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A significant proportion of HIV-infected patients experiencing a late diagnosis highlights the need to define immunological protocols able to help the clinicians in identifying patients at higher risk for immunological failure. The aim of the study was to evaluate the feasibility of easy cytometric tests in defining the effect of antiretroviral treatment (cART) on immunological homeostasis and in identifying predictive markers of early immune recovery. Chronic HIV infected patients (n = 202) were enrolled in a prospective multicentric study, and their immunological profile was studied before (w0) and after 24 weeks (w24) of antiretroviral treatment (cART) using a standardized flow cytometric panel. Based on CD4 T cell count before treatment, patients were divided in late (LP: CD4 <350/mmc), intermediate (IP: 350/mmc500/mmc) presenters. In all groups, cART introduction increased CD4 and CD4/CD8 T cell ratio, naïve T cell (CD4 and CD8) and CD127-expressing CD4 T cells. In parallel, cART significantly reduced effector memory T cells (CD4 and CD8) and T cell activation (CD38+CD8 and CD95+CD4 T cells). Moreover, the frequency of Naïve and Effector CD4 T cells before treatment correlated with several immune parameters key associated with the pathogenesis of HIV, thus mirroring the health of immune system. Interestingly, we identified the Naïve/Effector CD4 T cell ratio (N/EM) at w0 as a marker able to predict early immune recovery. Specifically, in LP, N/EM ratio was significantly higher in immunological responder patients (CD4>500/mmc at w24) when compared to immunological non responder (CD4 T cells <500/mmc at w24). Finally, a multivariate analysis indicates that after 24w patients with N/EM ratio higher than 1.86 at w0 recovered 96 CD4 T cells more than those with N/EM ratio lower than 0.46. Altogether, our data define an easy protocol able to define reliable immunological markers useful for the characterization of immune profile in viremic HIV patients and identify the naïve/effector CD4 T cell ratio as a new tool able to predict an early immune reconstitution potential., Competing Interests: The support of Becton Dickinson does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Before Pre-Exposure Prophylaxis (PrEP) was officially recommended and made available, a few surveys among gay and bisexual men, and persons living with HIV/AIDS (PLWHA), identified an informal use of antiretrovirals (ARVs) for PrEP among HIV-negative individuals. Before PrEP availability in Italy, we aimed to assess whether PLWHA in Italy shared their ARVs with HIV-negative individuals, whether they knew people who were on PrEP, and describe the level of awareness and discussion on this preventive measure among them and people in their close circle., Methods: Two anonymous questionnaires investigating personal characteristics and PrEP awareness, knowledge, and experience were proposed to HIV specialists and their patients on ARVs in a one-week, cross-sectional survey (December 2013-January 2014). Among PLWHA, a Multivariable Logistic Regression analysis was conducted to identify factors associated with PrEP discussion with peers (close circle and/or HIV associations), and experience (use in close circle and/or personal ARV sharing)., Results: Eighty-seven specialists in 31 representative Infectious Diseases departments administered the questionnaire to 1405 PLWHA. Among specialists, 98% reported awareness, 65% knew the dosage schedule, and 14% had previously suggested or prescribed PrEP. Among PLWHA, 45.6% were somehow aware, discussed or had direct or indirect experience of PrEP: 38% "had heard" of PrEP, 24% were aware of studies in HIV-negative individuals demonstrating a risk reduction through the use of ARVs, 22% had discussed PrEP, 12% with peers; 9% reported PrEP use in close circle and 1% personal ARV sharing. Factors predictive of either PrEP discussion with peers or experience differed between men and women, but across all genders were mainly related to having access to information, with HIV association membership being the strongest predictor., Conclusions: At a time and place where there were neither official information nor proposals or interventions to guide public policies on PrEP in Italy, a significant number of PLWHA were aware of it, and approximately 10% reported PrEP use in their close circle, although they rarely shared their ARVs with uninfected people for this purpose. Official policies and PrEP availability, along with implementation programs, could avoid risks from uncontrolled PrEP procurement and self-administration practices.

