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.
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). Logistic regression models were used to identify predictors of having LSIL/HSIL.
Among 875 pts, abnormal cytology findings were observed in 254 (29%, 95% CI: 26.1%-32.1%) subjects: 142 (16%) had LSIL and 49 (6%) HSIL. Overall, 581 (66%, 95%CI: 63.2%-69.5%) subjects had ≥1 HR-HPV type and 269 (31%) had ≥2 HR HPV types. Multivariate logistic regression showed that subjects with multiple HR-HPV genotypes (OR = 1.351, 95%CI: 1.005-2.111) and with HPV-16 type (OR = 2.032, 95%CI: 1.313-3.146) were more likely to have LSIL/HSIL in addition to a lower CD4+/CD8+ ratio, a previous diagnosis of syphilis and a positive viral load. In another multivariate model, the presence of multiple HPV types in subjects with HPV-16 type was associated with the highest adjusted OR of having a LSIL/HSIL (OR = 2.598, 95%CI: 1.460-4.624).
In HIV-infected men, the prevalence of abnormal cytological findings was of 29% and of HR-HPV was 66%. The concomitant presence of HPV-16 and multiple HR genotypes was associated with an increased risk of abnormal cytological findings. These data highlight the importance of screening multiple HPV genotypes in HIV-infected patients.
Mpox has caused a global outbreak since May 2022, particularly affecting people belonging to key populations, but cases among healthcare providers have been reported. The aim of this work is to ...present the experience of the Infectious Diseases Unit of San Raffaele Scientific Institute, Milan, Italy with respect to infection control and prevention of mpox occupational transmission. Between May–November 2022, 140 individuals were diagnosed with mpox and six required hospitalization. Overall, 12 medical doctors and 22 nurses provided care to people with mpox. A hospital policy aimed at controlling viral transmission was implemented in May 2022. Protective equipment was used for all healthcare providers. One accidental puncture occurred with a scalpel contaminated with blood from a mpox viremic individual (mpox plasma cycle threshold = 36); no mpox related symptoms were observed and mpox testing ruled out transmission. Six months following exposure, neutralizing antibodies were not detectable, ruling out contagion. Overall, we observed no mpox transmission among healthcare workers, despite the number of visits and procedures performed, including bodily-fluids sampling, and even following puncture with contaminated blood. Hospital preparedness for the management of new infectious disease outbreaks, with rapid implementation of policies aimed at controlling infection, is paramount to avoid occupational transmission.
HIV-positive patients are facing age-and disease-related comorbidities. Since gender differences in viro-immunological, clinical and therapeutic features have been described, aim of this analysis was ...to explore such differences in elderly HIV-positive females compared to males coming from the same cohort.
Cross-sectional study.
Ten Infectious Diseases Center participating to a new multicenter Italian geriatric Cohort aiming at describing health transition over time in HIV-positive individuals.
HIV-positive patients aged ≥65 years old.
We recorded clinical, viro-immunological and therapeutical data.
We included 210 women (17%) out of 1237 patients. Compared to males, elderly females were less likely to present a HIV-RNA <50 copies/mL (74.3% vs. 81.8%, OR 0.64, 95%CI 0.44-0.93); they showed higher CD4+/CD8+ ratio (p = 0.016). Combined antiretroviral therapy (cART) strategies were similar between genders (p>0.05), although women were less likely to be treated with protease Inhibitors (PIs) (p = 0.05); specifically, in triple-drug regimens females received less PIs (28% vs 38% p = 0.022) and more integrase inhibitors (30% vs. 20% p = 0.012). Bone disease was more common in females (p<0.001) while males presented more frequently cardiovascular disease (CVD) (p<0.001). In females with bone disease, PIs and boosted regimens (38% vs. 53.7% p = 0.026 and 30.4 vs 44.0% p = 0.048 respectively) were prescribed less frequently. Polypharmacy was common and similar in both genders (20% vs. 22.8%, p = >0.05). A higher use of lipid-lowering drugs (20.5% vs. 14.8%, p = 0.04) was observed in females and yet they were less likely to receive anti-thrombotic agents (18.6% vs. 26.3%, p = 0.019) even when CVD was recorded (57.1% vs. 83.1%, p = 0.018). In multivariate analysis, we found that female gender was independently associated with a higher CD4+/CD8+ ratio but not with virological suppression.
Elderly HIV-positive women display a worse virologic response despite a better immune reconstitution compared to males. The burden of comorbidities as well as the medications received (including cART) may slightly differ according to gender. Our data suggest that more efforts and focused interventions are needed in this population.
