HIV MDR is still a relevant issue despite its dramatic drop over the years.

OBJECTIVES: To evaluate the prevalence and therapeutic relevance of drug resistance among isolates from ART-experienced HIV-1-infected patients over the past two decades in Italy. METHODS: Dynamics of resistance to one, two and three or more antiretroviral classes were evaluated from 1999-2018. Virological success (VS) after the latest therapy switch was evaluated according to cumulative class resistance and cumulative genotypic susceptibility score (Stanford HIV_DB algorithm). RESULTS: Among 13 663 isolates (from 6739 patients), resistance to at least one drug class decreased sharply from 1999 to 2010 (≤2001, 84.6%; 2010, 43.6%; P < 0.001), then remained relatively constant at ∼40% during 2010-18, with the proportion of resistance to three or more classes also stable (∼5%). After 2008, integrase inhibitor resistance slightly increased from 5.6% to 9.7% in 2018 and contributed to resistance, particularly in isolates with resistance to three or more classes (one class, 8.4%; two classes, 15.3%; three or more classes, 34.7%, P < 0.001). Among 1827 failing patients with an available follow-up, by 1 year after genotype-guided therapy start the probability of VS was 87.6%. Patients with cumulative resistance to three or more classes and receiving a poorly active regimen showed the lowest probability (62.6%) of VS (P < 0.001) compared with all other patients (≥81.8%). By Cox regression analysis, cumulative MDR and receiving poorly active antiretroviral regimens were associated with a lower hazard of VS compared with those without resistance. CONCLUSIONS: A dramatic drop of HIV-1 drug resistance at failure has been achieved over the last two decades in Italy; resistance to three or more classes is low but present among currently failing patients. Its management still requires a rational and careful diagnostic and therapeutic approach.

Liver stiffness reduction and serum fibrosis score improvement in HIV/hepatitis C virus-coinfected patients treated with direct-acting antivirals.

OBJECTIVES: Only a few studies have addressed liver stiffness dynamics after hepatitis C virus (HCV) treatment in patients with HIV/HCV coinfection. The aim was to evaluate the variation in liver stiffness and in serum liver fibrosis scores in HIV/HCV-coinfected patients before and after treatment with direct-acting antivirals (DAAs). METHODS: Liver stiffness measured using transient elastography as well as serum liver fibrosis scores [fibrosis-4 (FIB-4) score and the aspartate aminotransferase to platelet ratio index (APRI)] were evaluated before and at 6-12 months after DAA treatment. Variation in the outcome variables was evaluated using the Wilcoxon nonparametric test. Univariate analysis and multivariate regression models were used. RESULTS: A total of 78 HIV/HCV-coinfected subjects were included in the study. Median values of hepatic stiffness significantly decreased after DAA treatment compared with baseline [16.8 (interquartile range (IQR) 10.2-27.0) kPa at baseline vs. 9.4 (IQR 6.7-15.0) kPa after DAA treatment; P < 0.01). Further, a decrease in median FIB-4 score [2.8 (IQR 1.5-4.8) vs. 2.0 (IQR 1.3-3.2), respectively; P < 0.01] and APRI [0.9 (IQR 0.5-2.2) vs. 0.4 (IQR 0.2-0.7), respectively; P < 0.01] was found. In univariate analysis, liver stiffness decrease was associated with increasing age, 'other' HCV genotype (vs. G1), the presence of cirrhosis, higher pre-DAA liver stiffness, sofosbuvir-based regimens and longer DAA treatment (all P < 0.05). Multivariate regression confirmed the significance of the association only with higher baseline liver stiffness (P < 0.01). Greater FIB-4 and APRI reductions were associated with higher respective baseline values, while the presence of hepatic steatosis correlated with lower score reduction after DAA. CONCLUSIONS: A reduction in liver stiffness and an improvement in fibrosis scores were observed in HIV/HCV-coinfected patients soon after DAA treatment. The clinical implications of these observations need to be evaluated in larger populations with longer follow-up.

