Toxic-Induced Encephalopathy Following Chemsex in a Young HIV-Positive Male: A Complex Case of Acute Cognitive Impairment with Anterograde Amnesia and Behavioral Alterations.

BACKGROUND: A broadened clinical spectrum of concomitant complications emerges among the escalating incidence of substance use, particularly within the 'chemsex' context. This case exemplifies the profound neurotoxic repercussions and neurological risk of chemsex in a young HIV-positive male and addresses the multifaceted challenges of such evolving paradigms in substance utilization. CLINICAL FINDING: After consuming cannabis, poppers, methamphetamine, and cocaine, a 28-year-old HIV-positive male exhibited significant neurological and cognitive impairment. The initial presentation included dysarthria and profound anterograde amnesia. Laboratory findings showed leukocytosis with a PCR of 3 mg/dl - elevated cerebrospinal fluid protein levels with no cells. Urine toxicology returned positive for cannabis and amphetamines. A brain CT scan revealed bilateral and symmetrical hippocampi and pale globes hypodensity, indicative of toxic-metabolic encephalopathy. MRI further identified lesions in the globus pallidus, cerebellum, and hippocampi. Following the detection of toxic encephalopathy, Initial neuropsychological was performed screening using the Montreal Cognitive Assessment (MoCA), which highlighted immediate memory deficits. An in-depth neuropsychological assessment conducted 3 weeks later included the Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV), the Rey Auditory Verbal Learning Test (RAVLT), and tests for visuospatial skills, motor functions, and memory recall. The evaluations revealed pronounced anterograde amnesia, persistent long-term memory inconsistencies, and notable executive function challenges, detailed in Table 1. CONCLUSIONS: The detailed analysis of this case underpins the severe neurological consequences that can manifest from heavy substance use. Comprehensive diagnostic evaluations, including neuroimaging and neuropsychological assessments, are crucial in elucidating the full spectrum of substance-induced cognitive impairments. There is an urgent need for enhanced public awareness and preventative measures, especially in the context of chemsex, to bring forth multifaceted health, social, and government implications that modern society must adeptly navigate.

Efficacy and safety of raltegravir plus lamivudine maintenance therapy.

BACKGROUND: Decreasing medication burden with raltegravir plus lamivudine in virologically suppressed persons with HIV (PWH) maintained efficacy and was well tolerated at 24 weeks, but more comprehensive data over longer follow-up are required. METHODS: Prospective 48 week extension phase of the raltegravir plus lamivudine arm from a previous 24 week pilot randomized clinical trial in which virologically suppressed PWH were randomized 2:1 to switch to fixed-dose combination 150 mg lamivudine/300 mg raltegravir twice daily or to continue therapy. In this 48 week extension phase, raltegravir was dosed at 1200 mg/day and lamivudine 300 mg/day. Primary outcome was the proportion of PWH with treatment failure at Week 48. Secondary outcomes were changes in ultrasensitive plasma HIV RNA, HIV DNA in CD4 cells, serum IL-6, ultrasensitive C-reactive protein and sCD14, body composition, sleep quality, quality of life and adverse effects. RESULTS: Between May 2018 and June 2019, 33 PWH were enrolled. One participant experienced virological failure without resistance mutations and re-achieved sustained virological suppression without therapy discontinuation, and two others discontinued therapy due to adverse effects. Treatment failure was 9% (95% CI 2%-24%) and 3% (95% CI 0%-17%) in the ITT and on-treatment populations. There were significant changes between baseline and Week 48 in serum cytokines but not in other secondary outcomes. CONCLUSIONS: Switching to raltegravir and lamivudine in PWH with virological suppression maintains efficacy and is well tolerated. This maintenance regimen might be a cost-effective option for PWH at risk of drug-drug interactions or needing to avoid specific toxicities of certain antiretroviral drugs or their negative impact on comorbidities.

Stillbirth of a mandrill (Mandrillus sphinx) in the wild: perinatal behaviors and delivery sequences.

Birth is a fundamental event in the life of animals, including our own species. More reports of wild non-human primate births and stillbirths are thus needed to better understand the evolutionary pressures shaping parturition behaviors in our lineage. In diurnal non-human primates, births generally occur at night, when individuals are resting. Consequently, they are difficult to observe in the wild and most of the current knowledge regarding perinatal behaviors comes from rare daytime births. Information about stillbirths is even rarer and their proximate causes are generally unknown. Here, we present detailed observations of a daytime birth of a stillborn wild mandrill (Mandrillus sphinx). During this event, which lasted an entire day, we recorded the behaviors of the parturient female ad libitum, using video recordings and photos. The 5-year-old female was primiparous and of low dominance rank. The length of her pregnancy was shorter than usual and the partum phase was extremely long compared to other birth reports in non-human primates. The female disappeared shortly after this event and was assumed to have died. We discuss the possible causes of this stillbirth including the infant's presentation at birth and maternal inexperience.

