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Vicarious stigma shows how indirect stigmatizing experiences can lead people living with HIV (PLWH) to feel discriminated against. We enrolled 350 PLWH, who were administered a 17-item questionnaire to investigate a subjective experience of stigma experienced in the hospital care setting. We found that at least once 215 PLWH (61.4%) did not want the HIV exemption indicated on the prescription for a specialist medical visit, 232 PLWH (66.3%) never used their HIV-related exemption to make a specialist medical visit, 230 PLWH (65.7%) avoided undergoing a medical assessment outside the infectious disease clinics and 241 patients (68.9%) felt unwelcome during a specialist medical visit. Moreover, 241 patients (61.1%) had heard at least once stories of health workers who did not want to touch PLWH, 213 patients (60.9%) had heard stories at least once of PLWH who had been mistreated by hospital staff, 180 patients (51.4%) had at least once heard stories about PLWH being refused treatment and services and 257 patients (73.4%) had at least once heard stories about health workers talking publicly about PLWH. This is a little explored area, especially regarding the vicarious stigma faced by PLWH. Our findings indicate the importance of combating HIV-related stigma for the wellbeing of PLWH.

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., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: AB received fee for advisory board by ViiV Healthcare, personal fee by Janssen Cilag. SDG received speakers’ honoraria and support for travel to meetings from Gilead, Janssen-Cilag (JC), Merck Sharp & Dohme (MSD) and ViiV Healtcare. AC received travel grants and confress’ fee from ViiV Healtcare. All other authors: none to declare.

Regimens containing darunavir are one of the first one with two drugs that demonstrated good efficacy as a simplification strategy. We wanted to describe the characteristics of patients followed in our center on a dual therapy regimen containing darunavir evaluating the metabolic aspects during follow-ups. We collected data from 208 patients switching to lamivudine plus darunavir with either ritonavir or cobicistat between 2010 and 2019. In all patients we found an increase in low-density lipoprotein (LDL), with no rising in creatinine, total cholesterol, or triglycerides. Twenty-five patients reached 120 weeks of follow-up. In these patients, no significant metabolic changes were described without concomitant treatment with drugs for dyslipidemia. These regimens seem to be more tolerable in metabolic profile compared with the data concerning three-drug therapies, leading only to a slight increase in LDL. The main reason for discontinuation was for a single-tablet therapy. None of the patients started treatment for dyslipidemia.

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., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

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.

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.

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.

Background: Dolutegravir (DTG)-based first-line regimens have shown superior efficacy versus darunavir (DRV)-based ones in randomized trials. We compared these two strategies in clinical practice, particularly considering the role of pre-treatment drug resistance mutations (DRMs) and of the HIV-1 subtype., Materials and Methods: The multicenter Antiretroviral Resistance Cohort Analysis (ARCA) database was queried to identify HIV-1-positive patients starting a first-line therapy with 2NRTIs plus either DTG or DRV between 2013 and 2019. Only adult (≥18 years) patients with a genotypic resistance test (GRT) prior to therapy and with HIV-1 RNA ≥1000 copies/mL were selected. Through multivariable Cox regressions, we compared DTG- versus DRV-based regimens in the time to virological failure (VF) stratifying for pre-treatment DRMs and the viral subtype., Results: A total of 649 patients was enrolled, with 359 (55.3%) and 290 (44.7) starting DRV and DTG, respectively. In 11 months of median follow-up time, there were 41 VFs (8.4 in 100 patient-years follow-up, PYFU) and 15 VFs (5.3 per 100 PYFU) in the DRV and DTG groups, respectively. Compared with a fully active DTG-based regimen, the risk of VF was higher with DRV (aHR 2.33; p = 0.016), and with DTG-based regimens with pre-treatment DRMs to the backbone (aHR 17.27; p = 0.001), after adjusting for age, gender, baseline CD4 count and HIV-RNA, concurrent AIDS-defining event and months since HIV diagnosis. Compared with patients harboring a B viral subtype and treated with a DTG-based regimen, patients on DRV had an increased risk of VF, both in subtype B (aHR 3.35; p = 0.011), C (aHR 8.10; p = 0.005), CRF02-AG (aHR 5.59; p = 0.006) and G (aHR 13.90; p < 0.001); DTG also demonstrated a reduced efficacy in subtypes C (versus B, aHR 10.24; p = 0.035) and CRF01-AE (versus B; aHR 10.65; p = 0.035). Higher baseline HIV-RNA and a longer time since HIV diagnosis also predicted VF., Conclusions: In line with randomized trials, DTG-based first-line regimens showed an overall superior efficacy compared with DRV-based regimens. GRT may still play a role in identifying patients more at risk of VF and in guiding the choice of an antiretroviral backbone.

