[Show abstract][Hide abstract] ABSTRACT: Thanks to the development of antiretroviral agents to control HIV replication, HIV infection has turned from a fatal disease into a treatable chronic infection. The present work collects the opinions of several experts on the efficacy and safety of recently approved second generation of integrase inhibitors and, in particular, on the role of this new class of drugs in antiretroviral therapy. The availability of new therapeutic options represents an opportunity to ameliorate the efficacy of cART in controlling HIV replication also within viral reservoirs. The personalization of the treatment driven mainly by the management of comorbidities, HIV-HCV co-infections and aging, will be easier with antiretroviral drugs without drug-drug interactions and with a better toxicity and tolerability profile. Future assessment of economic impact for the introduction of new innovative drugs in the field of antiretroviral therapy will likely need some degree of adjustment of the evaluation criteria of costs and benefit which are currently based almost exclusively on morbidity and mortality.
The New Microbiologica: official journal of the Italian Society for Medical Virology (SIVIM) 11/2015; 38(4):443-490. · 1.78 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objects:
The impact of HIV-1 tropism on the emergence of non-AIDS events was evaluated in a cohort of 116 antiretroviral (ART) responder patients.
The patients were followed for the emergence of hypertension, renal impairment, metabolic and bone disorders (defined as non-AIDS events) each 8 weeks at standard visits. A V3 plasma sequence genotype analysis was performed at the time of ART initiation and the geno2pheno algorithm with the results that defines the false positive rate (FPR) was used to infer HIV tropism. The associations between the non-AIDS events and the FPR at baseline were evaluated using the Chi-squared test for trend. A Cox regression analysis using the counting process formulation of Andersen and Gill was performed to define whether the emergence of non-AIDS events was correlated to FPR.
The prevalence of at least one non-AIDS event resulted higher in patients with a FPR <10% than in patients with a R5 virus (p-value = 0.033). Patients with a FPR <5.0% most frequently developed non-AIDS events during ART (p value = 0.01). A higher prevalence of patients with at least 2 AIDS events was found in the group of subjects with a FPR <5.0% respect to the others (p-value<0.001). At multivariate Cox regression analysis, having a X4 virus and age were independently associated with a higher probability of non-AIDS event development.
This study shows that an X4 virus, particularly a FPR <5%, is related to non-AIDS events development. Further studies are warranted to understand the mechanisms underlying this phenomenon.This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. http://creativecommons.org/licenses/by-nc-nd/4.0.
AIDS 11/2015; DOI:10.1097/QAD.0000000000000977 · 5.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: When treating HCV patients with conventional dual therapy in the current context of rapidly evolving HCV therapy, outcome prediction is crucial and HCV kinetics, as early as 48 hours after the start of treatment, may play a major role. We aimed at clarifying the role of HCV very early kinetics. We consecutively enrolled mono-infected HCV patients at 7 treatment sites in Central Italy and evaluated the predictive value of logarithmic decay of HCV RNA 48 hours after the start of dual therapy (Delta48). Among the 171 enrolled patients, 144 were evaluable for early and sustained virological response (EVR, SVR) prediction; 108 (75.0%) reached EVR and 84 (58.3%) reached SVR. Mean Delta48 was 1.68±1.22 log10 IU/ml, being higher in patients with SVR and EVR. Those genotype-1 patients experiencing a Delta48 >2 logs showed a very high chance of success (100% positive predictive value), even in the absence of rapid virological response (RVR). Evaluation of very early HCV kinetics helped identify a small but significant proportion of genotype-1 patients (close to 10%) in addition to those identified with RVR, who could be treated with dual therapy in spite of not reaching RVR. In the current European context, whereby sustainability of HCV therapy is a crucial issue, conventional dual therapy may still play a reasonable role in patients with good tolerance and early prediction of success.
The New Microbiologica: official journal of the Italian Society for Medical Virology (SIVIM) 10/2015; 38(4). · 1.78 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Aim:
To investigate the prevalence and genotypic profile of overt and occult hepatitis-B infection (OBI) among HIV-infected individuals in Cameroon.
212 HIV-infected Cameroonians, aged 37.6 [IQR: 32.6-46.6] followed-up at the University Health Centre in Yaoundé, were tested for HBsAg, anti-HBs, anti-HBc IgG/IgM, HBV-DNA and anti-HCV IgG. HBV positive cases were tested for Hepatitis Delta virus (HDV) using anti-HDV IgG and HDV-RNA. Liver function was assessed by alanine and aspartate aminotransaminases. OBI was defined as negative-HBsAg and detectable HBV-DNA. In occult or overt HBV-infected participants, HBV reverse transcriptase (RT)/surface (S) sequences were analyzed for drug resistance, immune-escape mutants, and phylogeny.
