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.

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.

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.

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.