Introduction: Young adults with vertical transmission (VT) of human immunodeficiency virus (HIV) represent a fragile population. This study evaluates factors associated with viro-immunological outcome of these patients., Methods: We performed a multicenter study including HIV-infected subjects with VT ≥ 18 years old from six Italian clinics. Subjects were observed from birth to death, lost to follow-up, or last visit until December 31, 2019. Condition of "optimal viro-immunological status" (OS) was defined as the simultaneous presence of HIV ribonucleic acid (RNA) < 50 copies/mL, CD4+ > 500 cells/mm 3 , and CD4+/CD8+ ratio ≥ 1., Results: A total of 126 subjects were enrolled. At 18 years of age, 52/126 (44.4%) had HIV-RNA > 50 copies/mL, 47/126 (38.2%) had CD4+ < 500/mm 3 , and 78/126 (67.2%) had CD4+/CD8+ < 1; 28 subjects (23.7%) presented in the condition of OS. Having a CD4+/CD8+ ratio ≥ 1 at 18 years of age was related with an increased probability of shift from suboptimal viro-immunological status (SOS) to OS (HR: 7.7, 95% confidence interval [CI]: 4.23-14.04), and a reduced risk of shift from the OS to the SOS (HR: 0.49, 95% CI: 0.26-0.92). Acquired immunodeficiency syndrome (AIDS) diagnosis significantly reduced the probability of shift from a viro-immunological SOS to OS (HR: 0.09, 95% CI: 0.03-0.30). Subjects who had not achieved an OS at 18 years of age had an increased risk of discontinuation of combination antiretroviral therapy (cART, p = .019)., Conclusions: Only a small proportion of subjects with VT of HIV reached the adult age with "OS". Transition to the adult care with a compromised viro-immunological condition represents a negative driver for future optimal infection control, with a higher risk of discontinuation of cART and a reduced probability to improve the immunological status later in the years., (© 2023 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Objectives: To evaluate the impact of a treatment switch to dolutegravir plus lamivudine on the soluble inflammatory biomarkers of HIV-infected patients treated in a real-life setting. Materials and methods: This was a longitudinal study that enrolled virologically-suppressed patients on stable 3-drug ART who switched at baseline to dolutegravir + lamivudine (2DR-group), based on the clinician's decision, or maintained triple therapy (3DR-group). Subjects in the 3DR-group were matched with those in the 2DR-group for age, gender and type of anchor drug. Plasma levels of interleukin-6 (IL-6), I-FABP, D-dimer and C-reactive protein (CRP) were quantified by a microfluidic ultrasensitive ELISA assay at baseline and at 48 weeks. Results: Overall 208 subjects were enrolled: 101 in the 2DR-group and 107 in the 3DR-group. At baseline, biomarker levels were comparable between groups. The differences in mean log 10 change from baseline to 48 weeks between groups (2DR versus 3DR) were: IL-6 (pg/L) -0.051(95% CI -0.115/0.009) versus 0.004 (95% CI -0.046/0.054) (p = 0.159); I-FABP (pg/mL), -0.088 (95% CI -0.14/-0.041) versus 0.033 (95%CI -0.007/0.072) (p < 0.001); D-dimer (pg/mL), -0.011(95% CI-0.055/0.033) versus -0.021 (95% CI -0.071/0.030) (p = 0.780) and CRP (pg/mL), -0.028 (95%CI -0.118/0.063) versus 0.118 (95% CI 0.024/0.211) (p = 0.028). Conclusions: At 1 year, switching to a dolutegravir plus lamivudine dual regimen in this setting showed a favorable trend for two biomarkers analyzed, i.e., I-FABP and CRP, as compared to continuing a triple therapy. These results add important new data in support of the safety of this approach in terms of its effect on the inflammatory milieu.

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.

Cabotegravir and rilpivirine are the first drugs to be approved as injectable therapy to treat individuals with HIV. Despite encouraging results, the guidelines specify strict criteria for eligibility that could limit the feasibility of this strategy. We collected the clinical data of HIV-positive patients who were being treated at a single, third-level center in Italy. All patients were on stable therapy and showed suppressed viral load on their most recent analyses. We performed a cross-sectional analysis of the clinical and viro-immunological characteristics of this population and excluded patients who had previous virological failures, resistance-associated mutations (RAMs) to rilpivirine or integrase inhibitors in the historical genotype, hepatitis B infection, absence of previous genotypes, and the coexistence of HIV-subtype A and obesity. Our aim was to evaluate the proportion of patients who could be eligible for switching to this strategy. one thousand seven hundred fifty-two patients were eligible. One hundred and forty-eight were excluded because of a detectable viral load. With regard to the exclusion criteria, 48 patients had coinfection with hepatitis B virus, and 744 had a history of previous virological failures. Of the 896 patients with at least one genotypic resistance test, 161 had one or more RAMs to rilpivirine and 3 had RAMs to cabotegravir. None of the patients presented the combination of obesity and the A viral subtype. Overall, 31.2% of the patients were ineligible for cabotegravir-rilpivirine, and the proportion increased to 47.3% when we considered only patients with all available information concerning resistance tests. Approximately half of our cohort of patients did not fulfill the criteria and even more patients were potentially ineligible for cabotegravir-rilpivirine due to the lack of genotypic resistance tests. Also, fertile women had to be excluded due to the lack of data about this combination during pregnancy and breastfeeding., (© 2022 Wiley Periodicals LLC.)

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., (© 2022. The Author(s).)

Two hundred two people living with HIV (PLWH) selected from outpatients at the Infectious Disease Institute, Fondazione Policlinico Universitario A. Gemelli IRCCS, in Rome (Italy) were consecutively enrolled from May to July 2021. We used an anonymous telephone questionnaire to investigate opinions of PLWH about combined antiretroviral (ARV) therapy and long-acting (LA) formulations of ARVs. All invited participants completed the questionnaire (100%). We found that most PLWH evaluated taking HIV pills for the rest of their life as a continuous, but undemanding commitment (61.4%; n  = 124), although they were willing to stop the daily intake of HIV drugs (78.2%, n  = 158). Moreover, most PLWH were unaware of the existence of LA therapies at the time of the investigation (60.4%, n  = 122). Almost half the PLWH evaluated the need for injections in the hospital as an obstacle (51.4%, n  = 104). Regarding the preference between monthly injections and taking pills everyday, most PLWH (68.8%, n  = 139) stated that the injection was more advantageous than pills even if they had some pain/swelling at the injection site. The concern about LA therapy indicated most by PLWH was the possible lower efficacy of the drug (83.7%, n  = 169). Regarding the possible benefits of LA therapy, those reported most by PLWH were feeling freer because they did not have to remember to take pills everyday (68,8%, n  = 139). In conclusion, to date, PLWH in our cohort seem willing to accept LA therapy, but still show some concern about the efficacy of the new therapy and the obligation to come to the hospital to receive it. Thus, clinicians must take into account the needs of their patients and help them overcome their concerns to facilitate the transition to this new therapeutic modality. Clinical Trial Registration Number ID: 2424.

