Identification of recent HIV-1 infection among newly diagnosed cases in Catalonia, Spain (2006-08).

BACKGROUND: Quantification and description of patients recently infected by HIV can provide an accurate estimate of the dynamics of HIV transmission. Between 2006 and 2008 in Catalonia, we estimated the prevalence of recent HIV infection among newly diagnosed cases, described the epidemiological characteristics of the infection according to whether it was recent, long-standing or advanced, and identified factors associated with recent infection. METHODS: A Test for Recent Infection (TRI) was performed in serum samples from patients newly diagnosed with HIV. Two different TRI were used: the Vironostika-LS assay (January 2006-May 2007) and the BED-CEIA CEIA (June 2007 onwards). Samples were obtained within the first 6 months of diagnosis. Patients whose samples tested positive in the TRI were considered recently infected. RESULTS: Of 1125 newly diagnosed patients, 79.9% were men (median age, 35.4 years), 38.7% were born outside Spain, 48.9% were men who have sex with men (MSM) and 10.6% presented other sexually transmitted infections. The overall percentage of recent infection was 23.0%, which increased significantly, from 18.1% in 2006 to 26.2% in 2008. This percentage was higher for patients from South America (27.6%). Factors associated with recent infection were acquiring infection through sexual contact between MSM [odds ratio (OR) 2.0; 95% confidence interval (95% CI) 1.1-3.9], compared with acquiring infection through heterosexual relations and being under 30 years of age (OR 5.9; 95% CI 1.9-17.4), compared with being over 50 years of age. CONCLUSION: The highest percentage of recent infection was identified in MSM, suggesting either a higher incidence or a greater frequency of HIV testing. Information regarding testing patterns is necessary to correctly interpret data from recently infected individuals. Systems to monitor the HIV epidemic should include both parameters.

Prevalence of Transmitted Antiretroviral Resistance and Distribution of HIV-1Subtypes Among Patients with Recent Infection in Catalonia (Spain) between2003 and 2005

Los objetivos de este estudio fueron evaluar la prevalencia de las resistencias primarias transmitidas (RPT)y de subtipos de VIH-1 en pacientes recientemente infectados en Cataluña entre 2003 y 2005, y describirlas características de estos pacientes según la presencia o ausencia de RPT y el subtipo de VIH-1.Métodos: Después de la aplicación del algoritmo de pruebas serológicas para la seroconversión reciente al VIH (STARHS), alícuotas residuales de las muestras de suero de individuos recientemente infectados no tratados previamente con antirretrovirales fueron genotipados. Las secuencias FASTA se analizaron conel programa HIV db. Se utilizó el listado de mutaciones de la Organización Mundial de la Salud del 2009para estimar la prevalencia de resistencias transmitidas. Resultados: De 182 pacientes recientemente infectados, 14 (7,7%) presentaron RPT. Siete personas (3,8%)presentaban evidencias genotípica de RPT a los inhibidores de la transcriptasa inversa no análogos anucleósidos, 6 (3,3%) frente a inhibidores de la transcriptasa inversa análogos de nucleósidos, 3 (1,6%)frente a los inhibidores de la proteasa, y solo 2 personas (1,1%) presentaron RPT a más de una familia de medicamentos. Treinta y cinco (19,2%) pacientes estaban infectados con un subtipo no-B del VIH-1.Conclusión: Este es el primer estudio que estima la prevalencia de RPT en pacientes recientemente infectadosen Cataluña, y los resultados son similares a los de estudios realizados en otras regiones españolas. Para el adecuado seguimiento de estos parámetros es necesaria la vigilancia epidemiológica sistemática de las RPT (AU)

