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BACKGROUND Results from clinical trials and observational studies suggest that dolutegravir plus lamivudine could be an effective and well-tolerated option for simplification in HIV-1-positive patients. We aimed to assess long-time efficacy and safety in our multicenter cohort. METHODS This was a retrospective study enrolling HIV-1-infected, virologically suppressed patients switching to dolutegravir + lamivudine. We performed survival analysis to evaluate time to virological failure (VF, defined by a single HIV-RNA ≥1000 copies/mL or by 2 consecutive HIV-RNA ≥ 50 copies/mL) and treatment discontinuation (defined as the interruption of either 3TC or dolutegravir), assessing predictors via Cox regression analyses. RESULTS Seven-hundred eighty-five patients were considered for the analysis: 554 were men (70.6%), with a median age of 52 years (interquartile range 45-58 years). Estimated probabilities of maintaining virological suppression at weeks 96, 144, and 240 were 97.7% (SD ±0.6), 96.9% (SD ±0.8), and 96.4% (SD ±0.9), respectively. A non-B HIV subtype (P = 0.014) and a previous VF (P = 0.037) resulted predictors of VF. We did not observe differences in probability of VF in people living with HIV with an M184V resistance mutation (P = 0.689); however, in a deeper analysis, M184V mutation was a predictor of VF (P = 0.038) in patients with time of virological suppression

Objectives Sex differences in COVID-19 severity and mortality have been described. Key aims of this analysis were to compare the risk of invasive mechanical ventilation (IMV) and mortality by sex and to explore whether variation in specific biomarkers could mediate this difference. Methods This was a retrospective, observational cohort study among patients with severe COVID-19 pneumonia. A survival analysis was conducted to compare time to the composite endpoint of IMV or death by sex. Interaction was formally tested to compare the risk difference by sex in subsets. Mediation analysis with a binary endpoint IMV or death (yes/no) by end of follow-up for a number of inflammation/coagulation biomarkers in the context of counterfactual prediction was also conducted. Results Among 415 patients, 134 were females (32%) and 281 males (67%), median age 66 years (IQR 54-77). At admission, females showed a significantly less severe clinical and respiratory profiles with a higher PaO2/FiO2 (254 mmHg vs 191 mmHg; p=0.023). By 28 days from admission, 49.2% (95% CI: 39.6-58.9%) of males vs. 31.7% (17.9-45.4%) of females underwent IMV or death (log-rank p-value Conclusions Our analysis confirms a difference in the risk of COVID-19 clinical progression by sex and provides a hypothesis for potential mechanisms leading to this. CRP showed a predominant role to mediate the difference in risk by sex.

Objective: Adherence to lipid-lowering drugs could be challenging in our patients as it is in the general population, which is described as low as 25%. Our aim was to evaluate adherence to statins and to investigate clinical event impact on it. Methods: This retrospective study on HIV+ patients attending to Clinic of Modena (Italy) was conducted in order to evaluate characteristics, clinical events, and adherence on lipid-lowering drugs. All drugs for comorbidities are distributed by the hospital pharmacy and recorded in an electronical database. Adherence was also evaluated in patients who were supplied with antilipemics in external pharmacies through phone calls. Patients were considered adherent if the percentage of correct time of drug refill was >80%. Findings: Totally 1123 patients were evaluated. Lipid-lowering drugs (statins, fenofibrate, and omega-3 oil) were prescribed in 242 patients (21.5%). Prescription occurred mainly in those who were older, males, and Italians. Two hundred of them (82.6%) used statins alone, 23 (9.5%) only fenofibrate or omega-3 oil, and 19 (7.8%) a combination of both drugs. The median adherence was 90% while patients with adherence >80% resulted 153 (63.2%). Forty-six (19%) had a clinical history of cardiovascular events; 59% of them, placed in secondary prophylaxis, and 76%, already in treatment, continued to adhere. No differences in terms of adherence according to the type of drug distribution (hospital pharmacy or outside pharmacies) were found. Conclusion: Linking the supply of these drugs to that of antiretrovirals led to a good level of adherence higher than that described in the general population. The majority of the patients who experienced a cardiovascular event remain adherent to the prescribed therapy.

Background & Aims There are limited data on patients with chronic HCV infection in whom combination voxilaprevir (VOX), velpatasvir (VEL), sofosbuvir (SOF) retreatment fails. Thus, we aimed to assess treatment failure and rescue treatment options in these patients. Methods Samples from 40 patients with HCV genotypes (GT) 1-4 in whom VOX/VEL/SOF retreatment failed were collected within the European Resistance Study Group. Population-based resistance analyses were conducted and clinical parameters and retreatment efficacies were evaluated retrospectively in 22 patients. Results Most VOX/VEL/SOF failure patients were infected with HCV GT3a (n = 18, 45%) or GT1a (n = 11, 28%) and had cirrhosis (n = 28, 70%). Previous treatments included an NS3-inhibitor (30%), an NS5A-inhibitor (100%) and SOF (85%). Baseline RAS data from a subgroup of patients before VOX/VEL/SOF retreatment (78%) showed few NS3 RASs apart from Q80K in GT1a (40%), typical NS5A RAS patterns in most patients (74%) and no S282T in NS5B. Sequencing after VOX/VEL/SOF failure was available in 98% of patients and showed only minor changes for NS3 and NS5A RASs. In 22 patients, rescue treatment was initiated with glecaprevir, pibrentasvir alone (n = 2) or with SOF±ribavirin (n = 15), VOX/VEL/SOF±ribavirin (n = 4) or VEL/SOF and ribavirin (n = 1) for 12 to 24 weeks. Sustained virologic response was achieved in 17/21 (81%) patients with a final treatment outcome. Of these, 2 GT3a-infected patients had virologic failure after rescue treatment with VEL/SOF or glecaprevir/pibrentasvir+SOF+ribavirin, and 2 patients with cirrhosis died during treatment or before reaching SVR12. Conclusions VOX/VEL/SOF failure was mainly observed in HCV GT3- and GT1a-infected patients with cirrhosis and was not associated with specific RAS patterns within NS3, NS5A or NS5B target regions. Rescue treatment with multiple targeted therapies was effective in most patients. Lay summary The advent of direct-acting antivirals has enabled the effective cure of chronic hepatitis C in most patients. However, treatment failure occurs in some patients, who are often retreated with a combination regimen called VOX/VEL/SOF, which is associated with very high rates of cure. However, VOX/VEL/SOF retreatment also fails in some patients. Herein, we analysed samples from patients in whom VOX/VEL/SOF retreatment failed and we assessed the efficacy of different rescue therapies, showing that rescue treatment is effective in most patients (81%).