Objectives: The aim of this study was to evaluate the impact of resistance mutations on efficacy of dolutegravir-based two-drug regimens (2DR)., Methods: Virologically suppressed patients with HIV-1 switching to dolutegravir + lamivudine or rilpivirine or to a dolutegravir-based three-drug regimen (3DR) with pre-baseline genotype were selected. Virological failure (VF) was defined as one HIV-RNA viral load (VL) >200 cps/mL or two consecutive VL >50 cps/mL; treatment failure (TF) was defined as VF or treatment discontinuation (TD). Resistance was defined as at least low-level resistance to at least one drug of the current regimen. Propensity score matching was used to conduct adjusted analyses within a competing risks framework., Results: A total of 971 dolutegravir-based regimens were selected: 339 (34.9%) 2DR and 632 (65.1%) 3DR. The adjusted cumulative 48-week incidence of VF was 4.2% (90% CI 3.1%-5.3%) with 2DR and 4.7% (90% CI 3.5%-5.8%) with 3DR. The cumulative 48-week incidence of TF was 15.8% (90% CI 13.9%-17.9%) with 2DR and 24.5% (90% CI 22.2%-27.0%) with 3DR. For VF, the estimated hazard ratio (HR) for 2DR vs. 3DR was 1.02 (90% CI: 0.78-1.34), with evidence of effect modification by low-level resistance (HR 3.96, 90% CI: 2.10-7.46). The estimated HR of TF for 2DR vs. 3DR was 0.54 (90% CI: 0.48-0.60). The 48-week cumulative incidence of TD was 11.7% (8.7%, 14.6%) in 2DR and 19.6% (16.9%, 22.4%) in 3DR., Conclusions: Dolutegravir-based 2DR showed high virological efficacy and durability; however, past resistance increased the risk of VF, but not of TD or TF., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The COVID-19 pandemic has changed outpatient clinical practice, which has led to the need defining digital healthcare modalities to provide telehealth services. The aim of our study was to explore opinions about HIV management via telehealth in a representative, southern central Italian cohort of individuals with HIV (PLWH) and doctors involved in the treatment process., Methods: We enrolled 80 PLWH who have never used telehealth tools and 60 doctors, who administered an anonymous self-report questionnaire to investigate their opinions about telehealth service use., Results: Most of the doctors and patients indicated that they would use telehealth services; however, 88.3% of the doctors and 40% of the PLWH did not want to substitute personal visits with telehealth services. Unlike PLWH, physicians seemed to agree with most of the possible risks of telehealth, such as patients' isolation from the hospital system (71.7%), interaction difficulty (46.7%) and lower quality of patient assessment (63.3%). The doctors focused on the qualitative aspects of telehealth services reducing patients' exposure to stigma (61.7%), improving quality of patient care (41.7%), and improving privacy (58.3%). By contrast, patients focused on the quantitative aspects of telehealth services improving timely access to care (44%), time saving (63%) and improving interaction with doctor (43%)., Conclusions: Both PLWH (especially older patients and those with longer experience of disease management) and doctors welcome the use of telehealth services but disagree using it to substitute medical consultation in person focusing on different possible benefits and risks of telehealth depending on the needs expressed. Thus, our results suggest the need to initiate and expand communication about telehealth between doctors and patients., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction Different single-tablet regimens (STRs), containing one or two nucleoside reverse transcriptase inhibitors (NRTIs) plus an anchor drug, are available for the use in naïve, HIV-infected patients. Despite some restrictions in the use of particular regimens in certain situations (e.g., HBV coinfection), International guidelines do not provide indications to prefer any regimen over others concerning the tolerability profile. We aimed to assess advantages and disadvantages of the most prescribed STRs. Areas covered An extensive review of articles published in English language was conducted on PubMed, looking for evidence about STRs in naïve, HIV-infected population. Safety outcomes of registrational trials were assessed, giving priority to studies directly comparing STRs included in our research (abacavir/lamivudine/dolutegravir, tenofovir alafenamide/emtricitabine/bictegravir, lamivudine/dolutegravir, tenofovir alafenamide/emtricitabine/darunavir/cobicistat, tenovofir disoproxil fumarate/lamivudine/doravirine). Data from cohort studies and meta-analyses were also assessed, extrapolating the main evidence about the combinations of interest. Expert opinion Integrase inhibitors (InsTIs)-based regimens have few interruptions for adverse events and few drug-related adverse events, with tenofovir alafenamide/emtricitabine/dolutegravir and lamivudine/dolutegravir being the most tolerable ones. However, neuropsychiatric adverse events and metabolic issues could prompt the alternative use of darunavir or doravirine-based combinations, even if a superior safety profile of these combinations over InSTIs has yet to be demonstrated.

