Background: The aim of the study was to evaluate the 12-month cumulative probability of treatment discontinuation (TD) in people with human immunodeficiency virus (HIV; PWH) and a long exposure to antiretroviral therapy (ART) switching to long-acting cabotegravir and rilpivirine (CAB/RPV). Methods: SCohoLART is a single-center, prospective, cohort study designed to collect both samples and clinical data from PWH with virological suppression who switched to bimonthly long-acting CAB/RPV. TD occurred at switch to another regimen for any reason including virological failure (VF); VF was defined as HIV RNA levels ≥50 copies/mL at 2 consecutive measurements or a single HIV RNA level ≥1000 copies/mL. Results were reported as median (interquartile range [IQR]) or frequency (percentage). Cumulative probabilities of TD were estimated using Kaplan-Meier curves. Results: We evaluated 514 participants; 467 (90.9%) were male, and their median age (IQR) was 49 (40–56) years. At the time of switching, the median time from HIV diagnosis and the median duration of ART were 14.0 (IQR, 8.8–20.5) and 11.4 (7.9–17.4) years, respectively; before starting CAB/RPV, the median number of antiretroviral regimens was 3 (2–4). During a median study follow-up (IQR) of 13.1 (9.1–15.5) months, 52 PWH (10.1%) experienced TD, including 4 (0.8%) for VF. The 12-month cumulative probability of TD was 11% (95% confidence interval, 8%–14%). The main cause of TD was injection site reaction (15 participants [28.8%]). Conclusions: The 1-year cumulative probability of TD with long-acting CAB/RPV was quite low in this cohort of people with a median exposure to ART of 10 years, in whom injection site reaction was the leading cause of TD. VFs were rare during study follow-up.

Purpose: The PRESTIGIO Registry was established in 2017 to collect clinical, virological and immunological monitoring data from people living with HIV (PLWH) with documented four-class drug resistance (4DR). Key research purposes include the evaluation of residual susceptibility to specific antiretrovirals and the validation of treatment and monitoring strategies in this population. Participants: The PRESTIGIO Registry collects annual plasma and peripheral blood mononuclear cell samples and demographic, clinical, virological, treatment and laboratory data from PLWH followed at 39 Italian clinical centres and characterised by intermediate-to-high genotypic resistance to ≥1 nucleoside reverse transcriptase inhibitors, ≥1 non-nucleoside reverse transcriptase inhibitors, ≥1 protease inhibitors, plus either intermediate-to-high genotypic resistance to ≥1 integrase strand transfer inhibitors (INSTIs) or history of virological failure to an INSTI-containing regimen. To date, 229 people have been recorded in the cohort. Most of the data are collected from the date of the first evidence of 4DR (baseline), with some prebaseline information obtained retrospectively. Samples are collected from the date of enrollment in the registry. Findings to date: The open-ended cohort has been used to assess (1) prognosis in terms of survival or development of AIDS-related or non-AIDS-related clinical events; (2) long-term efficacy and safety of different antiretroviral regimens and (3) virological and immunological factors predictive of clinical outcome and treatment efficacy, especially through analysis of plasma and cell samples. Future plans: The registry can provide new knowledge on how to implement an integrated approach to study PLWH with documented resistance to the four main antiretroviral classes, a population with a limited number of individuals characterised by a high degree of frailty and complexity in therapeutic management. Given the scheduled annual updates of PLWH data, the researchers who collaborate in the registry can send study proposals at any time to the steering committee of the registry, which evaluates every 3 months whether the research studies can be conducted on data and biosamples from the registry and whether they are aimed at a better understanding of a specific health condition, the emergence of comorbidities or the effect of potential treatments or experimental drugs that may have an impact on disease progression and quality of life. Finally, the research studies should aim to be inclusive, innovative and in touch with the communities and society as a whole. Trial registration number: NCT04098315 .

The general female population is not considered a high-risk group for screening for sexually transmitted infections (STIs). This retrospective study describes the prevalence of Human Immunodeficiency Virus (HIV), Treponema pallidum (T. pallidum), Chlamydia trachomatis (C. trachomatis), Neisseria gonorrhoeae (N. gonorrhoeae), Trichomonas vaginalis (T. vaginalis), Mycoplasma spp., Ureaplasma spp., genital Herpes simplex virus (HSV), Monkeypox (mpox), Hepatitis B virus (HBV), and Hepatitis C virus (HCV) infections in asymptomatic and symptomatic cisgender women attending our walk-in STI clinic for the first time. Furthermore, it analyzes the number of individuals who returned for follow-up and were diagnosed with new STIs. Over 20 months, 189 women with a median age of 28.4 years were screened [129 (68.3%) asymptomatic and 60 (31.8%) symptomatic]. In order of prevalence, the most common STIs were: Ureaplasma spp. infections (50.3%), C. trachomatis (10.6%), N. gonorrhoeae (5.8%), Mycoplasma hominis infections (5.8%), T. pallidum (2.65%), HSV2 infections (2.65%), and mpox (0.53%). No diagnosis of HIV, trichomoniasis, HBV, or HCV was registered. After the initial evaluation, 128 (67.7%) women returned for follow-up, but only 43 (22.8%) repeated screening; among them, 11 (25.6%) were diagnosed with new STIs. Given the high prevalence of STIs in cisgender women, awareness measures to improve screening and prevention strategies in this neglected population are required.

Background: Heavily treatment-experienced (HTE) people with HIV (PWH) have limited antiretroviral therapy (ART) treatment options, putting them at greater risk of unfavorable human immunodeficiency virus 1 (HIV-1) disease progression. Fostemsavir (BMS-663068) efficiently suppressed viremia and increased CD4 count when combined with other antiretrovirals in HTE PWH. Its active metabolite, temsavir (BMS-626529, GSK2616713), binds a conserved pocket within the envelope glycoprotein (Env) CD4 binding site and prevents CD4-induced conformational changes. Temsavir effect on Env conformation profoundly alters its glycosylation and cleavage, thereby modifying its antigenicity and reducing gp120 shedding. Here we evaluated if fostemsavir treatment in PWH modulated the levels of nonneutralizing gp120 CD4-induced (CD4i) antibodies (Abs) associated with CD4 depletion in vitro and in PWH. Methods: We measured the levels of anti-gp120 CD4i Abs in plasma samples taken before and after fostemsavir treatment in HTE participants from the BRIGHTE trial and the PRESTIGIO registry and compared them to those of a control ART-treated group from the SAILING trial. Results: We observed a significant decline of anti-gp120 CD4i Abs in the 2 fostemsavir-treated HTE groups, but not in the control group. Moreover, this effect was unique to anti-gp120 CD4i Abs, as no significant changes were observed in the levels of antibodies targeting Gag. Functionally, this decline in CD4i Abs was associated with a reduced capacity of plasma to recognize and eliminate uninfected primary CD4+ T cells coated with soluble gp120. Conclusions: Altogether, fostemsavir may provide additional immune benefits to PWH, beyond blocking viral entry, by reducing anti-gp120 CD4i Abs levels. Clinical Trials Registration: NCT04098315, NCT01231516, and NCT02362503.