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We present a pancreatic plastic stent migration case and the difficulty of an endoscopic approach to remove it, this time resolved with a hand-made loop catheter using a straight cannula and a NovaGold guide.

The capacity of 2,6-bis[((2-pyridylmethyl)oxy)methyl)]pyridine (BPMMP) to inhibit the corrosion of mild carbon steel in HCl was analyzed. In a polarization study, both the cathodic and anodic currents were appreciably decreased in the presence of BPMMP, suggesting that this ligand is effective at inhibiting corrosion at the metal surface. This conclusion is consistent with the results of impedance analysis, where only one time constant corresponding to one depressed capacitive loop was detected, and the diameter of the impedance plot was directly related to the concentration of BPMMP. Furthermore, when recurrence analysis was performed, a decrease in regular noise was observed due to the change of Shannon entropy when the inhibitor was present in the corrosive medium, showing that a high degree of recurrence increases the entropy of the system. Electrochemical data on some pyridyl-based inhibitors were collected from the literature and used to plot (i) I corr (A/cm 2 ) vs. inhibition efficiency (η%) and (ii) ΔG° ads vs. inhibition efficiency (ƞ%) in order to examine the general relationships between these parameters. Furthermore, the interactions of the ligand BPMMP with different iron clusters (Fe 15 , Fe 30 , Fe 45 , and Fe 60 ) were analyzed theoretically using density functional theory (DFT). The structural and electronic properties of BPMMP and its protonated form BPMMPH + were studied before and after the interactions of BPMMP with the iron clusters. The first protonation was found to occur at pyridine nitrogen atom N1, resulting in a Gibbs free energy ΔG of -10.2 kcal/mol, with an energy difference of 5.3 kcal/mol between the two possible protonated conformers. Graphical abstract Recurrence and Noise signal performance of BPMMP as corrosion inhibitor.

A total of 1,220 subjects from Equatorial Guinea living in Spain (median age = 41 years; 453 male and 767 female) was examined for antibodies to human immunodeficiency virus (HIV) and Hepatitis B (HBV), C (HCV), and D (HDV) viruses. Extracted RNA and DNA from the positive samples were used to quantify viral load. The prevalence of HIV antibodies, HCV RNA, and HBV surface antigen (HBsAg) was 10.8% (N = 132), 11.6% (N = 141), and 7.9% (N = 96), respectively. The most prevalent HIV variant was CRF02_AG (38.5%; N = 40). HCV genotype 4 (60%; N = 36) and HBV genotype A3 (32%; N = 8) were the hepatitis variants most frequently found. Superinfection with HDV was seen in 20.9% (N = 24) of HBsAg carriers. A control group of 276 immigrants from other sub-Saharan countries showed similar rates of HIV and HBsAg, although no HCV cases were found. Immigrants constitute a major source of HIV and hepatitis viruses in Spain; therefore, it is important that control measures are intensified.

Background: Submicroscopic malaria (SMM) can be defined as low-density infections of Plasmodium that are unlikely to be detected by conventional microscopy. Such submicroscopic infections only occasionally cause acute disease, but they are capable of infecting mosquitoes and contributing to transmission. This entity is frequent in endemic countries; however, little is known about imported SMM.The goals of this study were two-fold: a) to know the frequency of imported SMM, and b) to describe epidemiological, laboratorial and clinical features of imported SMM., Methods: A retrospective study based on review of medical records was performed. The study population consisted of patients older than 15 years attended at the Tropical Medicine Unit of Hospital Carlos III, between January 1, 2002 and December 31, 2007. Routinely detection techniques for Plasmodium included Field staining and microscopic examination through thick and thin blood smear. A semi-nested multiplex malaria PCR was used to diagnose or to confirm cases with low parasitaemia., Results: SMM was diagnosed in 104 cases, representing 35.5% of all malaria cases. Mean age (IC95%) was 40.38 years (37.41-43.34), and sex distribution was similar. Most cases were in immigrants, but some cases were found in travellers. Equatorial Guinea was the main country where infection was acquired (81.7%). Symptoms were present only in 28.8% of all SMM cases, mainly asthenia (73.3% of symptomatic patients), fever (60%) and arthromialgias (53.3%). The associated laboratory abnormalities were anaemia (27.9%), leukopaenia (15.4%) and thrombopaenia (15.4%). Co-morbidity was described in 75 cases (72.1%)., Conclusions: Results from this study suggest that imported SMM should be considered in some patients attended at Tropical Medicine Units. Although it is usually asymptomatic, it may be responsible of fever, or laboratory abnormalities in patients coming from endemic areas. The possibility of transmission in SMM has been previously described in endemic zones, and presence of vector in Europe has also been reported. Implementation of molecular tests in all asymptomatic individuals coming from endemic area is not economically feasible. So re-emergence of malaria (Plasmodium vivax) in Europe may be speculated.