We tried to investigate and compare the safety of a dual therapy (DT) with dolutegravir+lamivudine (DTG +3TC) versus bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). We performed a retrospective analysis in a cohort of virologically suppressed HIV+ pts switching to DT or BIC in our center. Primary endpoint was to evaluate time to treatment discontinuation (TD) for any cause. Survival analysis was employed to determine time to TD and its predictors were analyzed by Cox regression. Moreover, we collected viro-immunological parameters as well as markers of renal function and lipid profile at baseline and after 24 weeks and assessed changes through nonparametric tests. We analyzed 476 patients: 350 starting a DT and 126 starting BIC. Overall, we registered 21 TD: 15 in the DT group during 170 patient-years of follow-up (PYFU) (a rate of 8.8 per 100 PYFU) and 6 in the BIC one during 48 PYFU (12.5 per 100 PYFU). Estimated probabilities of maintaining study regimen after 24 weeks were 95.5% [standard deviation (SD) ±1.1] in the DT group and 94.9% (SD ±2.0) in the BIC group, with no significant differences between them (log-rank p  = .639). Concerning metabolic profile, in the DT group, after 24 weeks, triglycerides decreased significantly (median change -14 mg/dL, p  < .001), whereas high-density lipoprotein cholesterol increased (+3 mg/dL, p  = .031). In the BIC group, meanwhile, we observed a significant decrease in low-density lipoprotein cholesterol after 24 weeks (-13 mg/dL, p  = .026). Both optimization strategies showed high tolerability in the short term in experienced pts, with few differences between them. Further studies are needed to properly assess the matter.

The GEMINI trials have showed that the two drugs regimen of dolutegravir+lamivudine (DTG +3TC) was noninferior to a three-drug regimen as a first line regimen for treatment-naive people living with HIV. The aim of our study was to confirm, in a real-life setting, the efficacy of this regimen. We conducted a retrospective, observational study enrolling treatment-naive patients starting a first-line regimen with lamivudine plus dolutegravir. We evaluated the virological efficacy and the immunological and metabolic profiles. Changes from baseline were evaluated through linear-mixed models for repeated measures. Linear regression analyses were performed to explore variables associated to significant changes in laboratory parameters. We analyzed a total of 20 patients: 15 (75%) were men with a median age of 34.5 years. During a cumulative time of 15.4 patients years of follow up (PYFU), we did not observe any adverse event or treatment discontinuation and all patients achieved virological suppression in the first 6 months from treatment initiation. Increase in CD4 + cells was significant at both week 24 ( p  = .003) and week 48 ( p  = .007) of follow-up. Moreover, CD4/CD8 ratio also significantly improved [median increase of +0.22 ( p  = .028) after 48 weeks of follow-up]. As to metabolic parameters, we observed no significant changes in total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. In a subgroup of 11 patients, we further investigate HIV-1 DNA variations. Our results are in line with the findings of the GEMINI trials, confirming the efficacy and safety of DTG +3TC in treatment-naive patients.

Currently approved 2-drug therapies are as effective as 3-drug regimens but could potentially lead to increased cancer risk due to less efficient immune recovery. We conducted a longitudinal cohort study in a tertiary Italian hospital to investigate HIV+ patients starting a triple therapy (TT) (2 NRTIs +3rd agent) or a dual therapy (DT) (3TC/FTC+boosted-PI, boosted-DRV+RAL, and 3TC/FTC or RPV+DTG) regimen between 2009 and 2018. The effect of DT (vs. TT) on tumor onset was evaluated by the multivariable Cox regression and the marginal structural Cox model, after estimating the inverse probability of treatment weights (IPTW). One thousand one hundred and seven patients who had a median follow-up of 4.2 person-years (py) were evaluated; 69.2% were males, with a median age of 43 years. Overall 2,513 treatments were started during the study period (479 DT, 2,034 TT). Eight tumors occurred over 965 py with DT and 35 over 3,817 py during TT ( p  = .797). In the Cox regression, DT did not predict an increased risk of tumor compared with TT (HR 1.14; p  = .757) after adjusting for potential confounders. A marginal structural model using IPTW (HR 0.68; p  = .328) and stabilized IPTW (HR 0.69; p  = .361) confirmed this result. Preliminary findings from our cohort do not suggest an increased risk of tumors with DT compared to TT.

The aim of this study was to explore the psychological impact of the initial stage of the 2019 coronavirus (COVID-19) pandemic on people living with HIV (PLWH), a population at increased risk of psychological distress. PLWH participated in an online survey exploring demographic and clinical data, physical symptoms, contact history, knowledge and concerns, precautionary measures and additional information about COVID-19 during the first phase of the pandemic in Italy. The Impact of Event Scale-Revised (IES-R) (identifying the COVID-19 pandemic as a specific traumatic life event) and the Depression, Anxiety and Stress Scale (DASS-21) also formed part of the survey. Out of 98 participants, 45% revealed from mild to severe psychological impact from COVID-19 according to IES-R. A lower percentage, instead, complained of significant levels of depression (14%), anxiety (11%) or stress (6%) according to DASS-21. Higher education, being unemployed, number of perceived COVID-19 physical symptoms, concerns about risk of contracting COVID-19 and the pandemic situation in Italy, and needing additional information to prevent COVID-19 infection were positively associated to a higher risk of negative psychological impact. Moreover, among the participants, female gender, age, fewer years from HIV diagnosis and not being aware of their own viremia were associated to a higher risk of negative psychological outcomes. Almost half of our PLWH sample experienced significant levels of distress related to the COVID-19 pandemic. Women, elderly patients and those with recent HIV diagnosis appear to be the more psychologically fragile subgroups. Our findings could help identify patients most in need of psychological interventions to improve the wellbeing of PLWH.