Pre-existent NRTI and NNRTI resistance impacts on maintenance of virological suppression in HIV-1-infected patients who switch to a tenofovir/emtricitabine/rilpivirine single-tablet regimen.

Objectives: To evaluate the maintenance of virological suppression (VS) in antiretroviral-treated HIV-1-suppressed patients switching to a tenofovir/emtricitabine/rilpivirine (TDF/FTC/RPV) single-tablet regimen, by considering pre-existent resistance (pRes). Methods: pRes was evaluated according to resistance on all previous plasma genotypic resistance tests. Probability and predictors of virological rebound (VR) were evaluated. Results: Three hundred and nine patients were analysed; 5.8% of them showed resistance to both NRTIs and NNRTIs, while 12.6% showed resistance to only one of these drug classes. By 72 weeks, the probability of VR was 11.3%. A higher probability of VR was found in the following groups: (i) patients with NRTI + NNRTI pRes compared with those harbouring NRTI or NNRTI pRes and with those without reverse transcriptase inhibitor pRes (39.2% versus 11.5% versus 9.4%, P < 0.0001); (ii) patients with a virus with full/intermediate resistance to both tenofovir/emtricitabine and rilpivirine compared with those having a virus with full/intermediate resistance to tenofovir/emtricitabine or rilpivirine and those having a virus fully susceptible to TDF/FTC/RPV (36.4% versus 17.8% versus 9.7%, P < 0.001); and (iii) patients with pre-therapy viraemia >500 000 copies/mL compared with those with lower viraemia levels (>500 000: 16.0%; 100 000-500 000: 9.3%; <100 000 copies/mL: 4.8%, P = 0.009). pRes and pre-therapy viraemia >500 000 copies/mL were independent predictors of VR by multivariable Cox regression. Conclusions: TDF/FTC/RPV as a treatment simplification strategy shows a very high rate of VS maintenance. The presence of pRes to both NRTIs and NNRTIs and a pre-therapy viraemia >500 000 copies/mL are associated with an increased risk of VR, highlighting the need for an accurate selection of patients before simplification.

Pulmonary tuberculosis followed by sarcoidosis in an HIV-infected patient: A case report and a simplified diagnostic flowchart for diagnosis and treatment of sarcoidosis.

The diagnosis of sarcoidosis in a patient living with HIV infection is an uncommon event and a challenge for clinicians. Clinical manifestations are variable and fluctuating depending to adherence to ARV therapy and to the level of CD4 count. We analyze here one chronic case in which sarcoidosis appeared clinically two years after pulmonary tuberculosis. The course of the disease was influenced and prolonged by frequent interruptions of antiretroviral therapy. Moreover the diagnosis and the decision to treat have been delayed by the need of exclusion of other pathologies, principally tuberculosis reactivation/reinfection, other mycobacterial diseases, hematologic malignancies. We propose a simplified flowchart for diagnosis and follow up of sarcoidosis, which may also be applied to patients with HIV infection. Diagnosis of latent tuberculosis infection (LTBI) may be difficult in these patients, because the immunological paradox of sarcoidosis. For this reason, following exclusion of active tuberculosis, we advise to submit all sarcoidosis patients to IPT (isoniazid preventive therapy), when immunosuppressive therapy is started.

An imported case of acute pulmonary coccidioidomycosis in an Italian traveller.

Coccidioidomycosis is a fungal infection caused by the Coccidioides species, which is endemic in the deserts of the southwestern region of the United States, northern Mexico, and in some areas of Central and South America. We describe a case of pulmonary coccidioidomycosis in a 49-year-old Italian man who came to our hospital with fever and joint and muscle pain 10 days after his return to Italy from Venezuela. Computer Tomography revealed multiple bilateral pulmonary nodules with mediastinal lymphadenopathy. Pulmonary coccidioidomycosis was diagnosed by a serological test, and fluconazole was immediately started. The patient improved within 2 weeks, with complete clinical recovery after 6 months of therapy. This case appears to be part of a large serologically unconfirmed outbreak. In order to provide early diagnosis and treatment, healthcare providers should be aware of coccidioidomycosis, even in travellers returning home from short trips to endemic areas.

