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Background: The success of antiretroviral therapies has made human immunodeficiency virus (HIV) a chronic disease, changing the care scenario dramatically. This study aimed to measure adherence to diabetes mellitus standards of care provided for people living with HIV (PLWH). Diabetes represents a paradigmatic case for tackling chronic care management in this target group., Methods: This retrospective observational study was performed on administrative health data retrieved from 2014 to 2016, with a validated algorithm to identify patients with HIV using: (i) hospital discharge records (ICD9-CM codes); (ii) drug dispensing records (with ATC codes); and (iii) disease-specific exemptions from co-payments for healthcare services. HIV-related treatments, comorbidities and health service utilization were measured, as was adherence to clinical guidelines-recommended standards of care for diabetes., Results: A population of 738 cases were identified in two Local Health Authorities in Italy, representing a prevalence of 0.14% of the general population, in line with the expected prevalence. Thirty-one cases of HIV patients diagnosed with diabetes were identified, a prevalence ratio of 4.2% compared to the 8% in the overall population. Adherence to diabetes standards of care tested within the same population was low, with the exception of those tests commonly administered for standard HIV follow-up care., Conclusions: The use of administrative data, combined with a Population Health Management approach represents a powerful tool for evaluating system capacity to manage HIV comorbidities. Study findings prove that it is time to design new care models for PLWH, affected by one or more chronic conditions, both to prevent their onset and to manage their comorbidities., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Public Health Association.)

Background and Aims: We investigated the conditioning roles of viral tropism and other variables on plasma HIV RNA levels after 6 months of combination antiretroviral therapy (cART) in an HIV-infected Italian naïve population using regression tree, random forest regression, and path analysis (PA). Patients in this multicenter observational study were treated with all antiviral drugs that are currently recommended as first-line therapies., Methods: Adult patients with chronic HIV infection were enrolled at the beginning of first-line cART (T0). The main variables were age, gender, tropism, "lcd4&#95;0" and "lcd4&#95;6" (log10 CD4+counts at T0 and after 6 months of cART, respectively), and "lrna0" (log10 HIV RNA at T0). Regression tree and random forest analyses were applied. The predictive effect on lrna6 (log10-transformed plasma HIV RNA after 6 months of cART) was also investigated via PA (x4->lcd4&#95;0->lrna0->lrna6) with a treatment selection step included as a dependent (mediator) variable for each third drug and, as predictive covariates, age, female, x4&#95;10, x4&#95;5, lcd4&#95;0, and lrna0. Tropism was assessed in plasma using the Geno2pheno algorithm with 2 false positive rate (FPR) cut-offs: 5% (x4&#95;5) and 10% (x4&#95;10)., Results: The study included 571 subjects (21% x4&#95;10 and 10.7% x4&#95;5). The only important predictor of lrna6 was lrna0, and a positive indirect effect of bearing X4 virus in plasma was suggested. A significant direct positive effect of protease inhibitors on lrna6 was found (p = 0.022), and a significant negative effect of integrase strand transfer inhibitor (INSTI) was also detected (p = 0.003 for FPR ≤ 5% and p = 0.01 for FPR < 10%). PA predicted mean residual viremias of 40 copies/mL without INSTI and 3 copies/mL with INSTI., Conclusions: PA indicated a possible indirect role of HIV tropism on lrna6 with both FPR < 10% and ≤ 5%. Patients treated with INSTI had a predicted residual viremia of 3 copies/mL., Competing Interests: The authors have declared that no competing interests exist.

Objectives: To characterize the prevalence of transmitted drug resistance mutations (TDRMs) by plasma analysis of 750 patients at the time of HIV diagnosis from January 1, 2013 to November 16, 2016 in the Veneto region (Italy), where all drugs included in the recommended first line therapies were prescribed, included integrase strand transfer inhibitors (InNSTI)., Methods: TDRMs were defined according to the Stanford HIV database algorithm., Results: Subtype B was the most prevalent HIV clade (67.3%). A total of 92 patients (12.3%) were expected to be resistant to one drug at least, most with a single class mutation (60/68-88.2% in subtype B infected subjectsand 23/24-95.8% in non-B subjects) and affecting mainly NNRTIs. No significant differences were observed between the prevalence rates of TDRMs involving one or more drugs, except for the presence of E138A quite only in patients with B subtype and other NNRTI in subjects with non-B infection. The diagnosis of primary/recent infection was made in 73 patients (9.7%): they had almost only TDRMs involving a single class. Resistance to InSTI was studied in 484 subjects (53 with primary-recent infection), one patient had 143C in 2016, a total of thirteen 157Q mutations were detected (only one in primary/recent infection)., Conclusions: Only one major InSTI-TDRM was identified but monitoring of TDRMs should continue in the light of continuing presence of NNRTI-related mutation amongst newly diagnosed subjects, sometime impacting also to modern NNRTI drugs recommended in first-line therapy., (Copyright © 2017 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.)