Background: People living with human immunodeficiency virus are ageing under combination antiretroviral treatments but data on drug exposure in serum and cerebrospinal fluid are limited. Dolutegravir is a widely used second-generation integrase strand transfer inhibitor: conflicting data suggest that neuropsychiatric side effects may present at a higher frequency in patients with higher dolutegravir serum concentrations., Methods: We performed a retrospective analysis of our therapeutic drug monitoring registry identifying patients receiving once-daily dolutegravir without concomitant interacting drugs and significant clinical conditions. Data were analysed stratifying time after drug dose intake (maximum concentration 0.5-4 and trough concentration 21-27 h). Cerebrospinal fluid samples from patients enrolled in neurological studies and receiving dolutegravir were analysed for dolutegravir cerebrospinal fluid concentrations and cerebrospinal fluid-to-plasma ratios. Serum and cerebrospinal fluid concentrations were measured through validated chromatographic methods., Results: We included 207 (providing 457 serum samples) and 41 patients (providing 41 cerebrospinal fluid samples). Participants were mostly male (68.2-72.8%) of median age of 50 years (50-53 years). Non-significant changes in dolutegravir maximum concentration and trough concentration were observed with age at Spearman's test (p values > 0.05); linear logistic regression showed a significant effect of age on dolutegravir trough concentration (p = 0.0013) (Fig. 1). Dolutegravir maximum concentration [3830 ng/mL (2311-5057) vs 4230 ng/mL (2919-5272), p = 0.311] and trough concentration [838 ng/mL (362-1587) vs 966 ng/mL (460-2085), p = 0.056] were non-significantly or borderline higher in patients aged > 50 years. Cerebrospinal dolutegravir concentrations were associated with plasma concentrations (ρ = 0.374, p = 0.016) and age (ρ = 0.537, p = 0.003); cerebrospinal fluid dolutegravir concentrations (13.8 vs 7.3 ng/mL, p = 0.015) and cerebrospinal fluid-to-plasma ratios (0.57 vs 0.32%, p = 0.017] were higher in participants aged > 50 years., Conclusions: We observed an increase in dolutegravir exposure in serum and in cerebrospinal fluid in older patients living with human immunodeficiency virus.

Background: We explored predictors of CD4/CD8 ratio improvement and optimal immunological recovery (OIR) after initiation of antiretroviral therapy (ART) in naive people living with HIV (PLWH)., Methods: Retrospective multicenter study including naive PLWH starting ART with 2 nucleos(t)ide reverse transcriptase inhibitors + 1 integrase strand transfer inhibitor (InSTI) or non-NRTI or protease inhibitor (PI). PLWH were followed from the time of ART initiation (baseline) to the discontinuation of first-line regimen, virological failure, death, or loss to follow-up. Estimated incidence and predictors of time to CD4/CD8 ratio normalization (defined as ≥1) and OIR (defined as CD4/CD8 ratio ≥ 1 plus CD4 ≥ 500 cells/µL plus CD4% ≥ 30%) were explored by Kaplan-Meier curves and Cox regression analysis., Results: Overall, 1428 PLWH (77.8% males, median age 39 years, 55.1% with positive cytomegalovirus (CMV) antibodies, median HIV-RNA 4.80 log copies/mL, median CD4 323 cells/µL, median CD4/CD8 ratio 0.32) were included, of which 21.5% (n = 307), 44.5% (n = 636), and 34% (n = 485) treated with InSTI-, PI-, and NNRTI-based regimens, respectively. The estimated proportion of CD4/CD8 normalization and OIR at 36 months was 38.6% and 32.9%, respectively. Multivariate analysis showed that InSTI-based regimens had a higher probability of CD4/CD8 ratio normalization and OIR both in the total population (P < 0.001 versus PI) and in advanced naive PLWH (P ≤ 0.001 versus PI and NNRTI). Moreover, subjects with positive CMV serology showed a lower probability of CD4/CD8 ratio normalization and OIR (P < 0.001)., Conclusions: InSTI-based regimens showed a better immune recovery, suggesting that the type of first-line ART can influence immune reconstitution. PLWH with positive CMV serology showed an increased risk of suboptimal immune recovery.

Everyday functioning (EF) impairment is frequent in people living with HIV (PLWH). Our aim was to better explore EF and its association with PLWH cognition, by administering both the IADL scale, the most common functional scale, and a new and ecologic multi-domain (communication and financial skills) tool to measure EF as the University of California San Diego (UCSD) Performance-Based Skills Assessment-Brief Version (UPSA-B). Eighty-five PLWH on cART with very good immunological condition and 23 age- and education-matched healthy controls (HC) were enrolled. PLWH underwent a standardized neuropsychological battery plus IADL, and cognitive impairment was defined according to Frascati criteria. Both groups underwent the UPSA-B. Only 6 subjects (7%) were affected by cognitive impairment (asymptomatic profile). While IADL score was at ceiling for all patients, the UPSA-B total score was significantly worse in PLWH when compared with HC [mean 82.1 (SD 9.3) vs 89.2 (SD 6.2); p < 0.001]. At communication subtest, PLWH group and HC were significantly different (p = 0.002), while no difference emerged at financial skills (p = 0.096). Higher score at UPSA-B was independently associated with better global cognitive performance (composite Z-score) (β 7.79; p < 0.001). Also considering each single cognitive domain, UPSA-B performance (both total and at subtests) confirmed the association with neurocognitive performance. In conclusion, UPSA-B seems to better discriminate EF impairment than IADL in PLWH, and it was associated with cognitive functions, also in the absence of symptomatic cognitive impairment. Thus, it appears a promising tool in the context of HIV infection to avoid misdiagnosis and to better detect also mild EF.

