One Year of Long-Acting Cabotegravir and Rilpivirine in People With Human Immunodeficiency Virus and Long Exposure to Antiretroviral Therapy: Data From the SCohoLART Study.

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.

Outcome of Darunavir-Cobicistat-Based Regimens in HIV-Infected People Who Have Experienced Virological Failure.

Objective: To evaluate the virological outcome of darunavir-cobicistat (DRVc)-based regimens in adults living with HIV who had experienced virological failure (VF) on any previous drug combination. Methods: This was a retrospective cohort study (CSLHIV Cohort) of adults living with HIV who started a DRVc-based regimen with HIV-RNA >50 copies/mL after VF on any previous drug combination. Data on demographics, antiretroviral treatment since HIV diagnosis, and immunological and metabolic parameters from baseline (start of DRVc) to 48 weeks were analyzed in order to assess the cumulative proportion of those who achieved virological success (VS), defined as at least one instance of HIV-RNA <50 copies/mL within 12 months from baseline. Follow-up lasted from the start of the DRVc-based regimen (baseline) to the first instance of HIV-RNA <50 copies/mL, last available visit, or loss to follow-up or death, whichever occurred first. Univariate and multivariate Cox proportional-hazard regression models were used to identify baseline factors associated with VS. Results: A total of 176 individuals were included, and 120 (68.2%) achieved <50 HIV-RNA copies/mL within 12 months since baseline. On multivariate analysis, baseline HDL cholesterol was independently associated with the occurrence of VS (adjusted HR 1.021, 95% CI 1.004-1.038; p=0.014). Among the 120 subjects with VS, 27 (22.5%) had had VF during a median follow-up of 20.8 months since the first undetectable HIV-RNA. Resistance testing after VF was available in two cases, which harboured the HIV variant-bearing protease inhibitor-resistance mutations D30N, I50V, and N88D. During a median follow-up of 38.4 months, 65 of 176 (36.9%) individuals discontinued DRVc for any reason (37 of 120, 30.8%) and achieved VS vs. 28 of 56 (50%) without VS (p=0.019). Time to discontinuation was longer in people with VS (41.5 vs. 23.0 months, p=0.0007). No statistically significant changes were observed in immunological or lipid profiles during follow-up. Conclusion: Most individuals in this study achieved VS within 12 months from the beginning of a DRVc-based regimen; therefore, this treatment represent a viable option for people who have experienced VF on other regimens.

High Propensity to Switch to Long-acting Injectable HIV PrEP with Cabotegravir in a Cohort of Oral PrEP Experienced Men who Have Sex with Men in Italy.

Aim was to investigate the propensity to switch to long-acting injectable HIV pre-exposure prophylaxis (PrEP) with cabotegravir among oral PrEP-experienced men who have sex with men. Out of 377 PrEP users, 325 (86.2%) were interested (would like = 210) or considering (would consider = 115) switch to long-acting PrEP. At multivariable analysis, the odds ratio of interest in long-acting PrEP in non-adherent vs. adherent individuals to oral PrEP was 5.03 (95%CI = 1.73-14.61,p = 0.003) and of consideration 1.63 (95%CI = 0.51-5.23,p = 0.410). We observed very high propensity to switch to long-acting PrEP, particularly among non-adherent users. Rapid availability of long-acting PrEP might address unmet needs of PrEP users in Italy.

Anastrozole as a therapeutic option for gynecomastia in a person receiving antiretroviral therapy: Case report.

A middle-aged Caucasian man living with HIV, clinically stable (viral load <20 copies/mL) on injectable antiretroviral cabotegravir plus rilpivirine every 2 months presented with a 6-month history of bilateral enlargement of the breasts associated with pain. His hormonal profile was normal, and no other underlying cause was identified. He was diagnosed with idiopathic gynecomastia. Tamoxifen is an anti-oestrogen recommended for gynecomastia and has been described in people living with HIV but can potentially induce the activity of cytochrome P450 3A4 (CYP3A4), reducing rilpivirine concentrations, which consequently may cause virological failure and resistance. This is the same for other antiretroviral agents majorly induced by CYP3A4. To date, there have been no reported cases of using anastrozole as a treatment for gynecomastia in people living with HIV or of its co-administration with antiretroviral. We describe the use of an aromatase inhibitor instead of tamoxifen in a person living with HIV, diagnosed with gynecomastia.