Tolerability of bictegravir/tenofovir alafenamide/emtricitabine versus dolutegravir/lamivudine as maintenance therapy in a real-life setting.

BACKGROUND: While both the burden of therapy and the individual drugs in bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC) and dolutegravir/lamivudine differ, it is unclear whether their real-life tolerability may be also different. METHODS: Single-centre, clinical cohort analysis of all virologically suppressed persons with HIV (PWH) who were first prescribed bictegravir as BIC/TAF/FTC or dolutegravir as dolutegravir/lamivudine and had taken ≥1 dose of study medication. Major outcomes were discontinuations either for any reason or due to toxicity. Incidence was calculated as number of episodes per 100 person-years adjusted through propensity score analysis. RESULTS: Relative to persons treated with BIC/TAF/FTC (n = 1231), persons treated with dolutegravir/lamivudine (n = 821) were older and had more AIDS-defining conditions although better HIV control. After a median follow-up of 52 weeks, adjusted incidence rates for discontinuation were 6.68 (95% CI 5.18-8.19) and 8.44 (95% CI 6.29-10.60) episodes per 100 person-years for BIC/TAF/FTC and dolutegravir/lamivudine, respectively; adjusted incidence rate ratio for dolutegravir/lamivudine was 1.26 (95% CI 0.89-1.78) relative to BIC/TAF/FTC (P = 0.1847). Adjusted incidence rates for discontinuation due to toxicity were 3.88 (95% CI 2.70-5.06) and 4.62 (95% CI 3.05-6.19) episodes per 100 person-years for BIC/TAF/FTC and dolutegravir/lamivudine, respectively; adjusted incidence rate ratio for dolutegravir/lamivudine was 1.19 (95% CI 0.75-1.90) relative to BIC/TAF/FTC (P = 0. 4620). Adverse events leading to discontinuation were neuropsychiatric (n = 42; 2%), followed by gastrointestinal (n = 23; 1%), dermatological (n = 15; 1%) and weight increase (n = 15; 1%), without differences between regimens. CONCLUSIONS: Switching to BIC/TAF/FTC or dolutegravir/lamivudine showed no difference in the risks of overall or toxicity-related discontinuations or in the profile of adverse events leading to discontinuation.

Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate for Nonoccupational HIV-1 Postexposure Prophylaxis: A Prospective Open-Label Trial (DORAVIPEP).

Background: New regimens may provide better tolerability, convenience, and safety for nonoccupational human immunodeficiency virus (HIV) postexposure prophylaxis (PEP). For this reason, we evaluated the single-tablet regimen of doravirine/lamivudine/tenofovir disoproxil fumarate (DOR/3TC/TDF) for 28 days. Methods: This was a prospective, open-label, single-arm trial including individuals with potential HIV-1 exposure within 72 hours. The primary endpoint was noncompletion of PEP at day 28. Secondary endpoints were adverse effects, adherence, and rate of seroconversion. We performed follow-up at day 7, week 4, and week 12. Results: Between September 2019 and March 2022, the study enrolled 399 individuals. Median age was 30 (interquartile range [IQR], 27-36) years, and 91% (n = 364) were male. The mode of exposure was sex between men in 84% (n = 331) of cases; risk assessment for HIV-1 transmission was considered as "high" in 97% (n = 385) of the participants. Median time from exposure to consultation was 24 (IQR, 13-40) hours. Noncompletion of PEP was 29% (n = 114) (95% confidence interval [CI], 24%-33%) and 20% (n = 72) (95% CI, 16%-25%) per modified intention-to-treat. Main reasons for noncompletion were loss to follow-up (n = 104 [91%]) and intolerance (n = 8 [7%]). Older age was associated with a lower risk of premature discontinuation (OR, 0.94; P < .001). One hundred twenty-three (31%) participants reported adverse events, mostly mild and self-limited (82%); discontinuation occurred in 8 cases (2%). Adherence to PEP in the assessed users was 96%. There were no HIV seroconversions. Conclusions: DOR/3TC/TDF is a well-tolerated option for nonoccupational PEP. Clinical Trials Registration. NCT04233372.