In a longitudinal study on 181 naïve patients who responded to therapy (mean follow-up 4 years), high baseline human immunodeficiency virus (HIV)-RNA values correlated with high levels of cellular HIV-DNA at all time points (p < 0.0001, p 0.045, p 0.0055, and p 0.0025, respectively) and negatively correlated with undetectable residual viremia (URV; <2.5 copies/mL) at T1, T2, and T3 (p 0.026, p 0.0149, and p 0.0002, respectively). Baseline high HIV-DNA levels predicted the persistence of high values (p 0.0001) and negatively correlated with URV (p 0.0254, p 0.0481, and p 0.0085). These results suggest that baseline viral load, cellular HIV-DNA, and URV were strongly correlated over long-term follow-up of antiretroviral therapy responders., (Copyright © 2014 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: To determine if tropism for CXCR4 or CCR5 correlates with cellular HIV DNA load, residual viraemia and CD4 count in 219 successfully treated naive subjects with HIV infection enrolled in five infectious diseases units in Northeastern Italy., Methods: A subset of subjects, achieving plasma HIV RNA level <50 copies/ml after initiation of first-line therapy and maintaining it until follow-up time points, was retrospectively selected from a prospective cohort. Blood samples were collected before the beginning of therapy (T0), at the first follow-up time (T1) and, when available, at a second (T2) follow-up time., Results: HIV DNA, CD4 count and plasma viraemia were available from all 219 patients at T0 and T1, and in 86 subjects at T2, while tropism determinations were available from 109 subjects at T0, 219 at T1, and from 86 subjects at T2. Achieving residual viraemia <2.5 copies/ml at T1 correlated with having the same condition at T2 (p = 0.0007). X4 tropism at T1 was negatively correlated with the possibility of achieving viraemia<2.5 copies/ml at T2 (p = 0.0076). T1-T2 tropism stability was significant (p <0.0001). T0 tropism correlated with T1 and T2 tropism (p < 0.001); therefore the stability of the tropism over the two follow-up periods was significant (p = 0.0003). An effective viremic suppression (viraemia<2.5 copies/ml) correlated with R5 coreceptor affinity (p= 0.047)., Conclusions: The tropism of archived virus was stable during an effective treatment, with 15-18% of subjects switching over time, despite a viraemia<50 copies/ml. R5 tropism and its stability were related to achieving and maintaining viraemia<2.5 copies/ml.

Cellular human immunodeficiency virus type 1 (HIV-1) DNA may be considered a marker of disease progression with significant predictive power, but published data on its correlation with plasma HIV RNA levels and CD4 counts in acute and chronic patients are not conclusive. We evaluated a cohort of 180 patients naïve for antiretroviral therapy before the beginning of treatment and after a virological response in order to define the indicators correlated with HIV DNA load decrease until undetectability. The following variables were evaluated as continuous variables: age, CD4 cell count and log(10) HIV DNA level at baseline and follow-up, and baseline log(10) HIV RNA level. Primary HIV infection at the start of therapy, an HIV RNA level at follow-up of <2.5 copies/ml, origin, gender, and transmission risk were evaluated as binary variables. The decline of HIV DNA values during effective therapy was directly related to baseline HIV DNA and HIV RNA values, to an increase in the number of CD4 cells, and to the achievement of an HIV RNA load of <2.5 copies/ml. An undetectable cellular HIV DNA load was achieved by 21.6% of patients at the follow-up time point and correlated significantly with lower baseline cellular HIV DNA values and with being in the primary stage of infection when therapy started. In conclusion, early treatment facilitated the achievement of undetectable levels of plasma viremia and cellular HIV DNA and a better recovery of CD4 lymphocytes. HIV DNA levels before and during highly active antiretroviral therapy may be used as a new tool for monitoring treatment efficacy.

A survey of HIV coreceptor usage in cerebrospinal fluid (CSF) samples, peripheral blood mononuclear cells (PBMCs), and plasma samples from naïve seropositive patients was conducted. One hundred patients were enrolled in this study. Of the 100 patients, 36 had a primary or recent infection (P-RI), 31 had an early chronic infection (>350 CD4 cells) (ECI), and 33 had a late chronic infection (LCI). All 3 compartments were sampled in a subset of 33 participants, while the remaining 67 patients provided plasma samples and PBMCs only. Seventy-seven patients harbored the R5 virus in plasma samples and had a significantly higher median and percentage of CD4(+) T cells than patients with X4 virus (437 and 281 cells/μl, respectively; P = 0.0086; 20.6% and 18.6%, respectively). The X4 strain was detected more frequently in patients with LCI than in patients with P-RI or ECI (39.3%, 19.4%, and 9.6%, respectively; P = 0.0063). PBMC and plasma tropism was concordant in 90 patients, and 73 had the R5 strain. Among patients with discordant results, 4 had the R5 virus in their plasma and the X4 virus in PBMCs; 6 showed the opposite profile. Plasma, PBMC, and CSF tropism determinations were concordant in 26/33 patients (21 patients had R5, and 5 had X4). The tropism was discordant in 5/33 patients, with the X4 virus in plasma and R5 in CSF; the HIV tropism in PBMCs was X4 in 3 patients. The remaining 2/33 patients had the R5 virus in plasma and PBMCs and the X4 virus in CSF; one of these patients had a P-RI. The discordant tropism in CSF and blood may have implications for chemokine (C-C motif) receptor 5 (CCR5) antagonist use in patients with limited response to antiretroviral therapy (ART) or in responding patients evaluated for simplification of treatment.

