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). We included antiretroviral-naïve HIV-positive patients enrolled in the cohort with documented dates of HIV-negative and positive antibodies tests, grouped in RHI (estimated date of seroconversion within 12 months of enrolment) and NRHI. Proportion of RHI and the trend of this proportion by calendar period (1996-2014) were investigated (Chi-square test). Logistic regression analysis was employed to identify factors associated with RHI. The time from seroconversion to cART initiation was compared in RHI and NRHI overall and after stratification by calendar period (survival analysis). We finally explored the time from starting cART to HIV-RNA <50 copies/mL and to CD4+ gain ≥200 cells/mmc by Cox regression. HIV seroconversion could be estimated for 2608/12,616 patients: 981/2608 (37.6%) were RHI. Proportion of RHI increased in recent calendar periods and was associated with younger age, baseline higher HIV-RNA and CD4+ count. There wasn't difference in the 2-year estimates of cART start between RHI and NRHI, regardless of calendar period. Rates and hazards of virological response were similar in RHI versus NRHI. RHI showed a 1.5-fold higher probability of CD4+ gain, also following adjustment for calendar period and cART regimen, and for age, HCV and smoking; the difference in probability was however attenuated after further controlling for baseline HIV-RNA and CD4+ T-cells. The increased proportion of RHI over time suggests that in recent years in Italy HIV infections are more likely to be detected earlier than before. The similar rates of cART introduction and viro-immunological response in RHI and NRHI probably reflect the efficacy of the modern cART regimens. An improvement of the prevention services is warranted to allow an early cART access, also in the perspective of therapy as prevention.
Introduction
The aim of this study was to analyze the impact of COVID-19 pandemic restrictions on the prevalence and incidence of metabolic syndrome (MS), and to identify predictors of new MS cases ...in people living with HIV (PLWH).
Methods
This cohort study included PLWH followed at the IRCCS San Raffaele, Milan, Italy, with at least one body mass index (BMI) determination during the pre-pandemic period (1 December 2018 to 29 February 2020) and the pandemic period (1 March 2020 to 31 May 2021). MS diagnosis was based on NCEP ATP III 2005 criteria. Univariable Poisson regression model was used to compare MS incidence rates. Univariable mixed linear models estimated the crude mean change in metabolic parameters during each time period. Multivariable Cox proportional hazards model was used to assess risk factors for MS.
Results
This study included 1,564 PLWH, of whom 460 and 1,104 were with and without a diagnosis of MS, respectively, at the beginning of the pre-pandemic period, with an overall prevalence of MS of 29.4%. During the pre-pandemic period, 528/1,564 PLWH had MS, with a prevalence of 33.8% (95%CI = 31.5%–36.1%), while during the pandemic period, the number of PLWH with a diagnosis of MS increased to 628/1,564, with a prevalence of 40.2% (95%CI 37.8%–42.6%; McNemar’s test:
p
< 0.0001). Similarly, the MS incidence rate increased from 13.7/100 person-years of follow-up (PYFU; 95%CI = 11.7–16.0) in the pre-pandemic period to 18.5/100 PYFU (95%CI = 16.2–21.1) in the pandemic period (
p
= 0.004), with 201 subjects developing MS during the pandemic period. In addition, we observed a significant increase in the crude mean change during the pandemic period compared with the pre-pandemic period for: total cholesterol, LDL cholesterol, plasma glucose, blood pressure, and atherosclerotic cardiovascular disease (ASCVD) risk score. Finally, after adjustment for HIV risk factors, HBV, HCV, ART duration, duration of virologic suppression and use of INSTIs, age adjusted hazard ratio (AHR) per 3 years older = 1.12 (95%CI = 1.08–1.17), sex AHR female vs. male = 0.62 (95%CI = 0.44–0.87) and CD4+ cell count AHR per 100 cells/μL higher = 1.05 (95%CI = 1.01–1.09) were associated with the risk of MS.
