Non-B subtypes account for a large proportion of clustered primary HIV-1 infections in Italy.

Objectives And Design: Using sequences obtained for routine resistance testing, we characterised the molecular patterns of HIV-1 transmission and factors associated with being part of a transmission cluster among individuals who in 2008-2014 presented with primary HIV-1 infection (PHI) at 11 urban centres across Italy.

Methods: sequences were obtained by Sanger sequencing. Transmission clusters were identified by phylogenetic analysis (maximum likelihood method, confirmed by Bayesian analysis).

Broadly neutralizing antibody responses in the longitudinal primary HIV-1 infection Short Pulse Anti-Retroviral Therapy at Seroconversion cohort.

Objective: Development of immunogens that elicit an anti-HIV-1 broadly neutralizing antibody (bnAb) response will be a key step in the development of an effective HIV-1 vaccine. Although HIV-1 bnAb epitopes have been identified and mechanisms of action studied, current HIV-1 envelope-based immunogens do not elicit HIV-1 bnAbs in humans or animal models. A better understanding of how HIV-1 bnAbs arise during infection and the clinical factors associated with bnAb development may be critical for HIV-1 immunogen design efforts.

SARS-CoV-2 IgG/IgM Rapid Test as a Diagnostic Tool in Hospitalized Patients and Healthcare Workers, at a large Teaching Hospital in northern Italy, during the 2020 COVID-19 Pandemic.

We describe the outcome of a Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) IgG/IgM rapid test, and discuss the potential suitability of antibody testing. Retrospective single cohort study on patients with suspected Coronavirus Disease 2019 (COVID-19) and asymptomatic Healthcare Workers, enrolled from March to April 2020. Subjects had quantitative PCR (qPCR) test for detection of SARS-CoV-2 via nasal swab and serological testing using the COVID-19 IgG/ IgM Rapid Test (PRIMA Lab SA) immunochromatographic assay.

Enhanced Immunological Recovery With Early Start of Antiretroviral Therapy During Acute or Early HIV Infection-Results of Italian Network of ACuTe HIV InfectiON (INACTION) Retrospective Study.

Background: Viral load peak and immune activation occur shortly after exposure during acute or early HIV infection (AEHI). We aimed to define the benefit of early start of antiretroviral treatment (ART) during AEHI in terms of immunological recovery, virological suppression, and treatment discontinuation.

Setting: Patients diagnosed with AEHI (Fiebig stages I-V) during 2008-2014 from an analysis of 20 Italian centers.

Addition of Maraviroc Versus Placebo to Standard Antiretroviral Therapy for Initial Treatment of Advanced HIV Infection: A Randomized Trial.

Background: Patients diagnosed with advanced HIV infection have a poor prognosis despite initiation of combined antiretroviral therapy (c-ART).

Objective: To assess the benefit of adding maraviroc, an antiretroviral drug with immunologic effects, to standard c-ART for patients with advanced disease at HIV diagnosis.

Design: Randomized controlled trial.

The benefit of immediate compared with deferred antiretroviral therapy on CD4+ cell count recovery in early HIV infection.

Objective: To assess the impact of immediate vs. deferred antiretroviral therapy (ART) on CD4 recovery among individuals early in HIV infection.

Design: Using serologic markers of early infection together with self-reported dates of infection and HIV diagnosis, ART-naive participants who were randomized to immediate vs.

Long-term efficacy and safety of rilpivirine plus abacavir and lamivudine in HIV-1 infected patients with undetectable viral load.

Introduction: A regimen with rilpivirine (RPV), abacavir (ABC) and lamivudine (3TC) is simple and may allow the sparing of tenofovir and protease inhibitors. However, data on use of this combination as a strategy of switch are limited. Aims of the study were to assess the long-term efficacy and safety of this regimen.

Comparison of Self-report to Biomarkers of Recent HIV Infection: Findings from the START Trial.