BACKGROUND Syphilis represents a major public health concern disproportionately affecting HIV positive patients and in many cases both infections are newly diagnosed at the same time. To date, limited studies are available on syphilis incidence in patients with a new HIV diagnosis. METHODS Patients newly diagnosed with HIV in 2010-2018 were included in the study and screening tests for syphilis were performed at baseline and at least once a year. Primary aims were to analyse the incidence rate of HIV-syphilis co-infection and syphilis re-infection. Secondary objective was to identify characteristics independently associated with co-infection and re-infection. RESULTS Of 500 newly diagnosed HIV patients, 20% presented a concomitant positive syphilis serology. Among them, 54 patients had a serology indicative for an active syphilis requiring therapy, while 46 had a history of prior treatments. The independent factors for syphilis acquisition were: MSM contact (OR:2.64; 95%CI 1.48-4.72; p

The occurrence of COVID-19 pandemic had a significant negative effect on health care systems over the last year. Health care providers were forced to focus mainly on COVID-19 patients, neglecting in many cases equally important diseases, both acute and chronic. Therefore, also screening and diagnostic strategies for HIV could have been significantly impaired. This retrospective, multicenter, observational study aimed at assessing the number and characteristics of new HIV/AIDS diagnoses during COVID-19 pandemic in Italy and compared characteristics of people living with HIV at diagnosis between pre- and post-COVID-19 era (2019 vs 2020). Our results showed a significant reduction of HIV diagnoses during pandemic. By contrast, people living with HIV during pandemic were older and were diagnosed in earlier stage of disease (considering CD4+ T cell count) compared to those who were diagnosed the year before. Moreover, there was a significant decrease of new HIV diagnoses among men who have sex with men, probably for the impact of social distancing and restriction applied by the Italian Government. Late presentation incidence, if numbers in 2020 were lower than those in 2019, is still an issue. Routinely performing HIV testing in patients with suspected SARS-CoV-2 infection is identifying and linking to care underdiagnosed people living with HIV earlier. Thus, combined tests (HIV and SARS-CoV-2) should be implemented in patients with SARS-CoV-2 symptoms overlapping HIV's ones. Lastly, our results lastly showed how urgent implementation of a national policy for HIV screening is necessary.

ObjectivesTo evaluate HIV-1 tropism in 1382 combined antiretroviral therapy (cART)-experienced patients failing therapy to characterize those with exhausted therapeutic options.MethodsHIV-1 genotypic tropism was inferred through Geno2Pheno by estimating the false-positive-rate (FPR) values. Cumulative resistance and drug activity were evaluated by Stanford algorithm.ResultsOverall, median (IQR) CD4 count (cells/mm3) nadir and at last genotypic resistance test (GRT) available were 98 (33–211) and 312 (155–517), respectively. Considering HIV-1 tropism, 30.5% had X4/dual-mixed strains (FPR ≤5%: 22.2%; FPR 5%–10%: 8.3%). By stratifying according to tropism, by decreasing FPR, a significant decrease of CD4 nadir and at last GRT was observed. The proportion of individuals with CD4 count ConclusionsOur findings showed that a small proportion of cART failing individuals have limited therapeutic options. However, tropism determination might help to identify people who have accumulated a high level of resistance and have a greater risk of advanced disease.

We reported the efficacy and safety data for daclatasvir (DCV)-based all-oral antiviral therapy in patients treated in the Italian compassionate-use program. 275 patients were included (202 male-73.5%, mean age: 57.4 years, 62 HIV-coinfected, 94 with recurrence of hepatitis C post-OLT). Forty-nine patients (17.8%) had Child-Pugh B, Genotype(G) distribution was: G1a:72 patients (26.2%), G1b:137 (49.8%); G3:40 (14.5%) and G4:26 (9.5%). Patients received DCV with sofosbuvir(SOF) (n = 221, 129 with ribavirin(RBV) or with simeprevir (SMV) or asunaprevir (ASU) (n = 54, 19 with RBV) for up to 24 weeks. Logistic regression was used to identify baseline characteristics associated with sustained virological response at week 12 post-treatment (SVR12). Liver function changes between baseline and follow up were assessed in 228 patients. 240 patients achieved SVR12 (87.3%), post transplant and HIV co-infected patients were equally distributed among SVR and no SVR (35% vs 34.3%; p = 0.56 and 24.2% vs 11.4%, p = 0.13, respectively). SVR rate was significantly higher with the combination DCV + SOF compared with DCV + SIM or ASU (93.2% vs 63.0%, p

Objectives To compare the efficacy of dolutegravir plus lamivudine dual therapy (DT) with that of dolutegravir plus two NRTIs triple therapy (TT) as switch strategies. Methods A multicentre cohort of HIV-positive, HBsAg-negative patients with viral suppression (HIV-RNA ≤50 copies/mL) switching to DT or TT was retrospectively selected from the ARCA database. The effect of DT versus TT on virological failure (VF; defined as two consecutive HIV-RNA values >50 copies/mL or one HIV-RNA value ≥200 copies/mL) was evaluated by multivariable Cox regression models, overall and after stratifying for the presence of NRTI resistance-associated mutations (RAMs). Results From December 2014 to June 2020, 628 patients were eligible: 118 (18.8%) started tenofovir/emtricitabine/dolutegravir, 306 (48.7%) abacavir/lamivudine/dolutegravir and 204 (32.5%) lamivudine/dolutegravir. The DT group had significantly higher nadir and baseline CD4 counts, a higher duration of viral suppression and a lower prevalence of RAMs at historical genotype. Overall, 41 VF occurred after a median of 1.7 years of follow-up, with a lower, but not statistically significant, rate for DT [versus TT, adjusted HR (aHR) = 0.58, 95% CI = 0.25–1.34]. However, DT was associated with less VF in the absence of RAMs when compared with tenofovir-based TT (aHR = 0.20, 95% CI = 0.06–0.67), but not with abacavir-based TT (aHR = 0.43, 95% CI = 0.17–1.11). Conversely, in the setting of pre-existing M184V/I, DT showed a trend to increased risk of VF (versus tenofovir-based TT, aHR = 137.50, 95% CI = 4.24–4464.06; versus abacavir-based TT, aHR = 33.88, 95% CI = 1.75–656.47). Conclusions Lamivudine/dolutegravir maintenance DT showed similar efficacy to dolutegravir-based TT; however, past M184V/I may favour VF.

