Metabolic-Related Outcomes After Switching From Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide in Adults With Human Immunodeficiency Virus (HIV): A Multicenter Prospective Cohort Study.

BACKGROUND: Tenofovir alafenamide (TAF) has replaced tenofovir disoproxil fumarate (TDF) in many clinical settings. However, concerns remain about potential metabolic complications of TAF. We aimed to evaluate changes in weight, laboratory markers, and metabolic-related clinical events after replacing TDF with TAF. METHODS: Multicenter prospective cohort study in the Spanish CoRIS cohort. We included virologically suppressed adults with human immunodeficiency virus (HIV) receiving TDF for more than 12 months who either switched to TAF or maintained TDF, with no changes in the core agent. Participants were matched by propensity score. We fitted generalized equation models to assess changes in weight, blood lipids, and hepatic steatosis index, and to compare the incidence of diabetes, hypertension, and lipid-lowering drug use after 144 weeks. RESULTS: In total, 1446 participants were matched in each group. Median age was 38 years, 85% were male, mean weight at baseline was 73 kg. Participants who switched to TAF had a mean weight increase of +0.5 kg at 144 weeks over those who maintained TDF, with no difference in the occurrence of overweight or obesity. Individuals who switched to TAF had a significant increase in total cholesterol (+7.9 mg/dL) and triglycerides (+11.2 mg/dL), with no differences in the total cholesterol-high-density lipoprotein (HDL) ratio. However, no increased incidence of diabetes, hypertension, or lipid-lowering drug use was observed after the follow-up period. CONCLUSIONS: Switching from TDF to TAF is associated with modest weight gain and increases in total cholesterol and triglycerides, without an impact on the incidence of obesity or metabolic-related clinical events, in this Spanish cohort with a majority White male population.

Are the nerves supplying the anterior sacroiliac joint nociceptive?

BACKGROUND: Sacroiliac joint (SIJ) pain is often difficult to diagnose. Moreover, while its anatomical characteristics have been well studied, its innervation and the contributions of particular nerves remain controversial, especially in relation to posterior joint innervation. To our knowledge, previous studies have not investigated the presence of nociceptive fibres in the nerves innervating the anterior SIJ. MATERIALS AND METHODS: Eight adult cadaveric sides underwent dissection of the anterior SIJ. Adjacent anterior rami were examined for branches to the anterior SIJ. Any branches contributing to the anterior SIJ were measured and then resected. These samples were fixed in formalin and substance P was identified immunohistologically. RESULTS: On all sides, 1-2 small branches (mean diameter of 0.33 mm) arose from the posterior aspect of the L4 anterior ramus (12.5%), the L5 anterior ramus (62.5%), or simultaneously from both the L4 and L5 anterior rami (25%). These branches had a mean length of 13.5 mm. All histological samples contained nerve tissue. All samples of nerve fibres traveling to the anterior SIJ were positive for diffuse substance P reactivity. There were no histological differences between sides or sex. Each of the branches identified as travelling to the SIJ exhibited similar positivity for substance P. CONCLUSIONS: This cadaveric study demonstrates that the anterior SIJ nerve fibres carry pain fibres. This new knowledge has application to patients with SIJ syndrome and to its various treatments including interventional approaches to SIJ pain.

The petrosal artery and its variations: a comprehensive review and anatomical study with application to skull base surgery and neurointerventional procedures.

BACKGROUND: The petrosal artery supplies several structures at the skull base and is often the focus of various neurointerventional procedures. Therefore, knowledge of its anatomy and variations is important to surgeons and interventionalists. MATERIALS AND METHODS: Twenty latex injected cadaveric heads (40 sides) underwent microsurgical dissection of the petrosal artery. Documentation of the course of the artery and its branches were made. Measurements of the petrosal artery's length and diameter were performed using microcallipers. RESULTS: A petrosal artery was identified on all sides. The mean length and diameter of the artery within the middle cranial fossa was 2.4 cm and 0.38 mm, respectively. Branches included the following: dural, ganglionic, V3 branches, branches extending through the foramen ovale, branches directly to the greater petrosal and lesser petrosal nerves, branches to the floor of the hiatus of the greater and lesser petrosal nerves, branch to the arcuate eminence, and superior tympanic artery. No statistically significant differences were noted between male and female specimens, but right-sided petrosal arteries were in general, larger in diameter than left sides. CONCLUSIONS: A thorough anatomical knowledge of the petrosal artery and to its relationship to the facial nerve and other neurovascular structures is necessary to facilitate effective endovascular treatment and to preclude facial nerve complications.

