Impact of Human Immunodeficiency Virus and Recreational Drugs on Cognitive Functions.

BACKGROUND: This prospective study characterizes the structural and metabolic cerebral correlates of cognitive impairments found in a preclinical setting that considers the lifestyle of young European men exposed to human immunodeficiency virus (HIV), including recreational drugs. METHODS: Simultaneous structural brain magnetic resonance imaging (MRI) and positron emission tomography using [18F]-fluorodeoxyglucose (FDG-PET) were acquired on a hybrid PET-MRI system in 23 asymptomatic young men having sex with men with HIV (HIVMSM; mean age, 33.6 years [range, 23-60 years]; normal CD4+ cell count, undetectable viral load). Neuroimaging data were compared with that of 26 young seronegative men under HIV preexposure prophylaxis (PrEPMSM), highly well matched for age and lifestyle, and to 23 matched young seronegative men (controls). A comprehensive neuropsychological assessment was also administered to the HIVMSM and PrEPMSM participants. RESULTS: HIVMSM had lower performances in executive, attentional, and working memory functions compared to PrEPMSM. No structural or metabolic differences were found between those 2 groups. Compared to controls, HIVMSM and PrEPMSM exhibited a common hypometabolism in the prefrontal cortex that correlated with the level of recreational drug use. No structural brain abnormality was found. CONCLUSIONS: Abnormalities of brain metabolism in our population of young HIVMSM mainly relate to recreational drug use rather than HIV per se. A complex interplay between recreational drugs and HIV might nevertheless be involved in the cognitive impairments observed in this population.

Efficacy, durability, and tolerability of dolutegravir/lamivudine and dolutegravir/rilpivirine for the treatment of HIV in a real-world setting in Belgium.

OBJECTIVES: A paradigm shift from three-drug regimens to two-drug regimens (2DRs) is currently taking place in real-world clinical practice. This study aimed to describe the efficacy, durability, and tolerability of dolutegravir (DTG)/lamivudine (3TC) and DTG/rilpivirine (RPV) in a real-world setting. METHODS: This was a retrospective, observational, multicentre (ten centres in Belgium) study involving adult treatment-naïve and treatment-experienced people living with HIV on DTG/3TC or DTG/RPV between 1 January 2019 and 30 September 2020. The primary endpoint was rate of virological suppression (VS; plasma HIV-1 viral load [VL] <50 copies/ml) using an on-treatment analysis. Main secondary endpoints included the proportion of people that experienced loss of VS (LVS; defined as two consecutive HIV-1 VLs of >200 copies/ml after initially achieving VS) and a resistance analysis at the time of LVS; rate, incidence, and reasons for discontinuation of treatment (stopping treatment or changing any component of the 2DR); and change in weight, along with the proportion of people reporting a >10% weight gain. Ordinal logistic regression analysis examined associations between baseline variables and >10% on-treatment weight gain. RESULTS: Overall, 948 people were included, of whom 734 (77%) were on DTG/3TC and 214 (23%) were on DTG/RPV. Baseline characteristics included 54% aged ≥50 years, 31% female, 31% Black sub-Saharan African, 95% treatment-experienced, and 8% with HIV-1 VL ≥50 copies/ml. Through 48 weeks, the rate of VS for the overall cohort was 98.3% (99.1% with 3TC; 96.2% with RPV). LVS was observed in 0.5% (n = 5) of the overall population (n = 1 [3TC group], n = 4 [RPV group]). There were 40 treatment discontinuations (4.2%, n = 27 [3TC group]; n = 13 [RPV group]), corresponding to an incidence of 4.7 per 100 patient-years. The most common reason for discontinuation was an adverse event (1.4%), with neurotoxicity the most frequent (0.5%). Median on-treatment weight gain at week 48 was 1 kg (interquartile range [IQR] -1-3) overall, 1 kg (IQR -1-3) in the 3TC group, and 2 kg (IQR 0-4) in the RPV group. A >10% weight increase was observed in 6.3% of people. Regression analysis showed that being on a tenofovir disoproxil fumarate-based regimen prior to 2DR initiation was the only variable associated with a >10% increase in weight from baseline (odds ratio 3.48; 95% confidence interval 1.13-10.68; p = 0.038). CONCLUSION: In this real-world analysis, the 2DRs analysed were effective, durable, and safe for those who were treatment-naive and treatment-experienced. A slight increase in weight was associated with these regimens.