OBJECTIVES We evaluated the virological response and resistance profile in combined antiretroviral therapy (cART)-experienced HIV-1-infected patients starting a dual therapy with dolutegravir (DTG) and boosted darunavir (bDRV) for the first time. METHODS Survival analyses were used to evaluate virological success (VS) and virological rebound (VR) in viraemic and virologically suppressed patients, respectively. Major resistance mutations (MRMs) and genotypic susceptibility score (GSS) were evaluated at baseline and after switch. RESULTS Overall, 130 patients [62 (47.7%) viraemic; 68 (52.3%) virologically suppressed] were retrospectively analysed. At the moment of switch, 81.5% accumulated one or more MRM [protease inhibitor (PI), 35.7%; nucleoside(t)ide reverse transcriptase inhibitor (NRTI), 77.5%; non-NRTI, 69.0%; integrase inhibitor (INI), 10.1%), but 77.7% harboured strains fully susceptible to DTG + bDRV. In viraemic patients, the overall probability of VS by 12 months of treatment was 91.7%. In virologically suppressed patients, the overall probability of VR was 10.5% by 24 months after therapy start. Patients with previous time under virological suppression ≤ 6 months showed a higher VR probability compared with others (37.5% vs. 6.7%, P

Immune checkpoint inhibitors (ICIs) changed management of non-small-cell lung cancer, but resistance usually develops. Today, at ICIs failure, chemotherapy is the treatment of choice, but the chance of immunotherapy rechallenge is appealing. Another challenging issue is whether it is safe to treat HIV-positive patients with ICIs: safety and efficacy of immunotherapy have been marginally considered in this subgroup. We report the case of a non-small-cell lung cancer patient treated by PD-1 inhibitors rechallenge despite his HIV-positivity, achieving good partial response with significant clinical benefit and without toxicities. Our experience underlines that HIV-positive patients can be treated similarly to HIV-negative individuals. HIV-positivity should be considered similar to other comorbidities, and not as a sufficient reason to preclude them the best available treatments.

Objectives: Although outcomes of antiretroviral therapy (ART) have been evaluated in randomized controlled trials, experiences from subpopulations defined by age, CD4 count or viral load (VL) in heterogeneous real-world settings are limited. Methods: The study design was an international multicohort collaboration. Logistic regression was used to compare virological and immunological outcomes at 12±3months after starting ART with an integrase strand transfer inhibitor (INSTI), contemporary nonnucleoside reverse transcriptase inhibitor (NNRTI) or boosted protease inhibitor (PI/b) with two nucleos(t)ides after 1 January 2012. The composite treatment outcome (cTO) defined success as VL'200 HIV-1 RNA copies/mL with no regimen change and no AIDS/death events. Immunological success was defined as a CD4count '750cells/μL or a 33% increase where the baseline CD4 count was ≥500 cells/μL. Poisson regression compared clinical failures (AIDS/death≥14days after starting ART). Interactions between ART class and age, CD4 count, and VL were determined for each endpoint. Results: Of 5198 ART-naïve persons in the International Cohort Consortium of Infectious Diseases (RESPOND), 45.4% started INSTIs, 26.0% PI/b and 28.7% NNRTIs; 880 (17.4%) were aged ' 50years, 2539 (49.4%) had CD4 counts '350 cells/μL and 1891 (36.8%) had VL'100000 copies/mL. Differences in virological and immunological success and clinical failure among ART classes were similar across age groups (≤ 40, 40–50 and '50 years), CD4 count categories (≤ 350 vs. '350 cells/μL) and VL categories at ART initiation (≤ 100000 vs. '100000copies/mL), with all investigated interactions being nonsignificant (P'0.05). Conclusions: Differences among ART classes in virological, immunological and clinical outcomes in ART-naïve participants were consistent irrespective of age, immune suppression or VL at ART initiation. While confounding by indication cannot be excluded, this provides reassuring evidence that such subpopulations will equally benefit from contemporary ART.

Virological response and resistance profile were evaluated in drug-naïve patients starting their first-line integrase inhibitors (INIs)-based regimen in a clinical setting.Virological success (VS) and virological rebound (VR) after therapy start were assessed by survival analyses. Drug-resistance was evaluated at baseline and at virological failure.Among 798 patients analysed, 38.6 %, 27.1 % and 34.3 % received raltegravir, elvitegravir and dolutegravir, respectively. Baseline resistance to NRTIs, NNRTIs, PIs and INIs was: 3.9 %, 13.9 %, 1.6 % and 0.5 %, respectively. Overall, by 12 months of treatment, the probability of VS was 95 %, while the probability of VR by 36 months after VS was 13.1 %. No significant differences in the virological response were found according to the INI used. The higher pre-therapy viremia strata was (100,000 vs. 100,000-500,000 vs.500,000 copies/mL), lower was the probability of VS (96.0 % vs. 95.2 % vs. 91.1 %, respectively, P0.001), and higher the probability of VR (10.2 % vs. 15.8 % vs. 16.6 %, respectively, P = 0.010). CD4 cell count200 cell/mmOur findings confirm that patients receiving an INI-based first-line regimen achieve and maintain very high rates of VS in clinical practice.

Objectives Nucleoside reverse transcriptase inhibitor (NRTI) transmitted drug resistance mutations (TDRMs) could increase the risk of virological failure (VF) of first-line integrase strand transfer inhibitor (InSTI)-based regimens. Methods Patients starting two NRTIs (lamivudine/emtricitabine plus abacavir/tenofovir) plus raltegravir or dolutegravir were selected from the EuResist cohort. The role of NRTI genotypic susceptibility score and of specific TDRMs in VF (i.e. two consecutive viral loads > 50 HIV-1 RNA copies/mL or a single viral load ≥ 200 copies/mL after 3 months from antiretroviral therapy start) was evaluated in the overall population and according to the InSTI employed. Results From 2008 to 2017, 1095 patients were eligible for the analysis (55.5% men, median age 39 years). In all, 207 VFs occurred over 1023 patient-years of follow-up. The genotypic susceptibility score (GSS) had no effect on the risk of VF in the overall population. However, the presence of M184V/I independently predicted VF of raltegravir- but not dolutegravir-based therapy when compared with a fully-active backbone [adjusted hazard ratio (aHR) = 3.09, P = 0.035], particularly when associated with other non-thymidine analogue mutations (aHR = 27.62, P = 0.004). Higher-zenith HIV-RNA and lower nadir CD4 counts independently predicted VF. Conclusions NRTI backbone TDRMs increased the risk of VF with raltegravir-based but not dolutegravir-based regimens.

ObjectivesTo evaluate the prevalence and therapeutic relevance of drug resistance among isolates from ART-experienced HIV-1-infected patients over the past two decades in Italy.MethodsDynamics of resistance to one, two and three or more antiretroviral classes were evaluated from 1999–2018. Virological success (VS) after the latest therapy switch was evaluated according to cumulative class resistance and cumulative genotypic susceptibility score (Stanford HIV_DB algorithm).ResultsAmong 13 663 isolates (from 6739 patients), resistance to at least one drug class decreased sharply from 1999 to 2010 (≤2001, 84.6%; 2010, 43.6%; P ConclusionsA dramatic drop of HIV-1 drug resistance at failure has been achieved over the last two decades in Italy; resistance to three or more classes is low but present among currently failing patients. Its management still requires a rational and careful diagnostic and therapeutic approach.