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.

Cost of surgical intervention for reconstructive therapy of HIV-associated facial lipoatrophy.

This study aims to assess direct cost of reconstructive interventions with facial fillers for treatment of HIV (human immunodeficiency virus)-associated facial lipoatrophy (FLA). Evaluation was performed on data from patients enrolled in one arm of a comparative study of immediate versus delayed reconstructive treatment of facial lipoatrophy. Median costs were standardized for efficacy, estimated using data reported by physicians and patient reported outcomes. The variations of the results were evaluated with a sensitivity analysis. Evaluation was performed on 66 patients characterized by significant differences in terms of severity of FLA. Total cost resulted of €140,416.15, with a median cost per patient of €2126.04 (interquartile range [IQR]: 1599-2822). Taking into consideration severity of disease, median costs were €1641.67 (IQR: 1326.67-2126.04) and 2557.12 (IQR: 1939.34-2872.04) (P = 0.0) respectively for patients with low and high severity scores at baseline. Significant differences in term of cost-effectiveness ratios were also found between patients with different severity of FLA, and sensitivity analysis showed that these ratios increase with higher severity scores at baseline and vary widely depending on the costs of filler. Although these results cannot be considered representative because of important limitations, the present study suggests the severity of disease as an important determinant of costs.

[A rare presentation of Amyand's hernia. Case report and review of the literature]. / Un raro caso di ernia di Amyand.

Amyand's hernia is defined as an inguinal hernia within the hernial sac containing the appendix. It is a rare disease, reported in 1% of cases of inguinal hernia repair. The appendix can be complicated by acute appendicitis in 0.13% of cases. This disease is often very difficult to diagnose, and most of the time it can be confused with an incarcerated or strangulated inguinal hernia. Often, it requires an emergent surgical treatment. This article describes the case of a 82-year-old female who was admitted for an intestinal obstruction and a bulge in the right inguinal region. An abdominal computed tomography scan showed dilated small bowel loops with multiple air/liquid levels and one loop herniating into the right inguinal canal. The patient underwent a laparotomy that showed the presence of an acute appendicitis and a necrotized ileal loop protruding into the right inguinal canal. The patient underwent an appendectomy and small bowel resection and she was discharged on postoperative day 10. Amyand's hernia can be a challenge for the surgeon. Its treatment depends on the grade of inflammation of the appendix. In fact, it can range from the simple repair of the abdominal defect with a prosthetic mesh, to appendectomy, small bowel resection and repair of the abdominal wall defect without a mesh.

Haemorrhage following pancreaticoduodenectomy: risk factors and the importance of sentinel bleed.

AIM: To document the prevalence and to evaluate the management strategies of haemorrhagic complications following pancreaticoduodenectomy (PD). METHODS: All patients who underwent PD from 1/2000 to 10/2005 and experienced at least one episode of haemorrhage during the 30 first days postoperatively were recorded. Etiology of haemorrhage, treatment strategy and mortality rate were recorded and analyzed. RESULTS: A total of 362 patients underwent PD during this period and 32 (8.8%) had haemorrhage postoperatively of whom 15 died (47% mortality rate). Primary intraluminal haemorrhage was recorded in 13 patients, primary intra-abdominal haemorrhage in 5 patients and secondary haemorrhage in 14 patients. Successful management of haemorrhage with angioembilization occurred in 2 patients in the study group. Statistical analysis revealed sepsis and sentinel bleed as risk factors for post-PD haemorrhage and pancreatic leak and sentinel bleed as risk factors for secondary haemorrhage (p < 0.05). CONCLUSIONS: Haemorrhage after PD is a life-threatening complication. Sepsis, pancreatic leak, and sentinel bleed are statistical significant factors predicting post-PD haemorrhage. Sentinel bleed is not statistically significant associated with postoperative mortality, but with the onset of secondary haemorrhage. The effectiveness of therapeutic angioembolization was not demonstrated in our study.