Mpox DNA clearance in semen over 6-month follow-up.

Sexual intercourse is a well-established way of transmission of mpox infection. However, it is still uncertain whether semen may represent a viral reservoir. The aim of the study was to evaluate the clearance of viral DNA in semen samples from individuals diagnosed with mpox infection over 6-month follow-up. This prospective, observational, single-center study was conducted at IRCCS San Raffaele Scientific Institute, Milan, Italy, between May and October 2022 in 140 individuals who attended Sexual Health Clinic and diagnosed with mpox infection. Semen samples were collected and analyzed by real-time polymerase chain reaction assays. The baseline collection was performed in 64 (46%) of 140 men diagnosed with mpox infection. The viral DNA was detected in 43 (67%) with median cycle threshold (Ct) 34 (interquartile range [IQR] 31-36). The research was repeated in 32 (74%) and viral DNA clearance was observed in all within 6 months in a median time of 10.5 days (IQR 7-33). Viral clearance occurred in all tested individuals, mostly within 2 weeks since the first positive test. These findings suggest a transient presence of viral DNA in semen and do not support the hypothesis of reservoir. More studies on mpox DNA detection in semen with viral culture and extended follow-up are needed.

Mpox Outbreak 2022: A Comparative Analysis of the Characteristics of Individuals Receiving MVA-BN Vaccination and People Diagnosed with Mpox Infection in Milan, Italy.

Mpox caused a worldwide outbreak in 2022, disproportionately affecting MSM reporting high-risk sexual behaviors. The aim of this study was to compare the characteristics of people receiving MVA-BN vaccination with those of individuals diagnosed with mpox to guide future vaccination policies. This was a retrospective study on people with mpox infection or vaccination at San Raffaele Scientific Institute, Milan, Italy, from May to November 2022. Characteristics were compared using Mann-Whitney or chi-square/Fisher's exact tests; multivariable logistic regression and classification tree analysis were applied. Overall, 473 vaccinated individuals and 135 with mpox were included; 472/473 and 134/135 were MSM. People with mpox were more frequently living with HIV (48.9% vs. 22.4%, p < 0.001), had ≥1 previous STI (75.6% vs. 35.7%, p < 0.001), were chemsex users (37.8% vs. 6.34%, p < 0.001), were with a higher number of partners (23.0% vs. 1.69%, p < 0.001), and had engaged in group sex (55.6% vs. 24.1%, p < 0.001). At multivariable analysis, PLWH (aOR = 2.86, 95%CI = 1.59-5.19, p < 0.001), chemsex users (aOR = 2.96, 95%CI = 1.52-5.79, p = 0.001), those with previous syphilis (aOR = 4.11, 95%CI = 2.22-7.72, p < 0.001), and those with >10 partners (aOR = 11.56, 95%CI = 6.60-21.09, p < 0.001) had a higher risk of infection. This study underscores the importance of prioritizing MSM with prior STIs and multiple partners as well as chemsex users in vaccination policies to curb mpox spread. A destigmatized assessment of sexual history is vital for comprehensive sexual health strategies.

Viral blips and virologic failures following mpox vaccination with MVA-BN among people with HIV.

OBJECTIVES: The study aim was to evaluate whether mpox vaccination with modified vaccinia Ankara-Bavarian Nordic (MVA-BN) may be associated with viral blips or confirmed virologic failures (CVF) in people with HIV (PWH) receiving antiretroviral therapy and the associated factors. DESIGN: PWH who received MVA-BN, with HIV-RNA less than 50 copies/ml, and CD4 + lymphocytes at least 200 cells/µl in the 6 months prior to vaccination and at least 1 HIV-RNA determination within 3 months from vaccination. METHODS: The primary outcome was occurrence of viral blips (1 HIV-RNA ≥50 copies/ml) and CVF (1 HIV-RNA ≥1000 copies/ml or ≥2 consecutive HIV-RNA ≥50 copies/ml) following MVA-BN. Changes in CD4 + and CD4 + /CD8 + were secondary outcomes. Residual viremia was defined as detectable HIV-RNA less than 50 copies/ml. PWH already vaccinated against smallpox received single-dose MVA-BN. Mann--Whitney rank-sum test or chi-square/Fisher's test applied. RESULTS: Overall, 187 PWH were included: 147 received two doses of MVA-BN, 40 single-dose. Six viral blips [incidence rate = 1.59/100-person months of follow-up (PMFU), 95% confidence interval (95% CI) = 0.58-3.47], and three CVFs [incidence rate = 0.80/100-PMFU (95% CI = 0.16-2.33)] were observed. Two CVFs occurred at second dose with presence of detectable HIV-RNA following first one, with high compliance to antiretroviral therapy (ART). PWH with viral blips or CVFs had, prior to first vaccination, more frequently residual viremia [77% ( n  = 7) versus 35% ( n  = 62), P  = 0.01]. No differences in ART ( P  = 0.42) and number of MBA-BN doses ( P  = 0.40) was found. In two cases of CVFs, ART was changed; all VBs resolved within 1 month. CONCLUSION: Although rare, viral blips and CVFs following MVA-BN vaccination among PWH receiving ART were identified. Close monitoring of HIV-RNA during mpox vaccination should be encouraged.