Increasing of New CA-MRSA Infections Detected in people living with HIV Who Engage in Chemsex in Barcelona: An Ambispective Study.

INTRODUCTION: There are no data on community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections in the context of the chemsex phenomenon. This study aimed to characterize CA-MRSA-related infections in a cohort of people living with HIV (PLWH) who engage in chemsex. METHODS: At the Hospital Clinic of Barcelona, from February 2018 to January 2022, we analyzed CA-MRSA infections diagnosed in a cohort of PLWH who engage in chemsex. Epidemiological, behavioral and clinical variables were assessed. Mass spectrometry identification and antimicrobial susceptibility testing were performed on MRSA isolates. Pulse field electrophoresis was used to assess the clonality of the MRSA strains. The presence of Panton-Valentine leukocidin was also investigated. RESULTS: Among the cohort of 299 participants who engage in chemsex, 25 (8%) with CA-MRSA infections were identified, 9 at baseline and 16 with incident cases; the cumulative incidence was 5.5% (95% CI: 3.2%, 8.8%). The most common drugs were methamphetamine (96%) and GHB/GBL (92%). Poly-consumption and slamming were reported by 32% and 46%, respectively. CA-MRSA was isolated from the infection sites of 20 participants, and CA-MRSA colonization was confirmed in the remaining 5 persons. Seventy-one percent had used antibiotics in the previous year. All participants presented with skin and soft tissue infections, 28% required hospitalization, and 48% had recurrence. Of the 23 MRSA isolates further studied, 19 (82,6%) belonged to the same clone. Panton-Valentine leukocidin was detected in all isolates. CONCLUSION: PLWH who engage in chemsex may present with CA-MRSA infections. Clinical suspicion and microbiological diagnosis are required to provide adequate therapy, and CA-MRSA prevention interventions should be designed.

Hopelessness in Patients with Early-Stage Relapsing-Remitting Multiple Sclerosis.

Background: Hopelessness is a risk factor for depression and suicide. There is little information on this phenomenon among patients with relapsing-remitting multiple sclerosis (RRMS), one of the most common causes of disability and loss of autonomy in young adults. The aim of this study was to assess state hopelessness and its associated factors in early-stage RRMS. Methods: A multicenter, non-interventional study was conducted. Adult patients with a diagnosis of RRMS, a disease duration ≤ 3 years, and an Expanded Disability Status Scale (EDSS) score of 0-5.5 were included. The State-Trait Hopelessness Scale (STHS) was used to measure patients´ hopelessness. A battery of patient-reported and clinician-rated measurements was used to assess clinical status. A multivariate logistic regression analysis was conducted to determine the association between patients' characteristics and state hopelessness. Results: A total of 189 patients were included. Mean age (standard deviation-SD) was 36.1 (9.4) years and 71.4% were female. Median disease duration (interquartile range-IQR) was 1.4 (0.7, 2.1) years. Symptom severity and disability were low with a median EDSS (IQR) score of 1.0 (0, 2.0). A proportion of 65.6% (n=124) of patients reported moderate-to-severe hopelessness. Hopelessness was associated with older age (p=0.035), depressive symptoms (p=<0.001), a threatening illness perception (p=0.001), and psychological and cognitive barriers to workplace performance (p=0.029) in the multivariate analysis after adjustment for confounders. Conclusion: Hopelessness was a common phenomenon in early-stage RRMS, even in a population with low physical disability. Identifying factors associated with hopelessness may be critical for implementing preventive strategies helping patients to adapt to the new situation and cope with the disease in the long term.

Clinical use and effectiveness of dolutegravir and lamivudine: a long-term, real-world, retrospective study.

