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Letter to the Editor: Real-Life Experience of Long-Acting Cabotegravir-Rilpivirine Combination in a Person Living with HIV with Detectable Viremia: A Case Report

Background: First-line integrase strand transfer inhibitor-based regimens have become commonly used in clinical practice over the last decade. This study aimed to analyse and compare the efficacy and safety of bictegravir (BIC) and dolutegravir (DTG) when prescribed in association with emtricitabine/tenofovir alafenamide (FTC/TAF) as part of a first-line regimen for the treatment of human immunodeficiency-1 (HIV-1) infection.Methods: Treatment-naive people living with HIV (PLWHIV) starting a first-line regimen with either BIC/FTC/TAF (BIC group) or FTC/TAF + DTG (DTG group) were analysed. Snapshot analyses were performed after 24 and 48 weeks to evaluate virological efficacy. In addition, differences in the rate of treatment discontinuation (TD) between the two groups were evaluated using the Kaplan-Meier method and the log rank test.Results: Data from 327 PLWHIV were analysed: 140 in the DTG group and 187 in the BIC group. At 48 weeks, 90.0% of individuals in the DTG group and 86.7% of those in the BIC group achieved HIV -RNA < 50 copies/mL. In total, 88 and 38 cases of TD were observed in the DTG group and BIC group, respectively. The estimated probability of maintaining the study regimen at week 48 was 59.5% in the DTG group and 84.2% in the BIC group. Analysing changes in immunological parameters after 48 weeks, median improvements of + 169 cell/mm(3) ( P < 0.001) and + 233 cell/mm(3) ( P < 0.001) were observed in the DTG group and the BIC group, respectively.Conclusions: Both BIC and DTG, in combination with FTC/TAF, show promising efficacy and safety as first-line strategies in clinical practice, with favourable immunological recovery even in the short term.

Our aim was to assess the association between different types of stigma and physical, behavioural and emotional wellbeing, and to evaluate whether these associations were mediated by the level of social support, age, education, sex and time from HIV diagnosis in an Italian cohort of people living with HIV (PLWH). We enrolled 96 PLWH and had them complete a cross-sectional online survey that included the "HSS-12", the "SF-12" and the "DASS-21". We performed linear regression analyses to explore the associations between the HSS-12 scores and cART adherence, viral load, SF-12 and DASS-21 scores, and a mediation analysis to identify mediators in the significant associations. We showed that higher level of depression and worse perception of mental health were significantly associated with higher HSS-12 "personalised stigma" (p = .009, p = .020) "disclosure concerns" (p = .012, p = .039), "concerns about public attitudes" (p =.007, p = .005) and "negative self-image" scores; (p < .001, p = .001); worse perception of physical health status was associated with higher HSS-12 "personalised stigma" scores (p = .018); higher level of anxiety and stress were associated with higher "negative self-image" scores (0.001 and p < .001). The association between higher HSS-12 "negative self-image" and higher levels of depression, anxiety and stress were mediated by lower age (a*b = +0.10; a*b = +0.12; a*b = +0.11). This study may have important implications for clinical practice as it contributes to understanding the characteristics and consequences of HIV-related stigma in a population of PLWH with excellent viroimmunological status and therapeutic adherence.

