difficult to eradicate than non-toxigenic PCR ribotype 010. In general, impregnated cleaning/disinfection wipes performed better than ready-to-use sprays. Wipes with hydrogen peroxide (1.5%) showed the highest bactericidal activity.

Isolation unit for multidrug-resistant tuberculosis patients in a low endemic country, a step towards the World Health Organization End TB Strategy.

Tuberculosis (TB) remains a threat to public health and is the second cause of death due to a single infectious agent after HIV/AIDS. The worldwide distribution of TB is heterogeneous. The incidence is decreasing in most high-income regions, but the situation remains worrying in many parts of the world. The emergence of Mycobacterium tuberculosis strains resistant to key agents used in treatment (rifampin and isoniazid) contributes to TB transmission around the world. To achieve TB elimination, both high and low endemic countries must upscale their efforts to decrease disease transmission and improve cure rates. Management of drug-resistant TB is of particular importance. In this paper, we discuss the different models of care of multidrug-resistant TB (MDR-TB), the ethical considerations and the specific constraints present in high income countries. The management model chosen by the Belgian TB specialists in accordance with public health authorities as well as building of a specific MDR/XDR-TB isolation unit are also discussed.

rTMS affects working memory performance, brain activation and functional connectivity in patients with multiple sclerosis.

OBJECTIVE: To investigate the effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) of the right dorsolateral prefrontal cortex (DLPFC) on working memory performance, while measuring task-related brain activation and task-related brain connectivity in patients with multiple sclerosis (MS). METHODS: 17 patients with MS and 11 healthy controls (HCs) underwent 3 experimental sessions (baseline, real-rTMS, sham-rTMS), all including an N-back task (3 task loads: N1, N2, N3; control condition: N0) inside the MR scanner. Prior to imaging, real-rTMS (10 Hz) was applied to the right DLPFC. The stimulation site was defined based on individually assessed N-back task activation at baseline and located using neuronavigation. Changes in whole brain functional activation and functional connectivity with the right DLPFC were calculated. RESULTS: N-back task accuracy (N2 and N3) improved after real-rTMS (and not after sham-rTMS) compared with baseline (p=0.029 and p=0.015, respectively), only in patients. At baseline, patients with MS, compared with HCs, showed higher task-related frontal activation (left DLPFC, N2>N0), which disappeared after real-rTMS. Task-related (N1>N0) functional connectivity between the right DLPFC and the right caudate nucleus and bilateral (para)cingulate gyrus increased in patients after real-rTMS when compared with sham stimulation. CONCLUSIONS: In patients with MS, N-back accuracy improved while frontal hyperactivation (seen at baseline relative to HCs) disappeared after real-rTMS. Together with the changes in functional connectivity after real-rTMS in patients, these findings may represent an rTMS-induced change in network efficiency in patients with MS, shifting patients' brain function towards the healthy situation. This implicates a potentially relevant role for rTMS in cognitive rehabilitation in MS.

Reference curves for CD4 T-cell count response to combination antiretroviral therapy in HIV-1-infected treatment-naïve patients.

OBJECTIVES: The aim of this work was to provide a reference for the CD4 T-cell count response in the early months after the initiation of combination antiretroviral therapy (cART) in HIV-1-infected patients. METHODS: All patients in the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) cohort who were aged ≥ 18 years and started cART for the first time between 1 January 2005 and 1 January 2010 and who had at least one available measurement of CD4 count and a viral load ≤ 50 HIV-1 RNA copies/mL at 6 months (± 3 months) after cART initiation were included in the study. Unadjusted and adjusted references curves and predictions were obtained using quantile regressions. RESULTS: A total of 28 992 patients were included in the study. The median CD4 T-cell count at treatment initiation was 249 [interquartile range (IQR) 150, 336] cells/µL. The median observed CD4 counts at 6, 9 and 12 months were 382 (IQR 256, 515), 402 (IQR 274, 543) and 420 (IQR 293, 565) cells/µL. The two main factors explaining the variation of CD4 count at 6 months were AIDS stage and CD4 count at cART initiation. A CD4 count increase of ≥ 100 cells/mL is generally required in order that patients stay 'on track' (i.e. with a CD4 count at the same percentile as when they started), with slightly higher gains required for those starting with CD4 counts in the higher percentiles. Individual predictions adjusted for factors influencing CD4 count were more precise. CONCLUSIONS: Reference curves aid the evaluation of the immune response early after antiretroviral therapy initiation that leads to viral control.