Laparoscopic Heller myotomy with or without partial fundoplication: a matter of debate.

AIM: To present our experience of laparoscopic Heller stretching myotomy followed by His angle reconstruction as surgical approach to esophageal achalasia. METHODS: Thirty-two patients underwent laparoscopic Heller myotomy; an anterior partial fundoplication in 17, and angle of His reconstruction in 15 cases represented the antireflux procedure of choice. RESULTS: There were no morbidity and mortality recorded in both anterior funduplication and angle of His reconstruction groups. No differences were detected in terms of recurrent dysphagia, p.o. reflux or medical therapy. CONCLUSION: To reduce the incidence of recurrent achalasia after laparoscopic Heller myotomy, we believe that His' angle reconstruction is a safe and effective alternative to the anterior fundoplication.

[Solitary small bowel metastasis after resection of bile duct carcinoma]. / Metastasi ileale solitaria da neoplasia biliare extraepatica precedentemente resecata.

Small bowel solitary metastases are a very rare occurrence and are more frequently recognized only in the presence of a severe complication, such as intestinal hemorrhage or occlusion. We report the case of a 75 year-old man who was admitted with a recent history of mechanical ileus developed one year after the surgical removal of an endoscopically intubated carcinoma of the extrahepatic biliary tree (pT3 pN0 Mx). A solitary metastasis of the small bowel, 30 cm from the ileo-cecal valve, was excised during the emergency laparotomy and a side-to-side anastomosis was performed to reconstruct the intestinal continuity. Patient was, thereafter, discharged in the 9th postoperative day. Local recurrence and intrabdominal dissemination are often observed in patients treated for bilio-pancreatic carcinoma. Preoperative invasive (ERCP, FNA, PTBD, etc.) diagnostic procedures and surgical tumor manipulation are associated with a greater risk of metastasis implantation and intraabdominal dissemination. In accordance to the literature, the authors propose, in cases with resectable bilio-pancreatic neoplasms, the use of standard external low dose radiotherapy prior to any invasive diagnostic procedure and/or surgical removal.

Neurocognitive impairment influences quality of life in HIV-infected patients receiving HAART.

The objective of the study was to determine the association of neurocognitive impairment with health-related quality of life (HRQoL) in patients receiving highly active antiretroviral therapy (HAART). Seventy subjects were cross-sectionally analysed with a standardized neuropsychological test battery and a questionnaire including an Italian translation of the MOS-HIV Health Survey. The presence of neurocognitive impairment was significantly associated with lower HRQoL scores: pain (P = 0.03), physical functioning (P = 0.01), role functioning (P = 0.01), social functioning (P = 0.029), mental health (P = 0.001), energy (P = 0.036), health distress (P = 0.002), cognitive functioning (P = 0.05), current health perception (P <0.001), physical health summary score (PHS) (P = 0.005), mental health summary score (MHS) (P = 0.002). Years of education (odds ratio [OR] 0.79; 95% confidence interval [CI] 0.65-0.96), PHS (OR 0.71; 95% CI 0.54-0.95) and MHS (OR 0.67; 95% CI 0.51-0.88) were also associated with cognitive impairment. Neurocognitive impairment in patients receiving HAART was associated with reduced HRQoL. Identifying cognitive impairment may provide motivation for additional treatment to help patients to compensate for deficits in functioning.

[Ciliated hepatic foregut cysts: a case report]. / Cisti epatiche a derivazione dall'intestino primitivo. Caso clinico.

The ciliated hepatic foregut cysts (CHFC) are uncommon benign lesions with columnar ciliated epithelium covering a connective lapse tissue. They are solitary uniloculate cysts localized in the left lobe of the liver. The diagnosis is made occasionally during autopsy or imaging studies for not related symptoms. The Authors report a case of CHFC with a review of the literature that allowed them to find only 60 cases.