Treatment success of rescue regimens after dual therapy failure in people living with HIV in a real-life setting.

OBJECTIVES: Few data on management of two-drug regimen (2DR) failure in people living with HIV (PLWH) are available. METHODS: Retrospective study of treatment-experienced PLWH on a 2DR who experienced virological failure (VF) [two consecutive viral loads (VLs) ≥50 copies/mL, single VL ≥1000 copies/mL, or antiretroviral therapy (ART) switch after single VL ≥50 copies/mL with previous blips] or discontinuation for toxicity (baseline). Integrase strand transfer inhibitor (INSTI)-based [one INSTI plus one nucleoside reverse transcriptase inhibitor (NRTI) (n = 78) or one non-NRTI (n = 20)] or boosted protease inhibitor (PI/b)-based [one PI/b plus one NRTI (n = 116) or one INSTI (n = 12)] 2DRs were included. Probabilities of treatment success (TS), VF and discontinuation for any other cause of rescue regimens were estimated by Kaplan-Meier curves. A stepwise Cox model was performed to assess predictors of TS. RESULTS: Overall, 226 PLWH were evaluated: at baseline, 144 individuals discontinued 2DR for toxicity and 82 had VF [median viraemia 81 (63-212) copies/mL]; 171 switched therapy (49.7% to triple regimen, 40.9% to different 2DR), while 55 (exclusively with VF) maintained failing regimens. Probabilities of 12- and 24-month TS were 75.6% and 64.7%, respectively. Higher TS probabilities were observed in individuals who switched ART at 2DR failure (P = 0.003) and PLWH who discontinued 2DR for toxicity (P = 0.008). Therapy switch was the only predictor of TS (P = 0.002). CONCLUSIONS: Overall probability of rescue regimens' TS introduced after 2DR failure is good. Prompt ART switch after 2DR failure is advisable.

Viral Hepatitis and Human Papillomavirus Vaccination During HIV Pre-Exposure Prophylaxis: Factors Associated With Missed Vaccination.

BACKGROUND: We evaluated factors associated with lack of triple vaccination (hepatitis A virus [HAV], hepatitis B virus [HBV], and human papillomavirus [HPV]) among men who have sex with men using pre-exposure prophylaxis (PrEP). SETTING: PrEP users at the San Raffaele Scientific Institute, Italy, with ≥1 follow-up visit (May 2017-2022). METHODS: Participants were considered protected if (1) before PrEP access: positive serology (IgG-HAV+, hepatitis B surface antigen >10 mUI/mL) or vaccination history was recorded and (2) after starting PrEP: ≥1 dose of each vaccination was administered. Individuals were considered fully protected if they received the following before/during PrEP access: HAV vaccination/infection, HBV vaccination/infection, and HPV vaccination. χ 2 and Kruskal-Wallis tests were used to compare characteristics of those fully, partially, and not protected. Factors associated with the lack of triple vaccination were assessed by using multivariable logistic regression and classification tree analysis. RESULTS: Overall, 473 men who have sex with men were considered: 146 (31%) were fully protected, 231 (48%) partially, and 96 (20%) were not. Daily-based PrEP users (fully: 93, 63.7%; partially: 107, 46.3%; and not protected: 40, 41.7%; P = 0.001) and those with a sexually transmitted infection at the first visit (43, 29.5%; 55, 23.8%; 15, 15.6%; P = 0.048) were more frequently fully protected. At multivariable analysis, the odds of lack of triple vaccination was lower among daily-based users (adjusted odds ratio = 0.47, 95% confidence interval = 0.31-0.70, P < 0.001). Classification tree analysis showed that among daily-based users, with sexually transmitted infection prior and at the first PrEP visit, there was a lower chance of lack of triple vaccination ( P = 44%). CONCLUSIONS: Strategies targeting PrEP users at risk of missing HAV, HBV, and HPV vaccinations need to be implemented, focusing mostly on event-based users.