Conclusion
The COVID-19 pandemic affected the metabolic profile of PLWH and increased the prevalence and incidence of MS.
Several studies have demonstrated the efficacy of the oral pre-exposure prophylaxis (PrEP) with tenofovir (with or without emtricitabine) on preventing HIV-negative partners of HIV infected patients ...to become infected through sexual contacts. PrEP is already available in the United States and now is approved by European Medicine Agency. In this setting we would like to gauge physicians' knowledge, acquaintance with and attitude to include PrEP in their clinical practice. A cross sectional survey was conducted among Italian physicians expert on antiretroviral therapy. Out of 146 physicians, 35% of participants declared to be familiar with PrEP but only 46% of them believed that, currently, there are not enough reasons to make it available in Italy. 51% of physicians have already been attracted to prescribe it and 63.4% have been openly asked about PrEP. The main concerns noticed were: the risk of acquire other sexual transmitted diseases (STDs) (70% of physicians feared that PrEP could favor STDs spread), the potential harmful of PrEP if not adequately implemented and, especially the risk of possible side effects if not properly used. Nevertheless, 55.9% of participants believed that Health Authorities face an ethical obligation to make PrEP available as part of the strategies to protect from HIV transmission and half of the respondents asked for further researches to better define the role for PrEP. Attitudes regarding PrEP impact on Italian National Health Organization were also very interesting: 57.5% of participants did not believe that investing in PrEP would be an appropriate use of healthcare resources, while 70.6% affirmed that PrEP's financial coverage should not be funded by the Italian National System of Health (SSN). This survey showed a high awareness of PrEP potential among Italian physicians coupled with a great deal of skepticism about how and if implementing it in clinical practice.
Mpox caused a worldwide outbreak in 2022, disproportionately affecting MSM reporting high-risk sexual behaviors. The aim of this study was to compare the characteristics of people receiving MVA-BN ...vaccination with those of individuals diagnosed with mpox to guide future vaccination policies. This was a retrospective study on people with mpox infection or vaccination at San Raffaele Scientific Institute, Milan, Italy, from May to November 2022. Characteristics were compared using Mann–Whitney or chi-square/Fisher’s exact tests; multivariable logistic regression and classification tree analysis were applied. Overall, 473 vaccinated individuals and 135 with mpox were included; 472/473 and 134/135 were MSM. People with mpox were more frequently living with HIV (48.9% vs. 22.4%, p < 0.001), had ≥1 previous STI (75.6% vs. 35.7%, p < 0.001), were chemsex users (37.8% vs. 6.34%, p < 0.001), were with a higher number of partners (23.0% vs. 1.69%, p < 0.001), and had engaged in group sex (55.6% vs. 24.1%, p < 0.001). At multivariable analysis, PLWH (aOR = 2.86, 95%CI = 1.59–5.19, p < 0.001), chemsex users (aOR = 2.96, 95%CI = 1.52–5.79, p = 0.001), those with previous syphilis (aOR = 4.11, 95%CI = 2.22–7.72, p < 0.001), and those with >10 partners (aOR = 11.56, 95%CI = 6.60–21.09, p < 0.001) had a higher risk of infection. This study underscores the importance of prioritizing MSM with prior STIs and multiple partners as well as chemsex users in vaccination policies to curb mpox spread. A destigmatized assessment of sexual history is vital for comprehensive sexual health strategies.
to determine the immunogenicity of the monovalent vaccine against 2009 pandemic influenza A/H1N1 in HIV-1-infected individuals.
a total of 192 participants, including 44 HIV-1-positive individuals ...and 148 HIV-1-negative healthy controls were enrolled to receive a single dose of MF59-adjuvanted 2009 A/H1N1v vaccine formulated to contain 7.5 microg of haemagglutin antigen.