How to write an umbrella review? A step-by-step tutorial with tips and tricks.

The number of meta-analyses (MA) and systematic reviews (SR) on various medical issues has increased during the last two decades. The MA and SR results may differ from one another due to a number of factors such as inaccurate or diverse searches through the databases, discrepancies in the extraction process or in statistical analysis, among others. Some results may even contradict one another, resulting in confusion among readers. Umbrella reviews (UR) have allowed the collection of all available data on a medical issue into one concise study, making it the source of evidence-based medical knowledge to the highest degree. Furthermore, UR can resolve those problems by collecting all data and taking into account both MA and SR, making it the superior tool for physicians. Although the pros of UR are clear and the overall popularity of these types of study has increased tremendously, there is no available step-by-step guide on how to conduct one. Therefore, the objective of the present study was to provide researchers with a detailed tutorial on how to conduct an UR. UR represent the next major step in the advancement of evidence-based medicine, with great practical potential for physicians looking for the most up-to-date data on their topic of interest. We hope that our step-by-step guide may be a useful tool for researchers conducting UR in the future.

Uptake and Discontinuation of Integrase Inhibitors (INSTIs) in a Large Cohort Setting.

BACKGROUND: Despite increased integrase strand transfer inhibitor (INSTI) use, limited large-scale, real-life data exists on INSTI uptake and discontinuation. SETTING: International multicohort collaboration. METHODS: RESPOND participants starting dolutegravir (DTG), elvitegravir (EVG), or raltegravir (RAL) after January 1, 2012 were included. Predictors of INSTI used were assessed using multinomial logistic regression. Kaplan-Meier and Cox proportional hazards models describe time to and factors associated with discontinuation. RESULTS: Overall, 9702 persons were included; 5051 (52.1%) starting DTG, 1933 (19.9%) EVG, and 2718 (28.0%) RAL. The likelihood of starting RAL or EVG vs DTG decreased over time and was higher in Eastern and Southern Europe compared with Western Europe. At 6 months after initiation, 8.9% (95% confidence interval: 8.3% to 9.5%) had discontinued the INSTI (6.4% DTG, 7.4% EVG, and 14.0% RAL). The main reason for discontinuation was toxicity (44.2% DTG, 42.5% EVG, 17.3% RAL). Nervous system toxicity accounted for a higher proportion of toxicity discontinuations on DTG (31.8% DTG, 23.4% EVG, 6.6% RAL). Overall, treatment simplification was highest on RAL (2.7% DTG, 1.6% EVG, and 19.8% RAL). Factors associated with a higher discontinuation risk included increasing year of INSTI initiation, female gender, hepatitis C coinfection, and previous non-AIDS-defining malignancies. Individuals in Southern and Eastern Europe were less likely to discontinue. Similar results were seen for discontinuations after 6 months. CONCLUSIONS: Uptake of DTG vs EVG or RAL increased over time. Discontinuation within 6 months was mainly due to toxicity; nervous system toxicity was highest on DTG. Discontinuation was highest on RAL, mainly because of treatment simplification.

The E3 ubiquitin ligase WWP1 sustains the growth of acute myeloid leukaemia.

The E3 ubiquitin ligase (E3) WWP1 is an oncogenic factor implicated in the maintenance of different types of epithelial cancers. The role of WW domain-containing E3 ubiquitin protein ligase 1 (WWP1) in haematological neoplasms remains unknown. Acute myeloid leukaemia (AML) is characterized by the expansion of malignant myeloid cells blocked at different stages of differentiation. Here we report that the expression of WWP1 is significantly augmented in a large cohort of primary AML patients and in AML cell lines, compared with haematopoietic cells from healthy donors. We show that WWP1 inactivation severely impairs the growth of primary AML blasts and cell lines in vitro. In vivo, we observed a reduced leukaemogenic potential of WWP1-depleted AML cells upon transplantation into immunocompromised mice. Mechanistically, WWP1 inactivation induces the accumulation of its protein substrate p27Kip1, which ultimately contributes to G0/G1 cell cycle arrest of AML blasts. In addition, WWP1 depletion triggers the autophagy signalling and reduces survival of leukaemic cells. Collectively, our findings provide molecular insights into the anti-cancer potential of WWP1 inhibition, suggesting that this E3 is a promising biomarker and druggable target in AML.