Background An increase in pretreatment drug resistance (PDR) to first-line antiretroviral therapy (ART) in low-income countries has been recently described. Herein we analyse the prevalence of PDR and risk of virological failure (VF) over time among migrants to Italy enrolled in ARCA. Methods HIV-1 sequences from ART-naive patients of non-Italian nationality were retrieved from ARCA database from 1998 to 2017. PDR was defined by at least one mutation from the reference 2009 WHO surveillance list. Results Protease/reverse transcriptase sequences from 1,155 patients, mainly migrants from sub-Saharan Africa (SSA; 42%), followed by Latin America (LA; 25%) and Western countries (WE; 21%), were included. PDR was detected in 8.6% of sequences (13.1% versus 5.8% for B and non-B strains, respectively; PConclusions PDR appeared to be stable over the years in migrants to Italy enrolled in ARCA; however, it still remains an important cause of VF together with viral load at diagnosis.

Background: No therapy is approved for COVID-19 pneumonia. The aim of this study was to assess the role of tocilizumab in reducing the risk of invasive mechanical ventilation and death in patients with severe COVID-19 pneumonia who received standard of care treatment. Methods: This retrospective, observational cohort study included adults (≥18 years) with severe COVID-19 pneumonia who were admitted to tertiary care centres in Bologna and Reggio Emilia, Italy, between Feb 21 and March 24, 2020, and a tertiary care centre in Modena, Italy, between Feb 21 and April 30, 2020. All patients were treated with the standard of care (ie, supplemental oxygen, hydroxychloroquine, azithromycin, antiretrovirals, and low molecular weight heparin), and a non-randomly selected subset of patients also received tocilizumab. Tocilizumab was given either intravenously at 8 mg/kg bodyweight (up to a maximum of 800 mg) in two infusions, 12 h apart, or subcutaneously at 162 mg administered in two simultaneous doses, one in each thigh (ie, 324 mg in total), when the intravenous formulation was unavailable. The primary endpoint was a composite of invasive mechanical ventilation or death. Treatment groups were compared using Kaplan-Meier curves and Cox regression analysis after adjusting for sex, age, recruiting centre, duration of symptoms, and baseline Sequential Organ Failure Assessment (SOFA) score. Findings: Of 1351 patients admitted, 544 (40%) had severe COVID-19 pneumonia and were included in the study. 57 (16%) of 365 patients in the standard care group needed mechanical ventilation, compared with 33 (18%) of 179 patients treated with tocilizumab (p=0·41; 16 [18%] of 88 patients treated intravenously and 17 [19%] of 91 patients treated subcutaneously). 73 (20%) patients in the standard care group died, compared with 13 (7%; p

Objectives To compare virologic and immunologic outcomes of integrase inhibitor (INSTI)-containing, contemporary boosted protease inhibitor (PI/b)-containing and non-nucleotide reverse transcriptase inhibitor (NNRTI)-containing regimens in a real-life setting. Methods Using logistic regression, virologic and immunologic outcomes of INSTI use were compared to outcomes of PI/b or NNRTI treatment 12 months after treatment start or switch, for participants in the RESPOND cohort consortium. A composite treatment outcome (cTO) was used, defining success as viral load (VL), SCOPUS: ar.j, info:eu-repo/semantics/published

PurposeThe 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.ParticipantsThe 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 dateIn 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 plansTo continue to study long-term efficacy and tolerability of DTG-based regimens is the purpose of the ODOACRE cohort.

Background: Dolutegravir (DTG) is a next-generation HIV integrase inhibitor (INI) with an increased genetic barrier to resistance with respect to raltegravir (RAL) or elvitegravir (EVG). Few data are available on the durability of DTG-containing regimens. Objectives: We aimed at investigating the duration of the DTG-containing regimen, the occurrence of an HIV-1 RNA blip, and factors associated with DTG virological response. Study design: From the Antiviral Response Cohort Analysis database, we selected 89 HIV-1-positive four-class-experienced subjects who started DTG after receiving RAL or EVG. Factors associated with durability and virological response were analysed by logistic regression. Results: After a median duration of 18.8 [0.4-76.2] months, 79/89 (88.8%) subjects were still on DTG. All subjects remaining on DTG at the end of follow-up had undetectable HIV-1 RNA, compared to 5/10 subjects who discontinued DTG. DTG discontinuation was less frequent in patients who had experienced >=10 regimens (HR 0.11, p = 0.040). The probability of having an HIV-1 RNA positive value at the last follow-up significantly increased in patients with non-B HIV-1 subtype (HR 5.77, p 200/?L (HR 0.29, p = 0.038), with more than 10 previous regimens (HR 0.27, p = 0.040), and who harbored virus with IN mutations (HR 0.12, p = 0.023) at DTG start. Conclusions: After previous exposure to first-generation INIs, treatment with DTG showed long durability and did not show virological rebound after virological suppression. Subjects infected with a non-B HIV-1 subtype had a greater risk of having detectable HIV-1 RNA at the last observation.

Objectives To examine the impact of transmitted drug resistance (TDR) on response to first-line regimens with integrase strand transfer inhibitors (INSTIs) or boosted protease inhibitors (bPIs). Methods From an Italian observational database (ARCA) we selected HIV-1-infected drug-naive patients starting two NRTIs and either an INSTI or a bPI, with an available pre-ART resistance genotype. The endpoint was virological failure (VF; plasma HIV-1 RNA >200 copies/mL after week 24). WHO surveillance drug resistance mutations and the Stanford algorithm were used to classify patients into three resistance categories: no TDR (A), TDR but fully-active ART prescribed (B), TDR and at least low-level resistance to one or more prescribed drug (C). Results We included 1365 patients with a median follow-up of 96 weeks (IQR 54-110): 1205 (88.3%) starting bPI and 160 (11.7%) INSTI. Prevalence of TDR was 6.1%, 12.5%, 2.6% and 0% for NRTI, NNRTI, bPI and INSTI, respectively. Cumulative Kaplan-Meier estimates for VF at 48 weeks were 11% (95% CI 10.1%-11.9%) for the bPI group and 7.7% (95% CI 5.4%-10%) for the INSTI group. In the INSTI group, cumulative estimates for VF at 48 weeks were 6% (95% CI 4%-8%) in resistance category A, 5% (95% CI 1%-10%) in B and 50% (95% CI 30%-70%) in C (P

ObjectiveWe evaluated the characteristics of HIV-1 molecular transmission clusters (MTCs) in 1890 newly diagnosed individuals infected with non-B subtypes between 2005 and 2017 in Italy.MethodsPhylogenetic analyses were performed on pol sequences to characterise subtypes/circulating recombinant forms and identify MTCs. MTCs were divided into small (SMTCs, 2–3 sequences), medium (MMTCs, 4–9 sequences) and large (LMTCs, ≥10 sequences). Factors associated with MTCs were evaluated using logistic regression analysis.Results145 MTCs were identified and involved 666 individuals (35.2%); 319 of them (16.9%) were included in 13 LMTCs, 111 (5.9%) in 20 MMTCs and 236 (12.5%) in 112 SMTCs. Compared with individuals out of MTCs, individuals involved in MTCs were prevalently Italian (72.7% vs 30.9%, p9/L: 0.4 (0.265–0.587) vs 0.246 (0.082–0.417), p10 copies/mL: 4.8 (4.2–5.5) vs 5.0 (4.3–5.5), p=0.87). Logistic regression confirmed that certain factors such as being MSM, of Italian origin, younger age and higher CD4 cell count were significantly associated with MTCs.ConclusionsOur findings show that HIV-1 newly diagnosed individuals infected with non-B subtypes are involved in several MTCs in Italy. These MTCs include mainly Italians and MSM and highlight the complex phenomenon characterising the HIV-1 spread. This is important especially in view of monitoring the HIV epidemic and guiding the public health response.

