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ABSTRACT: We aimed to assess the persistence and clearance of HPV-DNA at anal site in a cohort of HIV-positive patients (pts) asymptomatic for sexually transmitted diseases (STD). Consecutive HIV-pos males underwent anoscopy, and each anal sample was analyzed for HPV-PCR detection/genotyping (high-risk genotypes: HR-HPV) and for cytologic abnormalities (Bethesda System 2001: low and high grade SIL, LSIL-HSIL). Immune activation in peripheral blood (CD8/CD38+) was assessed by flow cytometry. Pts were re-examined at a 12-18 months follow-up visit. Comparisons were assessed by Mann-Whitney and chi-square test. Factors related to HPV persistence were identified by logistic regression. 105 HIV-pos males were studied: 89 (84%) were MSM, 76 (72%) were on HAART, median age was 42 (IQR:34-47), median CD4 count of 500 cell/mmc (IQR:366-680). HPV-DNA was detected in anal swabs from 96 (91.4%) pts, 77 of them (80%) harbored HR-HPV; 46 were coinfected with>1 HR-HPV. Most frequent genotypes were HPV-16 (30%), HPV-58 (25%). In a median follow up of 18 months (IQR 12-24), 83/96 (86.4%) pts showed persistent HPV infection, while 13 (13.5%) became negative; conversely, 6 (5%) pts, HPV-negative at baseline, acquired HPV infection. Younger pts and those with a shorter duration of HIV infection showed a higher prevalence of HPV persistence (Table). Conversely being on HAART and a longer duration of therapy were associated to viral clearance. Interestingly, pts with persistent HPV infection showed an activated immune profile at baseline, with significantly higher CD8+CD38+%. In the multivariate analysis only SIL at baseline (AOR 4.11, 95% CI 0.89-18.9, p=.06), being MSM (AOR 5.11, 95% CI 0.87-29.8, p=.06) and higher CD8+CD38+% (AOR 1.93, 95% CI 0.88-4.24, p=.09) were borderline associated with persistent anal HPV infection. Our results confirm a higher prevalence and persistence of anal HPV infection in HIV-positive males; HIV-pos pts with anal HPV infection should be thus strictly followed-up for the early detection of pre-cancerous lesions.
Journal of the International AIDS Society 01/2012; 15(6):18435. · 3.26 Impact Factor
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ABSTRACT: Non-AIDS events are the leading cause of death in HIV-positive patients (pts) on effective HAART. The VACS index, composed by HIV-RNA, CD4+, age, hemoglobin, FIB-4, eGFR and HCV co-infection, has been validated as 5-year mortality index in HIV- positive pts [1]. The aim of our study was to evaluate the prevalence and any possible predictive factors of medium-high VACS index in a cohort of HIV-positive pts; we also evaluated whether it relates with markers of systemic immune activation. 501 consecutive HIV-positive asymptomatic pts on effective HAART (HIV-RNA <40 cp/ml) were enrolled. T-cell activation (CD38+, CD8+45R0, CD8+38R0) and differentiation (CD127+) was assessed by flow cytometry; VACS index was calculated closest to the sample timepoint. Comparisons were assessed by Chi-square test. Factors associated with VACS index equal or greater than 10% (gender, time on HAART, CD4+nadir, AIDS diagnosis, previous or current IDU, immune-activation markers) in univariate model entered the multivariate logistic regression. Of the 501 patients enrolled, 350 (70%) had a low VACS index (VACS <10%), 143 (28%) a medium index (VACS 10-30%) and 8 (1%) an high one (VACS >30%). Groups (pts with low and medium-high VACS index) were comparable for CD4+ nadir, AIDS diagnosis, CD8+45RO%, CD8+38RO%, CD127+%. Females, active or previous IDU, pts with shorter HAART exposure showed more frequently medium-high VACS index (table 1). In the multivariable model, female sex (AOR 6.26, 95% CI 3.45-11.38, p<0.000), IDU history (AOR 2.409, 95% CI 1.31-4.422, p=0.0045) and current CD38+/CD8% (each% more: AOR 1.122, 95% CI 1.03-1.21, p=0.004) were all independent predictors of VACS ≥10%. Our data suggest that a persistently-activated immune profile despite virologically-suppressive HAART may contribute to all-cause mortality risk, possibly through its role in accelerating degenerative disease. Possible determinants of gender differences in VACS index (such as hemoglobin) need to be further studied.
Journal of the International AIDS Society 01/2012; 15(6):18278. · 3.26 Impact Factor
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The Journal of Infectious Diseases 07/2010; 202(2):330-1; author reply 331-2. · 6.41 Impact Factor