Atazanavir and darunavir in pregnant women with HIV: evaluation of laboratory and clinical outcomes from an observational national study.

Background: Atazanavir and darunavir represent the main HIV PIs recommended in pregnancy, but comparative data in pregnant women are limited. We assessed the safety and activity profile of these two drugs in pregnancy using data from a national observational study. Methods: Women with atazanavir or darunavir exposure in pregnancy were evaluated for laboratory measures and main pregnancy outcomes (e.g. preterm delivery, low birthweight, non-elective caesarean section and neonatal gestational age-adjusted birthweight Z-score). Results: Final analysis included 500 pregnancies with either atazanavir (n = 409) or darunavir (n = 91) exposure. No differences in pregnancy outcomes, weight gain in pregnancy, drug discontinuations, undetectable HIV-RNA, haemoglobin, ALT, total cholesterol, HDL cholesterol and LDL cholesterol were observed between the two groups. At third trimester, exposure to darunavir was associated with higher levels of plasma triglycerides (median 235.5 versus 179 mg/dL; P = 0.032) and a higher total cholesterol/HDL cholesterol ratio (median 4.03 versus 3.27; P = 0.028) and exposure to atazanavir was associated with higher levels of plasma bilirubin (1.54 versus 0.32 mg/dL; P < 0.001). Conclusions: In this observational study, the two main HIV PIs currently recommended by perinatal guidelines showed similar safety and activity in pregnancy, with no evidence of differences between the two drugs in terms of main pregnancy outcomes. Based on the minor differences observed in laboratory measures, prescribing physicians might prefer either drug in some particular situations where the different impacts of treatment on lipid profile and bilirubin may have clinical relevance.

[Polytrauma and concomitant traumatic brain injury : The role of the trauma surgeon]. / Polytrauma und begleitendes Schädel-Hirn-Trauma : Die Rolle des Unfallchirurgen.

BACKGROUND: Concomitant traumatic brain injury (TBI) increases mortality and reduces quality of life of polytrauma patients. These facts demand effective treatment strategies while the growing specialization of medicine is questioning the role of the trauma surgeon in the management of these patients. OBJECTIVES: Which factors influence outcome of polytrauma with concomitant TBI? Who should be responsible for the management of these patients and what is the limit of management? MATERIALS AND METHODS: A literature search using Medline via PubMed was performed with Medical Subject Headings and text word search. RESULTS: The crucial factors for outcome are absence of hypotension, adherence to pre- and in-hospital standards like fast transportation to appropriate centers, priority-based diagnostic and therapeutic strategies and strict adherence to principles of damage control surgery. Patients with polytrauma and TBI are treated by different specialties around the world based on the trauma system, geographic circumstances and resources. Investigations of operative and conservative management by different medical specialties showed comparable outcomes. CONCLUSIONS: In an age of standardization and a high degree of specialization in the field of medicine, the trauma surgeon still seems to be able to ensure an optimal treatment of polytrauma and concomitant TBI by focusing on priority-based diagnostic and therapeutic strategies and adhering to principles of damage control surgery.

Long-term outcomes of direct acting antivirals in post-transplant advanced hepatitis C virus recurrence and fibrosing cholestatic hepatitis.

Long-term functional outcomes of sofosbuvir-based antiviral treatment were evaluated in a cohort study involving 16 Italian centres within the international compassionate use programme for post-transplant hepatitis C virus (HCV) recurrence. Seventy-three patients with cirrhosis (n=52) or fibrosing cholestatic hepatitis (FCH, n=21) received 24-week sofosbuvir with ribavirin±pegylated interferon or interferon-free sofosbuvir-based regimen with daclatasvir/simeprevir+ribavirin. The patients were observed for a median time of 103 (82-112) weeks. Twelve of 73 (16.4%) died (10 non-FCH, 2 FCH) and two underwent re-LT. Sustained virological response was achieved in 46 of 66 (69.7%): 31 of 47 (66%) non-FCH and 15 of 19 (79%) FCH patients. All relapsers were successfully retreated. Comparing the data of baseline with last follow-up, MELD and Child-Turcotte-Pugh scores improved both in non-FCH (15.3±6.5 vs 10.5±3.8, P<.0001 and 8.4±2.1 vs 5.7±1.3, P<.0001, respectively) and FCH (17.3±5.9 vs 10.1±2.8, P=.001 and 8.2±1.6 vs 5.5±1, P=.001, respectively). Short-treatment mortality was higher in patients with baseline MELD≥25 than in those with MELD<25 (42.9% vs 4.8%, P=.011). Long-term mortality was 53.3% among patients with baseline MELD≥20 and 7.5% among those with MELD<20 (P<.0001). Among deceased patients 75% were Child-Turcotte-Pugh class C at baseline, while among survivors 83.9% were class A or B (P<.0001). Direct acting antivirals-based treatments for severe post-transplant hepatitis C recurrence, comprising fibrosing cholestatic hepatitis, significantly improve liver function, even without viral clearance and permit an excellent long-term survival. The setting of severe HCV recurrence may require the identification of "too-sick-to-treat patients" to avoid futile treatments.

