Boceprevir plus pegylated interferon/ribavirin to re-treat hepatitis C virus genotype 1 in HIV-HCV co-infected patients: final results of the Spanish BOC HIV-HCV Study.

INTRODUCTION: Boceprevir (BOC) was one of the first oral inhibitors of hepatitis C virus (HCV) NS3 protease to be developed. This study assessed the safety and efficacy of BOC+pegylated interferon-α2a/ribavirin (PEG-IFN/RBV) in the retreatment of HIV-HCV co-infected patients with HCV genotype 1. METHODS: This was a phase III prospective trial. HIV-HCV (genotype 1) co-infected patients from 16 hospitals in Spain were included. These patients received 4 weeks of PEG-IFN/RBV (lead-in), followed by response-guided therapy with PEG-IFN/RBV plus BOC (a fixed 44 weeks was indicated in the case of cirrhosis). The primary endpoint was the sustained virological response (SVR) rate at 24 weeks post-treatment. Efficacy and safety were evaluated in all patients who received at least one dose of the study drug. RESULTS: From June 2013 to April 2014, 102 patients were enrolled, 98 of whom received at least one treatment dose. Seventy-three percent were male, 34% were cirrhotic, 23% had IL28b CC, 65% had genotype 1a, and 41% were previous null responders. The overall SVR rate was 67%. Previous null-responders and cirrhotic patients had lower SVR rates (57% and 51%, respectively). Seventy-six patients (78%) completed the therapy scheme; the most common reasons for discontinuation were lack of response at week 12 (12 patients) and adverse events (six patients). CONCLUSIONS: Response-guided therapy with BOC in combination with PEG-IFN/RBV led to an overall SVR rate of 67%, but an SVR rate of only 51% in patients with cirrhosis. The therapy was generally well tolerated. Although the current standards of care do not include BOC+PEG-IFN/RBV, the authors believe that this combination can be beneficial in situations where new HCV direct antiviral agent interferon-free therapies are not available yet.

Minimum spread of the new Swedish variant of Chlamydia trachomatis and distribution of C. trachomatis ompA genotypes in three geographically distant areas of Spain, 2011-2012.

PURPOSE: The aim of this study was to determine the presence of the new Swedish Chlamydia trachomatis (C. trachomatis) variant (nvCT) and the distribution of C. trachomatis ompA genotypes in three geographically distant regions of Spain. METHODS: The genotypes of strains causing 624 episodes of infection (January 2011-September 2012) were studied using a nested PCR that amplifies a fragment of the ompA gene, followed by sequencing. To detect nvCT, a real-time PCR was used that amplifies a fragment of the cryptic plasmid with a 377 base pair deletion, which identifies the nvCT. RESULTS AND CONCLUSION: The ompA genotype was identified in 565 (90.5%) episodes. Eleven genotypes were detected, of which nine were found in all three regions. Only one nvCT strain was detected (0.4%), despite the predominance of genotype E (41%). Other frequent genotypes were genotypes D (19%), F (13%), G (11 %), and J (7%). Genotype L2b, causing lymphogranuloma venereum, was detected in men who have sex with men (MSM) in all three regions. Genotypes E and F were more frequent in women and heterosexual men, and genotypes D, G, J and L2b in MSM. In men, the main factor causing differences in the distribution of C. trachomatis was sexual behavior (MSM versus heterosexual men), while the distribution of C. trachomatis genotypes was similar in women and heterosexual men.

Pegylated interferon {alpha}2a plus ribavirin versus pegylated interferon {alpha}2b plus ribavirin for the treatment of chronic hepatitis C in HIV-infected patients.

OBJECTIVES: The two currently available types of pegylated interferon (peg-IFN) used to treat hepatitis C have different pharmacokinetic properties. It is unclear how these differences affect response to therapy. We compared the effectiveness and safety of peg-IFN-alpha2a and peg-IFN-alpha2b, both with ribavirin, against chronic hepatitis C virus (HCV) infection in HIV-infected patients. METHODS: From the GESIDA HIV/HCV cohort, we analysed patients treated with peg-IFN-alpha2a (n = 315) or peg-IFN-alpha2b (n = 242). The primary endpoint was a sustained virological response (SVR). RESULTS: Both groups were well matched in baseline characteristics except for a higher frequency of injection drug users in the peg-IFN-alpha2b group than in the peg-IFN-alpha2a group (85% versus 76%; P = 0.01) and a higher frequency of bridging fibrosis and cirrhosis (F3-F4) in the peg-IFN-alpha2b group than in the peg-IFN-alpha2a group (42% versus 33%; P = 0.04). End-of-treatment response was significantly lower among patients treated with peg-IFN-alpha2b [40% versus 52%; odds ratio (OR), 1.63; 95% confidence interval (95% CI), 1.16-2.29; P < 0.01]. However, no significant differences were found in SVR between patients treated with peg-IFN-alpha2b and those treated with peg-IFN-alpha2a (31% versus 33%; OR, 1.09; 95% CI, 0.75-1.59; P = 0.655). Therapy was interrupted due to adverse events in 33 (14%) patients treated with peg-IFN-alpha2b and 47 (15%) patients treated with peg-IFN-alpha2a. CONCLUSIONS: No differences in effectiveness and safety were found between peg-IFN-alpha2b and peg-IFN-alpha2a for the treatment of chronic HCV infection in HIV-infected patients.