Efficacy, durability, and tolerability of bictegravir/emtricitabine/tenofovir alafenamide for the treatment of HIV in a real-world setting in Belgium.

OBJECTIVES: Our objective was to evaluate the efficacy, durability, and tolerability of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) in a real-world setting in Belgium. METHODS: This was a retrospective, multicentre cohort study involving adult treatment-naïve (TN) and treatment-experienced (TE) people living with HIV receiving BIC/FTC/TAF between 1 January 2019 and 30 September 2020. The primary outcome was rate of virological suppression (plasma HIV-1 viral load <50 copies/mL; on-treatment analysis) at weeks 24 and 48. The main secondary outcomes included loss of virological suppression (LVS; two consecutive viral loads of >200 copies/mL after being virologically suppressed) by week 48 and analysis of resistance-associated mutations at time of LVS; tolerability of BIC/FTC/TAF over the 48-week study period; and change in weight and proportion of participants reporting a >10% weight gain at week 48. RESULTS: Overall, 2001 participants were included. Through 48 weeks, overall rate of virological suppression was 93.5%, with similar results observed in the following subgroups: age ≥50 years (92.7%), women (92.8%), Black sub-Saharan African (91%), TN (94%), TE (93.2%), and non-suppressed at baseline (86.6%). LVS was observed in 0.7% (n = 14) of participants, with one participant developing resistance-associated mutations to nucleoside reverse transcriptase inhibitors (184 V) and integrase strand transfer inhibitors (263KR). Of the 131 (6.5%) treatment discontinuations, the most common reason was an adverse event (2.4%), with the most frequent being central nervous system/psychiatric (0.4%) and gastrointestinal (0.4%) toxicity. Median weight gain at week 48 was 2 kg (interquartile range -1 to 5), and a >10% weight increase was observed in 11.6% of participants. CONCLUSION: In this large real-world cohort, BIC/FTC/TAF showed excellent virological efficacy in a diverse population of patients with HIV. Rare occurrence of emergent drug resistance was observed, and treatment was well tolerated.

A public health value-based healthcare paradigm for HIV.

BACKGROUND: HIV patients face considerable acute and chronic healthcare needs and battling the HIV epidemic remains of the utmost importance. By focusing on health outcomes in relation to the cost of care, value-based healthcare (VBHC) proposes a strategy to optimize quality of care and cost-efficiency. Its implementation may provide an answer to the increasing pressure to optimize spending in healthcare while improving patient outcomes. This paper describes a pragmatic value-based healthcare framework for HIV care. METHODS: A value-based HIV healthcare framework was developed during a series of roundtable discussions bringing together 16 clinical stakeholder representatives from the Belgian HIV reference centers and 2 VBHC specialists. Each round of discussions was focused on a central question translating a concept or idea to the next level of practical implementation: 1) how can VBHC principles be translated into value-based HIV care drivers; 2) how can these value-based HIV care divers be translated into value-based care objectives and activities; and 3) how can value-based HIV care objectives and activities be translated into value-based care indicators. Value drivers were linked to concrete objectives and activities using a logical framework approach. Finally, specific, measurable, and acceptable structure, process and outcomes indicators were defined to complement the framework. RESULTS: Our framework identifies 4 core value areas where HIV care would benefit most from improvements: Prevention, improvement of the cascade of care, providing patient-centered HIV care and sustaining a state-of-the-art HIV disease management context. These 4 core value areas were translated into 12 actionable core value objectives. For each objective, example activities were proposed. Indicators are suggested for each level of the framework (outcome indicators for value areas and objectives, process indicators for suggested activities). CONCLUSIONS: This framework approach outlines how to define a patient- and public health centered value-based HIV care paradigm. It proposes how to translate core value drivers to practical objectives and activities and suggests defining indicators that can be used to track and improve the framework's implementation in practice.

