BackgroundThe use of combination regimens is paramount in the treatment of HIV infection. Virologically suppressed patients, may benefit to change their treatment in a two-drug regimen (2DR). Long acting (L-A) injectable 2DR may be a good option in selected patients (preference for a nondaily dosing, toxicity to oral therapy, prevention of long-term toxicity, adherence issues, dysphagia). The aim of this cohort study is to define the medical reasons (viral failure vs. others) and the changes in GRT in interruption of cabotegravir-rilpivirine (CAB-RPV) regimen in an Italian cohort of PWH who were subjected to a L-A injectable regimen according to prescriptive indications.MethodsWe analyzed the data supplied by 9 infectious diseases units, where CAB-RPV regimen is available and administered, to make a descriptive analysis of the causes of interruption and the impact of genotyping drug resistance, when available.ResultsThe total of patients receiving CAB-RPV was 574; 51 interrupted the treatment. The average age of the patients of this cohort was 54 years and average BMI was 24,8 kg/m2 (BMI max 44.28 kg/m2). Before starting the injectables, 28 patients took a triple oral therapy (regimen mostly used: TAF/FTC/RPV), while 22 assumed a 2DR regimen (regimens mostly used: DTG/3TC-DTG/RPV); as a whole, 32 took an INSTI-based regimen. Only one PWH received a mono therapy. 13 had an oral lead in. As far as the genotypic resistance pattern, 33 patients had a GRT before starting CAB-RPV; 1 patient had documented resistance to NNRTI (138A, which is an important risk factor of viral failure of RPV), while none had INSTI resistance. We collected 11 documented viral failures. All of them carried out a GRT post VF; the results are shown in table 1. The other 40 patients interrupted L-A therapy for other reasons (local pain, adverse events, toxicity, patient‘s choice, drugs interactions). The mean time of duration of L-A regimen was 5.3 months: 5.8 (+/- 4.73 SD) months for patients with VF and 5.25 (+/- 4.13 SD) for patients who interrupted for other reasons, without statistical significance. OC-11 Table 1ConclusionsOne. seven% of our cohort experienced a VF; this result is coherent with the main studies evaluating a low failure rate of CAB-RPV. NNRTI and INSTI mutations that arose during L-A treatment were all associated with a documented VF. CAB-RPV L-A regimen was well-tolerated in our cohort. Respect of eligibility criteria and awareness of risk factors for VF plus strict monitoring of viro-immunological parameters are fundamental in reducing the risk of VF and the possible onset of new NNRTI/INSTI resistance mutations.

Hepatitis C Virus (HCV) infection natural history and management in Paediatric population are still debated. We retrospectively evaluated the outcome of a HCV pediatric population managed at the Pediatric Infectious Disease Unit of Luigi Sacco Hospital (Milan,Italy) from January 1997 to January 2022 (median follow-up 10 yrs) and we focused on the role of new drugs and transient elastography (TE). Fiftyseven patients were enrolled: 8 (14%) had a spontaneous clearance, 33 were treated (58%), 7 (12%) were not treated because they were under 12 years old and 9 were lost at follow-up. HCV RNA was undetectable in all treated patients at the end of therapy, after 12 weeks (SVR12) and for the rest of their follow-up. All patients treated underwent elastography before and one year after therapy. Median stiffness pre-therapy was 5.6 kPa, and 9 patients (16%) had abnormal TE (> 7 kPa, median 8.7 kPa). Median stiffness after treatment in the abnormal group was 6.8 KPa. DAAs is a safe and effective therapy for HCV chronic infection in Paediatric population. Liver elastography is normal in the majority of vertically infected children before 12 years, but, when abnormal, it shows a significant improvement after DAAs treatment. Further studies are needed to evaluate the role of elastography at diagnosis and follow-up in children. P-214 Table 1