This study investigated the prevalence of doravirine (DOR) resistance mutations in non-nucleoside reverse transcriptase inhibitor (NNRTI)-experienced patients. DOR resistance was assessed in samples from NNRTI-experienced patients who underwent genotypic testing for virological failure from the Antiretroviral Response Cohort Analysis (ARCA) database. Intermediate DOR resistance was defined as detection of any of V106A/M, Y188C/H, V108I, and K103N+P225H. High-level DOR resistance was defined as detection of any of Y188L, M230L, G190E, V106A/M+F227L, and V106A/M+L234I. Overall, 6893 patients were included in the study: 64.2% had experienced efavirenz (EFV), 54.4% nevirapine (NVP), 6.8% etravirine (ETR), 7.7% rilpivirine (RPV) and 0.7% delavirdine. Among NNRTI-experienced patients, 12.7% and 6.1% of subjects had intermediate and high-level DOR resistance, respectively. The most common DOR resistance mutation was Y188L. In multivariable analysis, previous EFV use (OR = 1.52, 95% CI 1.15–2.02) and ETR use (OR = 1.91, 95% CI 1.34–2.73) were associated with detection of high-level DOR resistance, whilst RPV use was associated with a lower probability of high-level DOR resistance (OR = 0.39, 95% CI 0.22–0.71). Moreover, EFV use (OR = 1.76, 95% CI 1.19–2.58) and ETR use (OR = 1.72, 95% CI 1.10–2.68) were associated with detection of the Y188L mutation, whereas RPV use was not (OR = 0.16, 95% CI 0.05–0.50). In Italy, DOR resistance is uncommon among NNRTI-experienced patients, confirming a distinguishing resistance pattern within NNRTIs. However, previous EFV and ETR experience poses a higher risk of DOR resistance. These results support the use of DOR in NNRTI-experienced patients.

The accumulation of drug-resistance mutations on combined antiretroviral regimens (ART) backbone could affect the virological efficacy of the regimen. Our aim was to assess the impact of previous drug resistance to nucleoside reverse transcriptase inhibitors (NRTIs) on the probability of virological failure (VF) in patients, under virological control, who switched to dolutegravir (DTG)+2NRTIs regimens. All HIV-1 positive drug-experienced patients who started a regimen composed by DTG+2NRTIs [abacavir/lamivudine or tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF)/emtricitabine (FTC)] in the ARCA collaborative group with HIV-RNA50 cp/mL were included in the analysis. Patients with a previous VF to integrase inhibitors were excluded. The impact of single and combined NRTIs mutations on the probability of VF (defined as 2 consecutive HIV-RNA50 copies/mL or one HIV-RNA1000 copies/mL) was assessed by Kaplan Meier curves. A multivariable Cox regression analysis was constructed to assess factors potentially related to VF. Five hundred and eighty-eight patients were included in the analysis with a median time of viral suppression before the switch of 37 months (IQR 12-78), of whom 148 (25.2%) had at least one previous NRTIs resistance mutation. In the multivariable model no association was observed between NRTIs mutations and VF. Conversely, the duration of viral suppression before switch resulted associated with a lower risk of VF (for 1 month increase, adjusted Hazard Ratio 0.98, 95%CI 0.96-0.99; p=0.024). Previous NRTIs mutations appeared to have no impact on the risk of VF in patients switched to DTG+2NRTIs, whereas a longer interval on a controlled viremia decreased significantly the risk of VF.

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/mm3 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 Conclusions These findings confirm the efficacy and tolerability of 3TC+DTG in virologically suppressed patients.

Background PrEP with FTC/TDF has shown great efficacy in preventing new HIV infections but issues remain (low adherence, high costs, toxicity and resistance development). No data are available about the impact of circulating Resistance-Associated Mutations (RAMs) on its efficacy. Objectives describe the prevalence of FTC and/or TDF-related RAMs in Italian HIV-infected population and their potential impact on PrEP efficacy. Study design ARCA is a national database that collects data about RAMs and epidemiological correlates from sites throughout Italy; it was queried about the prevalence of these RAMs in the last decade. PrEP efficacy was adjusted for a dynamic score based on RAMs prevalence. Absolute and relative risk increases (ARI and RRI) and number needed to harm (NNH) were calculated after this score. Results the query retrieved 3579 HAART-naive and 5781 experienced subjects. Resistance to TDF is low and more common among naive MSM in the area of Milan (where it topped to 14.3%), without other significant differences. If good adherence is not attained, RRI for receptive anal sex increases by 16% (in naive) and 93.4% (in experienced MSM). NNH is largely above 10000 except for having receptive anal sex with a HAART-experienced MSM on a failing treatment (970). Conclusions according to this model, PrEP may be introduced in Italy without general concerns, but efficacy may be partly reduced in young MSM having sex in Rome and Milan.

Objectives We evaluated the virological response in patients starting a regimen based on darunavir/ritonavir (DRV/r), which is currently the most widely used ritonavir-boosted protease inhibitor. Methods Data from 206 drug-naive and 327 PI-experienced patients starting DRV/r 600/100 mg twice daily (DRV600) or 800/100 mg once daily (DRV800) were examined. The probabilities of virological success (VS) and virological rebound (VR) were evaluated in survival analyses. Baseline DRV/r resistance and its evolution at failure were also examined. Results DRV600 was preferentially administered in patients with complex requirements (older age, higher viraemia, lower CD4 cell count and DRV/PI resistance) compared with DRV800. By 12 months, the probability of achieving VS was 93.2% and 84.3% in drug-naive and PI-experienced patients, respectively. The higher the baseline viraemia, the longer was the time required to achieve VS, both in drug-naive patients [>500 000 HIV-1 RNA copies/mL: median [interquartile range (IQR)] 6.1 (5.1–10.3) months; 100 000–500 000 copies/mL: median (IQR) 4.9 (3.8–6.1) months