BACKGROUND: The use of dolutegravir/lamivudine is based on solid clinical trials; however, real-world data remain limited. OBJECTIVES: To provide data on the clinical use and effectiveness of dolutegravir/lamivudine in persons with HIV in a real-world scenario. PATIENTS AND METHODS: Retrospective, single-centre and observational study. We included all adults starting dolutegravir/lamivudine since November 2014. We reported all demographic, virological and immunological variables at baseline and assessed effectiveness [on treatment (OT), modified ITT (mITT) and ITT in those persons who reached 6 and 12 month follow-ups (M6 and M12). RESULTS: Of the 1058 persons, 9 were treatment-naive; the final analysis included 1049 treatment-experienced people with HIV. Median (IQR) follow-up was 1 (0.3-1.6) years, with 81% and 63% persons reaching M6 and M12, respectively. The longest use of dolutegravir/lamivudine was 7.4 years. Per OT, mITT and ITT, HIV-RNA < 50 copies/mL was 97%, 92% and 81% (M6) and 98%, 90% and 80% (M12), respectively. Females [adjusted risk ratio, aRR (95% CI): 1.69 (1.19-2.40)]; immediate, previous PI-based regimen [aRR (95% CI): 1.67 (1.09-2.56)]; and viral load (VL) ≥ 50 copies/mL at dolutegravir/lamivudine initiation [aRR (95% CI): 3.36 (2.32-4.88)] were independently associated with lack of effectiveness at M12; other demographic, immunological and virological variables like previous M184V/I substitutions or virological failure, were unrelated. Of the total, 944 (90%) continued dolutegravir/lamivudine. The most frequent known reason for discontinuation was toxicity [48 (46%) cases]. CONCLUSIONS: In our real-world experience, virological suppression rates were high for treatment-experienced persons on dolutegravir/lamivudine; however, we identified subgroups with a higher risk of lack of effectiveness at M12, who may benefit from closer follow-ups.

Perception of quality of care using patient reported experience measures (PREMs) in a cohort of adults with HIV: A cross-sectional study.

Human immunodeficiency virus (HIV) infection is considered a chronic disease. Antiretroviral therapy has allowed persons with HIV (PLWHIV) to achieve the 90-90-90 objectives proposed by the World Health Organization for 2020; but an additional challenge is getting an adequate health-related quality of life. A determining factor in the health-related quality of life of PLWHIV is the health care they perceive to receive. In this sense, we aimed to assess the perception of the outpatient care provided and to identify possible areas for improvement in a single-center, cross-sectional study at the HIV unit of Hospital Clínic, Barcelona. We sought patient reported experience measures by an anonymous e-survey with 11 statements based on a 1 to 6 Likert scale, and a final question measuring user satisfaction and loyalty through the Net Promoter Score (NPS). All PLWHIV with at least a clinical visit between January 1, 2020 and October 14, 2021 were invited. Of 5493 PLWHIV e-mailed, 1633 (30%) responded to the survey. The overall evaluation of clinical care was very favorable. The evaluation of the physical environment and facilities and the time spent in the waiting room received the lowest scores. According to the Net Promoter Score test results, 66% of respondents were willing to recommend this service, and 11% were not. Thus, monitoring patient reported experience measures in PLWHIV actively receiving outpatient care in our hospital allowed to identify the users' perception on quality of the care received, to determine the rate of satisfaction with the care, and to identify areas for improvement.

Sex-based epidemiological and immunovirological characteristics of people living with HIV in current follow-up at a tertiary hospital: a comparative retrospective study, Catalonia, Spain, 1982 to 2020.

BackgroundEpidemiological and immunovirological features of people living with HIV (PLWH) can vary by sex.AimTo investigate, particularly according to sex, characteristics of PLWH who consulted a tertiary hospital in Barcelona, Spain, in 1982-2020.MethodsPLWH, still in active follow-up in 2020 were retrospectively analysed by sex, age at diagnosis, age at data extraction (December 2020), birth place, CD4+ cell counts, and virological failure.ResultsIn total, 5,377 PLWH (comprising 828 women; 15%) were included. HIV diagnoses in women appeared to decrease from the 1990s, representing 7.4% (61/828) of new diagnoses in 2015-2020. From 1997, proportions of new HIV diagnoses from patients born in Latin America seemed to increase; moreover, for women born outside of Spain, the median age at diagnosis appeared to become younger than for those born in Spain, with significant differences observed in 2005-2009 and 2010-2014 (31 vs 39 years (p = 0.001), and 32 vs 42 years (p < 0.001) respectively), but not in 2015-2020 (35 vs 42 years; p = 0.254). Among women, proportions of late diagnoses (CD4+ cells/mm3 < 350) were higher than men (significantly in 2015-2020: 62% (32/52) vs 46% (300/656); p = 0.030). Initially, virological failure rates were higher in women than men, but they were similar in 2015-2020 (12% (6/52) vs 8% (55/659); p = 0.431). Women ≥ 50 years old represented 68% (564/828) of women actively followed up in 2020.ConclusionsWomen still have higher rates of late HIV diagnoses than men. Among currently-followed-up women, ≥ 50 year-olds, who need age-adapted care represent a high percentage. Stratifying PLWH by sex matters for HIV prevention and control interventions.