Immigration from developing regions to Western countries has resulted in an increased rate of non-B subtypes in the HIV population. However, it is unclear whether these HIV variants remain confined to foreigners or are already spreading among natives. Since many immigrants come from regions in which hepatitis B virus (HBV) and hepatitis C virus (HCV) are endemic, HIV-hepatitis coinfection might be more frequent in newly diagnosed HIV persons. Herein, we report changes in the prevalence and distribution of HIV-1 subtypes in Madrid, Spain over the past 10 years as well as the rate of chronic HBV and HCV coinfection in 1854 newly diagnosed HIV-1 individuals. Overall 18.2% carried HIV-1 non-B subtypes, although the prevalence increased over time reaching a peak of 19.4% in the last period (2007-2010). The most common non-B variants were CRF02_AG (37%), G (12%), A (9.9%), and C (7.8%). In native Spaniards the rate of non-B subtypes increased from 1.5% in 2000-2002 to 7.2% in 2003-2006 and to 11.4% in 2007-2010 (p = 0.04). Chronic hepatitis B and C were found, respectively, in 4.2% and 8.3% of the study population. While the prevalence of chronic hepatitis B has remained fairly stable over time across distinct populations, the rate of chronic HCV infection has experienced a significant decline, mainly in native Spaniards as a result of a reduction in intravenous drug use. In summary, the prevalence of HIV-1 non-B subtypes is rising in newly diagnosed HIV-1 individuals in Spain, including the native population. In contrast, the rate of HBV coinfection remains unchanged and the rate of HCV coinfection has declined.

Background: Universal vaccination and antiviral therapy have reduced chronic hepatitis B virus (HBV) in natives in the Western world. However, immigration from high HBV endemic areas continues to maintain a relatively stable prevalence of chronic hepatitis B in most developed countries., Methods: All foreigners attending a referral infectious diseases department in Madrid, Spain, from January 2007 to December 2008, were evaluated for serum HBV surface antigen (HBsAg). Positive cases underwent further virological characterization., Results: A total of 1718 foreigners were examined, of whom 1322 (77%) were sub-Saharan Africans. Serum HBsAg was positive in 121 (7%), HIV in 135 (7.9%) and hepatitis C virus antibodies in 212 (12.3%). HBV subgenotype A3, which so far had only been reported in people originating from Cameroon, was found in nearly half (14/29) of the tested specimens with detectable serum HBV-DNA. Interestingly, the lamivudine resistance mutation rtM204V was found in two Africans (6.9%), one infected with HBV-A3 and the other with HBV-E. Lack of prior exposure to antiviral therapy in these two patients was confirmed retrospectively., Conclusions: Circulation of uncommon HBV variants, including strains with primary drug resistance, may follow large immigrant flows from HBV endemic regions to Western countries. Close surveillance of this population is warranted, as early diagnosis and early antiviral therapy may reduce transmission and prevent clinical complications.

This paper reports a case of myiasis caused by Hypoderma sinense in a European man returning from a journey through northern India. The patient showed eosinophilia, systemic signs of inflammation, and painful swellings in several parts of the body. The diagnosis was confirmed by specific serology and parasite molecular identification., (© 2010 International Society of Travel Medicine.)

Background: Longitudinal assessment of liver fibrosis with transient elastometry (TE) in patients with chronic viral hepatitis is becoming routine clinical practice in many clinics, as this procedure is non-invasive, easy to perform and relatively inexpensive, allowing early detection of cirrhosis. Herein, we examine the incidence of cirrhosis, using TE assessment, in HIV-infected individuals with chronic hepatitis B or C receiving highly active antiretroviral therapy (HAART)., Methods: A longitudinal study was performed on a cohort of HIV-infected patients with chronic hepatitis B or C who were followed since 2004 at Hospital Carlos III (Madrid, Spain) with periodic TE assessments. The primary outcome was the development of cirrhosis, defined as liver stiffness >12.5 KPa., Results: A total of 508 HIV-infected patients were examined, of whom 54 developed liver cirrhosis during a mean ±(SD) follow-up of 2.6 ±1.0 years (overall incidence was 41.13 cases per 1,000 person-years). The risk of developing cirrhosis was significantly higher in 297 HCV-RNA-positive patients (either untreated or non-responders to hepatitis C therapy) compared with 55 patients who had cleared HCV with therapy (odds ratio 3.73, 95% confidence interval 1.06-13.17; P=0.04). By contrast, the risk of developing cirrhosis was low and similar in 24 HIV-HBV-coinfected patients under long-term suppressive HBV therapy (mainly tenofovir disoproxil fumarate), 132 HIV-infected patients without chronic liver disease and those who had cleared HCV with therapy., Conclusions: Development of liver cirrhosis in HIV-infected individuals in the HAART era is mainly associated with active HCV coinfection. The risk of developing cirrhosis is negligible in patients who cleared HCV with therapy, as well as in HIV-HBV-coinfected patients on long-term suppressive tenofovir disoproxil fumarate therapy.

Background: Rapid, simple, low-cost, sensitive, and specific tests are needed to detect antibodies to all HIV-1 subtypes, especially in developing countries., Objective: To evaluate the performance of a rapid diagnostic test for detection of HIV-1/2 antibodies in oral fluids and sera/plasma from subjects from geographic areas infected with different HIV-1 variants., Study Design: OraQuick Rapid HIV-1/2 Diagnostic Test was evaluated in sera and oral fluids from 100 subjects from Spain and South-America. It was also assessed in 56 plasma and 39 oral fluid specimens from 56 Africans carrying HIV-1 non-B subtypes or inter-subtype recombinants defined by phylogenetic analysis at pol and gp41 coding regions. All patients were previously diagnosed as HIV-1 positive by serological tests (Abbott AxSYM HIV-1/2; Western Blot HIV-1/HIV-2 and Pepti-LAV, BIO-RAD)., Results: OraQuick provided positive results in all 156 serum/plasma specimens regardless of the infecting HIV-1 subtype, and in 136/139 (97.8%) oral fluids. The three oral specimens (2.2%) that yielded false-negative results by OraQuick were taken from one subtype B-infected Spaniard and from two subtype D-infected Africans. The last two were also negative by Pepti-LAV using plasma samples. Ten additional sera and 32 oral fluids from HIV-negative individuals yielded negative results by OraQuick. This rapid test showed good sensitivity for detecting anti-HIV-1 antibodies in oral fluids and in serum/plasma specimens from subjects carrying different HIV-1 subtypes and recombinant variants., Conclusion: OraQuick demonstrated its utility for detecting infections due to HIV-1 subtypes and recombinants common in developing countries.