Background: To investigate perceptions and attitude to prescribe Pre-Exposure Prophylaxis (PrEP) among HIV specialists., Methods: A questionnaire developed through a Focus Group and literature review was administered to a convenience sample of HIV specialists during educational courses in two Regions and an online survey in February-May 2012. Participants were classified as having a positive or negative attitude according to their willingness to prescribe PrEP. Demographic and working information, experience with HIV-infected patients, information and provision of antiretrovirals to uninfected persons, self-reported knowledge, perceptions and concerns regarding PrEP were assessed. The association between a different attitude towards PrEP prescription and selected characteristics was assessed through univariate and multivariate regression analysis., Results: Of 311 specialists, 70% would prescribe PrEP, mainly to serodiscordant partners (64%) but also to people at ongoing, high risk of HIV infection (56%); 66% advocated public support of costs. A negative attitude towards PrEP was significantly associated with lack of provision of information on, and prescription of, antiretroviral post-exposure prophylaxis; specialists with a negative attitude believed behavioural interventions to be more effective than PrEP and were more concerned about toxicity. Overall, 90% of specialists disagreed regarding a lack of time for engaging in prevention counselling and PrEP monitoring; 79% would welcome formal guidelines, while those with a negative attitude did not consider this advisable., Conclusions: Although conflicting attitudes appear evident, most specialists seem to be willing, with guidance from normative bodies, to promote PrEP within multiple prevention strategies among vulnerable populations. More scientific evidence regarding effectiveness could overcome resistance.

Antiretroviral prophylaxis (PEP) after occupational exposure to HIV in healthcare workers (HCWs) is used across Europe, but not in a consistent manner. A panel of experts, funded by the European Commission, formulated a set of recommendations. When it has been decided that the characteristics of the exposure indicate the initiation of PEP, PEP should be started as soon as possible; initiation is discouraged after 72 hours. PEP should be initiated routinely with any triple combination of antiretrovirals approved for the treatment of HIV-infected patients; a two class regimen is to be preferred. The source patient's treatment history should be sought. Counselling, psychological support, HIV testing and clinical evaluation should be performed at baseline, at 6-8 weeks, and at least 6 months post exposure. Additional clinical and laboratory monitoring at one and two weeks should be considered, as adherence with and tolerance of the regimen can highlight adverse reactions and potential toxicity. Routine HIV resistance tests in the source patient, and direct virus assays in the exposed HCW are not recommended.

The European Commission funded a project for the standardisation of the management of occupational exposures to HIV/blood-borne infections and antiretroviral post-exposure prophylaxis (PEP) in Europe. Within this project, the following recommendations and rationale were formulated by experts representative of participating countries. Based on assessment of the exposure, material, and source characteristics, PEP should be started as soon as possible with any triple combination of antiretrovirals approved for the treatment of HIV-infected patients; initiation is discouraged after 72 hours Rapid HIV testing of the source could reduce inappropriate PEP. HIV testing should be performed at baseline, 4, 12, and 24 weeks, with additional clinical and laboratory monitoring of adverse reactions and potential toxicity at week 1 and 2. HIV resistance tests in the source and direct virus assays in the exposed HCW are not recommended routinely. These easy-to-use recommendations seek to maximise PEP effect while minimising its toxicity and inappropriate use.

In 655 individuals receiving HIV postexposure prophylaxis (PEP), drug-induced aminotransferase alterations were frequent and severe in the nevirapine-including regimen, rare and mild-to-moderate in other combinations, and always reversible. Grade 3-4 incidence in protease inhibitor or nevirapine PEP was 0.5 and 25.0 per 100 person-months, respectively. Apart from nevirapine, continuing PEP appears to be safe even in the case of aminotransferase alterations. The usefulness of routine monitoring of liver function during PEP could be re-considered.

Objective: To evaluate short-term toxicity from and discontinuation of antiretroviral combination prophylaxis in HIV-exposed individuals in Italy., Design: Longitudinal, open study conducted by prospective collection of data in the National Registry of PEP., Setting: All the Italian centres dedicated to HIV related care and licensed by the Ministry of Health to dispense antiretroviral drugs., Study Population: Health care workers and other persons consenting to be treated with post exposure prophylaxis (PEP) after exposures to HIV., Results: Until October, 2000, 207 individuals receiving two nucleoside reverse transcriptase inhibitors (NRTIs), and 354 receiving two NRTIs plus a protease inhibitor (PI) were enrolled. More individuals experienced side-effects in the 3-drug group (53% and 62%, respectively; OR 0.68, (95% CI 0.48-0.98), p < 0.03). However, the proportion of individuals discontinuing prophylaxis because of side-effects did not differ significantly between the 2 groups (21% and 25% respectively; OR 0.82 (95% CI 0.53-1.26); p=0.4). The 43 individuals in the 2 NRTI group discontinued PEP after a mean of 10.4 days of treatment (median 8, range 1-27), similarly to the 88 discontinuations observed in the 3-drug group (mean duration 10.5 days, median 7.5, range 1-26). Type and incidence of specific adverse effects were similar to those reported in the literature., Conclusion: Our study indicates that the difference in the proportion of individuals developing side effects and discontinuing PEP is not significant. The rate of discontinuation because of protease inhibitor side-effects does not justify per se the initial use of a less potent PEP regimen. We suggest initiating PEP with a three-drug regimen and discontinuing the protease inhibitor in the case of adverse effects.