Objectives: The objectives of this study were to assess the prevalence of transmitted HIV-1 drug resistances(TDR) and HIV-1 subtypes in recently infected patients in Catalonia between 2003 and 2005 and to describe the characteristics of these patients according to the presence or absence of TDR and HIV-1subtype.Methods: After application of the Serological Testing Algorithm for Recent HIV Seroconversion (STARHS),residual aliquots of serum samples from recently infected antiretroviral-naïve individuals were genotyped. FASTA sequences were analyzed using the HIVDB Program. The World Health Organization 2009List of Mutations for Surveillance of Transmitted HIV-1 Drug Resistant HIV Strains was used to estimate the prevalence of TDR. Results: Of 182 recently infected patients, 14 (7.7%) presented TDR. Seven (3.8%) had genotypic evidence of TDR against non-nucleoside reverse transcriptase inhibitors, 6 (3.3%) against nucleoside reverse transcriptase inhibitors, 3 (1.6%) against protease inhibitors (PIs), and only 2 individuals (1.1%) presented TDR against more than one class of drugs. Thirty-five (19.2%) patients were infected with a non-B HIV-1subtype.Conclusion: This is the first study to estimate the prevalence of TDR in recently infected patients in Catalonia. The results are similar to those of studies performed in other Spanish regions. Correct monitoring of these parameters requires systematic epidemiologic surveillance of transmitted resistance (AU)

Prevalence of transmitted antiretroviral resistance and distribution of HIV-1 subtypes among patients with recent infection in Catalonia (Spain) between 2003 and 2005.

OBJECTIVES: The objectives of this study were to assess the prevalence of transmitted HIV-1 drug resistances (TDR) and HIV-1 subtypes in recently infected patients in Catalonia between 2003 and 2005 and to describe the characteristics of these patients according to the presence or absence of TDR and HIV-1 subtype. METHODS: After application of the Serological Testing Algorithm for Recent HIV Seroconversion (STARHS), residual aliquots of serum samples from recently infected antiretroviral-naïve individuals were genotyped. FASTA sequences were analyzed using the HIVDB Program. The World Health Organization 2009 List of Mutations for Surveillance of Transmitted HIV-1 Drug Resistant HIV Strains was used to estimate the prevalence of TDR. RESULTS: Of 182 recently infected patients, 14 (7.7%) presented TDR. Seven (3.8%) had genotypic evidence of TDR against non-nucleoside reverse transcriptase inhibitors, 6 (3.3%) against nucleoside reverse transcriptase inhibitors, 3 (1.6%) against protease inhibitors (PIs), and only 2 individuals (1.1%) presented TDR against more than one class of drugs. Thirty-five (19.2%) patients were infected with a non-B HIV-1 subtype. CONCLUSION: This is the first study to estimate the prevalence of TDR in recently infected patients in Catalonia. The results are similar to those of studies performed in other Spanish regions. Correct monitoring of these parameters requires systematic epidemiologic surveillance of transmitted resistance.

The Rose Bengal Test in human brucellosis: a neglected test for the diagnosis of a neglected disease.

Brucellosis is a highly contagious zoonosis affecting livestock and human beings. The human disease lacks pathognomonic symptoms and laboratory tests are essential for its diagnosis. However, most tests are difficult to implement in the areas and countries were brucellosis is endemic. Here, we compared the simple and cheap Rose Bengal Test (RBT) with serum agglutination, Coombs, competitive ELISA, Brucellacapt, lateral flow immunochromatography for IgM and IgG detection and immunoprecipitation with Brucella proteins. We tested 208 sera from patients with brucellosis proved by bacteriological isolation, 20 contacts with no brucellosis, and 1559 sera of persons with no recent contact or brucellosis symptoms. RBT was highly sensitive in acute and long evolution brucellosis cases and this related to its ability to detect IgM, IgG and IgA, to the absence of prozones, and to the agglutinating activity of blocking IgA at the pH of the test. RBT was also highly specific in the sera of persons with no contact with Brucella. No test in this study outperformed RBT, and none was fully satisfactory in distinguishing contacts from infected patients. When modified to test serum dilutions, a diagnostic titer >4 in RBT resulted in 87.4% sensitivity (infected patients) and 100% specificity (contacts). We discuss the limitations of serological tests in the diagnosis of human brucellosis, particularly in the more chronic forms, and conclude that simplicity and affordability of RBT make it close to the ideal test for small and understaffed hospitals and laboratories.