Background: Tenofovir (TDF) is the most widely prescribed antiretroviral drug. Kidney abnormalities are the main concern using the drug. As glomerular function is infrequently affected in patients treated with TDF, herein, we report the results of an extensive examination of tubular function., Methods: Cross-sectional study of plasma and 24 h urine markers of kidney tubulopathy (glucosuria, hyperaminoaciduria, hyperphosphaturia, hyperuricosuria and beta2-microglobulinuria) could be allocated in three groups: patients under a TDF-containing HAART; patients on HAART never exposed to TDF; and antiretroviral-naive individuals. Significant tubular damage was defined when at least two of these parameters were repeatedly present, being at least one part of the Fanconi syndrome criteria (glucosuria, hyperaminoaciduria and hyperphosphaturia). Glomerular function was assessed using creatinine clearance., Results: A total of 284 consecutive HIV patients were examined, 154 on TDF, 49 on other HAART regimens and 81 drug-naive. No significant differences in creatinine clearance were observed when comparing distinct groups. The proportion of patients with tubular damage in groups 1, 2 and 3 were 22, 6 and 12%, respectively. In a multivariate analysis [odds ratio (OR) {95% confidence interval (CI)} P], the only independent predictors of tubular dysfunction were TDF use (21.6, 4.1-113, <0.001) and older age (1.1 per year, 1.0-1.1, 0.01)., Conclusion: Exposure to TDF is associated with an increased risk over time of kidney tubular abnormalities in the absence of significant impaired glomerular function. Although long-term consequences of this tubulopathy are unknown, close monitoring of accelerated bone mineral loss and renal insufficiency are warranted. Periodic screening of tubular function parameters should be recommended to patients receiving TDF.

Atazanavir (ATV) is one of the latest protease inhibitors (PI) approved for the treatment of HIV infection. The drug has a relatively long-life (~7 h) and large inhibitory quotient which allows once daily administration. It is generally well tolerated and the main side effect is hyperbilirubinemia, since ATV inhibits the hepatic uridin-glucoronyl-transferase. A signature mutation at the protease gene, I50L, may confer loss of susceptibility to the drug. Interestingly, it produces hypersusceptibility to all other PIs. When ATV is pharmacokinetically boosted with ritonavir (r) 100 mg/day, a greater genetic barrier for resistance is achieved, and generally more than 3 major PI resistance associated mutations are needed to result in ATV resistance. In drug-naïve subjects, regimens based on ATV/r have shown non-inferiority compared to lopinavir (LPV)/r (CASTLE study) or fosamprenavir/r (ALERT trial), generally with improved tolerance (less diarrhea and dyslipidemia). Given its good tolerance and convenience, ATV has been proven to be successful as a simplification strategy in switch studies (ie, SWAN and SLOAT) conducted in patients with complete virological suppression under other PI-based regimens. Finally, ATV/r-based combinations have shown to be equivalent in terms of viral response to other PI/r-containing regimens, including LPV/r, in rescue interventions in patients failing other PI regimens (ie, studies AI424-045 and NADIS).

Abstract The diagnosis of HIV-1 is increasing in African-born persons residing in Europe. They present a high prevalence of HIV-1 non-B variant infections and of parasitic infections, both of which are infrequent in Western countries. Immigration favors their presence in nonendemic countries. In this study, all newly HIV-diagnosed individuals at an HIV/AIDS and Tropical Medicine reference center in Madrid from 2005 through 2007 were retrospectively studied. HIV-1 subtyping was performed in gag, pol, and gp41 coding regions by phylogenetic analyses. The presence of other pathogens was also evaluated. Furthermore, all HIV-1-infected Africans were screened for parasitic infections. Newly diagnosed HIV-1 subjects included 90 sub-Saharan Africans and 188 non-Africans (116 Spaniards, 13 other Europeans, and 59 Latin Americans). Significantly higher numbers of HIV-1-infected Africans than non-Africans were females, acquired HIV-1 by heterosexual contact, and presented a more advanced clinical CDC stage and criteria for starting antiretroviral therapy in the first clinical visit. They predominantly carried non-B subtype infections, mainly intersubtype recombinants. Half of HIV-1-infected Africans had parasitic infections. CD4(+) T cell counts were lower among Africans than Europeans at the time of HIV-1 diagnosis. At 12 months of follow-up after starting antiretroviral treatment, a significantly lower proportion of Africans than non-Africans achieved undetectable viremia due to their higher loss to follow-up. However, CD4(+) T cell recovery and virological failure rates were similar. Therefore, the profile of African HIV-1-infected immigrants varies widely with respect to Spanish HIV-infected individuals. More advanced immunodeficiency and the coexistence of parasitic diseases and infections with a large diversity of HIV-1 non-B and recombinant variants are expected.