BACKGROUND Screening tests for human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) and syphilis infections performed in at-risk population show a higher number of positive tests compared to those carried out in the general population. 'Test & Counselling' Ambulatory of Infectious Disease Clinic (T&C-IDC) and Sexually Transmitted Diseases Ambulatory of Dermatology Unit (STDs-DU) of Modena began collaboration in 2010 and adopted a common diagnostic serological profile since 2013. OBJECTIVES The main objective was to analyse the number of screening tests performed in the T&C-IDC and STDs-DU, comparing the results obtained after the adoption of the shared protocol with the previous period. The secondary aim was to evaluate the linkage to care of newly diagnosed patients. METHODS Consecutive patients referred to the T&C-IDC and STDs-DU from January 2010 to December 2016, with at least one performed screening test for HIV, HBV, HCV and syphilis were enrolled. Referral of patients with a new infection was obtained by capture-recapture methods in hospital databases. RESULTS During the 7-year observation, we collected 13 117 admittances for 9154 patients. A significant increase in the number of screening tests (P

Background Dual therapy (DT) with boosted protease inhibitors (bPIs) plus lamivudine has been shown to be superior to bPI monotherapy in virologically suppressed patients despite previous selection of the lamivudine resistance M184V mutation. We compared the virological efficacy of lamivudine-based DT in patients with and without a history of M184V detection. Methods We retrospectively analyzed patients with HIV-RNA ≤50 copies/mL switching to DT with at least 1 previous resistance genotype in the ARCA database. Time to virological failure (VF; HIV-RNA ≥200 copies/mL or 2 consecutive HIV-RNA >50 copies/mL) and to treatment discontinuation (TD) was analyzed by survival analysis. Results Four hundred thirty-six patients switching to lamivudine plus bPIs (70%) or integrase inhibitors (30%) were included. Patients with M184V (n = 87) were older, had lower nadir CD4+ cell count, longer duration of antiretroviral therapy and of virologic suppression, and higher rate of hepatitis C virus infection compared with patients without M184V. The 3-year probability of remaining free from VF was 91.9% (95% confidence interval [CI], 86.6–97.2) without M184V and 87.8% (95% CI, 78.4–97.2) with M184V (P = .323). The time to TD did not differ between groups. Multivariate analysis adjusting for baseline variables differing between groups also did not detect M184V as being associated with VF or TD; however, the 3-year probability of remaining free of viral blips (isolated HIV-RNA 51–199 copies/mL) was 79.8% (95% CI, 67.8%–91.8%) with M184V vs 90.1% (95% CI, 84.0%–96.2%) without M184V (P = .016). Conclusions Previous selection of M184V did not increase the risk of VF or TD with lamivudine-based DT but was associated with a higher probability of viral blips.

Men who had sex with men (MSM) living with HIV are at higher risk of developing sexual transmitted diseases. This study reports two years incidence rate and prevalence of HCV in a cohort of HIV positive MSM.MSM HIV-positive outpatients negative to HCV-Ab at first observation entered a Kaplan-Meier model in order to assess the HCV infection incidence rate. Prevalence analysis was performed with MSM HIV-positive that were on follow-up at 2016. An MSM population HIV-negative served as control.421 patients entered the incidence analysis. The incidence rate of HCV infection among MSM-HIV people was 0.44 per 100 patients-years (19 events). 40 out of 442 (9%) patients were HCV-positive (prevalence analysis); they were mostly genotype 1a and 3 with APRI score0.7 (87.5%). Univariate analysis between MSM HIV-positive patients and MSM HIV-negative showed significant differences in the prevalence rate (9.0% vs 0.6%, P 0.001) and median age (39 vs 47, P 0.001).Incidence and prevalence rate of HCV amongst MSM HIV-positive patients is higher than in other settings. Annual HCV-Ab screening for MSM HIV-positive patients should be enforced and early treatment of HCV recommended.

Background Genotypic resistance test (GRT) performed in peripheral blood mononuclear cells (PBMC) represents a chance to evaluate resistance in virologically suppressed HIV infected patients. Objectives To evaluate the impact of baseline resistance detected through PBMC GRT on virological rebound after switching treatment. Study design Baseline genotypic susceptibility scores (GSS) from PBMC GRT (DNA-GSS) and from previous cumulative plasma GRTs (when available, pRNA-GSS) were evaluated. Survival analysis was used to assess the probability and predictors of virological rebound (VR). Results 227 virologically suppressed patients were analysed. Twenty-four months after switching therapy, the probability of VR was 15.3%. Patients showing an intermediate or full resistant DNA-GSS had a higher probability of experiencing VR compared to those carrying a fully susceptible DNA-GSS (27.2% vs. 13.7%, p = 0.001). By multivariable Cox regression, patients with an intermediate/full resistant DNA-GSS, with a nadir CD4 count In a sub-group of 114 patients with previous plasma GRTs available, patients with an intermediate or fully resistance showed by both GSSs (from plasma and PBMCs) had the highest probability of experiencing VR. Conclusions Resistance detected in proviral DNA, together with a low nadir CD4 count and a short previous virological control, predicts VR after therapy switching in virologically suppressed patients. PBMC GRT can be a useful tool for tailoring treatment switch, especially if paired with information about previous cumulative resistance and previous viro-immunological history.

Purpose: To analyse safety and efficacy of treatment based on ombitasvir/paritaprevir/ritonavir/dasabuvir plus ribavirin in the sub-group of GT1 patients older than 65years. Methods: We collected data extracted from the ABACUS compassionate-use nationwide Italian programme, in patients with cirrhosis due to hepatitis C virus (HCV) Genotype-1 (GT1) or 4 and at high risk of decompensation. GT1-HCV-infected patients received once-daily ombitasvir/paritaprevir, with the pharmacokinetic enhancer ritonavir (25/150/100mg) and twice-daily dasabuvir (250mg) plus Ribavirin (RBV) (OBV/PTV/r + DSV + RBV) for 12 (GT1b) or 24 (GT1a) weeks. Endpoints were to evaluate safety and efficacy, the latter defined as HCV RNA negative 12weeks after the end of treatment (SVR12). Results: Patients who suffered any adverse event (AE) were 74/240 (30.8%); 13/240 (5.4%) discontinued the treatment. A multivariate analysis found albumin < 3.5g/dL (OR 2.04: 95% CI 1.0–4.2, p < 0.05) and hypertension (OR 4.6: 95% CI 2.3–9.2, p < 0.001) as variables independently associated with AE occurrence. The SVR12 was 95% (228/240). Multivariate analysis identified baseline bilirubin < 2mg/dL (OR 4.9: 95% CI 1.17–20.71, p = 0.029) as the only variable independently associated with SVR12. Conclusion: Our findings suggest that OBV/PTV/r + DSV + RBV is safe and effective in real-life use in patients with compensated cirrhosis, HCV-GT1 infection, and age over 65.