The Mandrillus Face Database: A portrait image database for individual and sex recognition, and age prediction in a non-human primate.

The Mandrillus Project is a long-term field research project in ecology and evolutionary biology, monitoring, since 2012, a natural population of mandrills (Mandrillus sphinx; primate) located in Southern Gabon. The Mandrillus Face Database was launched at the beginning of the project and now contains 29,495 photographic portraits collected on 397 individuals from this population, from birth to death for some of them. Portrait images have been obtained by manually processing images taken in the field with DSLR cameras: faces have been cropped to remove the ears and rotated to align the eyes horizontally. The database provides portrait images resized to 224 × 224 pixels associated with several manually annotated labels: individual identity, sex, age, face view, and image quality. Labels are stored within the image metadata and in a table accompanying the image database. This database will allow training and comparing methods on individual and sex recognition, and age prediction in a non-human animal.

The Combination of an mRNA Immunogen, a TLR7 Agonist and a PD1 Blocking Agent Enhances In-Vitro HIV T-Cell Immune Responses.

The development of new strategies to achieve a functional cure for HIV remains a priority. We tested a novel HIV therapeutic vaccine using unmodified mRNA (TMEP-B) and mRNA modified by 1-methyl-3'-pseudouridylyl (TMEP-Bmod) expressing both a multiepitopic sequences from Gag, Pol, and Nef proteins, including different CD4 and CD8 T-cell epitopes functionally associated with HIV control in transfected monocyte-derived dendritic cells (MDDCs) obtained from HIV infected patients. In vitro assays were used to test the mRNAs alone and in combination with immunomodulator agents, such as the TLR-7 agonist Vesatolimod and the PD-1 antagonist Nivolumab to try to improve HIV-specific cellular immune responses. Combining the mRNAs with the immunomodulators enhanced HIV-specific T-cell responses, together with the secretion of IFNγ, IP10, MIP-1α, and MIP-1ß, which are fundamental mediators of viral control. Our data suggest that the mRNA vaccine prototypes TMEP-B and TMEP-Bmod, when combined with Vesatolimod and/or Nivolumab, could achieve functional cure for patients with HIV.

Experiencia de un programa de profilaxis preexposición en una unidad de virus de la inmunodeficiencia humana hospitalaria. Descripción del perfil basal del usuario e identificación de oportunidades de mejora / PrEP program experience in a hospital HIV unit. Description of baseline user profile and identification of opportunities for improvement

Introducción: La profilaxis preexposición (PrEP) es una intervención biomédica dirigida a prevenir la infección por el VIH en personas seronegativas con alto riesgo de contraer la infección. Esta estrategia fue aprobada por el Ministerio de Salud de España en octubre de 2019. Objetivo: Presentar la experiencia inicial de la PrEP en la Unidad de VIH del Hospital Clínic de Barcelona, poniendo especial atención en el análisis de los factores de vulnerabilidad de la cohorte. Materiales y métodos: Estudio retrospectivo, descriptivo. Se analizan las características epidemiológicas, sociodemográficas y clínicas basales de los usuarios incluidos en el programa durante el primer año de funcionamiento, prestando particular atención a las infecciones, las prácticas de riesgo y el consumo de sustancias. Resultados: Se incluyeron 190 individuos, 177 hombres y 12 mujeres transexuales con una edad media de 35 años (8DE). El 70% tenía estudios superiores y la mitad nacionalidad española. Informaron de tener 10 parejas de media al trimestre y el 60% de practicar sexo anal desprotegido. El 31% presentó al menos una PCR positiva para ITS, siendo la N. gonorrhoeae el germen más prevalente (51%) y la muestra rectal la más afectada (21%). El 63% reportó el uso de chemsex, el 19% policonsumo y el 8% slamming. La mitad expresó su preocupación por el consumo y/o prácticas sexuales y un 25% la necesidad de ayuda. Conclusiones: El perfil del usuario de PrEP visitado en nuestra unidad hospitalaria justifica la creación de equipos multidisciplinares que permitan prestar una atención holística de la vida sexual de estas personas.(AU)