Background and Objective: Dengue is the most common imported arbovirus infection in Europe. International travel and an increasing incidence of dengue fever in tropical areas have defined the disease as an emerging infection in returning travellers. We describe the clinical and microbiological features of imported dengue in 3 referral hospitals in Spain., Patients and Method: We included patients diagnosed with dengue infection during a 3-year period (2002--2005). We recorded clinical and epidemiological data and collected blood samples for serological and molecular studies of dengue infection. Data was analyzed with the statistical package Stata 9.2., Results: We diagnosed 61 dengue cases, mostly European tourists who travelled to Latin America. Fever was found in 98.4% of patients and 80.3% presented with cutaneous eruption. Five patients had severe symptoms. Eighteen percent were considered to have secondary infections, although no patients met the WHO criteria for hemorrhagic dengue. In 26 cases, dengue was confirmed through viral genome detection and 35 cases through serology. Four patients were considered as <> dengue infection, and 57 as <>., Conclusions: Dengue is a common diagnosis for returning travellers, and it may present with severe manifestations. In our sample, there was an elevated percentage of secondary infections even though no previous history of dengue was reported by the patients. Hemorrhagic dengue and septic shock dengue are a risk for travellers returning from endemic areas.

Background: Atazanavir seems to be a protease inhibitor (PI) with a more favourable metabolic profile. Information regarding the potential benefit of replacing lopinavir/ritonavir by atazanavir in HIV-infected patients with prolonged viral suppression is scarce. If proved, this strategy could be particularly attractive for the subset of patients with greater cardiovascular risk., Methods: SLOAT was a prospective, open, comparative trial in which patients receiving lopinavir/ritonavir-based regimens and having undetectable plasma HIV-RNA for longer than 24 weeks were randomized to continue on the same therapy or switch to atazanavir. Outcomes in viral rebound, CD4 counts, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides and glucose were compared in both groups of patients at 48 weeks of follow-up., Results: A total of 189 patients were recruited and took at least the first dose of the assigned treatment arm. Overall, 102 switched to atazanavir (49 on 400 mg once daily, and 53 on 300 mg plus 100 mg of ritonavir once daily due to concomitant tenofovir use) and 87 continued on lopinavir/ritonavir. All patients received the PI along with two nucleoside analogues. Virological failure occurred in 12 patients switched to atazanavir and 9 continuing on lopinavir/ritonavir. A reduction (P < 0.001) in median total cholesterol (-19 mg/dL) and triglycerides (-80 mg/dL) was observed after 48 weeks of atazanavir switching, whereas no significant changes occurred in the lopinavir/ritonavir arm. Greater reductions in total cholesterol and triglycerides were seen in patients switched to atazanavir without ritonavir boosting., Conclusions: The replacement of lopinavir/ritonavir by atazanavir provides an overall significant reduction in total cholesterol and triglycerides, without increased risk of virological failure.

The combination of didanosine (ddI) and lamivudine (3TC) is attractive considering its low cost, potency, tolerability, and convenience (once daily administration), but it is not recommended as first-line therapy for HIV infection. A prospective, multicenter, open, comparative trial was conducted in HIV-infected, antiretroviral-naive persons in Spain who begun a QD regimen with efavirenz (EFV), 3TC, plus ddI, the latter with or without food. A total of 103 patients were recruited in the study. Median baseline CD4 count was 229 cells/microl and plasma HIV-RNA was 4.9 logs copies/ml. In an intent-to-treat analysis, 78 (75.8%) had undetectable viremia at week 48 of therapy, without significant differences when comparing patients on and without fasting ddI (75% vs. 76.6%, respectively). The mean CD4 increase was of 199 cells/microl, with no significant differences between groups. Overall, 29 adverse events were recorded in 23 patients, the majority associated with neuropsychiatric symptoms of EFV. Treatment was discontinued in 10 (9.7%) patients due to adverse events. Virological failure was recognized in only six patients, four taking ddI with and two without food (p = 0.3). Drug resistance mutations were recognised in four of them. Plasma ddI concentrations did not differ significantly between groups. Mitochondrial DNA within peripheral blood mononuclear cells tended to increase in most subjects over 48 weeks of therapy regardless of treatment group. A QD regimen with ddI, 3TC, and EFV shows potency and tolerance similar to that reported using other currently recommended regimens in drug-naive HIV-infected patients. Its efficacy does not seem to be compromised when ddI is administered with food. Therefore, this regimen merits further investigation in larger comparative trials.

The incidence or severity of certain vaccine-preventable diseases is higher in HIV-infected individuals. However, immune responses to vaccination may be diminished, particularly in those with severe immunosuppression. Higher doses of vaccine, more frequent boosters, or revaccination after antiretroviral therapy-induced immune reconstitution are strategies to be considered for patients in certain circumstances. In addition, some vaccines may be harmful when given to severely immunocompromised patients. The challenge for healthcare providers is assessing the safety and effectiveness of vaccines for HIV-infected patients, especially when information on vaccines has not been fully characterized in the HIV-setting. This review presents state-of-the-art knowledge about immunizations for HIV-adults. The efficacy and safety of current vaccines, their current indications in HIV-infected adults, and the strategies aimed to enhance their results are discussed.