HCV-HIV coinfected pregnant women: data from a multicentre study in Italy.

PURPOSE: To provide information about main pregnancy outcomes in HIV-HCV coinfected women and about the possible interactions between HIV and HCV in this particular population. METHODS: Data from a multicenter observational study of pregnant women with HIV, conducted in Italian University and Hospital Clinics between 2001 and 2015, were used. Eligibility criteria for analysis were HCV coinfection and at least one detectable plasma HCV-RNA viral load measured during pregnancy. Qualitative variables were compared using the Chi-square or the Fisher test and quantitative variables using the Mann-Whitney U test. The Spearman's coefficient was used to evaluate correlations between quantitative variables. RESULTS: Among 105 women with positive HCV-RNA, median HCV viral load was substantially identical at the three trimesters (5.68, 5.45, and 5.86 log IU/ml, respectively), and 85.7 % of the women had at least one HCV-RNA value >5 log IU/ml. Rate of preterm delivery was 28.6 % with HCV-RNA <5 log IU/ml and 43.2 % with HCV-RNA >5log (p = 0.309). Compared to women with term delivery, women with preterm delivery had higher median HCV-RNA levels (third trimester: 6.00 vs. 5.62 log IU/ml, p = 0.037). Third trimester HIV-RNA levels were below 50 copies/ml in 47.7 % of the cases. No cases of vertical HIV transmission occurred. Rate of HCV transmission was 9.0 % and occurred only with HCV-RNA levels >5 log IU/ml. CONCLUSIONS: Coinfection with HIV and HCV has relevant consequences in pregnancy: HIV coinfection is associated with high HCV-RNA levels that might favour HCV transmission, and HCV infection might further increase the risk of preterm delivery in women with HIV. HCV/HIV coinfected women should be considered a population at high risk of adverse outcomes.

A Reduction Grade of Lipodystrophy and Limited Side Effects after HAART Regimen with Raltegravir, Lamivudine, Darunavir and Ritonavir in an HIV-1 Infected Patient after Six Years of Antiretroviral Therapy.

HIV-associated lipodystrophy commonly presents with fat loss in the face, buttocks, arms and legs, hypocomplementaemia, glomerulonephritis, and autoimmune disorders. The exact mechanism of HIV-associated lipodystrophy is not fully elucidated. There is evidence indicating that it can be caused by both antiretroviral medications and HIV infection in the absence of antiretroviral medication. Lipodystrophy seems to be mainly due to HIV-1 protease inhibitors. Interference with lipid metabolism is postulated as pathophysiology. Also, the development of lipodystrophy is associated with specific nucleoside reverse transcriptase inhibitors (NRTI). Mitochondrial toxicity is postulated to be involved in the pathogenesis associated with NRTI. Here, we analyse the side effects and examine the impact of the highly active antiretroviral therapy (HAART) regimen including raltegravir, lamivudine, darunavir and ritonavir in an HIV-1 infected patient with severe lipodystrophy after six years of antiretroviral therapy.

Gastric cancer associated variant of DNA polymerase beta (Leu22Pro) promotes DNA replication associated double strand breaks.