Structural and metabolic brain abnormalities in COVID-19 patients with sudden loss of smell.

OBJECTIVES: Sudden loss of smell is a very common symptom of coronavirus disease 19 (COVID-19). This study characterizes the structural and metabolic cerebral correlates of dysosmia in patients with COVID-19. METHODS: Structural brain magnetic resonance imaging (MRI) and positron emission tomography with [18F]-fluorodeoxyglucose (FDG-PET) were prospectively acquired simultaneously on a hybrid PET-MR in 12 patients (2 males, 10 females, mean age: 42.6 years, age range: 23-60 years) with sudden dysosmia and positive detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on nasopharyngeal swab specimens. FDG-PET data were analyzed using a voxel-based approach and compared with that of a group of healthy subjects. RESULTS: Bilateral blocking of the olfactory cleft was observed in six patients, while subtle olfactory bulb asymmetry was found in three patients. No MRI signal abnormality downstream of the olfactory tract was observed. Decrease or increase in glucose metabolism abnormalities was observed (p < .001 uncorrected, k ≥ 50 voxels) in core olfactory and high-order neocortical areas. A modulation of regional cerebral glucose metabolism by the severity and the duration of COVID-19-related dysosmia was disclosed using correlation analyses. CONCLUSIONS: This PET-MR study suggests that sudden loss of smell in COVID-19 is not related to central involvement due to SARS-CoV-2 neuroinvasiveness. Loss of smell is associated with subtle cerebral metabolic changes in core olfactory and high-order cortical areas likely related to combined processes of deafferentation and active functional reorganization secondary to the lack of olfactory stimulation.

Screening for Chlamydia trachomatis and Neisseria gonorrhoeae Infections in Men Who Have Sex With Men: Diagnostic Accuracy of Nucleic Acid Amplification Test on Pooled Urine, Anorectal, and Pharyngeal Specimens.

Neisseria gonorrhoeae and Chlamydia trachomatis screening was performed in a cohort of 100 men who have sex with men. A nucleic acid amplification test on a pooled sample of first-pass urine, pharyngeal, and anorectal specimens was compared with results on nonpooled samples. Despite an excellent agreement (Cohen κ, 0.932), pooling specimens reduced test sensitivity to 89.5%.

Belgian 2024 guidance on the use of pre-exposure prophylaxis.

OBJECTIVES: We aimed to develop a guidance on the use of pre-exposure prophylaxis (PrEP) for HIV tailored to the Belgian context. METHODS: Different aspects of PrEP care were judged by an expert group of nine Belgian clinicians, seeking consensus for areas of controversies. RESULTS: PrEP should be considered in HIV negative patients at high risk of acquiring HIV. Currently, only oral tenofovir/emtricitabine is available in Belgium for PrEP, which can be used daily, or also event-driven in cisgender men and trans women who are not taking exogenous estradiol-based hormones. Personal counselling directed at medication adherence and sexual health should have a central role in PrEP care. At the initial assessment clinicians should give attention to symptoms of an acute HIV infection, the patients' immunization status and renal function. A regular follow-up must be set up to diagnose HIV seroconversion, treat sexually transmitted infections, and manage side effects of PrEP. CONCLUSION: The Belgian guidance on the use of PrEP provides a point of reference for standard PrEP care in Belgium and will be periodically updated.

Understanding adaptive responses in PrEP service delivery in Belgian HIV clinics: a multiple case study using an implementation science framework.