Hepatitis C virus (HCV)-infected patients with normal transaminases may show significant liver damage. The proportion of subjects with alanine aminotransferase (ALT) levels within normal limits was examined in HIV-infected patients never exposed to interferon and with detectable plasma HCV-RNA on regular follow-up at one single institution. Liver fibrosis was evaluated using transient elastography (FibroScan). Out of 281 coinfected patients, 25 (8.9%) had persistently normal ALT levels. Patients with HCV genotypes 2 (1/5; 20%) and 4 (10/50; 20%), more often had significantly normal ALT than patients with HCV-1 (13/158; 8%) (p = 0.01) and HCV-3 (1/49; 2%) (p = 0.01). Liver fibrosis stages in these patients were as follows: F0-F1 in 13 (59.1%), F2 in 4 (18.2%), F3 in 2 (9.1%), and F4 in 3 (13.6%). Advanced liver fibrosis (F3-F4) tended to be more frequent in patients infected with HCV-4 than HCV-1 (33.3% versus 9.1%; p = 0.2). Of HIV-infected patients with chronic hepatitis C 8.9% show persistently normal ALT levels. Nearly 25% of HIV-HCV-coinfected patients with persistently normal ALT show advanced liver fibrosis. Therefore, HCV-HIV-coinfected patients with normal ALT levels should be closely monitored.

Malaria and HIV infection are both prevalent in the areas of the world where these diseases have the largest burden. Both diseases interact with one another and this interaction is especially important in areas with non-continuous malaria transmission, in pregnant women, and in patients with more severe immunodeficiency. Malaria has been implicated in transitory higher viral load and in low CD4 counts, so it could have an influence on higher transmission rates of HIV and perhaps in the course of HIV infection. Infection with HIV has been shown to cause more clinical malaria and higher parasitemia in patients living in perennial transmission areas, and higher rates of severe malaria episodes and mortality in areas where malaria is transmitted with seasonal frequency. The HIV-infected patients have also higher rates of malaria treatment failures. Co-trimoxazole prophylaxis has been shown to be effective in the prevention of some opportunistic infections in HIV-infected patients, but also in prevention of malaria episodes. Antiretroviral protease inhibitors demonstrate antimalarial effects that could have important clinical and therapeutic implications. For all of these reasons, HIV and malaria should be considered together as part of healthcare programs for both diseases in countries where their co-presence favors an interaction with important clinical consequences.

Objectives: To assess the effect of early syphilis on HIV viral load (VL) and CD4 cell count in patients with HIV and to analyze factors associated with changes in HIV VL and CD4 cell count., Design: Multicenter study of a series of patients with HIV who were diagnosed with early syphilis infection during 2004 through 2005. Patients who started or changed their highly active antiretroviral therapy (HAART) regimen during the analysis period were excluded., Results: One hundred eighteen patients were analyzed: 95.8% were men, mean patient age was 38.2 years, 83.9% were homosexual men, 50.8% were on antiretroviral therapy at the time syphilis was diagnosed, and HIV and syphilis diagnoses were coincident in 38 (32.2%) cases. CD4 cell counts were lower during syphilis than before (590 vs. 496 cells/microL; P = 0.0001) and after syphilis treatment (509 vs. 597 cells/microL; P = 0.0001). The HIV VL increased in 27.6% of patients during syphilis. The only factor associated with an HIV VL increase was not being on HAART, and the only factor associated with a CD4 count decrease >100 cells/microL during syphilis was the prior CD4 cell count., Conclusions: Syphilis infection was associated with a decrease in the CD4 cell count and an increase in the HIV VL in almost one third of the patients. In this series, more than two thirds of the syphilis cases were diagnosed in patients who were previously known to be infected with HIV.

Purpose: The extent and predictors of liver fibrosis were examined in a HIV/HBVcoinfected cohort with extensive exposure to anti-HBV active HAART., Method: Liver fibrosis was measured using transient elastography., Results: Thirty-seven patients of a median age of 43 were included in the study. All but 2 patients had received anti-HBV drugs for a median time of 40 months in the context of HAART. F0-F1 METAVIR fibrosis scores (minimal or no fibrosis) as measured by elastography were found in 21 (57%) patients. AST levels were significantly lower among F0-F1 patients (33 IU/L) compared to F2-F4 patients (48 IU/L) (p = .01). ALT levels were also lower in F0-F1 patients (38 IU/L) than in F2-F4 patients (54 IU/L) (p = .05)., Conclusion: In this HIV/HBV-coinfected cohort, with extensive HAART exposure including anti-HBV agents, more than half of the patients had no or minimal liver fibrosis. Higher transaminase levels were recognized in patients with higher degree of fibrosis.