[Multidisciplinary treatment in Budd-Chiari syndrome: clinical case]. / Trattamento multidisciplinare nella sindrome di Budd-Chiari: caso clinico.

Budd-Chiari Syndrome (BCS) is characterized by obstruction of hepatic venous outflow. When obstruction is limited to the suprahepatic veins, portocaval shunting provides an immediate relief of symptoms. If the obstacle results also from narrowing of the inferior vena cava (IVC), multimodality treatments seem to offer safer and easier alternative. In the patient herein reported, combination of side-to-side portocaval anastomosis with a cavo-atrial shunt through an expandible metallic stent provided immediate relief of symptoms. The patient is doing well after 85 months from combined treatment. In conclusion infracaval stenting combined to side-to-side portocaval shunting should represent the treatment of choice in acute or subacute forms of BCS.

Metabolic and morphologic disorders in patients treated with highly active antiretroviral therapy since primary HIV infection.

UNLABELLED: Our objective was to describe morphologic and metabolic disorders in patients treated with highly active antiretroviral therapy (HAART) since primary HIV infection (PHI). Our method was prospective evaluation of patients with PHI initiating HAART at the time of diagnosis. Outcome measures were: development of hyperglycemia, hypercholesterolemia, hypertriglyceridemia, and of body shape abnormalities indicative of lipodystrophy, assessed through self-reported questionnaires and physical examination. RESULTS: From May 1997 to April 2001, 41 patients (35 males) with PHI presented at the National Institute for Infectious Diseases "Lazzaro Spallanzani" in Rome, Italy. A protease inhibitor-including regimen was started in 30 patients, and a nonnucleoside reverse transcriptase-inhibitor in 11. Median interval between enrollment and treatment initiation was 30 days (mean 39, range 10-150). Median HAART duration was 19 months (mean 21.2, range 3-47). Thirty-eight patients had undetectable (less than 80 cp/mL) HIV RNA after a median of 3 months (mean 4.1, range 1-15). Mean CD4 cells count increased from 632/mmc at baseline to 936/mmc at the last follow up. No cases of hyperglycemia (glucose level greater than 110 mg/dL) were observed. After a median of 6 months on HAART, 10 patients developed beyond grade 2 (greater than 240 mg/dL) hypercholesterolemia, 5 developed beyond grade 2 (greater than 400 mg/dL) hypertrygliceridemia, and two developed both. Body mass index did not change significantly. Five patients (12.2%) developed lipodystrophy after a median of 14.5 months (mean 15.3, range 2-30), with an incidence of 7.3 per 100 patient-years. CONCLUSIONS: Dyslipidemia and lipodystrophy can occur in patients treated with HAART since PHI. This risk of should be taken into account when considering this early antiretroviral treatment of HIV infection.

Hemophilus influenzae type b meningitis: pediatric overview.

The authors valued the incidence and clinical therapeutic aspects of Haemophilus influenzae type b (Hib) meningitis in children. They report a retrospective study, in children, with diagnosis of acute purulent meningitis, from January 1982 to December 1994, aged between 1 month and 14 years. Particular attention was direct to Haemophilus influenzae type b meningitis (20 cases). The incidence rate of Hib meningitis in the overall cases (89) was 22.47% (20), while among children younger than 5 years Hib was the most frequently pathogen isolated (20/58-34.47%). In 1/4 of cases, particularly in children younger than 1 years, exordium was aspecific and unclear. At admission culture and examination of Cerebrospinal Fluid (CFS) have been done. CFS was cultured on blood agar and chocolate plates. A latex agglutination test was used for rapid detection of the bacterial antigens. In some cases we looked for bacterial antigens in urine. 20% of children had complications and 10% had sequelae (1 years of follow-up). We didn't have any dead. Antibiotic treatment was principally with Ampicillin, Cephalosporin and Chloramphenicol. The results of this study confirm the Hib gravity and suggest that the administration of conjugate vaccine against Hib to all living in Italy is justified.

