Niccolò Riccardi

Salvage therapy or simplification of salvage regimens with dolutegravir plus ritonavir-boosted darunavir dual therapy in highly cART-experienced subjects: An Italian cohort

BACKGROUND Dolutegravir plus darunavir provide a high genetic barrier to HIV-1 resistance and are suitable for simple salvage regimens. METHODS All HIV-1-infected subjects treated with dolutegravir plus boosted darunavir dual therapy between March 2011 and September 2015 were included in an observational cohort. Data were collected at baseline and at weeks 4, 12, 24 and 48. RESULTS We enrolled 113 subjects. After week 24, one was lost at follow-up, one dropped out for grade 2 elevation of liver enzymes, one died from illicit drug abuse and one from cancer-related sepsis. The mean age was 51, 26.5% were female and 9.7% were non-Caucasian. Twenty had never experienced failure. A total of 99 had reverse-transcriptase (RT) mutations, 87 had protease inhibitor mutations and 12 had integrase strand transfer inhibitor (INSTI) mutations. Viraemic patients declined from baseline to week 24 from 43.4% to 6.2%, the remainder being due to high baseline viraemia or adherence issues. The proportion of subjects with viraemia 1-49 copies/ml remained at 20.4% while those in whom no virus was detected (NVD) increased from 36.3% to 73.5% by week 24. All the 47 subjects who had a 48-week follow-up had <50 copies/ml and 42 (89.4%) had NVD. 18 subjects had reduced sensitivity to darunavir (Stanford median score 15, range 15-40), but none rebounded, 6 having a 24-week and 7 a 48-week follow-up. The median variation in serum creatinine was -0.01 (range +0.2 to -0.21) mg/dl. CONCLUSIONS This dual regimen provides a simple salvage regimen and proved safe and effective in this cohort.

Increasing prevalence of genitourinary schistosomiasis in Europe in the Migrant Era: Neglected no more?

1 Department of Health Sciences (DISSAL), Infectious Disease Section, IRCCS AOU San Martino-IST, Genoa, Italy, 2 Department of Health Sciences (DISSAL), Radiology Section, University of Genoa, Genoa, Italy, 3 Department of Surgical Science (DISC), Luciano Giuliani Department of Urology, University of Genoa, IRCCS AOU San Martino-IST, Genoa, Italy, 4 Department of Surgery (DISC), Pathology Section, University of Genoa, Genoa, Italy, 5 Department of Health Sciences (DISSAL), Radiology Section, University of Genoa, Emergency Radiology, IRCCS AOU San Martino-IST, Genoa, Italy

Switch from unboosted protease inhibitor to a single-tablet regimen containing rilpivirine improves cholesterol and triglycerides

This study aimed to evaluate the efficacy, tolerability and potential savings of combined antiretroviral therapy (cART) simplification from an unboosted protease inhibitor (PI) regimen with atazanavir or fosamprenavir to a single-tablet regimen (STR) based on rilpivirine/emtricitabine/tenofovir disoproxil fumarate (RPV/FTC/TDF) among HIV-1-infected patients with HIV-1 RNA <50 copies/mL. This was a retrospective, multicentre, open-label, 12-week trial. Plasma HIV-1-RNA levels, CD4+ cell counts, cholesterol, triglycerides, bilirubin, glycaemia, creatinine and physical examination were performed at baseline and at scheduled follow-up. All patient costs were calculated and were estimated for 52 weeks of therapy. Fifty-one patients were enrolled [28 male (54.9%)]. At baseline, 30 patients (58.8%) were treated with FTC/TDF, 20 (39.2%) with abacavir/lamivudine and 1 (2.0%) with lamivudine/zidovudine. Thirty-three patients (64.7%) received atazanavir. All patients maintained HIV-RNA <50 copies/mL; the median CD4+ cell count remained stable. Mean triglycerides decreased from 124 mg/dL (range, 39-625) at enrolment to 108.7 mg/dL (range, 39-561) at study end (P = 0.25). At baseline, mean cholesterol was 172.8 ± 38.1 mg/dL and decreased to 161.9 ± 38.6 mg/dL (P = 0.038); likewise, median total bilirubin decreased from 1.07 mg/dL (range, 0.2-4.7) to 0.6 mg/dL (range, 0.13-3.1) (P <0.001). cART-related annual cost reduction with a STR was €3155.47 per patient (-24%). Non-cART patient management expenses were €402.68 vs. €299.10 for atazanavir or fosamprenavir and STR regimens, respectively. Switching to RPV/FTC/TDF from an unboosted PI in virologically suppressed HIV-infected patients is safe and is associated with a reduction in triglycerides, cholesterol and cART-related costs.