Background: Lamivudine + dolutegravir maintenance dual therapy (DT) could be less effective than 3-drug therapy (TT) in the context of resistance-associated mutations to nucleoside reverse transcriptase inhibitors (NRTIs). The ARCA database was queried to test this hypothesis with a trial emulation strategy. Methods: People with HIV taking 2 NRTIs plus a protease inhibitor or a non-NRTI who switched to DT or dolutegravir-based TT were followed up from the first HIV RNA <50 copies/mL (baseline) to virologic failure (VF; ie, 2 consecutive HIV RNA ≥50 copies/mL or 1 HIV RNA ≥200 copies/mL). Those switching to DT within 6 months were assigned to the treatment arm and all other patients to the control arm. Each participant was also cloned, assigned to the opposite strategy, and censored at the time of deviation from that strategy. Using inverse probability of censoring weight Cox regression models, we calculated hazard ratios of VF for DT vs TT stratified for the presence of resistance-associated mutations. Results: Overall 626 people were analyzed: 204 with DT and 422 with TT (73% men; mean age, 44 years). Ten and 31 VFs occurred with DT and TT, respectively, over a median 5.8 years. When compared with a fully active TT, the DT had similar efficacy (adjusted hazard ratio, 0.88; 95% CI, .29-2.61; P = .812) when full susceptibility was confirmed at historical genotype. When previous M184V/I was present in both groups, the risk of VF was higher for DT vs TT but was not statistically significant (adjusted hazard ratio, 3.06; 95% CI, .45-20.84; P = .252). Conclusions: DT was not associated with a significantly higher risk of VF than dolutegravir-based TT.

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Evidence accumulated during past years confirm that people living with HIV (PLWH) still have to deal with comorbidities and chronic complications that can increase physical and psychological issues and can affect daily functioning, quality of life and mental health. Moreover, during the COVID-19 pandemic PLWH proved to be a population at increased risk of psychological distress. We explored the ongoing issues and the characteristics of the mental health interventions for which a cohort of Italian PLWH interacted with a psychologist over the past five years. We analysed a dataset that included 61 PLWH who underwent a psychological intervention between 2018 and 2022. We compared different frequencies in characteristics of mental health interventions according to different demographic and clinical variables, psychopathological symptoms and time of the request for intervention. We showed that psychopathological symptoms most frequently reported by patients were anxiety (55.7%), and depression (49.2%). Furthermore, we reported that most our patients undertook occasional psychological support meetings (31%), sought an intervention after the outbreak of the COVID-19 pandemic (62.3%) and complained about disclosure issues (48.5%). Disclosure issues were mainly reported by younger PLWH (p = 0.002) with a shorter disease (p = 0.031) and treatment history (p = 0.032), and higher interpersonal sensitivity (p = 0.042). It seems fundamental to integrate psychological interventions into the care of PLWH, to give particular attention to PLWH with risky demographic, clinical and mental health factors and to pay special attention to emergency conditions (such as the COVID-19 pandemic) and the most widespread issues to create ad hoc interventions.

Background Blood telomere length (BTL) is a validated biomarker of aging. ART reduces immunosenescence and has benefits in terms of BTL in people living with HIV (PLWH). However, it has also been observed that ART containing NRTIs, such as tenofovir or abacavir, which are potent inhibitors of human telomerase activity in vitro, might negatively affect BTL. Here we investigated the effects on BTL 1 year after switching to a dual therapy (DT) with dolutegravir + lamivudine versus maintaining a standard triple therapy (TT) with a two-NRTI backbone and an anchor drug. Methods This was a longitudinal, prospective, matched, controlled study that included virologically suppressed adults on stable three-drug ART who either switched at baseline (BL) to DT or maintained TT. The DT and TT groups were 1:1 matched for age, sex, years since HIV diagnosis, years on ART and anchor drug. BTL was assessed by a monochrome multiplex qPCR at BL and after 48 weeks (W48). Results We enrolled 120 PLWH, i.e. 60 participants in each group. At BL, the BTL means were comparable between the two groups (P = 0.973). At W48, viro-immunological status was stable and an overall increase in the mean BTL was observed, i.e., +0.161 (95%CI, 0.054-0.268) (P = 0.004). However, the within-group analysis showed a significant mean BTL gain in the DT group (P = 0.003) but not in the TT group (P = 0.656). Conclusions In this setting of virologically suppressed PLWH, simplifying to dolutegravir + lamivudine was associated with a higher gain in BTL than maintaining triple therapy after the 1 year follow-up. These findings suggest that as a simplification strategy dolutegravir + lamivudine might have a positive effect on BTL.