BackgroundConstruction of suppressive regimens in individuals with MDR HIV-1 can be challenging and can impact long term outcomes. Optimal regimens can reduce relative risk of opportunistic infections and improve survival. For a regimen to be successful, it should have robust efficacy as well as a favourable drug interaction and safety profile. Here we assess similar populations with limited treatment options from the BRIGHTE study using FTR-based regimens and from the VIKING-3 study using DTG-based regimens.MethodsBRIGHTE was a Phase III international registrational study 2016- ongoing [n= 371; randomised cohort (RC), n=272; Non-randomised cohort n=99], in adults who were failing their current ARV regimen (HIV-1 RNA >400 c/mL) with ≤2 fully active and approved ARVs. Participants with 1 or 2 active ARVs entered the RC and received open-label FTR + optimised background treatment (OBT) after an 8-day blinded placebo-controlled period. In BRIGHTE RC, the most common agent in the initial OBT was DTG (84%) with the majority taking it twice daily (64%). VIKING-3 (n=183) was a single-arm (2011–2015), open-label phase III study in which therapy-experienced adults with INI-resistant virus received DTG 50 mg BID while continuing their failing regimen (without raltegravir or elvitegravir) through day 7, after which the regimen was optimized with ≥1 fully active drug and DTG continued. Virologic and immunologic responses were analysed by baseline (BL) demographics and disease characteristics.ResultsBRIGHTE participants were male (n= 290, 78%), median age 48 years and White (n=259, 70%). The observed antiviral response in BRIGHTE (RC) was 81% (<40 c/mL, n=128), and 88% (<400 c/mL, n=140). Mean CD4 increase from baseline was 204.7 cells/mm3, with a BL mean CD4 count 152.5 cells/mm3. VIKING-3 participants were predominantly male, (n=141, 77%), median age 48 years, and 71% (n=130) White. Antiviral response observed in VIKING-3 was 84% (<50 c/mL, n=101) and 93% (<400 c/mL, n=111) . Mean CD4 increase was 192 cells/mm3, with a BL mean CD4 count of 202 cells/mm3. Safety for participants across study populations were as follows BRIGHTE (RC); n=92 (34%) any serious adverse event (AE), n=57 (21%) any drug-related AE and n=7 (3%) AE leading to withdrawal or discontinuation; for VIKING-3, n=60 (33%) any serious AE, n=52 (28%) any drug-related AE and n=8 (4%) AE leading to withdrawal or discontinuation.ConclusionsDespite limited treatment options in individuals with MDR HIV-1 these data demonstrate that over 96 weeks both DTG (BID) and FTR-based regimens provide a robust viral suppression and CD4 T-cell improvement. Although differences exist in the baseline characteristics, there is more profound immunosuppression in the BRIGHTE population. These agents were commonly used together in the BRIGHTE study, engaging their different mechanisms of action. This data provides further support for effective agents for individuals living with multidrug-resistant HIV-1.

BackgroundLong-acting injectable (LAI) regimen with cabotegravir (CAB) and rilpivirine (RPV) has been recently approved as switch strategy for virologically suppressed people living with HIV (PLWH). The aim was to describe safety and efficacy of LAI regimen in a real-life context in PLWH followed at Modena Clinic.MaterialsRetrospective descriptive cohort study including PLWH switched to LAI CAB/RPV from January 2023 to February 2024. Demographic, clinical and HIV and HBV-related characteristics were collected. Virological failure (VF) was defined as 2 consecutive HIV-RNA>20 copies/ml or a single HIV-RNA>200copies/ml. Virological suppression (VS) was defined as HIV-RNA<20 copies/ml.ResultsSeventy-four PLWH were included with a median follow-up of 322 days (IQR 210–379): 62%males, 53 years(IQR 44–59), BMI 24 Kg/m2, HIV duration 14 years. Six individuals had no VS at switch (median 27copies/ml, IQR 21–78), of whom 3 gained VS at follow-up; twenty-three (31%) individuals used oral lead-in. Twenty-two (30%) had positive HBcAb titre at switch: among these 4(15%) presented non-protective (<10U/ml) or negative HBsAb titre and 7(30%) switched from tenofovir-based regimen; none of them had detectable HBV-DNA at baseline and follow-up.More than a half (62%) of the individuals reported side effects, injection-site pain was the most represented.One individual moved to another clinic, ten(13,5%) discontinued LAI (median time to discontinuation [MTD] 84 days, IQR 28–196): 5 because of side effects, one had pre-existing mutations for NNRTI at genotypic resistance test (GRT), 3 for patient-related logistic reasons. One PLWH experienced severe and prolonged injection pain after the first administration, leading to discontinuation, and contemporary VF (HIV-RNA 4230copies/ml) at 4 weeks. He was switched to the previous oral regimen and gained VS in 2 months. The GRT performed on plasma revealed the emergence of RAMs 181I and 190A for NNRTI, G140S and Q148H for INSTI, thus treatment was modified to DRV/c+DTG, with stable VS. In another subject, HIV-RNA at 8 months on LAI regimen was 7975copies/ml: he was switched to DRV/c/FTC/TAF rescue therapy; at the GRT on plasma mutations 138K for NNRTI and Q148R for INSTI. He did not report any side effect neither presented previous failure risk factors.ConclusionsLAI CAB/RPV regimen was safe and effective in our population. Side effects were present and led to treatment interruption in 10 cases, with prevalence similar to literature. None of the individuals with VF had baseline known risk factors for LAI CAB+RPV failure. In the first case, the significant pain could reflect incorrect injection procedure, leading presumably to inadequate drug concentration (although therapeutic drug monitoring was not performed). Thus, we highlight the importance of correct injection administration, fundamental to maintain adequate drug concentration and reduce VF risk. Further studies could help understanding more failure mechanisms.