Introduction: Pre-Exposure Prophylaxis (PrEP) is a biomedical intervention to prevent HIV infection in seronegative people at high risk of becoming infected. This strategy was endorsed in October 2019 by the Spanish Ministry of Health. Objective: To present the PrEP initial experience in the HIV Unit of the Hospital Clínic of Barcelona, paying special attention to the analysis of the vulnerability factors in the cohort. Materials and methods: Retrospective, descriptive study. The epidemiological, sociodemographic, and clinical characteristics of the users included in the program during the first year are analyzed, paying particular attention to Infections, risky practices, and substance use. Results: 190 individuals were included, 177 men and 12 trans women with a mean age of 35 years (8 SD). 70% had higher education, and half had Spanish nationality. An average of 10 couples per trimester and 60% reported unprotected anal sex. 31% had at least one positive PCR for STIs, with N. gonorrhoeae being the most prevalent microorganism (51%) and the rectal sample the most affected (21%). 63% reported chemsex use, 19% polydrug use, and 8% “slamming”. Half expressed concern about consumption and/or sexual practices and 25% the need for help. Conclusions: The PrEP user profile attended in our Hospital Unit justifies the creation of multidisciplinary teams that allow us to provide holistic attention to the sexual life of these people.(AU)

PrEP program experience in a hospital HIV unit. Description of baseline user profile and identification of opportunities for improvement.

INTRODUCTION: Pre-Exposure Prophylaxis (PrEP) is a biomedical intervention to prevent HIV infection in seronegative people at high risk of becoming infected. This strategy was endorsed in October 2019 by the Spanish Ministry of Health. OBJECTIVE: To present the PrEP initial experience in the HIV Unit of the Hospital Clínic of Barcelona, paying special attention to the analysis of the vulnerability factors in the cohort. MATERIALS AND METHODS: Retrospective, descriptive study. The epidemiological, sociodemographic, and clinical characteristics of the users included in the program during the first year are analyzed, paying particular attention to Infections, risky practices, and substance use. RESULTS: 190 individuals were included, 177 men and 12 trans women with a mean age of 35 years (8 SD). 70% had higher education, and half had Spanish nationality. An average of 10 couples per trimester and 60% reported unprotected anal sex. 31% had at least one positive PCR for STIs, with N. gonorrhoeae being the most prevalent microorganism (51%) and the rectal sample the most affected (21%). 63% reported chemsex use, 19% polydrug use, and 8% "slamming". Half expressed concern about consumption and/or sexual practices and 25% the need for help. CONCLUSIONS: The PrEP user profile attended in our Hospital Unit justifies the creation of multidisciplinary teams that allow us to provide holistic attention to the sexual life of these people.

Evolution of Risk Behaviors, Sexually Transmitted Infections and PrEP Care Continuum in a Hospital-Based PrEP Program in Barcelona, Spain: A Descriptive Study of the First 2 Years' Experience.

INTRODUCTION: Pre-exposure prophylaxis (PrEP) is effective for HIV prevention, but the PrEP care continuum also involves improving PrEP awareness, uptake, adherence, and retention in care. Users' awareness is often compromised because of vulnerability factors and risk behaviors, such as chemsex practice or specific substance use, which could lead to risk compensation. Correct adherence and retention in care are essential to achieve the full effectiveness of PrEP. This study describes changes in users' risk behaviors and sexually transmitted infections (STIs), as well also PrEP care continuum details. METHODS: This was a descriptive single-center retrospective study including adults at high HIV risk screened between November 2019 and June 2021 in the PrEP program of our hospital. Demographic, behavioral, STI, adherence, and retention in care variables were assessed. Data were collected from medical records and self-report questionnaires. RESULTS: A total of 295 people were included, 94% men and 5% transgender women, with a mean age of 34 years (SD 10) and 10% sex workers. At baseline, 55% disclosed chemsex practice and 3% slamming. During follow-up, condom use for anal intercourse decreased from 41% to 13% (p ≤ 0.0001) and one HIV infection was detected; other risk behaviors and STIs remained stable. Chemsex, group sex, fluid exchange, and condomless anal intercourse were related to STI risk. Adherence was correct in 80% of users, and retention in care was 57%. Discontinuations and loss to follow-up were high, mainly affecting transgender women, sex workers, and people practicing fisting. CONCLUSION: PrEP program implementation in our hospital was adequate, since it allowed, in a population at high HIV risk, overall users' risk behaviors and STIs to remain stable, with only one HIV diagnosis during the follow-up. We should target specific strategies to improve adherence and retention in care, as vulnerable subgroups at higher risk of loss to follow-up are identified.

Mandrill mothers associate with infants who look like their own offspring using phenotype matching.