Noninvasive diagnosis of liver fibrosis in patients with HIV infection and HCV/HBV co-infection.

The measurement of fibrosis stage critically affects the identification of the progression of liver disease, the establishment of a prognosis and therapeutic decision making. Liver biopsy has been the single, most useful method to determine the degree of liver fibrosis (LF), but with recognized limitations, mainly associated with its invasiveness. In recent years, alternative noninvasive methods have been developed, including imaging methods, such as transient elastometry, and assays based on serum biomarkers. This article reviews the available studies evaluating the value of various noninvasive methods for the assessment of LF in patients with HIV-infection and HBV/HCV co-infection, and makes recommendations on how to best use and combine them in clinical practice.

[Administration of granulocyte colony-stimulating factor in patients infected with human immunodeficiency virus and prolonged neutropenia]. / Administración de factor estimulante de colonias de granulocitos en pacientes con infección por el virus de la inmunodeficiencia humana y neutropenia prolongada.

BACKGROUND: Persistent neutropenia is frequent in HIV infected patients with severe immunodeficiency. G-CSF induces proliferation and differentiation of granulocyte precursors. Our objective has been to assess the response to G-CSF therapy on patients with advanced HIV disease and prolonged neutropenia. METHODS: A retrospective analysis of databases containing demographic information, analytic controls and hospitalizations related to neutropenia for patients attending our Infectious Diseases Unit from December 1, 1992 to January 30, 98. The episodes with absolute neutrophil counts lower than 1,000 x 10(6)/l at least during 7 days which descend below 500 x 10(6)/l at any moment were included. RESULTS: 36 episodes were included. 9 episodes started on treatment with G-CSF. The median duration was 9 (3-76) weeks. Hospitalization with fever related to neutropenia was significantly less frequent in episodes which received G-CSF (22.2%) than episodes without (66.7%). CONCLUSION: In this study, a significantly lower risk of hospitalization due to fever and neutropenia was associated with administration of G-CSF in patients with absolute neutrophil counts lower than 500 x 10(6)/l.

Candidal meningitis in HIV-infected patients: treatment with fluconazole.

Although mucocutaneous candidiasis is a common occurrence in HIV-infected patients, candidal meningitis is uncommon. We report 3 cases of candidal meningitis in HIV-positive patients, all intravenous drug abusers, and we discuss the clinical course and outcome, the treatment with fluconazole and possible prophylaxis.

AIDS-associated cholangiopathy in a series of ten patients.

OBJECTIVE: To present the clinical, biological, radiologic and cholangiographic findings in patients with clinical suspicion of AIDS associated cholangiopathy in our hospital. PATIENTS AND METHODS: We have revised the clinical charts of 10 patients admitted in our hospital from 1991 to 1995. RESULTS: Ultrasonography and/or abdominal CT were carried out on all the patients. Biliary tract dilatation was observed in 11 cases. From the 12 ERCP, biliary tract was fulfilled in 11. In 5 cases papillary stenosis was diagnosed, sclerosing cholangitis in 2, normal biliary tract in 3 and acute cholangitis in one case. Sphincterotomy was done in 5 patients, with clinical improvement. In one case, another sphincterotomy was needed because of reestenosis. CONCLUSIONS: ERCP is very important in the diagnosis of AIDS associated cholangiopathy. Endoscopic sphincterotomy relieves abdominal pain in these patients. Cholangiopathy occurs in very immunocompromised HIV positive patients. Survival is very short.

[The usefulness of the desensitization to rifampin in the treatment of mycobacterial disease in patients with AIDS]. / Utilidad de la desensibilización a rifampicina en el tratamiento de enfermedades producidas por micobacterias en pacientes con SIDA.

BACKGROUND: Hypersensitivity reactions to rifampin are relatively uncommon, but they may result in cessation of therapeutic medications. PATIENTS AND METHODS: We report our experience with oral desensitization protocol to rifampin in a group of 35 HIV-positive patients with mycobacterial disease who had some hypersensitivity reaction to this drug. RESULTS: Adverse reactions with this protocol were few and easily treated. CONCLUSIONS: Oral desensitization to rifampin is safe and effective, allowing some of these patients (60%) to reintroduce the drug and to reduce the time of treatment.

[Prospective 3-month study of intravascular catheter complications in HIV-infected patients: relation between phlebitis and infection]. / Estudio prospectivo de 3 meses sobre complicaciones de catéteres intravasculares en pacientes infectados por el HIV: relación entre flebitis e infección.