Background: Liver damage is frequently seen in HIV-positive subjects, often resulting from coinfection with hepatitis B and/or C viruses (HCV), alcohol abuse, etc. However, the etiology of liver disease still remains unknown for a small subset of individuals., Methods: Cryptogenic liver disease (CLD) was defined as persistently elevated aminotransferases levels in the absence of hepatitis C and/or B viruses replication and of other common causes of liver disease (alcohol, medications, etc). We identified cases initially meeting this definition by examining all HIV-positive subjects attended during the year 2004 in 2 large HIV clinics in Spain. Their clinical charts were retrospectively reviewed, and their assessment completed when needed to rule out other less frequent causes of liver disease. The stage of liver fibrosis was assessed by liver biopsy and/or elastography. To assess which factors could be associated with CLD, HIV-positive controls were chosen and matched by age, gender, and CD4 status., Results: CLD was diagnosed in 17 (0.5%) out of 3200 HIV-positive patients. Their mean age was 43 years, 82.4% were male, and 76% had acquired HIV through homosexual relationships. The mean time from HIV diagnosis was >15 years, and all patients had been exposed to antiretroviral therapy. Nevirapine, stavudine, and didanosine were the drugs more frequently used by this subset of patients. None of them had liver function test abnormalities before initiating antiretroviral therapy. Advanced liver fibrosis (F3-F4 Metavir scores) was recognized in 10 (58.8%) individuals, and 9 (52.9%) had developed symptomatic liver complications, including ascites (8), portal thrombosis (6), variceal bleeding (5), and encephalopathy (2). In the case-control analysis, prolonged didanosine exposure was the only independent predictor of developing CLD in this population., Conclusions: CLD is an uncommon condition in HIV-positive individuals and might be associated with prolonged didanosine exposure. It may evolve causing severe liver complications, with variceal bleeding and portal thrombosis being particularly frequent.

The impact of HIV-1 subtype on clinical outcome following exposure to antiretroviral therapy is currently not well known. Natural polymorphisms are often present in HIV-1 non-B subtypes at positions known to be associated with drug resistance in clade B viruses. These changes might influence the emergence of drug-resistant viruses, modifying drug susceptibility and/or the virus replicative capacity. Moreover, different pathways may lead to drug resistance according to HIV-1 clade. Finally, the influence of subtype on the performance of phenotypic assays and in the interpretation of algorithms for genotypic resistance is currently a matter of debate. All these aspects explain why the response to antiretroviral therapy might vary in subjects infected with different HIV-1 clades.

Background: Liver fibrosis is accelerated in patients coinfected with hepatitis C virus (HCV) and human immunodeficiency virus (HIV). The reasons for this faster liver disease progression are unclear, although higher plasma HCV RNA levels and distinct HCV genotype distribution in this population, compared with in HCV-monoinfected subjects, could play a role., Methods: Liver fibrosis was assessed using elastometry in all consecutive HIV-infected patients with chronic hepatitis C who attended our institution (Hospital Carlos III, Madrid) during the past 12 months. Hepatic stiffness was measured in kiloPascal units (kPa) and was interpreted on the basis of Metavir score: no or mild fibrosis (score, F0-F1) when liver stiffness is < or =7.1 kPa, and fibrosis with septa or cirrhosis (F2-F4) when >7.1 kPa., Results: A total of 283 patients (71% were male; mean age, 42 years; 94% were injection drug users and 94% were receiving antiretrovirals; mean CD4 cell count, 554 cells/microL; 72% with plasma HIV RNA level of <50 copies/mL) were analyzed. The mean alanine aminotransferase level was 68 IU/L, and the mean plasma HCV RNA level was 5.9 log IU/mL. HCV genotype distribution was as follows: genotype 1, 60% of patients; genotype 2, 2%; genotype 3, 26%; and genotype 4, 12%. Overall, 164 (58%) of the patients had scores indicating advanced liver fibrosis (F2-F4), as determined using elastometry. In the univariate and multivariate analyses, respectively, a significant odds ratio (OR) for score F2-F4 was found for HCV genotype 3, compared with the other genotypes (OR, 1.9 [95% confidence interval {CI}, 1.1-3.4] vs. 4.3 [95% CI, 1.4-13.3]); for older age (OR, 1.1 [95% CI, 1.03-1.17] vs. 1.1 [95% CI, 1.01-1.25]); and for elevated alanine aminotransferase levels (OR, 1.02 [95% CI, 1.01-1.03] vs. 1.03 [95% CI, 1.01-1.04]). Although patients with HCV genotype 1 had higher mean serum HCV RNA levels than did those with HCV genotype 3 (6.1 log IU/mL vs. 5.7 log IU/mL; P=.01), patients with HCV genotype 3 tended to have F2-F4 scores more frequently than did those with HCV genotype 1 (69% vs. 58%; P = not significant)., Conclusions: HCV genotype 3, older age, and elevated alanine aminotransferase levels are independent predictors of advanced liver fibrosis in HCV-HIV-coinfected patients.