BrucellaCapt versus classical tests in the serological diagnosis and management of human brucellosis.

The BrucellaCapt test is an immunocapture agglutination test suggested as a possible substitute for the Coombs test in the diagnosis of human brucellosis. Here it is compared with classical tests using 321 samples from 48 patients with brucellosis (6.9 +/- 1.7 samples per patient), including 20 patients with focal disease and 8 patients with a total of 9 relapse episodes (mean follow-up, 18 months). The BrucellaCapt test was used according to the manufacturer's instructions, and we also used a variant of the BrucellaCapt test in which the microtiter plates were not coated with antibodies against total human immunoglobulin (BCAPV). The correlation between the BrucellaCapt and BCAPV tests was 0.982 (P < 0.001), with 260 coincident pairs of titers (81%). The areas under the receiver operating characteristic curve for the BrucellaCapt and BCAPV tests with respect to the Coombs test were 0.969 and 0.960, respectively. Upon admission, the BrucellaCapt, BCAPV, and Coombs tests and the microagglutination test (MAT) were positive for all cases: titers were 1/2,560 by the BrucellaCapt test, 1/2,560 by the BCAPV test, 1/1,280 by the Coombs test, and 1/320 by the MAT. The decreases in the BrucellaCapt and BCAPV titers over time were pronounced in comparison with the Coombs titers. Cumulative probabilities of persistence 12 months after therapy were as follows: 80% by the BrucellaCapt test, 80% by the BCAPV test, 87% by the Coombs test, and 35% by the MAT. Serological changes during relapse were detected in seven cases (88%) by the Coombs test, in five cases by the BrucellaCapt and BCAPV tests, and in three cases by the MAT. The BrucellaCapt test is a sensitive, specific, and simple test for routine use in human brucellosis. Similar results were obtained with the BCAPV test. However, in some cases of relapse and chronic forms of the disease, the slight changes observed in low-affinity antibodies alone are better detected by the Coombs test.

Efficacy and safety of pegylated interferon-alpha2b plus ribavirin for the treatment of chronic hepatitis C in HIV-infected patients.

Low response rates and concerns about safety have limited the implementation of treatment for chronic hepatitis C (CHC) in patients with HIV infection. The efficacy and safety of pegylated interferon (peg-IFN) plus ribavirin in HIV-infected patients with CHC were evaluated in a prospective, open-label, multicenter study. Sixty patients with persistently high transaminases, positive HCV-RNA, CD4 count > or = 300 cells/microl, and HIVRNA <10,000 copies/ml were included. Patients were given peg-IFN 80-150 microg/week plus ribavirin 800-1200 mg/day. Treatment was scheduled for 24 weeks for genotypes 2/3 and 48 weeks for genotypes 1/4. In an intent- to-treat analysis, 16 (26.7%) patients achieved a sustained virological response (SVR). Twenty patients (33.3%) discontinued treatment prematurely, but only in 10 (16.6%) was discontinuation due to adverse events. Negative predictive values for SVR on the basis of HCV-RNA decline between baseline and week 4 were 100% for 1- and 2-log10 fall, and positive predictive values were 40% and 58.3% for 1- and 2-log10 fall, respectively. CD4 fell by a median of 216 cells during treatment, but no HIV-associated complications occurred. In conclusion, treatment with peg-IFN alpha-2b plus ribavirin is safe and clears RNA-HCV in about one-quarter of HIV-infected patients with CHC. Efforts should be focused on optimizing management of side effects and counseling to improve adherence and to keep patients on treatment. Assessment of HCV-RNA at week 4 may help guide early therapeutic decision making.

Patient with hepatocellular carcinoma related to prior acute arsenic intoxication and occult HBV: epidemiological, clinical and therapeutic results after 14 years of follow-up.