INTRODUCTION: In Belgium, oral HIV pre-exposure prophylaxis (PrEP) is primarily provided in specialized clinical settings. Optimal implementation of PrEP services can help to substantially reduce HIV transmission. However, insights into implementation processes, and their complex interactions with local context, are limited. This study examined factors that influence providers' adaptive responses in the implementation of PrEP services in Belgian HIV clinics. METHODS: We conducted a qualitative multiple case study on PrEP care implementation in eight HIV clinics. Thirty-six semi-structured interviews were conducted between January 2021 and May 2022 with a purposive sample of PrEP care providers (e.g. physicians, nurses, psychologists), supplemented by 50 hours of observations of healthcare settings and clinical interactions. Field notes from observations and verbatim interview transcripts were thematically analysed guided by a refined iteration of extended Normalisation Process Theory. RESULTS: Implementing PrEP care in a centralized service delivery system required considerable adaptive capacity of providers to balance the increasing workload with an adequate response to PrEP users' individual care needs. As a result, clinic structures were re-organized to allow for more efficient PrEP care processes, compatible with other clinic-level priorities. Providers adapted clinical and policy norms on PrEP care (e.g. related to PrEP prescribing practices and which providers can deliver PrEP services), to flexibly tailor care to individual clients' situations. Interprofessional relationships were reconfigured in line with organizational and clinical adaptations; these included task-shifting from physicians to nurses, leading them to become increasingly trained and specialized in PrEP care. As nurse involvement grew, they adopted a crucial role in responding to PrEP users' non-medical needs (e.g. providing psychosocial support). Moreover, clinicians' growing collaboration with sexologists and psychologists, and interactions with PrEP users' family physician, became crucial in addressing complex psychosocial needs of PrEP clients, while also alleviating the burden of care on busy HIV clinics. CONCLUSIONS: Our study in Belgian HIV clinics reveals that the implementation of PrEP care presents a complex-multifaceted-undertaking that requires substantial adaptive work to ensure seamless integration within existing health services. To optimize integration in different settings, policies and guidelines governing PrEP care implementation should allow for sufficient flexibility and tailoring according to respective local health systems.

Effect of screening for Neisseria gonorrhoeae and Chlamydia trachomatis on incidence of these infections in men who have sex with men and transgender women taking HIV pre-exposure prophylaxis (the Gonoscreen study): results from a randomised, multicentre, controlled trial.

BACKGROUND: Guidelines recommend screening for Neisseria gonorrhoeae and Chlamydia trachomatis at three anatomical sites (urethra, anus, and pharynx) every 3 months (3 × 3) in men who have sex with men (MSM) and transgender women taking HIV pre-exposure prophylaxis (PrEP). We present the first randomised controlled trial to compare the effect of screening versus non-screening for N gonorrhoeae and C trachomatis on the incidence of these infections in MSM and transgender women taking PrEP. METHODS: A multicentre, randomised, controlled trial of 3 × 3 screening for N gonorrhoeae and C trachomatis versus non-screening was done among MSM and transgender women taking PrEP in five HIV reference centers in Belgium. Participants attended the PrEP clinics quarterly for 12 months. N gonorrhoeae and C trachomatis was tested at each visit in both arms, but results were not provided to the non-screening arm, if asymptomatic. The primary outcome was incidence rate of N gonorrhoeae and C trachomatis infections in each arm, assessed in the per-protocol population. Non-inferiority of the non-screening arm was proven if the upper limit of the 95% CI of the incidence rate ratio (IRR) was lower than 1·25. This trial is registered with ClinicalTrials.gov, NCT04269434, and is completed. FINDINGS: Between Sept 21, 2020, and June 4, 2021, 506 participants were randomly assigned to the 3 × 3 screening arm and 508 to the non-screening arm. The overall incidence rate of N gonorrhoeae and C trachomatis was 0·155 cases per 100 person-days (95% CI 0·128-0·186) in the 3 × 3 screening arm and 0·205 (95% CI 0·171-0·246) in the non-screening arm. The incidence rate was significantly higher in the non-screening arm (IRR 1·318, 95% CI 1·068-1·627). Participants in the non-screening arm had a higher incidence of C trachomatis infections and symptomatic C trachomatis infections. There were no significant differences in N gonorrhoeae infections. Participants in the non-screening arm consumed significantly fewer antimicrobial drugs. No serious adverse events were reported. INTERPRETATION: We failed to show that non-screening for N gonorrhoeae and C trachomatis is non-inferior to 3 × 3 screening in MSM and transgender women taking PrEP in Belgium. However, screening was associated with higher antibiotic consumption and had no effect on the incidence of N gonorrhoeae. Further research is needed to assess the benefits and harms of N gonorrhoeae and C trachomatis screening in this population. FUNDING: Belgian Health Care Knowledge Centre.