Identifying individuals with recent HIV infection is critical to research related to viral reservoirs, outbreak investigations and intervention applications. A multi-assay algorithm (MAA) for recency of infection was used in conjunction with self-reported date of infection and documented date of diagnosis to estimate the number of participants recently infected in the Strategic Timing of AntiRetroviral Treatment (START) trial. We tested samples for three groups of participants from START using a MAA: (1) 167 individuals who reported being infected ≤ 6 months before randomization; (2) 771 individuals who did not know their date of infection but were diagnosed within 6 months before randomization; and (3) as controls for the MAA, 199 individuals diagnosed with HIV ≥ 2 years before randomization.

HIV reservoir dynamics in HAART-treated poor immunological responder patients under IL-7 therapy.

Objectives: Recombinant Human IL-7 (rhIL-7) therapy allows reconstituting systemic and tissue-associated CD4 T-cell populations in HIV-infected poor immunological responder (PIR) patients. However, in-vitro studies suggest that the impact of rhIL-7 treatment on HIV-DNA loads in vivo remains questionable.

Design: We assessed the dynamics of circulating HIV-DNA loads in IL-7-treated HIV-infected PIR individuals.

Proportion and factors associated with recent HIV infection in a cohort of patients seen for care in Italy over 1996-2014: Data from the ICONA Foundation Study cohort.

In Italy the prevalence of recent HIV infection (RHI) isn't currently monitored. Early diagnosis is crucial to allow introduction of antiretroviral therapy (cART) in the recent phase of infection. We aimed to estimate the proportion and the determinants of RHI among patients enrolled in the ICONA cohort; we explored differences in the median time from HIV diagnosis to cART initiation and in the viro-immunological response between RHI and Less Recent HIV infections (NRHI).

Presence of multiple genotypes in subjects with HPV-16 infection is highly associated with anal squamous intraepithelial lesions in HIV-1 infected males.

Objectives: The aim of the study was to determine the prevalence of abnormal cytological findings, high risk (HR)-HPV genotypes and to identify factors associated with an abnormal cytological findings in a cohort of HIV-infected males.

Patients And Methods: Retrospective observational study on HIV-infected male patients who performed screening in the absence of clinical symptoms. Cytological abnormalities were classified as atypical squamous cells of undetermined significance (ASC-US), low-grade(LSIL) or high high-grade squamous intraepithelial lesion (HSIL).

HIV-1-mediated insertional activation of STAT5B and BACH2 trigger viral reservoir in T regulatory cells.

HIV-1 insertions targeting BACH2 or MLK2 are enriched and persist for decades in hematopoietic cells from patients under combination antiretroviral therapy. However, it is unclear how these insertions provide such selective advantage to infected cell clones. Here, we show that in 30/87 (34%) patients under combination antiretroviral therapy, BACH2, and STAT5B are activated by insertions triggering the formation of mRNAs that contain viral sequences fused by splicing to their first protein-coding exon.

Changes in Cardiovascular Disease Risk Factors With Immediate Versus Deferred Antiretroviral Therapy Initiation Among HIV-Positive Participants in the START (Strategic Timing of Antiretroviral Treatment) Trial.

Introduction: HIV infection and certain antiretroviral therapy (ART) medications increase atherosclerotic cardiovascular disease risk, mediated, in part, through traditional cardiovascular disease risk factors.

Methods And Results: We studied cardiovascular disease risk factor changes in the START (Strategic Timing of Antiretroviral Treatment) trial, a randomized study of immediate versus deferred ART initiation among HIV-positive persons with CD4 cell counts >500 cells/mm. Mean change from baseline in risk factors and the incidence of comorbid conditions were compared between groups.

Immunosenescence and hurdles in the clinical management of older HIV-patients.

People living with HIV (PLWH) who are treated with effective highly active antiretroviral therapy (HAART) have a similar life expectancy to the general population. Moreover, an increasing proportion of new HIV diagnoses are made in people older than 50 y. The number of older HIV-infected patients is thus constantly growing and it is expected that by 2030 around 70% of PLWH will be more than 50 y old.

Activating Killer Immunoglobulin Receptors and HLA-C: a successful combination providing HIV-1 control.