Behavioral discrimination of kin is a key process structuring social relationships in animals. In this study, we provide evidence for discrimination towards non-kin by third-parties through a mechanism of phenotype matching. In mandrills, we recently demonstrated increased facial resemblance among paternally related juvenile and adult females indicating adaptive opportunities for paternal kin recognition. Here, we hypothesize that mandrill mothers use offspring's facial resemblance with other infants to guide offspring's social opportunities towards similar-looking ones. Using deep learning for face recognition in 80 wild mandrill infants, we first show that infants sired by the same father resemble each other the most, independently of their age, sex or maternal origin, extending previous results to the youngest age class. Using long-term behavioral observations on association patterns, and controlling for matrilineal origin, maternal relatedness and infant age and sex, we then show, as predicted, that mothers are spatially closer to infants that resemble their own offspring more, and that this maternal behavior leads to similar-looking infants being spatially associated. We then discuss the different scenarios explaining this result, arguing that an adaptive maternal behavior is a likely explanation. In support of this mechanism and using theoretical modeling, we finally describe a plausible evolutionary process whereby mothers gain fitness benefits by promoting nepotism among paternally related infants. This mechanism, that we call 'second-order kin selection', may extend beyond mother-infant interactions and has the potential to explain cooperative behaviors among non-kin in other social species, including humans.

Do ART and Chemsex Drugs Get Along? Potential Drug-Drug Interactions in a Cohort of People Living with HIV Who Engaged in Chemsex: A Retrospective Observational Study.

INTRODUCTION: People living with HIV (PLWH) who engaged in chemsex are at risk of potential drug-drug interactions (pDDIs) with recreational drugs. This study aimed to characterize pDDIs between antiretroviral treatment (ART) and chemsex drugs and evaluate their association with unscheduled relevant hospital consultations. METHODS: We conducted a single-center, retrospective, observational study in a series of gay, bisexual, and other men who have sex with men (gbMSM) living with HIV who engaged in chemsex and who attended a tertiary hospital in Barcelona, Spain, from February 2018 through August 2019. Associations between all recorded pDDIs and relevant unscheduled consultations were estimated using the incidence rate (IR) per 100 person-years of those events compared between patients with no pDDI (green flag) or moderate severity pDDI (orange flag) with patients with high severity pDDI (red flag) using the incidence rate ratio (IRR). RESULTS: Among 172 PLWH engaged in chemsex, 249 ART regimens were prescribed: 44% based on integrase inhibitors, 30% on boosted ART, and 26% based on non-nucleoside reverse transcriptase inhibitors. The substances and recreational drugs most frequently used were erectile dysfunction agents (83%), methamphetamine (79%), GHB (77%), and alkyl nitrites (71%). Polydrug use was reported in 52%. We observed 2048 pDDIs. Of these, 23% were orange flag pDDIs; 88% related to boosted ARTs. The IR of the 285 unscheduled relevant episodes in patients with orange flag pDDIs was 64.67 (95% CI 40.07-89.28). The IRR of green flag pDDIs was 1.05 (95% CI 0.60-1.8; p = 0.876). CONCLUSION: One in four pDDIs were of moderate severity but no significant increase in the incidence of unscheduled relevant consultations was observed. A high number of unscheduled consultations, predominantly for psychiatric events and intoxication, were observed. Beyond using non-boosted ART to minimize pDDIs, other factors related to the practice of chemsex must be addressed, in order to offer a better approach.

Chemsex Practices in PrEP: Beyond Addiction and Risk Toward a Healthy Sex Life-Baseline Experiences from a Hospital-Based PrEP Program in Barcelona, Spain.

Pre-exposure prophylaxis (PrEP) is a biomedical intervention that has demonstrated efficacy in HIV prevention in individuals at high-risk, among them chemsex users. Out of 190 PrEP users followed at Hospital Clinic of Barcelona until October 2020, 89% reported drug use, and 63% disclosed that they had engaged in chemsex practices, initiated in 64% of cases within the past year. Twenty-one percent used 3 or more drugs simultaneously, being GHB/GBL, nitrites, sildenafil, and methamphetamine the most prevalent combination. Eight percent reported slamming. Forty-one percent described having had negative experiences and 8% did not remember the last time they had sober sex. Methamphetamine, mephedrone, GHB/GBL, and having had open relationships, group sex, double penetration, and fisting were significantly more prevalent. Forty-nine percent admitted being worried about chemsex use, and 18% said they needed help. A comprehensive, interdisciplinary approach is mandatory to enable the attainment of a healthy approach to one's sex life.