Little is known about the long-term survivors of acute arsenic intoxication. We present here a clinical case report of a man with chronic hepatitis B virus (HBV) infection who developed hepatocellular carcinoma four years after acute arsenic poisoning. HBsAg was detected in serum in 1990 when he voluntarily donated blood. In 1991, the patient suffered from severe psychological depression that led him to attempt suicide by massive ingestion of an arsenic-containing rodenticide. He survived with polyneuropathy and paralysis of the lower limbs, and has been wheelchair-bound since then. During participation in a follow-up study conducted among HBV carriers, abdominal ultrasound detected a two-centimeter liver mass consistent with hepatocellular carcinoma. The tumor was confirmed by computed tomography (CT) and magnetic resonance image (MRI). Because of his significant comorbidity, the patient received palliative treatment with transarterial lipiodol chemoembolization (TACE) on three occasions (1996, 1997 and 1999). At his most recent visit in May 2005, the patient was asymptomatic, liver enzymes were normal and the tumor was in remission on ultrasound.

Cofactors associated with liver disease mortality in an HBsAg-positive Mediterranean cohort: 20 years of follow-up.

The risk of developing liver cancer in hepatitis B virus (HBV) carriers differs across geographical areas, suggesting that exposure to other risk factors may contribute to HBV-linked cancer risk. Our study estimates the mortality due to liver disease and the role of other risk factors in a Spanish HBV cohort. 2,352 hepatitis B surface antigen (HBsAg)-positive and 15,504 HBsAg-negative subjects were identified among blood donors during 1972-1985 and were followed until December 2000 through the Mortality Registry. Clinical examination and an epidemiological questionnaire were performed on 1,000 HBsAg-positive survivors during 1994-1996. In subjects deceased from liver disease, medical records were revised and relatives were interviewed. A nested case-control analysis was conducted comparing both groups. In HBsAg-positive men, an excess mortality from liver cancer [standardized mortality ratio (SMR): 14.1; 7.7-23.6], cirrhosis (SMR: 10.5; 7.0-15.1), haematological neoplasms (SMR: 3.2; 1.2-6.9) and AIDS was detected (SMR: 5.5; 2.2-11.4). In women, an excess was found for cirrhosis (SMR: 7.2; 1.4-21.1). Progression factors to liver disease were alcohol intake [odds ratio (OR): 6.3; 3.1-12.8], diabetes (OR: 3.6; 1.3-9.6), HBV replication (OR: 50.0; 14.9-167.3) and hepatitis C virus (HCV) infection (OR: 27.4; 7.1-107.7). In conclusion, in Spain after 20 years of follow-up, chronic HBV exposure appears as a major risk factor for liver cancer among men and for cirrhosis in both sexes. The risk of death from liver disease among HBV carriers with the presence of HBV replication, HCV, alcohol consumption and diabetes was significantly increased and suggests synergism among these exposures and HBV. Mortality from haematological neoplasms was detected and could be associated to HIV coinfection. These results support screening and adequate follow-up among HBsAg-positive subjects at high risk to develop liver disease, particularly when these risk cofactors are present.

Successful treatment with tenofovir in a child C cirrhotic patient with lamivudine-resistant hepatitis B virus awaiting liver transplantation. Post-transplant results.

Antiviral treatment can be complex in decompensated hepatitis B virus (HBV) cirrhosis because of potential emergence of lamivudine-resistant mutants and worsening liver function, and to multifactorial nephrotoxicity. Negative HBV-DNA status by hybridization before liver transplantation is a favorable prognostic factor. We present the case of a 54-year-old HBV+ liver transplantation candidate who, after testing negative for HBV-DNA, developed YMDD lamivudine-resistant mutants resulting in a deteriorated clinical condition. After 8 months of adefovir plus lamivudine double therapy, only partial response was achieved. Tenofovir was added to this regimen, and an early decline of HBV-DNA was seen at 4 weeks without adverse events. The patient underwent transplantation. At 21-month postoperative follow-up, the patient's outcome was excellent. Post-transplantation HBV prophylaxis, taking into account the prior development of mutants, consists of hepatitis B immunoglobulin plus lamivudine and adefovir. Tenofovir was well tolerated and produced a fast antiviral response, suggesting its potential value in combined antiviral treatment for liver transplantation candidates.