Incidence of bacterial colonization in the throat and in urines at paediatric age with evaluation of sensitivity to common antibiotics.

OBJECTIVES: To evaluate the incidence of bacterial colonization in the throat and in urines of children admitted to a paediatric ward in the year 1994. To test the sensitivity of isolates on the most common antibiotics used in therapy. METHODS: The investigation was carried out on a group of 270 children (125 male and 145 female), aged between 3 months and 12 years, hospitalized with feverish infectious pathology in the department of infectious and Tropical Diseases of the University "La Sapienza" of Rome. The cultures of the throat swabs and on urines were performed on the admission of the children before the beginning of the therapy. RESULTS: The throat-swab cultures showed pathogenous microrganisms in 232 samples (85.9%) with a slight prevalence of Gram-negative bacteria (122) with respect to Gram-positive (110) and saprophytic microbial flora (38). The urine cultures proved to be positive in 81 cases (30%) with a prevalence of Gram-negative (56) above Gram-positive isolates (25). CONCLUSIONS: The two/thirds of paediatric patients hospitalized in an Infectious Diseases Department appeared to be colonized in the upper respiratory tract, whereas in about 10% of them a marked bacteriuria was clearly evident, often in the absence of specific symptoms. A few isolates either from the throat or from urines, showed resistance to the common antibacterial agents.

[Seroepidemiologic study of the prevalence of anti-HAV antibodies in children in Rome]. / Studio sieroepidemiologico della prevalenza degli anticorpi anti HAV nei bambini di Roma e Provincia.

The authors evaluated the incidence of infection by hepatitis A virus (HAV) in a paediatric population through a seroepidemiological investigation in a group of 278 children (0-12 years old), apparently healthy. The determination of anti-HAV antibodies was carried out by ELISA-test. Of the 287 examined sera, 27 cases turned out HAV positive antibodies (9.7%), with the following distribution, according to the groups of age: 0-3 months: 2 of 6 children were positive (mother's antibodies); 3 months-2 years: 6 of 112 (5.35%); 2-6 years: 10 of 93 (10.75%); 6-12 years: 11 of 67 (16.41%). With regard to distribution of anti-HAV antibodies by sex, 23 (15.03%) males of 153 resulted positive, whereas 4 (3.2%) females of 125 resulted positive. The decline of HAV infection in the paediatric age involves a possible shift of the risk to the adult age. It's advisable that the vaccination against hepatitis A in first period should be reserved for the subjects at risk and later both for unweaned and children in order to eradicate the infection.

[Acyclovir in the treatment of varicella in immunocompetent children]. / L'acyclovir nel trattamento della varicella nei bambini immunocompetenti.

We evaluated safety and tolerance of acyclovir ACV per os in immunocompetent children affected by chicken-pox admitted to our department from January 1993 to December 1994. 183 subjects (102 males and 81 females) aged between 0 and 14 years were treated by ACV (80 mg/kg/daily in 4 divided doses): 88 children were treated within 24 hours and 95 subjects within 48 hours from the onset of symptoms. The control group consisted of 83 children (52 males and 31 females) aged between 0 to 14 years. In all patients routine blood-test were performed and in those with respiratory illness Chest-Rx was also done. We evaluated clinical course, degree of eruption, the appearance and kind of complications, duration of hospitalization, the compliance and the potential consequences on specific antibody response. Our results show a faster improvement of clinical symptoms in treated patients with respect to the control group with shortening of the period of the fever, itch and appearance of new vescicles. The percentage of complications was lower in treated than in untreated patients. 16 cases tested for specific antibody response showed protective titers six months after treatment. In conclusion, ACV administered per os within 48 hours from onset of exanthema causes reduction of the period and the degree of general symptoms and exanthema, a lower incidence of complications even if non statistically significant. The drug is safe and well-tolerated.