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The prevalence of HIV/AIDS among people in midlife and late adulthood has been increasing in Western countries over the last decade. We analyzed data from a prospective, observational multi-centre study on individuals newly diagnosed with HIV between January 2004 and March 2007 in 10 public counselling and testing sites in Latium, Italy. At diagnosis, routine demographic, epidemiological, clinical and laboratory data are recorded, and patients are asked to complete a questionnaire investigating socio-demographic and psycho-behavioural aspects. To analyze the association of individual characteristics with age, we compared older adults (≥50 years) with their younger counterpart (18-49 years). To adjust for potential confounding effect of the epidemiological, clinical and behavioural characteristics, to identify factors associated with older age at HIV diagnosis, multivariate logistic regression analysis was performed. Overall, 1073 individuals were identified, 125 of whom (11.6%) were aged 50 years or above. The questionnaire was completed by 41% (440/1073). Compared with their younger counterparts, a higher proportion of older patients were males, born in Italy, reported heterosexual or unknown HIV risk exposure, were never tested for HIV before and were in a more advanced stage of HIV infection at diagnosis. In addition, older adults had a lower educational level and were more frequently living with their partners or children. With respect to psycho-behavioural characteristics, older patients were more likely to have paid money for sex and have never used recreational drugs. Interestingly, no differences were found regarding condom use, which was poor in both age groups. These findings may have important implications for the management of older adults with HIV, who should be targeted by appropriate public health actions, such as opportunistic screening and easier access to healthcare. Moreover, strategies including information on HIV and prevention of risk behaviours are needed. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Predisposition of Antiretroviral Prophylaxis for Solid Organ Transplantation in Human Immunodeficiency Virus-Infected Patients," by G. De Carli, V. Puro, N. Orchi and G. Ippolito.

Background and Objectives: HIV-1 provirus integration in host genomes provides a lifelong reservoir of virally infected cells. Although not able to generate viral progeny, the expression of defective proviruses has been associated with activation. Provirus integration may influence host gene transcription and shifts may occur during disease progression or antiretroviral therapy (ART). The study aimed to analyze intact/defective provirus and sites of provirus integration in acute infections: changes after 48 weeks of early therapy were also evaluated., Methods: DNA from peripheral blood lymphomonocytes of 8 acute HIV-1 infections at serodiagnosis (T0) and after 48 weeks of therapy (T1) was used to quantify intact and defective provirus by digital-droplet PCR and to analyze provirus integration sites, by next-generation sequencing of libraries derived from ligation-mediated PCR., Results: A high variability in the amount of intact proviral DNA was observed at both T0 and T1, in the different subjects. Although the ratio of intact/total proviral HIV-1 DNA did not dramatically change between T0 (8.05%) and T1 (9.34%), after early therapy both intact and total HIV-1 DNA declined significantly, p = 0.047 and p = 0.008, respectively. The median number of different (IQR) integration sites in human chromosomes/subject was 5 (2.25-13.00) at T0 and 4 (3.00-6.75) at T1. Of all the integration sites observed at T1, 64% were already present at T0. Provirus integration was observed in introns of transcriptionally active genes. Some sites of integration, among which the most represented was in the neuregulin 2 gene, were shared by different patients, together with the orientation of the insertion. Provirus integration was also observed in intergenic regions, with median (IQR) % of 15.13 (6.81-21.40) at T0 and 18.46 (8.98-22.18) at T1 of all read matches., Conclusions: In acute HIV-1 infection, the amount of intact proviral DNA in peripheral lymphomonocytes did not exceed 10% of total HIV-1 DNA, a percentage that was not substantially changed by early administrated ART. Provirus displayed a relatively small number of recurrent integration sites in introns of transcriptionally active genes, mainly related to cell-cycle control. Consideration should be given to therapeutic strategies able to target the cells harboring defective proviruses, that are not reached by conventional antiviral drugs, these potentially also impacting on replicative competent integrated provirus., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors. Published by Elsevier Ltd.)