DNA polymerase beta (Pol ß) is a key enzyme for the protection against oxidative DNA lesions via its role in base excision repair (BER). Approximately 1/3 of tumors studied to date express Pol ß variant proteins, and several tumors overexpress Pol ß. Pol ß possesses DNA polymerase and dRP lyase activities, both of which are known to be important for efficient BER. The dRP lyase activity resides within the 8kDa amino terminal domain of Pol ß, is responsible for removal of the 5' phosphate group (5'-dRP). The DNA polymerase subsequently fills the gaps. Previously, we demonstrated that the human gastric cancer-associated variant of Pol ß (Leu22Pro (L22P)) lacks dRP lyase function in vitro. Here, we report that L22P-expressing cells harbor significantly increased replication associated DNA double strand breaks (DSBs) and defective maintenance of the nascent DNA strand (NDS) during replication stress. Moreover, L22P-expressing cells are sensitive to PARP1 inhibitors, which suggests trapped PARP1 binds to the 5'-dRP group and blocks replications forks, resulting in fork collapse and DSBs. Our data suggest that the normal function of the dRP lyase is critical to maintain replication fork integrity and prevent replication fork collapse to DSBs and cellular transformation.

Multifocal phaeohyphomycosis caused by Exophiala xenobiotica in a kidney transplant recipient.

In recent years, black fungi have been increasingly reported as causing opportunistic infections after solid organ transplantation. Here, we report a case of insidious, relentless, and multifocal Exophiala xenobiotica infection in a kidney transplant recipient that eventually required multiple surgical excisions along with oral and intravenous antifungal combination therapy using liposomal amphotericin B and posaconazole. We compare the present case with all previously reported cases of Exophiala infection after kidney transplantation.

Rate, predictors, and consequences of late antenatal booking in a national cohort study of pregnant women with HIV in Italy.

OBJECTIVE: To evaluate the prevalence and consequences of late antenatal booking (13 or more weeks gestation) in a national observational study of pregnant women with HIV. METHODS: The clinical and demographic characteristics associated with late booking were evaluated in univariate analyses using the Mann-Whitney U test for quantitative data and the chi-square test for categorical data. The associations that were found were re-evaluated in multivariable logistic regression models. Main outcomes were preterm delivery, low birthweight, nonelective cesarean section, birth defects, undetectable (<50 copies/mL) HIV plasma viral load at third trimester, delivery complications, and gender-adjusted and gestational age-adjusted Z scores for birthweight. RESULTS: Rate of late booking among 1,643 pregnancies was 32.9%. This condition was associated with younger age, African provenance, diagnosis of HIV during pregnancy, and less antiretroviral exposure. Undetectable HIV RNA at third trimester and preterm delivery were significantly more prevalent with earlier booking (67.1% vs 46.3%, P < .001, and 23.2% vs 17.6, P = .010, respectively), whereas complications of delivery were more common with late booking (8.2% vs 5.0%, P = .013). Multivariable analyses confirmed an independent role of late booking in predicting detectable HIV RNA at third trimester (adjusted odds ratio [AOR], 1.7; 95% CI, 1.3-2.3; P < .001) and delivery complications (AOR, 1.8; 95% CI, 1.2-2.8; P = .005). CONCLUSIONS: Late antenatal booking was associated with detectable HIV RNA in late pregnancy and with complications of delivery. Measures should be taken to ensure an earlier entry into antenatal care, particularly for African women, and to facilitate access to counselling and antenatal services. These measures can significantly improve pregnancy management and reduce morbidity and complications in pregnant women with HIV.

A reduced grade of liver fibros-steatosis after raltegravir, maraviroc and fosamprenavir in an HIV/HCV co-infected patient with chronic hepatitis, cardiomyopathy, intolerance to nelfinavir and a marked increase of serum creatine phosphokinase levels probably related to integrase inhibitor use / Grado reducido de fibroesteatosis tras la administración de raltegravir, maraviroc y fosamprenavir en un paciente co-infectado de VIH/VHC con hepatitis crónica, cardiomiopatía, intolerancia al nelfinavir y un aumento pronunciado de los niveles de creatina fosfoquinasa sérica probablemente debido al uso del inhibidor de la integrasa

The use of new antiretroviral drugs in HIV infection is particularly important in patients with intolerance or resistance to other antiretroviral agents. Raltegravir and maraviroc represent new, important resources in salvage regimens. A reduced grade of liver fibro-steatosis after a combination of raltegravir and maraviroc (second-line) has not been studied and the mechanism by which these new drug classes induced a marked reduction of grade of liver diseases is currently unknown. In the present case report, nested in an ongoing multicentre observational study on the use of new antiretroviral inhibitors in heavy treatment-experienced HIV patients, we evaluated the correlation between a "short therapeutic regimen" raltegravir, maraviroc and fosamprenavir and liver diseases. The aim of this report is to describe the use of a three-drug regimen based on two novel-class antiretroviral agents (raltegravir and maraviroc) plus the protease inhibitor fosamprenavir, in an experienced HIV-infected patient with chronic progressive hepatitis C complicated by liver fibrosis; an overwhelming increased serum creatine kinase level occurred during treatment, and is probably related to integrase inhibitor administration. At present no information is available regarding this correlation.