Thanks to the modern ARV regimens and the fact that the morbidity and mortality of metabolic syndrome increases with age, clinicians are continuously researching effective and safe antiretroviral regimens with low impact on the lipid profile. Doravirine (DOR) is the latest non-nucleoside reverse-transcriptase inhibitor (NNRTI) that shows long-term safety and tolerability and a favorable lipid profile. The aim of this study is to assess the impact of DOR-based three-drug regimens on the lipid profile in clinical practice. We retrospectively analyzed a cohort of 38 treatment-experienced, virologically suppressed people living with HIV (PLWH) switching to this regimen, following the eligibility criteria. We carried out comparison analysis of immunological and metabolic parameters between baseline and 48 weeks of follow up. In our cohort of treatment-experienced, virologically suppressed PLWH, three-drug regimens with DOR showed good efficacy and a positive profile on lipid metabolism at 48 weeks of follow up.

Neuropsychiatric symptoms have been reported in patients receiving dolutegravir, a known inhibitor of the renal and neuronal-expressed organic anion transporter 2 (encoded by SLC22A2 gene). The effect of the genetic variant SLC22A2 808C>A on dolutegravir discontinuation was assessed and analyzed by real-time PCR. We enrolled 627 participants: CA/AA carriers showed a higher prevalence of pre-existing psychiatric comorbidities and use of antidepressants. After 27.9 months, 108 participants discontinued dolutegravir, 64 for neuropsychiatric symptoms. Patients with pre-existing psychiatric comorbidities were at higher risk of dolutegravir discontinuation, while patients carrying the SLC22A2 CA/AA genotype were not. Combining the two variables, an opposite effect of SLC22A2 variants according to pre-existing psychiatric disorders was observed. Using multivariate Cox models, the combined variable pre-existing psychiatric comorbidities/SLC22A2 variants and the use of non-tenofovir alafenamide containing antiretroviral regimens were predictors of dolutegravir discontinuation for neuropsychiatric symptoms. Within 30 days, the majority of participants had a complete resolution of symptoms (61.8%), while 32.7% and 5.5% had partial or no change after dolutegravir discontinuation, respectively. Discontinuation of dolutegravir for neuropsychiatric symptoms was not uncommon and more frequent in participants with pre-existing psychiatric disorders. We described an interaction between SLC22A2 genetic variant and psychiatric comorbidities. In 38.2% of patients, a complete neuropsychiatric symptoms resolution was not observed after dolutegravir discontinuation suggesting the involvement of additional factors.

Based on the available literature, women living with HIV (WLWH) seem to show greater cognitive and emotional disadvantages than men living with HIV (MLWH). Our aim was to compare the cognitive performance of MLWH and WLWH in an Italian cohort of People Living With HIV (PLWH) and to analyse factors potentially contributing to sex differences in cognitive function. We ran a retrospective, cross-sectional analysis of a monocentric dataset of PLWH who were administered a standardized neuropsychological test battery (SNB) during routine clinical care. We enrolled 161 Italian PLWH who are on combined antiretroviral therapy (cART): 114 (70.8%) MLWH and 47 (29.2%) WLWH. Global cognitive performance (composite z score) (GCP) was significantly higher in MLWH than WLWH [mean 0.19 (SD 0.85) vs − 0.13 (SD 0.96); p = 0.039]. Moreover, WLWH obtained significantly higher scores on the Zung Depression Scale than MLWH [mean 41.8 (SD 10.9) vs 36.7 (SD 9.2); p = 0.003]. However, there was no statistically significant direct effect between male sex and better GCP (p = 0.692) in the context of a mediation model. On the contrary, the associations between male sex and better GCP were mediated by higher level of education (a*b = + 0.15, Bootstrap CI95 = 0.05 and 0.27) and a lower Zung depression score (a*b = + 0.10, Bootstrap CI95 = 0.02 and 0.21). In conclusion, the global cognitive performance of WLWH is lower than that of MLWH. However, other demographic and clinical factors besides sex might help explain differences in their neurocognitive functions and make it possible for us to monitor them and identify those patients most in need.