The combination of didanosine (ddI) and tenofovir (TDF) has potential advantages, but because of several pitfalls (unexpected decreases in CD4+ T cells, increased risk of pancreatitis) its use has been questioned. Since anecdotal cases of transient insulin-dependent diabetes mellitus were seen in our clinic in patients on ddI + TDF-containing regimens, we explored the rate of this complication in more detail. Retrospective analysis of plasma glucose levels in patients who completed 12 months of treatment with three different triple antiretroviral regimens including ddI + TDF, TDF, or ddI was done. Patients taking antidiabetic drugs and/or those with baseline glucose levels >125 mg/dl were excluded. Weight, age, concomitant antiretrovirals, and ddI dose were assessed. At 12 months without treatment changes, fasting glucose levels were compared to baseline. A multivariate analysis was performed to evaluate which variables were associated with glucose elevations. A total of 177 HIV-infected patients were assessed (78 on ddI + TDF, 42 on TDF, and 57 on ddI). Mean baseline features were well balanced between groups for age (mean, 39 years), gender (78% male), CD4+ count (mean, 507 cells/mm3), weight (mean, 67 kg), and glucose level (mean, 95 mg/dl). There were only significant differences between groups for baseline viral load and protease inhibitor (PI) use (13% in the ddI + TDF arm vs. 7% and 9% in the TDF and ddI arms, respectively). At 12 months, 60% of the patients in the ddI + TDF arm were taking ddI 250 mg/day and the rest were on ddI 400 mg/day. At 12 months, hyperglycemia was significantly more frequent in the ddI + TDF arm (33%) when compared to patients on TDF or ddI separately (5% and 10%, respectively). In the multiple linear regression analysis, a lower weight (beta -0.35; 95% CI -0.67 to -0.03; p = 0.033) and use of ddI + TDF (beta: 13.05; 95% CI: 0.2 to 26; p = 0.047) were independently associated with a higher risk of developing hyperglycemia. The risk of hyperglycemia is increased in patients treated with ddI + TDF, particularly in those with lower weight. As high ddI exposure has been associated with endocrine pancreatic dysfunction and diabetes, ddI "overdosing" as result of concomitant TDF use and low weight might explain our findings. These results add a further note of caution to the use of TDF and ddI in combination.

Study Objectives: To study the changing etiology of prosthetic valve endocarditis (PVE) and the impact of nosocomial acquisition of the infection on prognosis in a single hospital., Methods: Retrospective review of 121 cases of PVE during a period of 34 years. Two different periods (the period from 1970 to 1986 [P1], and the period from 1987 to 2003 [P2]) were analyzed., Results: During P1, 58 patients with PVE were treated (30 early PVE and 28 late PVE); during P2, 63 patients with PVE were treated (13 early PVE and 50 late PVE). The frequency of early-onset PVE decreased from 0.94% in P1 to 0.34% in P2 (p < 0.001), but the incidence rate of late-onset PVE did not change (0.33% and 0.42% per year, respectively). The microbiology of early PVE changed over the years: Gram-negative bacilli decreased from 40% during P1 to 7.7% in P2 (p = 0.033). Staphylococci remained the main causes of early PVE in both periods. The microbial etiology of late PVE also changed over the years with enterococci and Staphylococcus aureus as the leading causes during P2. Streptococcus viridans decreased from a leading position to a fourth position. Methicillin-resistant S aureus endocarditis appeared first in 1992. Eleven cases of late-onset PVE in P2 were hospital acquired (22%). In comparison, only two cases (7.1%) of hospital-acquired, late-onset PVE were seen in P1 (p = 0.11). Mortality of early-onset PVE decreased from 80% in P1 to 46% in P2 (p = 0.026). The overall mortality of late-onset PVE did not change between periods: 39% vs 34%. Mortality associated with nosocomial PVE in P2 was 63.6% (7 of 11 patients). In comparison, the mortality of community-acquired cases was 25.6% (10 of 39 patients; p = 0.03). In the multivariate analysis, the presence of comorbidities and hospital acquisition were associated with an excess of mortality (odds ratio [OR], 13.9; 95% confidence interval [CI], 1.23 to 158 [p = 0.033]; and OR, 10.8; 95% CI, 2.16 to 54.7 [p = 0.0037], respectively)., Conclusion: Although the mortality associated with early-onset PVE has significantly decreased, in this series the mortality of patients with late-onset PVE remained high due mainly to an increasing number of patients with comorbidities who acquired the infection during admission for other diseases.

Nucleoside/nucleotide analogs (NAs) are essential components of most current antiretroviral regimens. Although many dual NA combinations may be used as backbones, not all display optimal results. For instance, some associations should be avoided due to antagonism (eg, zidovudine plus stavudine), high rates of toxicity (eg, didanosine plus stavudine) and/or increased risk of virological failure (eg, didanosine plus tenofovir). Moreover, the knowledge of plasma and intracellular interactions between different NAs is important for choosing appropriate combinations and optimal doses in order to optimize antiviral efficacy and minimize toxicities.

Background: Whether asymptomatic human immunodeficiency virus (HIV)-infected patients can interrupt treatment remains unknown., Methods: We performed a prospective, observational study of 46 patients who started therapy with >300 CD4+ cells/mm3 and/or <70,0000 HIV-1 RNA copies/mL. Patients had been receiving highly active antiretroviral therapy (HAART) for at least 6 months. HAART was discontinued, and plasma HIV-1 RNA loads and CD4+ cell counts were determined at 4-month intervals., Results: At the time of HAART discontinuation, the median CD4+ cell count was 793 cells/mm3, and all patients had undetectable viral loads. A rapid decrease of 173 cells/mm3 in the median CD4+ cell count was observed during the first 4 months after HAART was stopped, followed by a slower decrease of 234 cells/mm3 between months 5 and 20. The decrease in the median CD4+ cell count early after HAART discontinuation was inversely correlated with the increase that occurred during receipt of therapy (r=-0.653) and with the count at the time of HAART discontinuation (r=-0.589). The decrease in the median CD4+ cell count after the fourth month without HAART was correlated with the nadir count before HAART initiation (r=-0.349) and the increase during treatment (r=-0.322). The median follow-up duration was 20 months. After 12, 24, and 36 months of observation, 33 patients (71.7%), 22 patients (47.8%), and 16 patients (34.7%), respectively, remained free of therapy. Adverse clinical events were not seen, and all patients who reinitiated HAART responded rapidly., Conclusion: Selected asymptomatic HIV-infected patients can safely discontinue therapy for prolonged periods of time.