During HIV-1 infection the B-cell compartment undergoes profound changes towards terminal differentiation, which are only partially restored by antiretroviral therapy (cART).
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.
Determination of B-cell subsets at baseline showed that total and Naive B-cells were decreased whereas Activated Memory (AM), Tissue-like Memory (TLM) B-cells and Plasma cells were increased in both PHI and CHI patients. After 4 weeks of cART total B-cells increased, while AM, TLM B-cells and Plasma cells decreased, although without reaching normal levels in either group of individuals. This trend was maintained until week 48, though only total B-cells normalized in both PHI and CHI. Resting Memory (RM) B-cells were preserved since baseline. This subset remained stable in CHI, while was expanded by an early initiation of cART during PHI. Untreated CHI patients showed IgM-overexpression at the expenses of switched (IgM-IgD-) phenotypes of the memory subsets. Interestingly, in PHI patients a significant alteration of Immunoglobulin-expression was evident at BL in TLM cells, and after 4 weeks, despite treatment, in AM and RM subsets. After 48 weeks of therapy, Immunoglobulin-expression of AM and RM almost normalized, but remained perturbed in TLM cells in both groups.
In conclusion, aberrant activated and exhausted B-cell phenotypes rose already during PHI, while most of the alterations in Ig-expression seen in CHI appeared later, despite 4 weeks of effective cART. After 48 weeks of cART B-cell subsets distribution improved although without full normalization, while Immunoglobulin-expression normalized among AM and RM, remaining perturbed in TLM B-cells of PHI and CHI.
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.
Retrospective study on HIV-1 infected patients followed at the Infectious Disease Department of the San Raffaele Scientific Institute, HBsAg-negative, HLA B5701-negative, with no documented resistance to RPV, ABC and 3TC, with HIV-RNA<50 copies/mL who started RPV plus ABC/3TC from March 2013 to September 2015. The primary outcome was durability no treatment failure (TF). Secondary objectives were to evaluate changes in immunological, metabolic and other safety parameters. TF was defined as the occurrence of virological failure (VF, 2 consecutive values >50 copies/mL) or discontinuation of any drug in the regimen for any reason. Patients' follow-up accrued from the date of RPV plus ABC/3TC initiation to the date of TF (VF or discontinuation of any drug in the regimen) or to the date of last available visit. Time to TF was evaluated by use of the Kaplan-Meier curves. Mixed linear models were applied to evaluate changes in immunological, metabolic and other safety parameters.
In this analysis, 100 patients starting RPV plus ABC/3TC were included. By 12, 24 and 36 months after switching to RPV plus ABC/3TC, the proportions of individuals without TF were 88% 95% confidence interval (CI): 79%-93%, 82% (95% CI:73%-89%) and 78% (95% CI:68%-86%), respectively. Time to TF was not significantly influenced by CD4+ nadir (≤200 vs >200 cells/μl; log-rank test: p = 0.311) or pre-ART viral load (<100000 vs ≥100000 copies/mL; log-rank test: p = 0.574) or the type of previous antiretroviral regimen (PI+2NRTIs vs NNRTI+2NRTIs vs Other; log-rank test: p = 0.942). Over a median follow-up of 2.9 years (IQR: 1.9-3.5), 26 subjects discontinued the treatment 10 due to toxicity, 7 for interactions with other drugs, 3 due to cardiovascular risk concern, 2 due to single viral blip, 1 due to VF, 1 for asthma, 1 patient's decision, 1 due to enrolment in a study protocol.
In this retrospective study, long-term use of RPV plus ABC/3TC regimen is effective and safe. Efficacy of this regimen was not found to be affected by low CD4+ nadir or high pre-ART viral load.
Tat, a key HIV virulence protein, has been targeted for the development of a therapeutic vaccine aimed at cART intensification. Results from phase II clinical trials in Italy (
) and South Africa (
) ...indicated that Tat vaccination promotes increases of CD4
T-cells and return to immune homeostasis while reducing the virus reservoir in chronically cART-treated patients. Here we present data of 92 vaccinees (59% of total vaccinees) enrolled in the ISS T-002 8-year extended follow-up study
).