Chemotherapy Mass Campaigns and Migratory Flows: An Unexpected Connection

TO THE EDITOR—Chami and colleagues describe in their recent interesting work the shortcomings of current mass drug administration (MDA) for identification and targeting of individuals who escape to treatment and the characteristics of those who are not reached by MDA in Uganda [1]. Indeed, this work points out how untreated individuals were also more likely to belong to households that did not purify drinking water, had no home latrine, and had no members who were part of the village government. These characteristics could also describe individuals with increased likelihood to become migrants looking for better life conditions. According to United Nations High Commissioner for Refugees data among the top 10 nationalities of sea migrants in the current migratory flow to Italy and North Mediterranean countries [2] at least 4 (Nigeria, Mali, Sudan, Senegal) are in high endemicity areas. Accumulating evidence reports the occurrence of urinary Schistosomiasis among migrants [3, 4]. In view of the asymptomatic carriage period, however, the real prevalence and future incidence is underestimated [5]. Indeed, recently we observed a sharp surge in schistosomiasis diagnosis in our area Genova, Liguria, Italy (from 5/year to 15/6 months) where a minor number of migrants to Italy has been relocated. Renewed efforts on MDA in all areas of high endemicity and migration represent a tool to prevent morbidity and distress also for the most vulnerable individuals undergoing the weight of migration. Improved targeting of this neglected disease would thus improve health also for would-be migrant populations and reduce the burden of treating migrants once arrived or transiting in a hosting nation, where schistosomiasis could be unexpected. In conclusion, thepath to amore efficient hospitality is based on two different pillars, the first being updating Italian protocols for diagnosis and treatment of Tropical Diseases and the second being improving World Health Organization recommendations for MDA in endemic areas [6, 7] to include more desperate individuals and less advanced households that are more likely to enter migration.

History of schistosomiasis (bilharziasis) in humans: from Egyptian medical papyri to molecular biology on mummies

ABSTRACT Schistosomiasis is a parasitic infection that has evolved together with the humankind. Evidence in ancient Egyptian medical papyri or Assyrian medical texts reported signs and symptoms that could resemble schistosomiasis; similarly, some biblical passages describe an epidemic (depicted as a ‘curse’) that has been hypothesized to be associated with schistosomiasis’ spread in Mesopotamia. In the modern era, Theodor Maximilian Bilharz and Patrick Manson (the ‘father of tropical medicine’) gave an impetus to the knowledge about the parasite and its spread until the present time, when immunoassays and molecular biology on mummies allowed retracing important milestones regarding schistosomiasis’ evolution. Schistosomiasis affects more than 200 millions of people worldwide and it is an emblem of how hard it is to prevent, control and treat neglected tropical diseases. Our work reviews the history of schistosomiasis with regard to human infections.

Predictors of retention in care in HIV-infected patients in a large hospital cohort in Italy

Retention in care is a key feature of the cascade of continuum of care, playing an important role in achieving therapeutic success and being crucial for reduction of HIV transmission. The aim of this study was to evaluate the rate of retention in care in a large referral centre in the North of Italy and to identify predictors associated with failed retention. All new HIV-infected subjects were consecutive enrolled from 1 January 2008 to 31 December 2014. Demographics, immune-virological status, hepatitis co-infection and timing of initiation of combined antiretroviral therapy (cART) data were collected at baseline and at the time of last observation. Failed retention in care was defined as lack of laboratory data, clinical visits and drug dispensation for more than 6 months from the last visit. Cox regression analysis was used. Multivariate analysis of variables with P<0.05 in univariate analysis was performed. We enrolled 269 patients (mean age 46.1 years). Males were 197 (73%), Italian 219 (81%) with mean length of disease of 5.1 years. cART was prescribed for 257 patients (95%). The rate of retention in care was 78.4% and the rate of virological suppression was 75%. Predictors of being loss to follow-up were foreign origin (P = 0.048), CD4+ count <200/mmc (P = 0.001) and not being treated for HIV infection (P = 0.0004). Predictors of cART efficacy were shorter duration of HIV infection and baseline HIV-RNA <100 000 copies/ml. These findings underline the necessity to improve retention in care by identifying groups at increased risk of being loss to follow-up. Retention in care of vulnerable population is crucial to reach 90-90-90 UNAIDS endpoint.