Overall, 78.3% (166/212) participants had past/ongoing HBV-exposure, with 39.1% (83/212) carrying "HBcAb-positive alone". Prevalence of overt HBV (HBsAg positive) was 11.8% (25/212), OBI prevalence was 6.9% (12/175), and HDV prevalence was 12% (3/25). Phylogeny of HBV-RT/S revealed the co-circulation of genotypes A and E. All HBV-coinfected participants harbored HBV strains with at least one immune-escape mutation. Of note, one HBV variant carried the vaccine-escape mutation G145R that hinders HBsAg neutralization by antibodies. For the ever-first time, a novel 9 aa-deletion (s115-s123), located in the HBsAg "a" determinant, was found in association with OBI. A stop codon in the S region (associated with increased risk of hepatocellular carcinoma) was found in six cases.
High prevalence of overt/occult HBV-infection and circulating atypical strains highlight the importance of HBV surveillance and strategies to detect OBI in highly endemic countries like Cameroon.
Current HIV research 09/2015; 13(999). DOI:10.2174/1570162X13666150930114742 · 1.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The pathogen safety of blood/plasma-derived products has historically been a subject of significant concern to the medical community. Measures such as donor selection and blood screening have contributed to increase the safety of these products, but pathogen transmission does still occur. Reasons for this include lack of sensitivity/specificity of current screening methods, lack of reliable screening tests for some pathogens (e.g. prions) and the fact that many potentially harmful infectious agents are not routinely screened for. Methods for the purification/inactivation of blood/plasma-derived products have been developed in order to further reduce the residual risk, but low concentrations of pathogens do not necessarily imply a low level of risk for the patient and so the overall challenge of minimising risk remains. This review aims to discuss the variable level of pathogenic risk and describes the current screening methods used to prevent/detect the presence of pathogens in blood/plasma-derived products.
[Show abstract][Hide abstract] ABSTRACT: This article examines the dynamics and factors underlying hepatitis C virus (HCV) resistance, along with their impact on daily clinical management of HCV-infected patients.
Across available treatment-regimens, GT-3 is the most difficult-to-cure genotype, but also genotype-1a may show lower success-rates compared with genotype-1b. Natural resistance to NS3, NS5A and NS5B inhibitors may contribute to treatment failures. The Q80K NS3-protease mutation affects sensibility to simeprevir + peg-interferon/ribavirin combinations. It reaches up to 48% prevalence in genotype-1a in some studies (but it is lower in other). Resistant variants (particularly in NS5A) developed at failure can persist, in a substantial proportion of patients, even 3 years after treatment-discontinuation, potentially affecting readministration of the same direct-acting antiviral agent (DAA)-class. This will become an issue for those patients failing all-oral regimens with multiple-resistant viruses.
Recent data support the importance of an accurate genotype and genotype-1 subtype (1a/1b) assignment prior therapy. Resistance testing at baseline has no clear indication so far in clinical practice for all-DAA regimens selection, while it remains a valuable option at the retreatment of patients who failed DAA-containing regimens, provided that data are generated to inform treatment decisions based on the results of resistance testing. In this context, long-term RAVs persistence after failure should be taken into account.
Current opinion in HIV and AIDS 09/2015; 10(5):381-9. DOI:10.1097/COH.0000000000000177 · 4.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Increased evidence of relevant HIV-1 epidemic transmission in European countries is being reported, with an increased circulation of non-B-subtypes. Here, we present two recent HIV-1 non-B transmission clusters characterized by NNRTI-related amino-acidic mutations among newly diagnosed HIV-1 infected men, living in Rome (Central-Italy).
METHODS: Pol and V3 sequences were available at the time of diagnosis for all individuals. Maximum-Likelihood and Bayesian phylogenetic-trees with bootstrap and Bayesian-probability supports defined transmission-clusters. HIV-1 drug-resistance and V3-tropism were also evaluated.