standard haemagglutination inhibition (HAI) assay was performed to evaluate seroconversion and seroprotecsion rates against the pandemic virus in serum samples collected at baseline (T0) and 3-5-week postvaccination (T28). Seroconversion to vaccination was defined by either prevaccination HAI titer less than 1: 10 with a postvaccination titer higher than 1: 40, or a prevaccination titer higher than 1: 10 and increase of at least four-fold or more after vaccination. Seroprotection was defined by HAI titers higher than 1: 40.
the vaccine induced specific antibody titers in HIV-1-positive individuals similar to those of HIV-1-negative controls 215.3, 95% confidence interval (CI) 150.4-308.1 vs. 275.9, 95% CI 232.6-327.3 with postvaccination seroprotection rates higher than 97%. In contrast, the seroconversion rate was lower in the HIV-1-positive individuals as compared with the HIV-1-negative controls (36.4 vs. 79.0%, P < 0.0001), likely as a consequence of their high HAI baseline titers. Multivariable logistic regression analysis showed that seroconversion was less likely in HIV-1-positive individuals odds ratio (OR) = 0.237, 95% CI 0.104-0.539, P = 0.0006) and with increasing age (OR = 0.805, 95% CI 0.684-0.947, P = 0.009).
a single dose of MF59-adjuvanted 2009 influenza H1N1 vaccine induced an immune response against pandemic H1N1 virus in HIV-1-positive individuals reaching titers similar to those of HIV-1-negative individuals. The seroconversion rate was negatively associated with HIV infection and increasing age.
Low-level HIV viremia originating from virus reactivation in HIV reservoirs is often present in cART treated individuals and represents a persisting source of immune stimulation associated with ...sub-optimal recovery of CD4+ T cells. The HIV-1 Tat protein is released in the extracellular milieu and activates immune cells and latent HIV, leading to virus production and release. However, the relation of anti-Tat immunity with residual viremia, persistent immune activation and CD4+ T-cell dynamics has not yet been defined.
Volunteers enrolled in a 3-year longitudinal observational study were stratified by residual viremia, Tat serostatus and frequency of anti-Tat cellular immune responses. The impact of anti-Tat immunity on low-level viremia, persistent immune activation and CD4+ T-cell recovery was investigated by test for partitions, longitudinal regression analysis for repeated measures and generalized estimating equations.
Anti-Tat immunity is significantly associated with higher nadir CD4+ T-cell numbers, control of low-level viremia and long-lasting CD4+ T-cell recovery, but not with decreased immune activation. In adjusted analysis, the extent of CD4+ T-cell restoration reflects the interplay among Tat immunity, residual viremia and immunological determinants including CD8+ T cells and B cells. Anti-Env immunity was not related to CD4+ T-cell recovery.
Therapeutic approaches aiming at reinforcing anti-Tat immunity should be investigated to improve immune reconstitution in people living with HIV on long-term cART.
ISS OBS T-002 ClinicalTrials.gov identifier: NCT01024556
Italian Ministry of Health, special project on the Development of a vaccine against HIV based on the Tat protein and Ricerca Corrente 2019/2020.
Switch strategies based on rilpivirine/tenofovir/emtricitabine or on an integrase inhibitor (InSTI) plus tenofovir/emtricitabine have never been compared in randomized clinical trials. The main aim ...of the study was to investigate the durability of these two switch regimens in virologically suppressed, HIV-infected patients.
Retrospective analysis of patients who started rilpivirine or an InSTI (both with tenofovir and emtricitabine) with <50 HIV-RNA copies/mL and had at least one HIV-RNA assessed while receiving the study regimen. Virological failure (VF) was defined as two consecutive measurements of HIV-RNA >50 copies/mL. Treatment failure (TF) was define as either VF or discontinuation of any drug of the regimen. Durability was assessed by the Kaplan-Meier method and compared by Log-rank test. Residual viremia was defined as any detectable HIV-RNA below 50 copies/mL, as assed by a real-time PCR assay.