ObjectivesAntibiotic resistance in gonorrhoea is of significant public health concern with the emergence of resistance to last-line therapies such as ceftriaxone. Despite around half of Neisseria gonorrhoeae isolates tested in the UK being susceptible to ciprofloxacin, very little ciprofloxacin is used in clinical practice. Testing for the S91F mutation associated with ciprofloxacin resistance is now available in CE-marked assays and may reduce the requirement for ceftriaxone, but many patients are treated empirically, or as sexual contacts, which may limit any benefit. We describe the real-world impact of such testing on antimicrobial use and clinical outcomes in people found to have gonorrhoea in a large urban UK sexual health clinic.MethodsMolecular ciprofloxacin resistance testing (ResistancePlus GC assay (SpeeDx)) was undertaken as an additional test after initial diagnosis (m2000 Realtime CT/NG assay (Abbott Molecular)) in those not already known to have had antimicrobial treatment. Data from a 6-month period (from March to September 2022) were analysed to determine treatment choice and treatment outcome.ResultsA total of 998 clinical samples tested positive for N. gonorrhoeae in 682 episodes of infection. Of the 560 (56%) samples eligible for resistance testing, 269 (48.0%) were reported as wild-type, 180 (32.1%) were predicted to be resistant, 63 (11.3%) had an indeterminate resistance profile, and in 48 (8.6%) samples, N. gonorrhoeae was not detected. Ciprofloxacin was prescribed in 172 (75%) of 228 episodes in which the wild-type strain was detected. Four (2%) of those treated with ciprofloxacin had a positive test-of-cure sample by NAAT, with no reinfection risk. All four had ciprofloxacin-susceptible infection by phenotypic antimicrobial susceptibility testing.ConclusionsIn routine practice in a large UK clinic, molecular ciprofloxacin resistance testing led to a significant shift in antibiotic use, reducing use of ceftriaxone. Testing can be targeted to reduce unnecessary additional testing. Longer term impact on antimicrobial resistance requires ongoing surveillance.

BackgroundHIV incidence among men who have sex with men (MSM) in sub-Saharan Africa (SSA) remains high compared with the general population. Many countries in the region still criminalise consensual homosexual relationships, and some are yet to adopt WHO-recommended interventions for MSM into national HIV policies. This study examines how HIV testing of adult MSM in SSA varies according to the legal climate and presence of targeted HIV policy using data from the cross-sectional 2019 Global LGBTI Internet Survey study.MethodsUsing data from 3191 MSM in 44 SSA countries, we assessed associations of legal climate and HIV policy with ever and recent HIV testing using linear ecological and logistic multilevel analyses. From the single-level analysis, we can compare our findings to previously reported data, then, extending to a two-level multilevel analysis, we account for the hierarchical structure of the population and simultaneously adjust for differences in context and composition in each country. We then test the sensitivity of our analyses to excluding countries from the model.ResultsWe find evidence that legalised same-sex relationships were associated with increased odds of ever testing (OR=2.00, 95% CI 1.04, 3.82) in multilevel analyses. We also find evidence of an association of targeted HIV policies with increased odds of ever testing (OR=2.49, 95% CI 1.12, 5.52). We did not find evidence of an association of the legal climate (OR=1.01, 95% CI 0.69, 1.46) and targeted HIV policies (OR=1.26, 95% CI 0.78, 2.04) with recent testing.ConclusionsThis study suggests elimination of discriminatory laws and policies might be important for increasing HIV status awareness of MSM, an important first step in epidemic control. Additionally, we highlight heterogeneity between South Africa and other SSA countries, which has implications for studying SSA countries as a homogeneous group.