Vincenzo Vullo

Central nervous system involvement as a relapse of disseminated histoplasmosis in an Italian AIDS patient

A case of an Italian AIDS patient who developed both meningitis and cerebral mass lesion as a final relapse of disseminated histoplasmosis is reported. Central nervous system (CNS) involvement occurred while the patient was receiving both amphotericin B and itraconazole as maintenance therapy, thus indicating the difficulty of eradicating histoplasmosis in patients with AIDS.

Serologic responses to Rhodococcus equi in individuals with and without human immunodeficiency virus infection

Thirty healthy blood donors, 15 workers from horse-breeding farms, 69 human immunodeficiency virus (HIV)-negative persons at risk for HIV infection, 125 HIV-infected subjects withoutRhodococcus equi infection, and nine HIV-infected patients withRhodococcus equi pneumonia were evaluated in order to detect serum antibodies toRhodococcus equi precipitate-soluble antigen by an enzyme immunoassay (EIA). Whereas EIA values for healthy donors, horse farm workers, individuals at risk for HIV infection, and HIV-positive subjects withoutRhodococcus equi infection were comparable, HIV-infected patients with rhodococcal disease had significantly higherRhodococcus equi antibody levels (p<0.0001). The clinical outcome ofRhodococcus equi pneumonia was more severe in subjects who had low levels of specific antibodies, whereas patients who recovered had elevatedRhodococcus equi antibody levels over time. Immunoblot studies showed that bothRhodococcus equi-infected patients and foals recognized a protein band of approximately 60 kDa in theRhodococcus equi precipitate-soluble antigen. On the other hand, theRhodococcus equi-infected patients did not react with the diffuse 15 to 17 kDa virulence-associated proteins that represent important virulence factors both in mice and horses.

Virological failure at one year in triple-class experienced patients switching to raltegravir-based regimens is not predicted by baseline factors

We evaluated rates and determinants of virological failure in triple-class experienced patients receiving raltegravir-based regimens from a national observational study over 48 weeks, defined by any one of the following: (1) no HIV-RNA suppression to undetectable levels (<50 copies/mL) during follow-up; (2) detectable viral load after obtaining undetectable levels; and (3) leaving the study before 48 weeks. Among 101 eligible patients, 26 (25.7%; 95% CI 17.2–34.2) had virological failure. No significant differences between patients with and without virological failure were observed for gender, age, route of transmission, baseline CD4/HIV-RNA, CDC group, hepatitis B or C co-infections, resistance (based on the last genotype available), type and number of concomitant drug classes, concomitant use of darunavir, atazanavir, etravirine, enfuvirtide or maraviroc, and health-related quality-of-life measures. A high rate of treatment response was observed. The analyses did not identify any baseline factor associated with failure, including resistance status. Even if we cannot exclude the presence of pre-existing minority resistant variants not captured by genotypic tests, the lack of baseline predictors of failure suggests the need to monitor patients closely during follow up for other factors, such as potential drug interactions and reduced levels of adherence, which may favour virological failure.

Urolithiasis Under Atazanavir Boosted and Tenofovir Therapy: A Case Report

To date the Adverse Event Reporting System (AERS) has reported 30 cases of nephrolithiasis in HIV patients under atazanavir based regimen, of whom 13 had received concomitant tenofovir.1 Only three cases of nephrolithiasis associated with atazanavir have been reported in the literature and of these, two of the patients were under coadministration of boosted-atazanavir and tenofovir.2-4 The recent published results of a retrospective study reported an overall prevalence of atazanavir urolithiasis of 0.97% among a total of 1134 patients treated with atazanavir. In addition to eleven patients diagnosed with urolithiasis, five were in treatment with atazanavir and tenofovir at same time.5 We describe a case of urolithiasis in patient during treatment with ritonavir-boosted atazanavir and tenofovir. A 43-year-old bisexual Italian male was found to be HIV-1 antibody-positive in 1999. At the time of diagnosis he did not present co-morbidities and his renal and hepatic functions were normal. The CD4+ T lymphocytes were 462 cells/mm3 (13.3%) and plasma HIV-1 RNA load was 1.2 x 106 copies/mL, thus antiretroviral treatment was prescribed including lamivudine-zidovudine and nevirapine. After 18 months virologic failure occurred (plasma HIV-1 RNA load 5.2 x 103 copies/mL), and the therapy was switched to lamivudine didanosine and ritonavirboosted lopinavir treatment that rapidly induced virological suppression. In May 2005, due to a second virologic failure (plasma HIV-1 RNA load 7.3 x 103 copies/mL), we Journal of Chemotherapy Vol. 20 n. 1 (143-144) 2008