HIV testing was offered to 2,185 people receiving mpox (formerly monkeypox) vaccination, who reported not being HIV positive. Among them 390 were current PrEP users, and 131 had taken PrEP in the past. Of 958 individuals consenting testing, six were newly diagnosed with HIV. Two patients had symptomatic primary HIV infection. None of the six patients had ever taken PrEP. Mpox vaccination represents an important opportunity for HIV testing and counselling about risk reduction and PrEP.

The optimal therapeutic approach for primary HIV infection (PHI) is still debated. We aimed to compare the viroimmunological response to a four- versus a three-drug regimen, both INSTI-based, in patients with PHI. This was a monocentric, prospective, observational study including all patients diagnosed with PHI from December 2014 to April 2018. Antiretroviral therapy (ART) was started, before genotype resistance test results, with tenofovir/emtricitabine and either raltegravir plus boosted darunavir or dolutegravir. Cumulative probability of virological suppression [VS] (HIV-1 RNA< 40 cp/mL), low-level HIV-1 DNA [LL-HIVDNA] (HIV-1 DNA < 200 copies/106PBMC), and CD4/CD8 ratio ≥1 were estimated using Kaplan−Meier curves. Factors associated with the achievement of VS, LL-HIVDNA, and CD4/CD8 ≥ 1 were assessed by a Cox regression model. We enrolled 144 patients (95.8% male, median age 34 years): 110 (76%) started a four-drug-based therapy, and 34 (24%) a three-drug regimen. Both treatment groups showed a comparable high probability of achieving VS and a similar probability of reaching LL-HIVDNA and a CD4/CD8 ratio ≥1 after 48 weeks from ART initiation. Higher baseline HIV-1 RNA and HIV-1 DNA levels lowered the chance of VS, whereas a better preserved immunocompetence increased that chance. Not statistically significant factors associated with LL-HIVDNA achievement were found, whereas a higher baseline CD4/CD8 ratio predicted the achievement of immune recovery. In PHI patients, the rapid initiation of either an intensified four-drug or a standard three-drug INSTI-based regimen showed comparable responses in terms of VS, viral reservoir size, and immunological recovery.

Molecular investigation of primary HIV infections (PHI) is crucial to describe current dynamics of HIV transmission. Aim of the study was to investigate HIV transmission clusters (TC) in PHI referred during the years 2013-2020 to the National Institute for Infectious Diseases in Rome (INMI), that is the Lazio regional AIDS reference centre, and factors possibly associated with inclusion in TC. These were identified by phylogenetic analysis, based on population sequencing of pol ; a more in depth analysis was performed on TC of B subtype, using ultra-deep sequencing (UDS) of env . Of 270 patients diagnosed with PHI during the study period, 229 were enrolled (median follow-up 168 (IQR 96-232) weeks). Median age: 39 (IQR 32-48) years; 94.8% males, 86.5% Italians, 83.4% MSM, 56.8% carrying HIV-1 subtype B. Of them, 92.6% started early treatment within a median of 4 (IQR 2-7) days after diagnosis; median time to sustained suppression was 20 (IQR 8-32) weeks. Twenty TC (median size 3, range 2-9 individuals), including 68 patients, were identified. A diagnosis prior to 2015 was the unique factor associated with inclusion in a TC. Added value of UDS was the identification of shared quasispecies components in transmission pairs within TC.

Background: The Italian Society of Infectious and Tropical Diseases performed a survey on the application of guidelines for the management of persons living with HIV (PLWH), to evaluate current practice and the yield of screening for latent tuberculosis infection (LTBI) in newly-diagnosed PLWH; in addition, the offer of preventive therapy to LTBI individuals and the completion rate were analysed., Materials and Methods: Newly-diagnosed PLWH in nine centres were evaluated retrospectively (2016/2017) using binary and multinomial logistic regression to identify factors associated with LTBI diagnostic screening and QuantiFERON (QFT) results., Results: Of 801 patients evaluated, 774 were studied after excluding active TB. LTBI tests were performed in 65.5%. Prescription of an LTBI test was associated with being foreign-born (odds ratio (OR) 3.19, p < 0.001), older (for 10-year increments, OR 1.22, p = 0.034), and having a CD4 count <100 cells/mm 3 vs ≥500 cells/mm 3 (OR 2.30, p = 0.044). LTBI was diagnosed in 6.5% of 495 patients evaluated by QFT. Positive results were associated with being foreign-born (relative risk ratio (RRR) 30.82, p < 0.001), older (for 10-year increments, RRR 1.78, p = 0.003), and having a high CD4 count (for 100 cells/mm 3 increments, RRR 1.26, p < 0.003). Sixteen LTBI individuals started TB preventive therapy and eight completed it., Conclusions: LTBI screening is inconsistently performed in newly-diagnosed PLWH. Furthermore, TB preventive therapy is not offered to all LTBI individuals and compliance is poor., (Copyright © 2019. Published by Elsevier Ltd.)