Time to change the single-centre approach to management of patients with tuberculosis: A novel network platform with automatic data import and data sharing

Ending the global tuberculosis (TB) epidemic by the year 2035 is one of the most ambitious goals of the World Health Organization (WHO). The WHO strategy is based on three major pillars: improving TB prevention and care, supporting bold policies, and enhancing research and innovation [1]. A better understanding of TB epidemiology, enhanced retention in care and employment of standardised regimens are mandatory to get closer to TB eradication both in low- and high-prevalence countries [2–5]. Mathematical modelling can be a useful tool to understand epidemiology and control of TB in low-prevalence countries, thus leading to better approaches in terms of public health interventions [6]. In this tough challenge for clinicians, the key actions are early diagnosis of TB patients with symptoms or signs suggestive for TB within migratory flux through a nation, and tracking of these patients as well as dealing with increased TB presentation in iatrogenically immunocompromised patients [7, 8]. Low-cost interventions aimed at improving patient-contacts recording, containing outbreaks, and enhancing adherence to diagnostic work-up and follow-up are welcome to better manage the disease burden [9]. Furthermore, a dramatic improvement in diagnostic paths and therapeutic approaches is needed nationally and globally to reach the WHO endpoint [10]. Therefore, healthcare providers who take daily care of TB patients require proper tools to access comprehensive data, for managing patients during follow-up, and for data collection and analysis in multicentre observational clinical trials (MCTs) [11]. Time to change the single-centre approach to TB http://ow.ly/lCeM30hBcbB

A case report of mucocutaneous tuberculosis after orthotopic liver transplantation: a challenging diagnosis

BackgroundMycobacterium tuberculosis is responsible for high morbidity and mortality in immune-compromised hosts.Case presentationWe present a rare case of cutaneous tuberculosis after orthotopic liver transplantation without involvement of any other organs.ConclusionTB risk-factors assessment, careful LTBI screening and treatment according to national guidelines, as well as a reduction in missed opportunity for prevention are necessary to avoid MTB related disease in fragile patients.

Short Communication: Tenofovir Disoproxil Fumarate/Emtricitabine Fits for All as Appropriate HIV-1 Pre-Exposure Prophylaxis?

Abstract Pre-exposure prophylaxis (PrEP) with TDF/FTC significantly reduces the risk for HIV-1 transmission, but, to date, nobody knows if PrEP can still be useful in case of viruses harboring resi...

PrEP in Italy: The time may be ripe but who’s paying the bill? A nationwide survey on physicians’ attitudes towards using antiretrovirals to prevent HIV infection

Several studies have demonstrated the efficacy of the oral pre-exposure prophylaxis (PrEP) with tenofovir (with or without emtricitabine) on preventing HIV-negative partners of HIV infected patients to become infected through sexual contacts. PrEP is already available in the United States and now is approved by European Medicine Agency. In this setting we would like to gauge physicians’ knowledge, acquaintance with and attitude to include PrEP in their clinical practice. A cross sectional survey was conducted among Italian physicians expert on antiretroviral therapy. Out of 146 physicians, 35% of participants declared to be familiar with PrEP but only 46% of them believed that, currently, there are not enough reasons to make it available in Italy. 51% of physicians have already been attracted to prescribe it and 63.4% have been openly asked about PrEP. The main concerns noticed were: the risk of acquire other sexual transmitted diseases (STDs) (70% of physicians feared that PrEP could favor STDs spread), the potential harmful of PrEP if not adequately implemented and, especially the risk of possible side effects if not properly used. Nevertheless, 55.9% of participants believed that Health Authorities face an ethical obligation to make PrEP available as part of the strategies to protect from HIV transmission and half of the respondents asked for further researches to better define the role for PrEP. Attitudes regarding PrEP impact on Italian National Health Organization were also very interesting: 57.5% of participants did not believe that investing in PrEP would be an appropriate use of healthcare resources, while 70.6% affirmed that PrEP’s financial coverage should not be funded by the Italian National System of Health (SSN). This survey showed a high awareness of PrEP potential among Italian physicians coupled with a great deal of skepticism about how and if implementing it in clinical practice.