BACKGROUND: The aim of this study was to evaluate the etiology of phlebitis (chemical or infectious) and the prevalence of infections related to intravascular catheters (IRIC) in patients with HIV infection admitted to a 22-bed Infectious Disease Unit with a high rate of HIV infection. MATERIAL AND METHODS: A 3-month prospective study from November 1, 1994 to January 31, 1995 was carried out following a formula for data collection of all the intravenous catheters used during that time period. Cultures of the catheters withdrawn on Wednesdays and those with signs of phlebitis were performed. RESULTS: One hundred fifty-two intravenous catheters in 71 patients with HIV infection with a mean age of 37 years (range: 21-73) and mean hospital stay of 10.2 days were reported. During the study period 42 phlebitis were produced, of which 37 catheters (7 central and 30 peripheral) were processed. Of the 37 phlebitis processed, 29 (78.9%) were considered to be of physiochemical origin. Of the 21 catheters withdrawn Wednesday, 18 were processed, 8 with phlogotic signs, 2 with IRCI, equivalent to 1.9 IRCI/100 days of catheterization. During the study period no local or severe systemic infections related to the catheter were reported. Staphylococcus epidermidis was the organism involved in all the cases of IRCI. CONCLUSIONS: Despite the high number of immunosuppressed patients in related to HIV infection, a greater incidence of IRCI was not found in these patients. The most frequent cause of phlebitis by catheter was of chemical origin.

[Pulmonary cavitation lesions in patients infected with the human immunodeficiency virus: an analysis of a series of 78 cases]. / Lesiones pulmonares cavitadas en los pacientes infectados por el virus de la inmunodeficiencia humana: análisis de una serie de 78 casos.

BACKGROUND: To assess the clinical, radiologic and microbiological features of lung cavitation and HIV infection. Evaluation of the differences related to this disease in the last years. PATIENTS AND METHODS: Retrospective review of all patients with lung cavitation and HIV infection admitted at our hospital from January 1989 until December 1994 and prospective study of all patients with the same characteristics during 1995 and 1996. Lung cavitation was defined as any parenchymal lesion, with air content, visible in a simple X-ray and greater than 1 cm of diameter. Criteria for confirmed, probable or possible diagnosis were defined. RESULTS: 78 cases of lung cavitation have been identified in 73 patients. The radiologic patterns included unilobar and multilobular involvement in 31 and 47 cases, respectively. Cavities were multiple and single in 40 and 38 cases respectively. Findings with fine needle aspiration biopsy (FNAB) were diagnostic in 11 out of 14 cases. A clinical diagnosis was performed in all 78 cases, with microbiological results in 69 cases (88.5%): Mycobacterium tuberculosis in 20, Pneumocystis carinii in nine, Pseudomonas aeruginosa in nine, Staphylococcus aureus in eight (5 endocarditis with cavitary septic emboli), Rhodococcus equi in six, P. aeruginosa and S. aureus in three, Salmonella enteritidis in three, Cryptococcus neoformans in two, Aspergillus fumigatus in two and others in 7 cases. Confirmed, probable and possible diagnosis was considered in 54, 15 and 9 cases, respectively. Thirteen episodes of spontaneous pneumothorax were found. CONCLUSIONS: The lung cavitation rate is low, compared with the number of admissions related to HIV infection; nevertheless, many of them are in close relationship with HIV infection, and most of them are caused by treatable infections. It is important to know the clinical and radiological characteristics, in order to establish an early diagnosis and an appropriate therapy. Pseudomonas aeruginosa is becoming an important cause of lung cavitation. In our series, spontaneous pneumo-thorax was not related to Pneumocystis carinii pneumonia in 61.5% of cases.

[Coinfection by mycobacteria in HIV-positive patients]. / Coinfección por micobacterias en pacientes HIV-positivos.

BACKGROUND: The aim of this study was to describe the clinical characteristics and therapeutic management of coinfection by mycobacteria in the authors hospital. METHODS: Two cases of coinfection detected in mixed cultures in agar 7H11 or simultaneous positive cultures in several evaluable clinical samples (blood cultures for MAI and M. kansasii and sputum or stools for M. tuberculosis). RESULTS: One coinfection by MAI and M. tuberculosis and another by MAI and M. kansasii in two severely immunosuppressed HIV positive patients with less than 0.010 CD4 lymphocytes/10(9)/l. The clinical manifestations were unspecific, with fever and deterioration of the general state predominating over the 30-45 days of evolution. One of the patients improved with treatment which, in both cases, included a macrolide. Survival was very short and death was by intercurrent causes. CONCLUSIONS: For the diagnostic of coinfection in severely immunosuppressed patients multiple organic samples should be taken and appropriately processed to detect the mixed cultures or the presence of different mycobacteria in different samples from the same patients. Although the diagnosis of the species is fundamental, the empiric treatment of a disease by mycobacteria in severely immunosuppressed patients should include at least: ethambutol and clarithromycin or azithromycin in addition to other first line tuberculostatic drugs until definitive identification.