Severe rhabdomyolysis and acute asymptomatic pancreatitis following the concomitant use of Biktarvy in the setting of hyperosmolar diabetic crisis.

Biktarvy (bictegravir/emtricitabine/tenofovir alafemanide), which has been recently approved for the treatment of HIV, is a single-pill regimen that associates bictegravir and a novel integrase strand transfer inhibitor (INSTI) with a combination of two nucleoside reverse transcriptase inhibitors (NRTI) of emtricitabine and tenofovir alafemanide. Among treatment complications, rhabdomyolysis has been reported in association with some NRTI and INSTI but never with bictegravir. Acute pancreatitis has also been reported recently with another INSTI, dolutegravir. We report here a 62-year-old man with diabetes and HIV infection, and receiving Biktarvy for 1 month. He presented to the emergency department for muscular pain and fatigue. He was on treatment with Descovy (tenofovir alafenamide/emtricitabine) and Viramune (nevirapine) for 2 years but he recently asked for a regimen simplification. Severe rhabdomyolysis and acute pancreatitis were diagnosed. Although the aetiology of these events could be multifactorial, it cannot be ruled out that this episode could be linked to a potential side effect of bictegravir.

Eosinopenia in COVID-19 Patients: A Retrospective Analysis.

Objectives: The aim of this study was to assess the diagnostic role of eosinophils count in COVID-19 patients. Methods: Retrospective analysis of patients admitted to our hospital with suspicion of COVID-19. Demographic, clinical and laboratory data were collected on admission. Eosinopenia was defined as eosinophils < 100 cells/mm3. The outcomes of this study were the association between eosinophils count on admission and positive real-time reverse transcription polymerase chain reaction (rRT-PCR) test and with suggestive chest computerized tomography (CT) of COVID-19 pneumonia. Results: A total of 174 patients was studied. Of those, 54% had positive rRT-PCR for SARS-CoV-2. A chest CT-scan was performed in 145 patients; 71% showed suggestive findings of COVID-19. Eosinophils on admission had a high predictive accuracy for positive rRT-PCR and suggestive chest CT-scan (area under the receiver operating characteristic-ROC curve, 0.84 (95% CIs 0.78-0.90) and 0.84 (95% CIs 0.77-0.91), respectively). Eosinopenia and high LDH were independent predictors of positive rRT-PCR, whereas eosinopenia, high body mass index and hypertension were predictors for suggestive CT-scan findings. Conclusions: Eosinopenia on admission could predict positive rRT-PCR test or suggestive chest CT-scan for COVID-19. This laboratory finding could help to identify patients at high-risk of COVID-19 in the setting where gold standard diagnostic methods are not available.

Early postmortem brain MRI findings in COVID-19 non-survivors.

OBJECTIVES: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is considered to have potential neuroinvasiveness that might lead to acute brain disorders or contribute to respiratory distress in patients with coronavirus disease 2019 (COVID-19). This study investigates the occurrence of structural brain abnormalities in non-survivors of COVID-19 in a virtopsy framework. METHODS: In this prospective, monocentric, case series study, consecutive patients who fulfilled the following inclusion criteria benefited from an early postmortem structural brain MRI: death <24 hours, SARS-CoV-2 detection on nasopharyngeal swab specimen, chest CT scan suggestive of COVID-19, absence of known focal brain lesion, and MRI compatibility. RESULTS: Among the 62 patients who died of COVID-19 from March 31, 2020, to April 24, 2020, at our institution, 19 decedents fulfilled the inclusion criteria. Parenchymal brain abnormalities were observed in 4 decedents: subcortical microbleeds and macrobleeds (2 decedents), cortico-subcortical edematous changes evocative of posterior reversible encephalopathy syndrome (PRES; 1 decedent), and nonspecific deep white matter changes (1 decedent). Asymmetric olfactory bulbs were found in 4 other decedents without downstream olfactory tract abnormalities. No brainstem MRI signal abnormality was observed. CONCLUSIONS: Postmortem brain MRI demonstrates hemorrhagic and PRES-related brain lesions in non-survivors of COVID-19. SARS-CoV-2-related olfactory impairment seems to be limited to olfactory bulbs. Brainstem MRI findings do not support a brain-related contribution to respiratory distress in COVID-19.