Several studies demonstrated a relevant role of polymorphisms located within the HLA-B and -C loci and the Killer Immunoglobulin Receptors (KIRs) 3DL1 and 3DS1 in controlling HIV-1 replication. KIRs are regulatory receptors expressed at the surface of NK and CD8+ T-cells that specifically bind HLA-A and -B alleles belonging to the Bw4 supratype and all the -C alleles expressing the C1 or C2 supratype. We here disclose a novel signature associated with the Elite Controller but not with the long-term nonprogressor status concerning 2DS activating KIRs and HLA-C2 alleles insensitive to miRNA148a regulation.

Maraviroc in addition to cART during primary HIV infection: Results from MAIN randomized clinical trial and 96-weeks follow-up.

Background: Multi-targeted treatment strategies including maraviroc (MVC) during Primary HIV Infection (PHI) may benefit from the immune-modulatory properties of this CCR5-inhibitor.

Objectives: We conducted a proof-of-concept clinical trial aimed at assessing whether maraviroc in addition of a combination antiretroviral therapy (cART) initiated during PHI would improve immunological and virological parameters.

Study Design: The MAIN (Maraviroc in HIV Acute INfection) study was a randomized open-label clinical trial (EUDRACT number: 2008-007004-29) which enrolled 29 patients with PHI.

Brief Report: Enhanced Normalization of CD4/CD8 Ratio With Earlier Antiretroviral Therapy at Primary HIV Infection.

Background: Total CD4 T-cell counts predict HIV disease progression but do not necessarily reflect normalization of immune function. CD4/CD8 ratio is a marker of immune dysfunction, a prognostic indicator for non-AIDS mortality, and reflects viral reservoir size. Despite antiretroviral therapy (ART), recovery of CD4/CD8 ratio in chronic HIV infection is incomplete; we hypothesize enhanced CD4/CD8 ratio recovery with earlier treatment initiation in recently infected individuals.

HHV-8 DNA replication correlates with the clinical status in AIDS-related Kaposi's sarcoma.

Background: The value of plasma levels of human herpesvirus 8 (HHV-8) DNA as a marker of clinical status in acquired immunodeficiency syndrome-related Kaposi's sarcoma (AIDS-KS) remains to be elucidated.

Objectives: To investigate the relationship between the plasma HHV-8 DNA viral load and the clinical status of AIDS-KS.

Study Design: A total of 378 blood samples were obtained from 62 patients with AIDS-KS followed longitudinally.

Treatment intensification followed by interleukin-7 reactivates HIV without reducing total HIV DNA: a randomized trial.

Background: As a first step towards HIV cure, we assessed a strategy of antiretroviral therapy (ART) intensification followed by interleukin-7 (IL-7) used as an HIV-reactivating agent.

Methods: A multicentre, randomized clinical trial included patients on suppressive ART with CD4 cell counts at least 350/μl and HIV-DNA between 10 and 1000 copies/10 peripheral blood mononuclear cells (PBMCs). After an 8-week raltegravir and maraviroc intensification, patients were randomized to intensification alone or with 3 weekly IL-7 injections at weeks 8, 9 and 10.

An update on integrase inhibitors: new opportunities for a personalized therapy? The NEXTaim Project.

Thanks to the development of antiretroviral agents to control HIV replication, HIV infection has turned from a fatal disease into a treatable chronic infection. The present work collects the opinions of several experts on the efficacy and safety of recently approved second generation of integrase inhibitors and, in particular, on the role of this new class of drugs in antiretroviral therapy. The availability of new therapeutic options represents an opportunity to ameliorate the efficacy of cART in controlling HIV replication also within viral reservoirs.

Beneficial Effects of cART Initiated during Primary and Chronic HIV-1 Infection on Immunoglobulin-Expression of Memory B-Cell Subsets.

Introduction: During HIV-1 infection the B-cell compartment undergoes profound changes towards terminal differentiation, which are only partially restored by antiretroviral therapy (cART).

Materials And Methods: To investigate the impact of infection as early as during primary HIV-1 infection (PHI) we assessed distribution of B-cell subsets in 19 PHI and 25 chronic HIV-1-infected (CHI) individuals before and during 48 weeks of cART as compared to healthy controls (n = 23). We also analysed Immunoglobulin-expression of memory B-cell subsets to identify alterations in Immunoglobulin-maturation.