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.

Objective: We 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., Methods: Phylogenetic 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., Results: 145 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%, p<0.001), male (82.9% vs 62.3%, p<0.001) and men who have sex with men (MSM) (43.5% vs 14.5%, p<0.001). Individuals in MTCs were also younger (median (IQR) years: 41 (35-49) vs 43 (36-51), p<0.001) and had higher CD4 cell count in comparison with individuals out of MTCs (median (IQR): 10 9 /L: 0.4 (0.265-0.587) vs 0.246 (0.082-0.417), p<0.001). The viral load remained stable between the two groups (median (IQR) log 10 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., Conclusions: Our 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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Treatment of chronic HCV infection with direct acting antivirals can achieve high rates of sustained viral response in persons with HIV. In the perspective of HCV elimination in this population, high rates of HCV detection will be needed. We evaluated the unawareness of HCV infection in 2927 persons newly diagnosed with HIV during 2004-2015 in Rome, Italy. Two-hundred-fifty persons (8.5%) were anti-HCV positive. The proportion of HCV-unaware individuals at the time of HIV diagnosis was 58.0% (145/250), without significant variations over time, 17.2% showed an advanced fibrosis stage. The absence of previous HIV testing was significantly associated with HCV unawareness., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The impact of baseline HIV-1 reverse transcriptase (RT) polymorphisms on response to first-line modern HAART containing tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) was evaluated. The impact of each RT polymorphism on virological success (VS) was evaluated in 604 HIV-1 subtype B-infected patients starting TDF+FTC-containing HAART. TDF and FTC antiviral activity was also tested in PBMCs infected by mutagenised HIV. Structural analysis based on docking simulations was performed. A98S was the only mutation significantly correlated with an increased proportion of patients achieving VS at 24 weeks (94.0% vs. 84.3%; P=0.03). Multivariate regression and Cox model analyses confirmed this result. At concentrations close to the minimal concentration achieved in patient plasma, TDF and FTC exhibited higher potency in the presence of A98S-mutated virus compared with wild-type (IC 90,TDF , 8.6±1.1 vs. 19.3±3.5nM; and IC 90,FTC , 12.4±7.7 vs. 16.8±9.8nM, respectively). The efficacy of FTC, abrogated by M184V, was partially restored by A98S (IC 90,FTC , 5169±5931nM for A98S+M184V vs. 18477±12478nM for M184V alone). Docking analysis showed the higher potency of TDF and FTC in the presence of A98S-mutated virus was mainly due to higher binding affinity between drugs and mutated RT compared with wild-type. In the presence of FTC, A98S also partially restored the RT binding affinity impaired by M184V alone. A98S polymorphism improves virological response to TDF+FTC-containing HAART. This may help clinicians in the choice of the optimal NRTI backbone aimed at achieving maximal virological inhibition., (Copyright © 2016 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.)