Human Monkeypox Experience in a Tertiary Level Hospital in Milan, Italy, between May and October 2022: Epidemiological Features and Clinical Characteristics.

BACKGROUND: Monkeypox virus (mpxv) started to spread to Europe and North America at the beginning of the current outbreak in May 2022, and the World Health Organization (WHO) declared Human Monkeypox (mpox) as a public health emergency of international concern (PHEIC) in July 2022. The aim of this observational analysis is to describe demographical data, symptoms presentation and clinical course till outcome of individuals diagnosed with mpox, between May and October 2022, at our open-access Sexual Health Clinic in IRCCS San Raffaele Hospital in Milan, Italy. METHODS: Among people who accessed our Sexual Health Clinic, we considered, as suspected diagnosis of mpox, individuals with consistent symptoms and epidemiological criteria. Following the physical examination, oropharyngeal, anal, genital and cutaneous swabs, plus plasma, urine and seminal fluid were collected as biological materials to detect mpxv DNA. We also performed a screening for sexually transmitted infections (STIs). RESULTS: Overall, 140 individuals with mpox were included in this study. Median age was 37 (interquartile, IQR 33, 43) years old. Males were 137 (98%) and men who have sex with men (MSM) were 134 (96%). As risk factors, we detected travels abroad in 35 (25%) individuals and close contact with mpox cases in 49 (35%). There were 66 (47%) people living with HIV (PLWH). Most frequent symptoms were fever (59%), lymphadenopathy (57%), cutaneous (77%), genital (42%), anal (34%) and oral (26%) lesions, proctitis (39%), sore throat (22%) and generalized rash (5%). At mpox diagnosis, we also observed N. gonorrhoeae in 18 (13%) cases, syphilis in 14 (10%) and C. trachomatis in 12 (9%). Two (1%) people received a concomitant diagnosis of HIV infection. We attended to 21 (15%) complications, with nine (6%) cases of hospitalization including six (IQR 3,7) median hospital days. Forty-five (32%) patients were treated with non-steroidal anti-inflammatory drugs (NSAIDs), 37 (26%) with antibiotics and eight (6%) with antiviral drugs. CONCLUSIONS: Similarly to other international cohorts, sexual transmission was most frequently present, and concomitant STIs were common. Symptoms were heterogenous, self-resolving and responsive to therapy. Hospitalization was necessary in few patients. There is uncertainty about the future development of mpox and further studies (e.g., potential disease reservoirs, other possible means of transmission, predictors of severe disease) are still needed.

Use of Pembrolizumab for Treatment of Progressive Multifocal Leukoencephalopathy in People Living with HIV.

Progressive Multifocal Leukoencephalopathy (PML) is a demyelinating disease occurring in advanced HIV infection, caused by the reactivation of poliomavirus JC (JCV). The use of pembrolizumab for treatment is based on the inhibition of programmed cell death protein 1 (PD-1), potentially improving the anti JCV-specific response. We used pembrolizumab with combined antiretroviral treatment (cART) on a compassionate-use basis. At each administration, clinical evaluation, MRI and laboratory testing, including CD3, CD4, CD8, PD-1 markers, HIV-RNA and JCV-DNA in cerebrospinal fluid (CSF)/plasma pairs, were performed. The JCV-specific T cell response was analysed by Elispot assay. This study included five HIV patients: four male, median age 43 years (29-52), median CD4 and CD8 count 150 (15-158) and 973 (354-1250) cell/mm3, respectively; median JCV-DNA and HIV-RNA in CSF/plasma pairs 9.540/1.503 cps/mL and 2.230/619 cp/mL, respectively. Overall, patients received between two and seven doses of pembrolizumab. After treatment, we observed JCV-DNA reduction and PD-1 down-regulation both in CSF and in plasma (high in circulating CD4 and CD8 at baseline), which remained stable at low levels in all patients. Three out of five patients showed stability of clinical picture and neuroimaging, while two others died. More data are needed in order to identify predictors of response to therapy.