To evaluate the relevance and the virological and immunological markers of Kaposi sarcoma herpesvirus 8 (KSHV) viremia in Italian male patients at the time of diagnosis of infection with HIV-1, 481 men infected with HIV were recruited consecutively. The presence of KSHV DNA was evaluated in peripheral blood mononuclear cells (PBMCs) and in plasma and correlated with demographic and viro-immunological parameters. Seventy-four patients had KSHV DNA detected in PBMCs. By univariate analysis, the presence of KSHV DNA was associated significantly with unprotected homosexual relationships (P=0.003) and it was significantly higher in patients with CD4+ cell <350 (P=0.025). By multivariate analysis, homosexual relationships were associated independently with KSHV DNA in PBMCs (OR: 3.25; 95% CI: 1.1-9.7; P=0.035). Among the 74 patients with KSHV DNA detected in PBMCs, plasma samples from 60 were analyzed and 33 were positive for KSHV DNA. The CD4+ cell counts and percentages were significantly lower in patients with KSHV DNA in both PBMCs and plasma as compared to patients with only KSHV DNA in PBMCs (P=0.006 and P=0.019, respectively). Among the patients with KSHV DNA detected in PBMCs, all 13 patients with CD4+ cells count <200 had detectable levels of KSHV in their plasma. By multivariate analysis adjusted for the epidemiologic and virological parameters, low CD4+ cell count was the only independent variable associated with the presence of KSHV DNA in plasma (OR, 0.001; 95% CI: <0.001-0.001; P=0.03). In HIV-positive antiretroviral therapy-naïve males, KSHV active replication as detected by KSHV DNA in plasma was associated significantly with low CD4+ cell count., (Copyright © 2011 Wiley-Liss, Inc.)

Prevalence and impact of occult HBV infection in HIV positive patients is controversial. The aims of this study were to determine the prevalence of occult HBV infection and its impact on histological and virological parameters. 52 HIV/HCV (but HBsAg-negative) co-infected patients, 29 HBsAg and anti-HCV negative chronic hepatitis, and 20 HBsAg positive chronic hepatitis controls were studied. DNA was extracted from frozen biopsies and amplified with primers for S, C and X regions, and for (ccc) HBV-DNA. Sera were tested for HBV-DNA with two quantitative assays (Cobas Amplicor HBV Monitor, and the real-time COBAS (r) Taqman HBV Test, Roche Diagnostics, UK). Occult HBV infection was detected in 7 (13.4%) liver biopsies of the study group, and in none case of the non viral chronic hepatitis group (p=0.04). All serum samples were HBV-DNA negative with Cobas Amplicor HBV monitor assay, while 3 cases were found positive with real time PCR. Statistical analysis didn't show any impact of occult HBV infection on liver histology, CD4+ cells count, HIV and HCV load, and ALT levels. Occult B infection is relatively frequent in HIV/HCV co-infected patients, and is underestimated by common HBV-DNA serological assays. However, it doesn't seem to exert a relevant impact.

Genotypic antiretroviral testing is recommended for newly infected drug-naive subjects, and the material of choice is plasma RNA. Since drug resistance mutations (DRMs) may persist longer in cellular DNA than in plasma RNA, we investigated whether the use of peripheral blood mononuclear cell (PBMC) human immunodeficiency virus (HIV) DNA increases the sensitivity of genotypic testing in antiretroviral-drug-naive subjects. We compared the rate of primary drug resistance in plasma RNA and PBMC DNA in 288 HIV type 1-infected drug-naive persons tested at a single clinical virology center from June 2004 to October 2006. Resistance in the plasma compartment to at least one drug was detected for 64 out of 288 (22.2%) naive patients and in the PBMC compartment for 56 (19.4%) patients. Overall, DRMs were found in 80 out of 288 (27.8%) patients. PBMC DNA [corrected] DRMs were present in [corrected] 16 subjects with wild-type virus in their plasma RNA [corrected] Another nine patients had additional DRMs in their PBMC DNA [corrected] with respect to those detected in their [corrected] plasma RNA. On the other hand, extra plasma RNA [corrected] DRMs were detected in [corrected] 24 and 8 subjects with wild-type and drug-resistant virus in their PBMC DNA [corrected] respectively. Resistance to more than one class of antiretroviral drug was detected by plasma and PBMC analysis for 25.0% and 36.2% of the subjects, respectively. Our data support the potential utility of genotypic resistance testing of PBMC DNA in conjunction with the currently recommended plasma RNA analysis.