Objectives: To assess the impact of switching to dolutegravir plus lamivudine maintenance therapy on the HIV cellular reservoir size., Patients and Methods: This was a prospective, longitudinal, matched, controlled study. We enrolled virologically suppressed patients on stable three-drug ART who switched at baseline (BL) to dolutegravir/lamivudine (DT group) or maintained triple therapy (TT group); subjects in the TT group were matched 1:1 with those in the DT group according to age, gender, years since HIV diagnosis, years on ART and anchor drug. Total blood-associated HIV DNA levels were assessed by droplet digital PCR at BL and after 48 weeks (T48). Results were expressed as log10 HIV DNA copies/106 leucocytes., Results: We enrolled 40 patients in the DT group and 40 in the TT group; the two groups were homogeneous for all main characteristics except nadir CD4 cell count. At BL, HIV DNA levels were comparable between the DT and TT groups: 2.27 (IQR 1.97-2.47) and 2.26 (IQR 2.05-2.61) log10 HIV DNA copies/106 leucocytes, respectively. Change in HIV DNA load from BL to T48 was -0.105 (IQR -0.384 to 0.121, P = 0.041) in the DT group and -0.132 (IQR -0.362 to 0.046, P = 0.005) in the TT group, with a comparable decline observed between the two groups (P = 0.821). A higher HIV DNA decline was associated with higher BL CD4/CD8 ratio., Conclusions: Maintenance therapy with dolutegravir/lamivudine had the same impact as the triple regimen on HIV DNA levels after 48 weeks of treatment. These data seem to support the effectiveness of a dolutegravir/lamivudine dual regimen in controlling the magnitude of the cellular reservoir (www.clinicaltrials.gov, number NCT02836782)., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction : Recent data on the 2-drug regimen (2DR) with dolutegravir (DTG) plus lamivudine (3TC) have shown high efficacy and tolerability both in treatment-naïve and experienced HIV-positive patients. Current guidelines recommend DTG+3TC as an alternative to triple antiretroviral therapy (ART) in selected patients to reduce long-term toxicity and costs. Areas covered : This review is intended to provide insight about the efficacy, safety, and tolerability of a 2DR with DTG+3TC in naïve and treatment-experienced patients. Expert opinion : Data from clinical trials and from real-life show that DTG+3TC is an effective and safe switch option for the treatment of experienced patients. In treatment-naïve patients, DTG+3TC has shown non-inferiority compared to standard 3-drug regimens but is less effective in severely immunocompromised naïve patients (i.e. with a CD4+ cell count below 200 cell/mm3); furthermore, current guidelines have upgraded this dual regimen to recommended first-line strategy, but indicate that it should not be used without genotypic resistance results. Moreover, this regimen is not feasible for HBV-coinfected individuals and should not be used during pregnancy. Currently, out of 2-drug regimens, DTG+3TC is one of clinicians' preferred option as it requires no pharmacokinetic booster, has a low risk of drug interaction, and does not require food intake.