El uso de nuevos medicamentos antiretrovirales para la infección por VIH es particularmente importante en los pacientes con intolerancia o resistencia a otros agentes antiretrovirales. Raltegravir (RTV) y maraviroc (MRV) representan nuevos e importantes recursos en las terapias de salvamento. Un grado reducido de fibroesteatosis hepática después de una combinación de raltegravir y maraviroc (terapia de segunda línea) no ha sido estudiado, y el mecanismo por el cual estas nuevas clases de droga indujeron una marcada reducción de grado de las enfermedades hepáticas se desconoce hasta el momento. Como parte de la realización en curso de un estudio observacional multicentro acerca del uso de nuevos inhibidores antiretrovirales en pacientes de VIH altamente experimentados en el tratamiento, en el presente reporte de caso se evalúa la correlación entre un "régimen terapéutico corto" (raltegravir, maraviroc y fosamprenavir) y las enfermedades del hígado. El objetivo de este reporte es describir el uso de un régimen de tres medicamentos - basado en dos agentes antiretrovirales de nuevo tipo (raltegravir y maraviroc) además del fosamprenavir inhibidor de la proteasa - en un paciente de VIH experimentado. El paciente también sufre de hepatitis C evolutiva, progresiva, crónica, complicada por fibrosis hepática. Durante el tratamiento, se produjo un aumento extraordinario del nivel de creatina quinasa sérica, el cual probablemente esta relacionado con la administración del inhibidor de la integrasa. Actualmente no hay información disponible con respecto a esta correlación.

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.

A reduced grade of liver fibro-steatosis after raltegravir, maraviroc and fosamprenavir in an HIV/HCV co-infected patient with chronic hepatitis, cardiomyopathy, intolerance to nelfinavir and a marked increase of serum creatine phosphokinase levels probably related to integrase inhibitor use.

The use of new antiretroviral drugs in HIV infection is particularly important in patients with intolerance or resistance to other antiretroviral agents. Raltegravir and maraviroc represent new, important resources in salvage regimens. A reduced grade of liver fibro-steatosis after a combination of raltegravir and maraviroc (second-line) has not been studied and the mechanism by which these new drug classes induced a marked reduction of grade of liver diseases is currently unknown. In the present case report, nested in an ongoing multicentre observational study on the use of new antiretroviral inhibitors in heavy treatment-experienced HIV patients, we evaluated the correlation between a "short therapeutic regimen" raltegravir maraviroc and fosamprenavir and liver diseases. The aim of this report is to describe the use of a three-drug regimen based on two novel-class antiretroviral agents (raltegravir and maraviroc) plus the protease inhibitor fosamprenavir, in an experienced HIV-infected patient with chronic progressive hepatitis C complicated by liver fibrosis; an overwhelming increased serum creatine kinase level occurred during treatment, and is probably related to integrase inhibitor administration. At present no information is available regarding this correlation.

Intestinal lymphangiectasia: an undescribed cause of malabsorption and incomplete immunological recovery in HIV-infected patients.

BACKGROUND: Although paradoxical virological and immunological response after HAART has been well studied, intestinal lymphangiectasia (IL) in HIV-1 infected patients has not previously described. METHODS: To describe HIV patients who developed IL. DESIGN: Clinical Case series. PATIENTS: 4 patients with HIV and IL diagnosis based on clinical, endoscopic and pathological findings. RESULTS: All four cases had prior mycobacterial infections with abdominal lymph node involvement and a very low CD4 cell count nadir. They developed intestinal lymphangiectasia despite appropriate virological suppression with HAART and repeatedly negative mycobacterial cultures. Two patients were clinically symptomatic with oedemas, ascites, diarrhoea, asthenia, weight loss; but the other two were diagnosed with malabsorption as a result of laboratory findings, with hypoproteinemia and hypoalbuminemia. Three of them were diagnosed by video capsule endoscopy. CONCLUSIONS: IL should be considered in HIV-1 infected patients who present with clinical or biochemical malabsorption parameters when there is no immunological recovery while on HAART.