The renal function is a key-issue in HIV/HCV co-infected patients, nevertheless, it has not established so far whether HCV treatment with new direct acting agents could impact on estimated glomerular filtration rate (eGFR) variations. In the present work, we examined the real-life data on renal function that have been prospectively collected in the SIMIT compassionate-use program of ombitasvir/paritaprevir/ritonavir plus dasabuvir (OBV/PTV/r + DSV) in 144 HIV/HCV genotype 1 co-infected patients. The population was 74% male, 30.5% in CDC stage C, with median age of 52 years (48.0-56.5) and median liver stiffness of 7.8 kPa (6.7-9.2). Median baseline eGFR was 102.0 (90.8-108.1), changing to 99.8 (83.5-104.8) at the end of treatment (EoT), and 100.0 (87.3-105.6) 12 weeks after the EoT (FU12), p

Previous article in issueNext article in issue Introduction: There is a limited documentation about the retreatment of patients failing a recommended NS5A-containing regimen in Italy. Materials & methods: Within the VIRONET-C network, 386 NS5A-failing patients infected with different HCV-genotypes (GT) (GT1a/1b/2a-c/3a-b-g-h/4a-d-n-o-v=93/124/19/112/38) were analyzed. Retreatment of 105 failures was investigated. HCV-resistance-test was performed by Sanger-sequencing. Results: Failures following seven different NS5A-containing regimens were studied: 3D/2D (paritaprevir/ombitasvir ± dasabuvir) ± ribavirin (N = 72/4), daclatasvir/ledipasvir/velpatasvir + sofosbuvir ± ribavirin (N = 105/131/20), grazoprevir/elbasvir ± ribavirin (N = 34), glecaprevir/pibrentasvir (N = 20). Notably, 18.1% of NS5A-failing patients did not show any resistance-associated-substitutions (RAS), while 81.9% showed at least one NS5A-RAS, with multiclass-resistance in 35.5%. NS5A-RAS were observed more frequently in glecaprevir/pibrentasvir failures (GT1a 83.3%: Y93H + Q30H/D or +H58D; GT3a: 83.3% Y93H + A30K/G or +L31I) compared to sofosbuvir/velpatasvir (GT1a 16.6%: Y93H + Q30H, p = 0.08; GT3a 20.0%: Y93H/N + A30K/T, p = 0.03). To date, 105 failures have started a retreatment: sofosbuvir/velpatasvir ± ribavirin (N = 30), sofosbuvir/velpatasvir/voxilaprevir ± ribavirin (N = 67), glecaprevir/pibrentasvir (N = 4), grazoprevir/elbasvir ± sofosbuvir + ribavirin (N = 3), 3D + sofosbuvir + ribavirin (N = 1). The majority of patients were cirrhotic (51.9%) and relapsers (87.5%). The prevalence of NS5A-RASs before retreatment was 80.9%, with multiclass-resistance 29.5%. Among patients completing post-retreatment follow-up, a sustained-viral-response at week 12 (SVR12) was observed in 26/33 (78.8%). SVR4 was documented in 49/56 (87.5%). SVR12 was 76.0% with sofosbuvir/velpatasvir ± ribavirin (N = 25). Differently, SVR12 was 100% with glecaprevir/pibrentasvir for 8/12/16 weeks (N = 3), grazoprevir/elbasvir ± sofosbuvir + ribavirin for 12/24 weeks (N = 3) or 3D + sofosbuvir + ribavirin for 24 weeks (N = 1), despite the presence of NS5A-RASs. Until now, 67 patients started sofosbuvir/velpatasvir/voxilaprevir ± ribavirin recommended-retreatment for 12 weeks. 54/67 (80.6%) showed at least one baseline NS5A-RAS, 23/67 (34.3%) multiple-NS5A-RASs, and 22/67 (32.8%) multiclass-resistance. Of 25 patients with available outcome, 96.0% had SVR4. Only 1 GT1b infected patient was non-responder, without RASs before retreatment. Conclusions: In this real-life setting, NS5A-RASs were frequently detected at failure, and multiclass-resistance was around 30%. Overall, SVR after resistance-test-guided retreatment was >95%, with the exception of the sofosbuvir/velpatasvir retreatment. Our results show how HCV resistance-test at failure may be useful to optimize retreatment strategies.

Background We tested whether pre-HAART viraemia affects the achievement and maintenance of virological success in HIV-1-infected patients starting modern first-line therapies. Methods A total of 1,430 patients starting their first HAART (genotype-tailored) in 2008 (median; IQR: 2006–2009) were grouped according to levels of pre-HAART viraemia (≤30,000, 30,001–100,000, 100,001–300,000, 300,001–500,000 and >500,000 copies/ml). The impact of pre-therapy viraemia on the time to virological success (viraemia ≤50 copies/ml) and on the time to virological rebound (first of two consecutive viraemia values >50 copies/ml after virological success) were evaluated by Kaplan–Meier curves and Cox regression analyses. Results Median pre-HAART viraemia was 5.1 log10 copies/ml (IQR 4.5–5.5), and 53% of patients had viraemia >100,000 copies/ml. By week 48, the prevalence of patients reaching virological success was >90% in all pre-HAART viraemia ranges, with the only exception of range >500,000 copies/ml (virological success =83%; P500,000 copies/ml showed the lowest hazard of virological undetectability after adjusting for age, gender, pre-HAART CD4+ T-cell count, transmitted drug resistance, calendar year and third drug administered (adjusted hazard ratio [95% CI]: 0.27 [0.21, 0.35]; P500,000 copies/ml was also associated with higher probability of virological rebound compared with patients belonging to lower viraemia strata at weeks 4, 12 and 24 ( P=0.050). Conclusions At the time of modern HAART, and even though an average >90% of virological success, high pre-HAART viraemia remains an independent factor associated with delayed and decreased virological success. Patients starting HAART with >500,000 copies/ml represent a significant population that may deserve special attention.

Background Aim of the study was to assess predictors of discontinuation/toxicity of boosted PI-based (PI/r) dual therapy (DT). Methods Observational, retrospective switch study in patients successfully treated with triple drugs regimen. Patients switched to PI/r based DT [darunavir (DRV/r), lopinavir (LPV/r) or atazanavir (ATV/r)] plus a second drug: [raltegravir (RAL), maraviroc (MVC) etravirine (ETR), lamivudine (3TC) or tenofovir (TDF)] between 2009 and 2014 were included. The effect of each drug as well as other clinical and virological cofactors over treatment discontinuation (TD) was assessed using survival analysis. Results Overall, 376 patients were included with mean follow-up of 73 weeks. The most commonly used drugs in DT were DRV/r (63.0 %) and RAL (53.7 %). TD was observed in 77 (20,4 %) patients: 38 (10,1 %) virological failure, 35 (9,3 %) toxicity/intolerance (4 deaths) and 4 (1 %) interruptions for patients decision. At Cox Model, adjusted by demographic and laboratory variables, DRV/r and ATV/r significantly reduced the likelihood of TD and longer treatment was associated with lower risk, while low CD4 count at baseline and number of previous regimens with a higher risk. Moreover, RAL and 3TC use were significantly associated with lower TD by toxicity. Conclusions In our clinical practice experience, switching virologically suppressed patients to PI/r based DT showed adequate safety and efficacy, so that it may be used in selected patients with specific medical needs.