Long-term immune response after liver transplantation in patients with spontaneous or post-treatment HCV-RNA clearance.

Recurrent HCV infection after liver transplantation is universal and sustained clearance of HCV-RNA rarely occurs. The aim of this study was to characterize cell-mediated immunity and cytokine production in HCV-infected patients after liver transplant. The study included 6 pretransplantation patients (PT) and 15 liver transplanted patients, including 5 with spontaneous HCV-RNA clearance (SC group), 5 with sustained virological response after antiviral treatment (SVR group), and 5 no response (NR group). The control group included 5 HCV-RNA negative, anti-HCV negative healthy individuals. This study examines proliferative T-cell response and cytokine production (gamma-interferon and IL-10) after HCV specific and phytohemagglutinin (PHA) stimulation in cultured peripheral blood mononuclear cells (PBMCs) from each group. Multispecific proliferative responses to HCV antigens (mean Stimulation Index; SI) were higher in the SVR group (mean SI 7.4 +/- 2) and SC group, as compared with the NR group (P <.05, vs SVR) and PT group (P <.05, vs SVR and SC). After PHA stimulation, gamma-interferon levels were similar to controls (4330 +/- 640 pg/ml) in the SC (4474 +/- 300 pg/mL) and SVR groups (3647 +/- 300 pg/mL), but were significantly lower than controls in the PT (401 +/- 331 pg/mL; P <.02) and NR groups (546 +/- 360 pg/mL; P <.01). IL-10 production after PHA stimulation was similar in SC, SVR, and controls (647 +/- 279 pg/mL, 674 +/- 310 pg/mL and 841 +/- 294 pg/mL, respectively), but was lower in PT patients (232 +/- 94 pg/mL). The NR group showed high basal IL-10 production with little increase after stimulation. In conclusion, liver post-transplantation patients with spontaneous clearance of HCV-RNA and those with sustained viral response after therapy showed an immune response despite immunosuppression that might have contributed to their favorable outcome.

Infección por virus respiratorio sincitial en adultos ingresados por neumonía adquirida en la Comunidad / Respiratory syncytial virus infection in adults patients hospitalized with community-acquired pneumonia

Fundamento: Determinar la incidencia y distribución de la infección por el virus respiratorio sincitial en adultos ingresados por neumonía de la comunidad. Pacientes y métodos: Pacientes adultos no inmunodeprimidos, ingresados por neumonía de la comunidad en nuestro centro y estudiados de forma prospectiva. Como parte del protocolo diagnóstico, se realizaron serologías para virus respiratorio sincitial, con sueros de la fase aguda y de convalescencia, a los pacientes ingresados entre febrero de 1995 y mayo de 1997, y se compararon las características clínicas y epidemiológicas de los pacientes con y sin criterios serológicos de infección aguda por el virus respiratorio sincitial. Resultados: Se realizaron serologías en pareado para el virus respiratorio sincitial en 250 pacientes ingresados por neumonía de la comunidad. En la mayoría de ellos (97 por ciento) se detectó la presencia de anticuerpos IgG, pero sólo 17 pacientes (6,8 por ciento) tuvieron evidencia serológica de infección aguda, seroconversión en ocho e IgM positiva en nueve. Catorce pacientes (82 por ciento) con infección aguda ingresaron entre noviembre y mayo. Tres pacientes fueron diagnosticados de neumonía neumocócica, dos de neumonía por Legionella pneumophila y 12 de neumonía no filiada. No se observaron diferencias clínicas entre los pacientes con y sin infección aguda por el virus respiratorio sincitial, aunque aquellos con infección aguda presentaron afectación pulmonar bilateral con mayor frecuencia y entre ellos hubo una mayor proporción de neumonías no filiadas. Conclusiones: El virus respiratorio sincitial es causa de infección aguda entre los pacientes adultos ingresados por neumonía de la comunidad en nuestro medio, fundamentalmente entre los meses de noviembre y mayo. Deberían realizarse estudios dirigidos a dilucidar su papel como agente productor de neumonía en esta población (AU)