RESUMEN: La PrEP es una intervención biomédica eficaz en la prevención del VIH en personas con alto riesgo, entre ellas las personas que practican chemsex. De los 190 usuarios de PrEP seguidos en el Hospital Clínic de Barcelona hasta octubre de 2020, el 89% refirió utilizar drogas y el 63% en contexto de chemsex, iniciando el consumo el 64% durante el último año. El 21% refería policonsumo, siendo GHB/GBL, nitritos, sildenafilo y metanfetamina la combinación más prevalente. El 8% reportó slamming. El 41% describió haber tenido experiencias negativas y el 8% no recordaba la última vez que tuvo sexo sobrio. Metanfetamina, mefedrona, GHB/GBL y haber tenido relaciones abiertas, sexo en grupo, doble penetración y fisting fueron significativamente más frecuentes. El 49% refirió estar preocupado por la práctica de chemsex y el 18% necesitar ayuda. Un abordaje integral e interdisciplinar mejoraría el acompañamiento global de la sexualidad en estas personas.

Simplification from tenofovir disoproxil fumarate plus lamivudine or emtricitabine plus ritonavir-boosted protease inhibitor to ritonavir-boosted atazanavir plus lamivudine in virologically suppressed HIV-infected adults with osteopenia: a pilot study.

BACKGROUND: Tenofovir disoproxil fumarate, particularly when given with a ritonavir-boosted PI, reduces bone mineral density (BMD) and increases bone turnover markers (BTMs). Ritonavir-boosted atazanavir plus lamivudine is a feasible simplified option. We evaluated whether switching from a triple ritonavir-boosted PI plus tenofovir disoproxil fumarate to a two-drug regimen of lamivudine plus ritonavir-boosted atazanavir would improve BMD. METHODS: Single-arm pilot study. Virologically suppressed patients on tenofovir disoproxil fumarate plus lamivudine or emtricitabine plus ritonavir-boosted PI with low BMD, without previous resistance mutations and/or virological failure to study drugs were switched to 100/300 mg of ritonavir-boosted atazanavir plus 300 mg of lamivudine once daily. The primary endpoint was BMD change by DXA at Week 48. RESULTS: There were 31 patients, 4 (13%) female, and median age was 40 years. Seven participants (22.5%) had osteoporosis. At 48 weeks, mean (SD) changes in spine and hip BMD were +0.01 (0.03) (P = 0.0239) and +0.013 (0.03) g/cm2 (P = 0.0046), respectively. Mean (SD) T-score changes were +0.1 (0.23) (P = 0.0089) and +0.25 (0.76) (P = 0.0197), respectively. N-telopeptide and urine tenofovir disoproxil fumarate toxicity markers showed significant improvements. One participant withdrew from the study and two were lost to follow-up. There were no virological failures, or serious or grade 3-4 adverse events. CONCLUSIONS: Switching from a tenofovir disoproxil fumarate plus ritonavir-boosted PI triple therapy to a lamivudine plus ritonavir-boosted atazanavir two-drug regimen in virologically suppressed HIV-infected adults with low BMD was safe, increased low BMD and reduced plasma markers of bone turnover and urine markers of tenofovir disoproxil fumarate toxicity over 48 weeks.

Impact of SARS-CoV-2 viral load and duration of symptoms before hospital admission on the mortality of hospitalized COVID-19 patients.

PURPOSE: Assess the impact of viral load estimated by cycle threshold (Ct) of reverse transcription real time-polymerase chain reaction (rRT-PCR) and the days from symptoms onset on mortality in hospitalized patients with COVID19. METHODS: Retrospective observational study of 782 patients with a positive rRT-PCR from a nasopharyngeal swab was performed within the first 24 h from admission. Demographic data, clinical manifestations and laboratory parameters were collected. Uni- and multivariate analyses were performed to identify factors associated with mortality at 60 days. RESULTS: Ct was divided into three groups and the mortality rate decreased from 27.3 to 20.7% and 9.8% for Ct values of ≤ 20, 21-25 and > 25, respectively (P = 0.0001). The multivariate analysis identified as predictors of mortality, a Ct value < 20 (OR 3.13, CI 95% 1.38-7.10), between 21-25 (OR 2.47, CI 95% 1.32-4.64) with respect to a Ct value > 25. Days from symptoms onset is a variable associated with mortality as well (DSOA) ≤ 6 (OR 1.86, CI 95% 1.00-3.46), among other factors. Patients requiring hospital admission within 6 DSOA with a Ct value ≤ 25 had the highest mortality rate (28%). CONCLUSIONS: The inclusion of Ct values and DSOA in the characterization of study populations could be a useful tool to evaluate the efficacy of antivirals.