Background: Antiretroviral drug resistance mutations remain a major cause of treatment failure., Objectives: To evaluate the impact of NRTI resistance mutations on virological effectiveness of elvitegravir-containing regimens., Materials and Methods: We selected treatment-experienced HIV-1-infected patients starting elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) or elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF), with at least one protease/reverse transcriptase genotype available before switching and at least one HIV-1 RNA viral load (VL) measurement during follow-up. The primary endpoint was virological failure (VF), defined as one VL value of ≥1000 copies/mL or two consecutive VL values of >50 copies/mL., Results: We included 264 ART regimens: 75.6% male, median (IQR) age 47 years (39-53), 7 years (3-16) of HIV infection, nadir CD4+ 247 cells/mm3 (105-361), 81.5% with VL ≤50 copies/mL and 11.7% with at least one NRTI mutation at baseline. Eleven (5.2%) VFs occurred in virologically suppressed patients versus eight (15.1%) in viraemic patients. The estimated probability of VF at 48 weeks with versus without any NRTI mutation was 7.4% (95% CI 2.3-12.5) versus 3.8% (2.1-5.5) in virologically suppressed patients and 66.7% (39.5-93.9) versus 11.2% (6.5-15.9) (P<0.001) in viraemic patients. The only predictor of VF was time on therapy (per 1 year more, adjusted HR 1.14, 95% CI 1.02-1.27, P=0.024) in viraemic patients., Conclusions: A switch to E/C/F/TDF or E/C/F/TAF is safe for virologically suppressed patients without documented NRTI resistance, but not recommended in viraemic patients with a history of NRTI resistance. Although we did not detect a detrimental effect of past NRTI resistance in virologically suppressed patients, a fully active regimen remains preferred in this setting due to possible rebound of drug-resistant virus in the long term., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose: The Observational cohort for the study of DOlutegravir in Antiretroviral Combination REgimens (ODOACRE) cohort was established in Italy in 2016 to evaluate the overall efficacy and tolerability of dolutegravir (DTG)-based antiretroviral (ARV) regimens in clinical practice., Participants: The ODOACRE cohort enrols all adult HIV-1-infected patients, both treatment-naïve and treatment-experienced, starting a DTG-based ARV regimen, in 11 clinical centres in Italy from 2014., Findings to Date: In recent years, various works by the ODOACRE cohort have been produced, demonstrating the high efficacy and tolerability of DTG-based ARV regimens in clinical practice, both in ART-naïve (in the setting of acute HIV-1 infection and late presenters patient) and experienced patients. We confirmed the virological efficacy of DTG-based regimens and we evaluated predictors of virological failure. We investigated cause of discontinuation and evaluated tolerability and metabolic profile of the regimens. Within these investigations, we explored particularly the use of DTG in simplification in two-drug regimen with either rilpivirine or lamivudine. We also compared DTG-based regimens with other integrase inhibitors in clinical practice., Future Plans: To continue to study long-term efficacy and tolerability of DTG-based regimens is the purpose of the ODOACRE cohort., Competing Interests: Competing interests: GB received travel grant from Gilead. ACa has received a personal grant from AB, Gilead and ViiV. GS has received funds for speaking by Gilead, Merk, Janssen, Abbvie, ViiV. AL received personal fees from BMS, Gilead, Merck, ViiV, AbbVie and Janssen and grants from BMS, Gilead, ViiV and Janssen. GM is in an ongoing relation as board member for ViiV Healthcare, Gilead Sciences and Jannsen. BR received travel grants from Jannsen, ViiV, Gilead MSD and received grants for consultancy from Abbvie, MSD, Viiv. AG received speaker fees from Mylan. AB has received non-financial support from Bristol-Myers Squibb and ViiV Healthcare, and personal fees from Gilead Sciences. CM has participated in advisory boards, received study grants and/or speaker honoraria from Abbvie, Gilead, Viiv, Janssen, Angelini, BMS and MSD. SR received research grants to his Institution from ViiV Heathcare, Gilead Sciences and Jannsen, outside the submitted work; he was also a paid consultant for ViiV Heathcare, Gilead Sciences, Merck Sharp and Dohme, Bristol-Myers Squibb, Janssen and Mylan. SDG was a paid consultant or member of advisory boards for Gilead, ViiV Healthcare, Janssen-Cilag, Merck Sharp & Dohme and Bristol-Myers Squibb., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Results from clinical trials and observational studies suggest that lamivudine plus dolutegravir (3TC+DTG) could be an effective and tolerated option for simplification in human immunodeficiency virus (HIV)-1-positive patients., Materials and Methods: This observational study enrolled HIV-1-infected, virologically suppressed patients switching to 3TC+DTG. Kaplan-Meyer survival analysis was performed to evaluate time to virological failure (VF; defined by a single HIV-RNA determination ≥1000 copies/mL or by two consecutive HIV-RNA determinations ≥50 copies/mL) and time to treatment discontinuation (TD; defined as interruption of either 3TC or DTG), Cox regression was performed to assess predictors, and linear mixed model was performed for repeated measures to measure changes in immunological and metabolic parameters., Results: Five hundred and fifty-six patients were eligible for analysis. Their median CD4+ count at baseline was 668 cells/mm 3 and median time of virological suppression was 88 months. Estimated probabilities of maintaining virological suppression at 96 and 144 weeks of follow-up were 97.5% [standard deviation (SD) 0.8] and 96.5% (SD 1.0), respectively. Years since HIV diagnosis was the only predictor of VF. In patients with time of virological suppression <88 months, the rate of VF was higher in the presence of the M184V mutation. Estimated probabilities of remaining on 3TC+DTG at 96 and 144 weeks of follow-up were 79.2% (SD 1.9) and 75.2% (SD 2.2), respectively. A significant increase in CD4 cell count (+44 cells/mm 3 , P=0.015), CD4/CD8 ratio (+0.10, P=0.002) and high-density lipoprotein cholesterol (+5.4 mg/dL, P=0.036) was found at 144 weeks of follow-up; meanwhile, total cholesterol (-9.1 mg/dL, P=0.007) and triglycerides (-2.7, P=0.009) decreased significantly., Conclusions: These findings confirm the efficacy and tolerability of 3TC+DTG in virologically suppressed patients., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The contribution of HCV-related variables to cognitive impairment in HIV-HCV-coinfected patients has been poorly investigated. We selected HIV-HCV-coinfected patients undergoing cognitive examination (exploring memory, language, speed of mental processing and fine motor function) at three clinical centres. Cognitive performance was evaluated using Z-transformed scores. Logistic regression analysis was used to investigate variables associated to cognitive impairment (defined as a composite Z-score ≤ - 1). Overall, 146 HIV-HCV-coinfected patients were enrolled. Median HCV-RNA was 6.2logU/mL. HCV genotype 1a/b was the most represented (53.4%). Liver fibrosis was mild (Fib4 ≤ 1.45) in the majority of patients (44.5%). Global cognitive impairment was diagnosed in 35 (24%) subjects. Exploring each domain, a higher proportion of impairment was observed for memory (37%) followed by speed of mental processing (32.2%), fine motor functioning (24%) and language (18.5%). Among HCV-related variables, the duration of HCV infection was independently associated with global cognitive impairment (aOR 1.13 per +1 year, p = 0.016) and abnormal speed of mental processing (aOR 1.16 per +1 year, p = 0.001), while higher HCV-RNA was independently associated to fine motor functioning impairment (aOR 1.98 per +1log, p = 0.037). HCV genotype, fibrosis stage, transaminases or bilirubin levels were not related to cognitive performance. Of note, integrase inhibitor (InSTI) use was independently associated to a pathological performance in fine motor functioning (aOR 3.34, p = 0.035) and memory (aOR 3.70, p = 0.014). In conclusion, the duration of HCV infection and HCV-RNA load showed an association with cognitive impairment, suggesting a role of hepatitis-related factors in the development of cognitive disorders in HIV-HCV-coinfected patients. The association between InSTI use and altered cognitive performance should prompt investigations about potential neurotoxicity of these drugs.

Purpose: Our aim was to better explore the association between liver fibrosis (LF) and neurocognitive impairment (NCI) in people living with HIV (PLWH)., Methods: We performed a cross-sectional cohort study by consecutively enrolling PLWH at two clinical centers. All subjects underwent a comprehensive neuropsychological battery; NCI was defined as having a pathological performance (1.5 SD below the normative mean) on at least two cognitive domains. LF was explored using FIB4 index; in a subgroup of PLWH, LF was also assessed by transient elastography., Results: A total of 386 subjects were enrolled, of whom 17 (4.4%) had FIB4 > 3.25. In the subgroup of PLWH (N = 127) performing also liver transient elastography, 14 (11%) had liver stiffness > 14 kPa. Overall, 47 subjects (12%) were diagnosed with NCI. At multivariate regression analyses, participants with FIB4 > 1.45 showed a higher risk of NCI in comparison with those with lower values (aOR 3.04, p = 0.044), after adjusting for education (aOR 0.71, p < 0.001), past AIDS-defining events (aOR 2.91, p = 0.014), CD4 cell count, past injecting drug use (IDU), HIV-RNA < 50 copies/mL, and HCV co-infection. Also a liver stiffness > 14 kPa showed an independent association with a higher risk of NCI (aOR 10.13, p = 0.041). Analyzing any single cognitive domain, a higher risk of abnormal psychomotor speed was associated with a liver stiffness > 14 kPa (aOR 223.17, p = 0.019) after adjusting for education (aOR 0.57, p = 0.018), HIV-RNA < 50 copies/mL (aOR 0.01, p = 0.007), age, past IDU, and HCV co-infection., Conclusions: In PLWH, increased LF, estimated through non-invasive methods, was associated to a higher risk of NCI independently from HCV status.