Background: Increased evidence of relevant HIV-1 epidemic transmission in European countries is being reported, with an increased circulation of non-B-subtypes. Here, we present two recent HIV-1 non-B transmission clusters characterized by NNRTI-related amino-acidic mutations among newly diagnosed HIV-1 infected men, living in Rome (Central-Italy)., Methods: Pol and V3 sequences were available at the time of diagnosis for all individuals. Maximum-Likelihood and Bayesian phylogenetic-trees with bootstrap and Bayesian-probability supports defined transmission-clusters. HIV-1 drug-resistance and V3-tropism were also evaluated., Results: Among 534 new HIV-1 non-B cases, diagnosed from 2011 to 2014, in Central-Italy, 35 carried virus gathering in two distinct clusters, including 27 HIV-1 C and 8 CRF17&#95;BF subtypes, respectively. Both clusters were centralized in Rome, and their origin was estimated to have been after 2007. All individuals within both clusters were males and 37.1% of them had been recently-infected. While C-cluster was entirely composed by Italian men-who-have-sex-with-men, with a median-age of 34 years (IQR:30-39), individuals in CRF17&#95;BF-cluster were older, with a median-age of 51 years (IQR:48-59) and almost all reported sexual-contacts with men and women. All carried R5-tropic viruses, with evidence of atypical or resistance amino-acidic mutations related to NNRTI-drugs (K103Q in C-cluster, and K101E+E138K in CRF17&#95;BF-cluster)., Conclusions: These two epidemiological clusters provided evidence of a strong and recent circulation of C and CRF17&#95;BF strains in central Italy, characterized by NNRTI-related mutations among men engaging in high-risk behaviours. These findings underline the role of molecular epidemiology in identifying groups at increased risk of HIV-1 transmission, and in enhancing additional prevention efforts.

Introduction: Diagnosis of HIV infection during early stages is mandatory to catch up with the challenge of limiting HIV viral replication and reservoirs formation, as well as decreasing HIV transmissions by immediate cART initiation., Objectives: Aims were to describe (a) virological characteristics of AHI identified, (b) epidemiological and clinical factors associated with being diagnosed with AHI., Methods: Cross-sectional, retrospective study. All individuals diagnosed with AHI according to Fiebig's staging between Jan 2013 and Mar 2014 at the INMI "L. Spallanzani" were included. Serum samples reactive to a fourth generation HIV-1/2 assay (Architect HIV Ag/Ab Combo, Abbott) were retested with another fourth generation assay (VIDAS DUO HIV Ultra, Biomérieux) and underwent confirmation with HIV-1 WB (New Lav I Bio-Rad) and/or with Geenius confirmatory assay (Bio-Rad). WHO criteria (two env products reactivity) were used to establish positivity of confirmatory assays. In case of clinically suspected AHI, HIV-1 RNA (Real time, Abbott) and p24 assay (VIDAS HIV P24 Bio-Rad) were also performed. Avidity test was carried out, on confirmed positive samples lacking p31 reactivity, to discriminate between recent (true Fiebig V phase) and late infections; to avoid possible misclassifications, clinical data were also used. Demographic, epidemiological, clinical and laboratory data are routinely, and anonymously recorded in the SENDIH and SIREA studies., Results: During the study period, we observed 483 newly HIV diagnosed individuals, of whom 40 were identified as AHI (8.3%). Fiebig classification showed: 7 stage II/III, 13 stage IV, 20 stage V. Demographic, epidemiological, and clinical characteristics of patients are shown in the Table. Overall, the study population had a median S/Co ratio at fourth generation EIA (Architect) of 49.50 (IQR, 23.54-98.05): values were significantly lower in Fiebig II-IV than in Fiebig V (38.68 [IQR, 20.08-54.84] vs 75.72 [IQR, 42.66-249.80], p=0.01). Overall, median HIV-1 RNA was 5.44 log copies/mL (IQR, 4.29-6.18) and the value observed in Fiebig phase II-IV was higher than that found in Fiebig stage V (6.10 [IQR, 5.49-7.00] vs 4.69 [3.71-5.44], p<0.001). Median CD4+ cell count was 596/mmc (IQR, 410-737). cART was started in 26 patients: TDF/FTC/DRV/r/RAL=18; TDF/FTC/DRV/r=2; TDF/FTC/ATV/r=2; TDF+FTC+EFV=2; TDF/FTC/RAL=1; DRV/r+RAL=1., Conclusions: Integration of careful epidemiological investigation, partner notification, and technical advances in virological testing are key elements in AHI case-finding. Significant differences were found between Fiebig stages II-IV and Fiebig V with regard to virological exams.