Anti-Tat antibodies (Abs) induced upon vaccination persisted for the entire follow-up in 34/92 (37%) vaccinees, particularly when all 3 Ab classes (A/G/M) were present (66% of vaccinees), as most frequently observed with Tat 30 μg regimens. CD4
T cells increased above study-entry levels reaching a stable plateau at year 5 post-vaccination, with the highest increase (165 cells/μL) in the Tat 30 μg, 3 × regimen. CD4
T-cell increase occurred even in subjects with CD4
nadir ≤ 250 cells/
L and in poor immunological responders and was associated with a concomitant increase of the CD4
/CD8
T-cell ratio, a prognostic marker of morbidity/mortality inversely related to HIV reservoir size. Proviral DNA load decreased over time, with a half-life of 2 years and an estimated 90% reduction at year 8 in the Tat 30 μg, 3 × group. In multivariate analysis the kinetic and amplitude of both CD4
T-cell increase and proviral DNA reduction were fastest and highest in subjects with all 3 anti-Tat Ab classes and in the 30 μg, 3 × group, irrespective of drug regimens (NNRTI/NRTI vs. PI). HIV proviral DNA changes from baseline were inversely related to CD4
/CD8
T-cell ratio and CD4
T-cell changes, and directly related to the changes of CD8
T cells. Further, HIV DNA decay kinetics were inversely related to the frequency and levels of intermittent viremia. Finally, Tat vaccination was similarly effective irrespective of the individual immunological status or HIV reservoir size at study entry.
Tat immunization induces progressive immune restoration and reduction of virus reservoirs above levels reached with long-term cART, and may represent an optimal vaccine candidate for cART intensification toward HIV reservoirs depletion, functional cure, and eradication strategies.
Monkeypox virus (MPXV) infection confirmation needs reliable polymerase chain reaction (PCR) assays; in addition, viral clade attribution is a key factor in containment measures, considering a more ...severe syndrome in clade I and the possibility of simultaneous circulation. This study evaluates the performance of all-in-one STANDARD M10 MPX/OPX (SD BIOSENSOR, South Korea - M10). Frozen samples from 205 subjects were selected and stratified according to routine test results (RealStar® Orthopoxvirus PCR Kit 1.0, Altona DIAGNOTICS, Germany - RS; RS-1): in detail, 100 negative skin lesions (SL) and 200 positive samples at the variable stage of infection were analysed. Positive samples were retested with RS (RS-2). Positive and Negative Percent Agreements (PPA, NPA) were calculated. The median (IQR) Ct values of RS and M10 (OPXV target) assays were highly similar. The PPA of M10 compared to RS-1 was 89.5% considering system interpretation, and 96.0% when the operator classified results as positive if any target was detected; NPA was 100%. Comparing the RS-2 run and M10, an overall concordance of 95.3% between assays was found; however, considering operator interpretation, M10 returned more positive results than RS-2. The occurrence of False-Negative results was likely associated with the influence of thawing on low viral concentration; no False-Positive tests were observed. All samples collected at the time of Mpox diagnosis were positive and M10 correctly attributed the clade (West-Africa/II). The M10 MPX/OPX assay demonstrated high reliability in confirming MPXV infection and clade attribution.
In vitro, gp120 of both X4 and R5 HIV-1 strains activates human hepatic stellate cells, but if it can promote liver fibrosis in vivo is unknown. We aimed to evaluate if patients carrying X4 or R5 ...strains have a different liver fibrosis (LF) progression over time.
A total of 1,137 HIV-infected patients in ICONA cohort (21% females, 7% HCV co-infected) with an available determination of HIV-1 co-receptor tropism (CRT), a Fibrosis-4 Index for Liver Fibrosis (FIB-4) <3.25 and at least one-year follow-up were included. CRT was assessed by gp120 sequencing on plasma RNA and geno2pheno algorithm (10% false positive rate) or by Trofile. LF was assessed by means of FIB-4. LF progression was defined as an absolute score increase or a transition to higher fibrosis stratum and/or occurrence of liver-related clinical events.
A total of 249 (22%) patients carried X4 strains, which were associated with older age, lower CD4 count, lower nadir CD4, and intravenous drug use. Overall, X4 and R5 patients had similar baseline FIB-4 scores and similar mean FIB-4 slope after a median follow-up of 35 months. There was no difference between X4 and R5 for time to LF progression (p = 0.925). Estimated risk of LF at 24 months (95% CI) after baseline in X4 and R5 was 10.6% (8.3-12.9) and 9.9% (5.9-14.0), respectively. Age, HCV co-infection, diabetes, HIV-duration, HIV-RNA>100.000 cp/mL, antiretroviral therapy exposure were associated with LF progression at multivariate analysis.
A slight LF progression over time was observed in HIV-infected patients. No difference was demonstrated for X4 and R5 HIV-1 strains in accelerating LF evolution.
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. Overall, our findings support a crucial role of NK cells in the control of HIV-1 viremia.
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.
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