Objectives: To compare mucosal flora in HIV-positive and HIV-negative subjects, to assess chemosusceptibility patterns of carriage isolates and to evaluate possible predisposing factors within the two groups., Methods: We analyzed microbes isolated from nasopharyngeal swabs in virologically suppressed and immunologically stable HIV-positive adult outpatients (n=105) at baseline and after 12 months and in an age-matched cohort of HIV-negative outpatients (n=100) at baseline. Bacteria and Candida spp strains were isolated and identified through standard biochemical assays and chemosusceptibility tests were performed. Multi Locus Sequence Typing was also determined to characterize Staphylococcus aureus isolates from HIV-infected persistent carriers., Results: In HIV-positive patients a significantly higher rate of colonization by S. aureus as compared to HIV-negative controls was observed (19% vs 8%, p=0.02), with a relevant percentage of penicillin resistant strains (15% vs 0, p=0.24). Methicillin resistant strains were recovered only from HIV-positive subjects. Overall HIV-positive status was the only predictor of S. aureus colonization (OR 2.77, 95% CI 1.03;7.41, p=0.04)., Conclusions: The nasopharyngeal bacterial flora differs between HIV-positive and HIV-negative subjects and appears relevant for possible development of staphylococcal infections in HIV-positive patients.

Bone toxicity is a well-known side effect of several antiviral agents. In a cohort of virologically suppressed HIV-infected patients, we investigated the effects of a lamivudine/dolutegravir dual therapy on bone mineral density (BMD). We observed a significant improvement in lumbar spine BMD as well as T-score after 12 months of observation with concomitant bisphosphonate therapy independently predicting a greater improvement. These preliminary data show a favorable effect of this 2-drug regimen on bone health.

Background: Biomarkers of systemic inflammation predict non-AIDS events and overall mortality in virologically suppressed HIV-1-infected patients., Objectives: To determine whether switching to a dual antiretroviral maintenance therapy was associated with modification of biomarkers of systemic inflammation as compared with continuation of successful standard triple therapy., Methods: In this substudy of the randomized ATLAS-M trial, we compared in virologically suppressed patients the impact at 1 year of simplification to a dual therapy with atazanavir/ritonavir plus lamivudine versus maintaining atazanavir/ritonavir plus two NRTI triple therapy on markers of systemic inflammation. Plasma levels of interleukin-6, C-reactive protein (CRP), soluble CD14 (sCD14) and D-dimer were quantified by ELISA at baseline and at 48 weeks., Results: A subset of 139 of 266 randomized patients with available samples was analysed: 69 in the triple therapy arm and 70 in the dual therapy arm. The baseline biomarker levels were comparable between randomization arms. No significant differences in changes from baseline to week 48 were observed between arms (dual therapy versus triple therapy): IL-6, -0.030 versus -0.016 log10 pg/L; CRP, +0.022 versus +0.027 log10 pg/mL; sCD14, -0.016 versus +0.019 log10 pg/mL; and D-dimer, -0.031 versus +0.004 log10 pg/mL. A history of cancer was associated with higher baseline levels of IL-6 (P = 0.002) and CRP (P = 0.049). No relationship was observed between baseline biomarker level and persistent residual viraemia, HIV-1 DNA load, plasma lipids and other potential explanatory variables., Conclusions: Simplification with atazanavir/ritonavir plus lamivudine does not affect plasma markers of systemic inflammation in virologically suppressed patients. The association between these findings and clinical outcomes requires further evaluation.

Background: The influence of HIV-1 co-receptor usage on the course of therapy in subjects fully responding to ART has been poorly investigated., Objectives: To explore the relationship between co-receptor tropism and cellular reservoir size, residual viremia and subsequent virological outcome in ART-treated patients with HIV-1 RNA stable <50 copies/mL., Study Design: Viral co-receptor usage was predicted by viral env DNA sequencing with geno2pheno interpretation (FPR20%) and classified as R5 and non-R5. Total blood-associated HIV-1 DNA levels (log 10 copies/10 6 leukocytes) were measured by qRT-PCR (5'LTR). Residual plasma viremia was categorized as detectable (1-49 cps/mL) or undetectable (<1 copy/mL). Virological rebounds (any HIV-1 RNA >50 copies/mL) were evaluated over 96 weeks., Results: The study included 116 subjects. Patients with R5 virus (n = 59) and non-R5 virus (n = 57) were homogeneous for the main characteristics except for the lower nadir CD4 cell count in the non-R5 group. Patients with non-R5 variants showed higher levels of HIV-1 DNA as compared to patients with R5 virus: mean 2.47 (95% CI 2.37-2.56) vs 2.17 (2.08-2.26) (p < 0.001). Moreover, a higher proportion of patients in the non-R5 group displayed detectable residual viremia with respect to the R5-group (54.4% vs 32.2%, p = .016). Detectable residual viremia was found to be significantly associated with viral rebounds., Conclusion: The presence of non-R5 viral DNA variants is related to a higher probability of residual viremia and to a larger size of the cellular viral reservoir in this setting. These data highlight a potential role of viral tropism in the monitoring of HIV-1 infection in virologically controlled subject., (Copyright © 2018 Elsevier B.V. All rights reserved.)