Six hundred seventy-five patients (466 switched to a rilpivirine-, 209 switched to an InSTI-based regimen 18% dolutegravir, 39% raltegravir, 43% elvitegravir/cobicistat were included in the analysis. The median (interquartile range, IQR) follow-up in the rilpivirine and in the InSTI group was 16.7 (8.8-22.2) and 10.4 (5.4-19.6) months. The 1-year cumulative probabilities (95%CI) of VF and TF were 0.97% (0.36%-2.62%) and 9.73% (7.21%-13.06%) in the rilpivirine group and 1.83% (0.57%-5.77%) and 8.75% (5.25%-14.4%) in the InSTI group, with no difference between groups (p = 0.328 and 0.209 for VF and TF). The proportion of time spent with residual viremia was comparable in the two groups (9% IQR 0.5%-49% and 17% IQR 0.5%-50% in the rilpivirine and in the InSTI group, p = 0.087). By the multivariable Cox regression model, TF was independently associated with being on therapy with a protease inhibitor vs. a non-nucleoside reverse transcriptase inhibitor at switch (AHR = 0.52; 95%CI = 0.31-0.90; p = 0.018), baseline total/HDL-cholesterol ratio (AHR = 1.19 per 0.5-units increments; 95%CI = 1.06-1.34; p = 0.004), baseline estimated glomerular filtration rate (AHR = 0.78 per 10-units increments; 95%CI = 0.67-0.90; p = 0.001) and baseline hemoglobin (AHR = 0.78 per 1-unit increments; 95%CI = 0.64-0.94; p = 0.009), but not with treatment group (rilpivirine vs. InSTI).
In our clinical practice, the durability of the two regimens was comparable and both showed a very low probability of VF.
Undiagnosed HIV infection is a prominent clinical issue throughout Europe that requires the continuous attention of all healthcare professionals and policymakers to prevent missed testing ...opportunities and late diagnosis. This systematic review aimed to evaluate interventions to increase HIV testing rates and case detection in European hospitals. Out of 4598 articles identified, 29 studies fulfilled the selection criteria. Most of the studies were conducted in single Western European capital cities, and only one study was from Eastern Europe. The main interventions investigated were test-all and indicator-condition-based testing strategies. Overall, the prevalence of undiagnosed HIV was well above 0.1%. The studied interventions increased the HIV testing rate and the case detection rate. The highest prevalence of undiagnosed HIV was found with the indicator-condition-driven testing strategy, whereas the test-all strategy had the most profound impact on the proportion of late diagnoses. Nevertheless, the HIV testing rates and case-finding varied considerably across studies. In conclusion, effective strategies to promote HIV testing in European hospitals are available, but relevant knowledge gaps regarding generalizability and sustainability remain. These gaps require the promotion of adherence to HIV testing guidelines, as well as additional larger studies representing all European regions.
HIV-1 sexual transmission occurs mainly via mucosal semen exposures. In the female reproductive tract (FRT), seminal plasma (SP) induces physiological modifications, including inflammation. An ...effective HIV-1 vaccine should elicit mucosal immunity, however, modifications of vaccine responses by the local environment remain to be characterized. Using a modified vaccinia virus Ankara (MVA) as a vaccine model, we characterized the impact of HIV-1
SP intravaginal exposure on the local immune responses of non-human primates. Multiple HIV-1
SP exposures did not impact the anti-MVA antibody responses. However, SP exposures revealed an anti-MVA responses mediated by CD4
T cells, which was not observed in the control group. Furthermore, the frequency and the quality of specific anti-MVA CD8
T cell responses increased in the FRT exposed to SP. Multi-parameter approaches clearly identified the cervix as the most impacted compartment in the FRT. SP exposures induced a local cell recruitment of antigen presenting cells, especially CD11c
cells, and CD8
T cell recruitment in the FRT draining lymph nodes. CD11c
cell recruitment was associated with upregulation of inflammation-related gene expression after SP exposures in the cervix. We thus highlight the fact that physiological conditions, such as SP exposures, should be taken into consideration to test and to improve vaccine efficacy against HIV-1 and other sexually transmitted infections.
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