RESULTS: Among 534 new HIV-1 non-B cases, diagnosed from 2011 to 2014, in Central-Italy, 35 carried virus gathering in two distinct clusters, including 27 HIV-1 C and 8 CRF17_BF subtypes, respectively. Both clusters were centralized in Rome, and their origin was estimated to have been after 2007. All individuals within both clusters were males and 37.1% of them had been recently-infected. While C-cluster was entirely composed by Italian men-who-have-sex-with-men, with a median-age of 34 years (IQR:30-39), individuals in CRF17_BF-cluster were older, with a median-age of 51 years (IQR:48-59) and almost all reported sexual-contacts with men and women. All carried R5-tropic viruses, with evidence of atypical or resistance amino-acidic mutations related to NNRTI-drugs (K103Q in C-cluster, and K101E+E138K in CRF17_BF-cluster).
CONCLUSIONS: These two epidemiological clusters provided evidence of a strong and recent circulation of C and CRF17_BF strains in central Italy, characterized by NNRTI-related mutations among men engaging in high-risk behaviours. These findings underline the role of molecular epidemiology in identifying groups at increased risk of HIV-1 transmission, and in enhancing additional prevention efforts.
PLoS ONE 08/2015; 10(8). DOI:10.1371/journal.pone.0135325. · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
European guidelines recommend treatment of chronic hepatitis B virus infection (CHB) with the nucleos(t)ide analogs (NAs) entecavir or tenofovir. However, many European CHB patients have been exposed to other NAs, which are associated with therapy failure and resistance. The CAPRE study was performed to gain insight in prevalence and characteristics of NA resistance in Europe.
A survey was performed on genotypic resistance testing results acquired during routine monitoring of CHB patients with detectable serum hepatitis B virus DNA in European tertiary referral centers.
Data from 1568 patients were included. The majority (73.8%) were exposed to lamivudine monotherapy. Drug-resistant strains were detected in 52.7%. The most frequently encountered primary mutation was M204V/I (48.7%), followed by A181T/V (3.8%) and N236T (2.6%). In patients exposed to entecavir (n = 102), full resistance was present in 35.3%. Independent risk factors for resistance were age, viral load, and lamivudine exposure (P < .001).
These findings support resistance testing in cases of apparent NA therapy failure. This survey highlights the impact of exposure to lamivudine and adefovir on development of drug resistance and cross-resistance. Continued use of these NAs needs to be reconsidered at a pan-European level.
The Journal of Infectious Diseases 07/2015; DOI:10.1093/infdis/jiv363 · 6.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Thymosin α-1 (Tα1) exploits a specific action on lymphoid cells and is able to induce in peripheral blood mononuclear cells (PBMCs) a strong transcriptional response. CD8 antiviral factor activity plays a role in the control or prevention of HIV-1 infection by a non-cytolytic mechanism. The ability of Tα1 to modulate the release of antiretroviral soluble factors by CD8(+) cells was investigated.
Supernatants from lipopolysaccharide (LPS) stimulated CD8(+)-isolated cells treated with Tα1 were screened on in vitro infection of human monocyte-derived macrophages (MDMs) and PBMCs with HIV-1, and of PBMCs with human T lymphotropic virus 1 (HTLV-1). In CD8(+) cells, as well as in PBMCs of healthy donors as from HIV(+) individuals, a microarray analysis to assess the transcriptional response after treatment was performed.
Tα1 potentiates the release, in LPS-stimulated CD8(+) cells, of soluble factors able to inhibit both in vitro HIV-1 infection of MDMs and PBMCs and in vitro HTLV-1 infection of PBMCs. A distinctive transcriptional profile was induced by Tα1 in PBMCs from HIV(+) donors.
These findings suggest that Tα1 would represent a re-evaluated approach to antiretroviral therapy in combination with innovative treatments and with vaccine administration.
[Show abstract][Hide abstract] ABSTRACT: Since the first acquired immunodeficiency syndrome cases were reported in 1981, more than 1.5 million people have been diagnosed with Human Immunodeficiency Virus-1 in Europe, including more than 136,000 new HIV cases in 2013. Recent epidemiological data estimate an incidence of 5-10 newly diagnosed HIV infections per 100,000 population per year in Europe and an average prevalence of infection of 5.7 cases per 100,000 population. In the absence of an effective curative strategy for HIV, optimization of prevention policies and clinical management of HIV positive patients is fundamental to reduce the impact of the HIV pandemic on public health. Clinical trials represent an essential tool for translating research findings into routine clinical practice. Careful evaluation and planning of clinical trials are therefore mandatory in order to provide relevant information to clinicians. The HEFFICON Project was conceived to investigate and pinpoint methodological issues and critical points that need to be addressed in future clinical studies to increase the translation of experimental results to the real life environment.
The New Microbiologica: official journal of the Italian Society for Medical Virology (SIVIM) 05/2015; 38(2):149-84. · 1.78 Impact Factor