2018 Belgian guidelines for the screening for latent tuberculosis in HIV-infected patients.

Objectives: To review the current knowledge on screening for latent tuberculosis infection (LTBI) in HIV-infected adults and provide specific guidelines for Belgium. Focus is given to who to test, which testing method to use, timing of screening and choice of LTBI treatment. Methods: Expert review by the members of the Belgian LTBI group, in consultancy with the ARC College. Results: Target population, timing of screening, testing method, active TB exclusion, treatment of LTBI and guideline implementation are all reviewed. Conclusions: The principal changes include a selective approach to screen for LTBI (screening only of the HIV-infected patients at highest risk of active TB) as well as the timing of screening (testing for LTBI performed only after immune-restauration by antiretroviral therapy).

Proportions of interferon-γ-producing ascites lymphocytes in response to mycobacterial antigens: A help for early diagnosis of peritoneal tuberculosis in a low TB incidence country.

BACKGROUND: Peritoneal tuberculosis (TB) remains difficult to diagnose because of its non-specific clinical features and the lack of efficient microbiological tests. As delayed diagnosis is associated with high mortality rates, new diagnostic tools are needed. METHODS AND FINDINGS: We investigated for 24 patients prospectively enrolled with a possible diagnosis of peritoneal TB, the diagnostic value of the analysis of IFN-γ production by peritoneal fluid lymphocytes in response to a short in vitro stimulation with mycobacterial antigens. The patients were classified in two groups: non-TB and confirmed or highly probable TB. Diagnosis of TB was based on microbiological and histopathological criteria and/or a favorable response to anti-TB treatment. The IFN-γ production by peritoneal CD4+ T lymphocytes was analyzed by flow cytometry after an overnight in vitro stimulation with three different mycobacterial antigens, purified protein derivative (PPD), heparin-binding haemagglutinin (HBHA) or early-secreted-antigen-target-6 (ESAT-6). The percentages of PPD-, HBHA- or ESAT-6-induced IFN-γ-producing peritoneal fluid CD4+ T lymphocytes were higher in the TB group than in the non-TB group (p = 0.0007, p = 0.0004, and p = 0.0002 respectively). Based on cut-off values determined by ROC curve analysis of the results from TB and highly probable TB compared to those of non-TB patients, the sensitivity of these three tests was 100% with a specificity of 92%. CONCLUSIONS: The analysis of mycobacterial-induced IFN-γ production by peritoneal lymphocytes is a promising tool to reliably and rapidly diagnose peritoneal TB. Further studies should be performed on larger cohorts of patients in high-TB-incidence countries to confirm the clinical value of this new diagnostic approach for peritoneal TB.

Belgian guidelines for non-occupational HIV post-exposure prophylaxis 2017.

We present the updated Belgian guidelines for the use of non-occupational HIV post-exposure prophylaxis (NONOPEP). This document is inspired by UK guidelines 2015, adapted to the Belgian situation and approved by all AIDS reference centers in Belgium. When recommended, NONOPEP should be initiated as soon as possible, preferably within 24 h of exposure but can be offered up to 72 h. The duration of NONOPEP should be 28 days. These current guidelines include epidemiologic estimations, which can be used to calculate the risk of infection after a potential exposure and help to decide whether or not to start prophylaxis. We review which medications to use in the context of the last Belgian NONOPEP convention, provide a checklist for initial assessment, and make recommendations for monitoring individuals receiving NONOPEP.