Dynamics and phylogenetic relationships of HIV-1 transmitted drug resistance according to subtype in Italy over the years 2000–14

BackgroundnTransmitted drug-resistance (TDR) remains a critical aspect for the management of HIV-1-infected individuals. Thus, studying the dynamics of TDR is crucial to optimize HIV care.nnnMethodsnIn total, 4323 HIV-1 protease/reverse-transcriptase sequences from drug-naive individuals diagnosed in north and central Italy between 2000 and 2014 were analysed. TDR was evaluated over time. Maximum-likelihood and Bayesian phylogenetic trees with bootstrap and Bayesian-probability supports defined transmission clusters.nnnResultsnMost individuals were males (80.2%) and Italian (72.1%), with a median (IQR) age of 37 (30-45)u2009years. MSM accounted for 42.2% of cases, followed by heterosexuals (36.4%). Non-B subtype infections accounted for 30.8% of the overall population and increased over time (<2005-14: 19.5%-38.5%, Pu2009<u20090.0001), particularly among Italians (<2005-14: 6.5%-28.8%, Pu2009<u20090.0001). TDR prevalence was 8.8% and increased over time in non-B subtypes (<2005-14: 2%-7.1%, Pu2009=u20090.018). Overall, 467 transmission clusters (involving 1207 individuals; 27.9%) were identified. The prevalence of individuals grouping in transmission clusters increased over time in both B (<2005-14: 12.9%-33.5%, Pu2009=u20090.001) and non-B subtypes (<2005-14: 18.4%-41.9%, Pu2009=u20090.006). TDR transmission clusters were 13.3% within the overall cluster observed and dramatically increased in recent years (<2005-14: 14.3%-35.5%, Pu2009=u20090.005). This recent increase was mainly due to non-B subtype-infected individuals, who were also more frequently involved in large transmission clusters than those infected with a B subtype [median number of individuals in transmission clusters: 7 (IQR 6-19) versus 4 (3-4), Pu2009=u20090.047].nnnConclusionsnThe epidemiology of HIV transmission changed greatly over time; the increasing number of transmission clusters (sometimes with drug resistance) shows that detection and proper treatment of the multi-transmitters is a major target for controlling HIV spread.

Adherence and Genotypic Drug Resistance Mutations in HIV-1-Infected Patients Failing Current Antiretroviral Therapy

Abstract The aim of this study was to assess the correlation between the estimated adherence of HIV-1 infected patients with antiretroviral (ARV) therapy failure and drug-resistant mutations. We studied 40 patients with virological and immunological ARV-therapy failure. in order to assess the adherence of patients we used the SERAD questionnaire. Genomic sequencing of the HIV-1 pol gene was performed. 100% adherence was reported by 27 patients (67.5%) (adherent patients). multivariate analysis showed that only baseline and nadir CD4+ counts maintained a significant correlation with the adherence. for PR and NNRTI mutations, we did not find any difference between the two groups of patients. baseline NRTI mutations were higher in adherent patients than in non-adherent patients (p<0.05). No differences were found between plasma mutations and PBMC mutations. The authors conclude that genotypic resistance mutations were found in the majority of patients with ARV-therapy failure despite a good self-reported adherence to therapy. Adequate adherence to therapy is not the only key factor in viral suppression.

Single‐strain vs multi‐strain probiotic supplementation strategy against rheumatoid arthritis

We read with interest the papers recently published by Marietta EV etxa0al. on the gut microbial dysbiosis as a key factor in the pathogenesis of inflammatory diseases such as Rheumatoidxa0arthritisxa0(RA).1 Altered microbiota, well described in patients affected by RA, seems associated with perturbation of certain metabolic pathways and the therapies addressed to correct gut microbiome dysbiosis could help in the maintenance of immune homeostasis of the host. n nThis article is protected by copyright. All rights reserved.