Purpose: The pandemic diffusion of Coronavirus Disease 2019 (COVID-19) has highlighted significant genderrelated differences in disease severity. Despite several hypotheses being proposed, how the genetic background of COVID-19 patients might impact clinical outcomes remains largely unknown. Methods: We collected blood samples from 192 COVID-19 patients (115 men, 77 women, mean age 67 +/- 19 years) admitted between March and June 2020 at two different hospital centers in Italy, and determined the allelic distribution of nine Single Nucleotide Polymorphisms (SNPs), located at the 3 ' Regulatory Region (3 ' RR)-1 in the immunoglobulin (Ig) heavy chain locus, including *1 and *2 alleles of polymorphic hs1.2 enhancer region. Results: In COVID-19 patients, the genotyped SNPs exhibited strong Linkage Disequilibrium and produced 7 specific haplotypes, associated to different degrees of disease severity, including the occurrence of pneumonia. Additionally, the allele *2, which comprises a DNA binding site for the Estrogen receptor alpha (ER alpha) in the polymorphic enhancer hs1.2 of 3 ' RR-1, was significantly enriched in women with a less severe disease. Conclusions: These findings document genetic variants associated to individual clinical severity of COVID-19 disease. Most specifically, a novel genetic protective factor was identified that might explain the sex-related differences in immune response to Sars-COV-2 infection in humans.

Aim of this study is to assess the impact of doravirine (DOR)-based regimens on cardiovascular risk in treatment-experienced people living with HIV (PLWHIV). We retrospectively analyzed a cohort of 40 treatment-experienced PLWHIV switching to a DOR-based three-drug regimen, evaluating 10-year risk of manifesting clinical cardiovascular diseases (CD) through the Framingham Risk Score at baseline, 12, and 24 weeks of follow-up. At baseline, median predicted 10-year risk of cardiovascular disease (10Y-CD) was 8.0% (interquartile range 4.0-13.0). After 12 weeks, we observed a significant reduction in 10Y-CD (mean decrease -2.21, p = .012); similarly, we observed a nonsignificant reduction at week 24 (p = .336). Regarding metabolic parameters, after 24 weeks we observed a significant reduction in total cholesterol (median change -8.8 mg/dL, p = .018), low-density lipoprotein cholesterol (median -9.5 mg/dL, p = .007), and triglycerides (median -19.8 mg/dL, p < .001). Our results show a favorable metabolic impact of DOR-based regimens along with a promising reduction in 10-year risk of cardiovascular disease.

During the COVID-19 pandemic, people living with HIV (PLWH) could have had to face problems with treatment adherence because of the difficulty of accessing services connected with antiretroviral therapy (ART) dispensation, which could have undermined their health. In this article, we described, over the period 2015-2020, both the activities of our home care assistance unit, the "Unita di Trattamento Domiciliare (UTD)", and the characteristics of the comorbid HIV patients followed-up. To determine whether the COVID-19 pandemic affected this service, we compared the number/type of services provided in 2020 with those provided in the preceding 5 years, i.e., 2015-2019. We also compared the proportion of monthly interventions carried out in 2018, 2019 and 2020. We found comparable values with some differences in the types of performances due to the heterogeneity of the population and their medical assistance needs. We also observed a stable viro-immunological status of the patients. All of these data suggest that the UTD was consistently active during the lockdown months and pandemic waves preventing therapy discontinuation, and was able to maintain optimal control of patients' HIV infections.

The care engagement of people living with HIV (PLWH) measured with the patient health engagement (PHE) model and its association with HIV-related internalized stigma are not well established. Indeed, currently there are no data yet about the engagement of PLWH measured with the PHE model. This study aimed to evaluate the effects of HIV-related internalized stigma on care engagement and mental health and to fill the lack of data on PHE model applied to PLWH. We found that the internalized stigma score was significantly higher for PLWH (n=82) in worse care engagement phase and both higher internalized stigma scores and worse engagement were associated to major depression symptoms.In conclusion, our findings describe for the first time the engagement in care of PLWH measured with PHE and highlight the importance of PLWH support to find strategies to cope stigma-related stress and optimize their care engagement.