We present a 68-y-old female who had undergone aortocoronary bypass and developed Staphylococcus aureus sternal osteomyelitis. Despite prolonged therapy with different antibiotics and several local debridements and drainage, the wound remained open and suppurative. Only after sternectomy and wide excision of infected costal cartilage was the diagnosis of sternal tuberculosis made, 24 months later. This case illustrates the necessity of a high degree of suspicion to diagnose this very rare entity which coexists with more common causes of sternal osteomyelitis.

A case is reported of cryptococcal meningitis in a 27-y-old male suffering from X-linked hyper-IgM1 syndrome. This congenital disorder is characterized by multiple infections of the respiratory and gastrointestinal tracts, but also opportunistic infections commonly seen in patients with cell-mediated immunity. His clinical recovery was good but the need for life-long secondary chemoprophylaxis to prevent relapses is unknown.

Background: Simplified highly active antiretroviral therapy (HAART) regimens are becoming widely used, particularly as a result of the side effects of and difficult compliance with protease inhibitor (PI) therapy. However, the long-term efficacy of HAART has not been properly assessed., Methods: We performed a prospective study of 110 patients infected with human immunodeficiency virus type 1 (HIV-1) with undetectable virus load who discontinued PI therapy and initiated therapy with nevirapine without changing nucleoside analogues. Reasons for switching were treatment simplification (45%), lipodystrophy (24%), renal problems (23%), and dyslipidemia (8%). HIV-1 load, CD4 cell count, and fasting biochemistry profiles were performed at the time of switching (baseline) and every 3-4 months thereafter. The aim of the study was to evaluate the long-term efficacy and safety of this combination., Results: Sixty-eight patients (61.8%) had a duration of follow-up of 3 years. The mean increase in the CD4 cell count after 3 years was 90 cells/microL (13.8% from baseline). Virus loads remained undetectable in all patients but 9 (8.2%). Triglyceride levels dramatically improved at 12 months (a 75% decrease; P<.02) and remained statistically significant over time (P<.04). The same occurred with serum cholesterol levels: there was an initial reduction of 25% (P<.02) and at the end of the follow-up period (P<.015). However, at the long-term evaluation, complete normalization of mean serum cholesterol and triglyceride levels could not be achieved. Sixteen patients (14.5%) had to stop therapy as a result of nevirapine-associated side effects., Conclusions: The switching of a PI to nevirapine is a safe and well-tolerated option for maintaining long-term virological suppression and immunological control. Three years after starting nevirapine therapy, rates of hypercholesterolemia and hypertriglyceridemia improved, although normal cholesterol and triglyceride values were not achieved.

Visceral leishmaniasis is basically a disease of healthy infants and adults. However, in the last decade an increasing number of cases of kala azar in immunocompromised patients have been reported with emphasis on atypical manifestations of the disease. During a period of 11 years, 20 immunocompromised patients with AIDS (12 patient), haematological neoplasia (3 patients), corticosteroid therapy (3 patients) or renal transplantation (2 patients) were studied by one or more of the authors. We did not find differences in the presentation of leishmaniasis between patient with or without AIDS and most patients had fever, enlargement of the liver and spleen, blood cytopenias and biochemical abnormalities. Serology was more frequently positive in HIV-negative than in HIV-positive patients (100% versus 63.6%; P=0.13). Bone marrow biopsy was diagnostic in 66% and 87% of patients with and without AIDS, respectively. Failure of anti-leishmanial therapy occurred in 6 of 19 patients treated (31.5%), and 3 patients with AIDS and another 3 without AIDS died during the first episode of leishmaniasis. Of 12 survivors, relapses occurred in five (41.6%). Only patients in whom immunosuppression was ameliorated by means of antiretroviral therapy or by reduction of corticosteroid and other immunosuppressive drugs did not relapse. Treatment of kala azar in immunocompromised host is in satisfactory and new drugs or strategies are urgently needed.

Introduction: Endocarditis due to Listeria monocytogenes is a rare but serious disease often leading to valve dysfunction and heart failure. Two cases of listerial prosthetic valve endocarditis are reviewed along with 66 cases previously reported., Results: The mean age of patients with listerial endocarditis increased from 47.1 years in the decades from 1955-1984 to 65.5 years from 1985-2000. Chronic debilitating diseases, solid tumours and immunosuppression associated with organ transplantation, hematologic neoplasia or AIDS were found in 41.1% of cases. Listerial endocarditis was a vegetative and destructive process, with dehiscense of the prosthesis and occasionally, abscess formation, fistulization and pericarditis. Treatment with penicillin or ampicillin alone or combined with gentamicin was adequate therapy in most cases. Vancomycin together with gentamicin may be a reasonable alternative therapy., Conclusions: Despite problems associated with microbial persistence and relapses in other forms of human listeriosis, antimicrobial therapy alone may be a successful treatment for listerial endocarditis, including cases occurring on prosthetic valves. Valve replacement may be reserved for complicated cases with valve dehiscense, cardiac failure or myocardial abscess. Overall mortality was 35.3%, although most patients who died did so before 1985 and since then mortality has been significantly reduced to 12%.