In 2012, we conducted a retrospective cross-sectional study to assess the number of people living with HIV linked to care and, among these, the number of people on antiretroviral therapy. The health authority in each of the 20 Italian Regions provided the list of Public Infectious Diseases Clinics providing antiretroviral therapy and monitoring people with HIV infection. We asked every Public Infectious Diseases Clinic to report the number of HIV-positive people diagnosed and linked to care and the number of those on antiretroviral therapy during 2012. In 2012, 94,146 people diagnosed with HIV and linked to care were reported. The majority were males (70.1%), Italians (84.4%), and aged between 25 and 49 years (63.4%); the probable route of transmission was heterosexual contact in 37.5% of cases, injecting drug use in 28.1%, and male-to-male contact in 27.9%. Among people in care, 20.1% had less than 350 CD4 cells/μl, 87.6% received antiretroviral therapy, and among these, 62.4% had a CD4 cell count higher than 350 cells/μl. The overall estimated prevalence of individuals diagnosed and linked to care in 2012 in Italy was 0.16 per 100 residents (all ages). Adding the estimated proportion of undiagnosed people, the estimated HIV prevalence would range between 0.19 and 0.26 per 100 residents. In Italy, the majority of people diagnosed and linked to care receive antiretroviral therapy. A higher prevalence of individuals diagnosed and linked to care was observed in Northern Italy and among males. More information for developing the HIV care continuum is necessary to improve the entire engagement in care, focusing on test-and-treat strategies to substantially reduce the proportion of people still undiagnosed or with a detectable viral load.

Background : To assess the role of drugs used in dual therapy (DT), as cART simplification, over the risk of treatment failure. Material and Methods : Patients starting DT regimen composed by a boosted protease inhibitor (PI/r): darunavir (DRV/r), lopinavir (LPVr) or atazanavir (ATV/r) plus a second drug: raltegravir (RAL), maraviroc (MRV) etravirine (ETR), lamivudine (3TC) or tenofovir (TDF), this one generally used in HBV co-infected patients, were included. The effect of each drug as well as other clinical and virological cofactors over treatment failure was assessed using survival analysis. Results : Overall, 480 patients from six reference Italian centres were included: all switched to DT with HIV-RNA

We conducted a retrospective, multicenter study evaluating the safety of discontinuing maintenance therapy for cryptococcal meningitis after immune reconstitution. Inclusion criteria were a previous definitive diagnosis of cryptococcal meningitis, a CD4 cell count of100 cells/microL while receiving highly active antiretroviral therapy (HAART), and the subsequent discontinuation of maintenance therapy for cryptococcal meningitis. The primary end point was relapse of cryptococcal disease. As of July 2002, 100 patients were enrolled. When maintenance therapy was discontinued, the median CD4 cell count was 259 cells/microL and the median plasma virus load was2.30 log10 copies/mL, and serum cryptococcal antigen was undetectable in 56 patients. During a median follow-up period of 28.4 months (range, 6.7-64.5; 262 person-years), 4 events were observed (incidence, 1.53 events per 100 person-years; 95% confidence interval, 0.42-3.92). Three of these patients had a CD4 cell count of100 cells/microL and a positive serum cryptococcal antigen test result during the recurrent episode. In conclusion, discontinuation of maintenance therapy for cryptococcal meningitis is safe if the CD4 cell count increases to100 cells/microL while receiving HAART. Recurrent cryptococcal infection should be suspected in patients whose serum cryptococcal antigen test results revert back to positive after discontinuation of maintenance therapy.

A retrospective evaluation was conducted in patients with AIDS and an autopsy diagnosis of cytomegalovirus (CMV) encephalitis to determine the relevance of clinical and laboratory findings in establishing a diagnosis. On autopsy of 100 patients, CMV encephalitis was diagnosed in 13 patients; eight had periventricular CMV encephalitis, four micronodular CMV encephalitis, and one both conditions. Seven patients had had a CMV infection previously (6 cases of retinitis, 1 case of colitis), and at the onset of encephalitis all of them were receiving a maintenance dose of ganciclovir. Examination of the CSF showed specific changes in patients with periventricular encephalitis. CT revealed no characteristic findings, while MRI showed an increased signal intensity on T2 weighted images. CMV DNA amplification by nested PCR was performed in nine patients with CMV encephalitis; PCR was positive in eight patients whose CSF was collected during CMV encephalitis, and negative in one patient whose CSF was collected six months before death. In conclusion, some clinical findings suggest a presumptive diagnosis, especially of periventricular encephalitis, and nested PCR appears to be a reliable and rapid technique for making an antemortem diagnosis.

AIMS--To evaluate the presence of cytomegalovirus (CMV) DNA in the cerebrospinal fluid of patients with AIDS and suspected viral encephalitis using an in situ hybridisation assay with digoxigenin labelled CMV DNA probes. METHODS--The presence of CMV DNA was evaluated in cerebrospinal fluid cells of 10 patients with AIDS using in situ hybridisation. The positivity of CMV DNA was confirmed by the presence of CMV induced antigens in the same specimens. The presence of CMV DNA and CMV induced antigens was also analysed in peripheral blood leucocytes. The time required to perform the in situ hybridisation assay was about eight hours. RESULTS--The in situ hybridisation assay was sensitive, specific, and provided good resolution. Six patients proved positive for the presence of CMV DNA in CSF cells and all six also proved positive for CMV DNA in blood leucocytes. Of the six CMV positive patients, five were treated with specific antiviral drugs: of these, one died during the treatment while four clinically recovered after one month of treatment. CONCLUSIONS--The in situ hybridisation assay using digoxigenin labelled CMV DNA probes can be used as a valuable diagnostic test for the detection of CMV DNA in the cerebrospinal fluid cells of patients with suspected CMV encephalitis and can therefore prompt adequate antiviral therapeutic intervention.

Objectives: We analyzed clinical progression among persons diagnosed with HIV at the time of an AIDS-defining event, and assessed the impact on outcome of timing of combined antiretroviral treatment (cART). Methods: Retrospective, European and Canadian multicohort study.. Patients were diagnosed with HIV from 1997-2004 and had clinical AIDS from 30 days before to 14 days after diagnosis. Clinical progression (new AIDS event, death) was described using Kaplan-Meier analysis stratifying by type of AIDS event. Factors associated with progression were identified with multivariable Cox regression. Progression rates were compared between those starting early (