The absence of HIV mutations in cerebrospinal fluid and in peripheral blood mononuclear cells during a regimen containing trizivir plus tenofovir

both in antiretroviral-naive patients and in heavily pretreated patients have antiviral activity comparable to protease inhibitor (Pi)-containing regimens, but when these regimens are administered to patients with prior suboptimal nRTi drug exposure they may be not so effective 8,9. The purpose of this study was to evaluate the virological efficacy in terms of suppression of viremia in plasma and in cerebrospinal fluid (CsF) and to evaluate the presence of drug-associated mutations archived in peripheral blood mononuclear cells (PBMC). This prospective 5-year cohort study include 23 HiV-infected patients with simplified therapy including TZV and TDF; all patients were antiretroviral pretreated for almost 1 year with one protease inhibitor combined with two analogue nucleosides with fast and durable virological responses. All patients enrolled were not able to switch therapy to efavirenz-based regimens due to a history of neurological problems. All patients enrolled at the Department of infectious and Tropical Diseases of the University “sapienza” of Rome gave informed consent to blood sampling and processing. Antiretroviral-experienced HiV-1-infected patients were eligible for inclusion criteria if they were at least 18 years of age and had HiV-RnA under 50 copies/ml over the past 12 months due to a stable regimen including Pi/boosted and 2 nRTi. All patients were followed up for evaluation of plasma HiV-RnA levels, CD4 T-cell count every 3 months for at least 5 years. HiV-RnA levels in CsF were measured in 8 patients. The total HiV-DnA in PBMC was measured at the moment of simplification therapy and after 24 months. The HiV-1 DnA was sequenced from PBMC after 5 years. All analyses were exploratory. Differences between year 1, 2, 3, 4, 5 and baseline were calculated for CD4 T cells and PBMC HiV-DnA by using the Wilcoxon signed rank test. statistical significance of the longitudinal changes in these parameters was assessed using student’s t test. P<0.05 was considered significant. The study population included 23 HiV-infected patients (18 men and 5 women; age 53±10.24 years mean ± sD) who had suppressed viral load (<50 copies/ml) over the past 12 months of a stable Pibased therapy. The mean time of viral suppression for all patients was 29 months (sD ± 5.3). The median CD4+ at the moment of simplification therapy was 400 cell/mm3 (range 300 cell/mm3 814 cell/mm3), while the nadir of CD4+ was 188 cell/mm3 (range 144 cell/mm3 322 cell/mm3). After 5 years of follow-up, all patients showed a persistent undetectable viremia <50 copies/ml. We performed lumbar puncture only in 8 patients who gave informed consent. in these 8 patients the HiVRnA measured in CsF after 5 years of treatment with bRief COmmUNiCAtiON

Modelling treatment response could reduce virological failure in different patient populations

Background: HIV drug resistance can cause viral re-bound in patients on combination antiretroviral therapy, requiring a change in therapy to re-establish virological control. The RDI has developed computational models that predict response to combination therapy based on the viral genotype, viral load, CD4 count and treatment history. Here we compare two sets of models developed with different levels of treatment history information and test their generalisability to new patient populations. nMethods: Two sets of five random forest models were trained to predict the probability of virological response (follow-up viral load <50 copies/ml viral RNA) following a change in antiretroviral therapy using the baseline viral load, CD4 count, genotype and treatment history from 7,263 treatment change episodes. One set used six treatment history variables and the other 18 - one for each drug. The accuracy of the models was assessed in terms of the area under the receiver-operator characteristic curve (AUC) during cross validation and with 375 TCEs from clinics that had not contributed data to the training set. nResults: The mean AUC achieved by the two sets of models during cross validation was 0·815 and 0.820. Mean overall accuracy was 75% and 76%, sensitivity 64% and 62% and specificity 81% and 84%. The AUC for each committee tested with the independent test set was 0.87 and 0.855. Mean overall accuracy was 89% and 87%, sensitivity 67% and 61% and specificity 90% and 87%. There were no significant differences between the two sets. The models correctly predicted 330 (92%) of the 357 treatment failures observed in practice and were able to identify alternative regimens that were predicted to be effective for up to 267 (75%) of the failures and regimens with a higher probability of response for all cases. nConclusions: Computational models can predict accurately the virological response to antiretroviral therapy from a range of variables including genotype and treatment history even for patients from unfamiliar settings. This approach has potential utility as a useful aid to treatment decision-making and may reduce treatment failure