Although hepatitis C virus (HCV) is a recognized cause of circulating cryoglobulins, the role of human immunodeficiency virus (HIV) in the pathogenesis of cryoglobulinemia has not been investigated extensively. To evaluate the prevalence of circulating cryoglobulins and to assess the relationship with clinical and virological parameters, 162 HIV-positive subjects (84 anti-HCV(+)) were tested for cryoglobulins, C3, C4, RF, autoantibodies, HIV-viral titer, and CD4(+) count. Anti-HCV-positive subjects were tested for HCV-RNA, HCV-viral titer, and HCV genotype. All patients were examined for the presence of signs or symptoms of vasculitis and tested for cryoglobulins using a standard biochemical assay. Cryoglobulins were found in 30 (18.5%) cases. Of the 30 positive cases, 29 (96.7%) were anti-HCV-positive and 28 (93.3%) HCV-RNA-positive. The presence of cryoglobulins was significantly associated (P < 0.01) with HCV-RNA positivity (OR = 27), liver cirrhosis (OR = 16), decreased levels of C3 (OR = 8.6), C4 (OR = 13.6), increased levels of IgG and IgM (OR = 6.1 and 7.9, respectively), and RF positivity (OR = 6.3), but was unrelated to CD4(+) cell count, HIV viral load, diagnosis of AIDS, HCV viral load and the presence of autoantibodies. Interestingly, the presence of cryoglobulins was not significantly associated with signs and symptoms commonly associated with cryoglobulinemia. In conclusion, HIV infection does not seem to play a significant role in the production of circulating cryoglobulins, which strongly correlates with HCV co-infection and liver cirrhosis. Typical signs and symptoms of cryoglobulinemia do not correlate with the detection of circulating cryoglobulins in HIV and HCV patients., (Copyright 2003 Wiley-Liss, Inc.)

Sixty-seven consecutive patients infected with the human immunodeficiency virus (HIV-1), 72% of which with overt AIDS, were examinated by upper endoscopy due to various indications and evaluated for the prevalence of H. pylori infection. The infection was studied by performing both histological examination of gastric biopsies and serological testing for anti-H. pylori IgG antibodies. The H. pylori prevalence rate was 55% in histology; no significant differences were observed in HIV-infected subjects and those with overt AIDS (52% vs 63%, respectively; P = NS). Positive histological testing appeared to be directly related to the peripheral CD4+ lymphocyte count (minimum rates of 43% were detected in patients with CD4+ < 100 x 10(6)/liter and maximum rates of 78% in patients with CD4+ > 200 x 10(6)/liter, respectively; P < 0.05) and inversely related to the frequency of antibiotic treatments performed over the six months prior to endoscopy. Low CD4+ counts were also apparently associated with low-grade H. pylori infection. Serological testing was positive for anti-H. pylori IgG antibodies in 39% of patients; compared to histology, serology displayed a sensitivity of 57% and a specificity of 81%. The discrepancy between histological and serological positive results for H. pylori was noted to be higher in the more advanced phases of HIV infection. Based upon our results, the serological testing for anti-H. pylori IgG antibodies seems to require cautious interpretation in HIV-positive patients.

59 (18.3%) of 323 patients with tuberculosis (TB) tested for HIV-1 antibody by ELISA technique (Wellcozyme) were seropositive. In the control group selected among the health personnel working in the Arua Hospital, 7.7% were found positive for HIV-1 antibody, thus showing a significantly lower prevalence compared with the TB patients (P < 0.005). The prevalence of HIV infection was 50% in the urban TB patients, 7% in TB patients living in rural areas surrounding Arua town and 1.6% in the peripheral rural setting. Of 27 TB patients with clinical AIDS, 18 died during the course of the study. The AIDS patients' survival rate was 46.4% 6 months after diagnosis, and 21.4% after 16 months, the median period of survival being 5.0 months. Risk factors, sputum conversion rate, clinical and radiological findings were analysed. No significant difference was found between seropositive and seronegative TB patients for clinical drug-related toxicity (P > 0.05).

At the end of 1985, when the AIDS epidemic was in its early stages in Uganda, a survey was carried out in a peripheral area of the country. Sera were collected from groups of people, and examined for the presence of HIV infection. The results show a very limited number of positive cases, present only among sexually active subjects. High specificity and sensitivity in the laboratory tests was shown by the Western blot technique.