Manuel Torres-Tortosa

Efficacy of pegylated interferon plus ribavirin treatment in HIV/hepatitis C virus co-infected patients receiving abacavir plus lamivudine or tenofovir plus either lamivudine or emtricitabine as nucleoside analogue backbone

OBJECTIVES To compare the response to hepatitis C virus (HCV) therapy among human immunodeficiency virus (HIV)/HCV co-infected patients receiving a nucleos(t)ide reverse transcriptase inhibitor [N(t)RTI] backbone consisting of abacavir plus lamivudine with that observed in subjects who receive tenofovir plus lamivudine or emtricitabine. METHODS A total of 256 subjects, enrolled in a cohort of 948 HIV-infected patients who received pegylated interferon and ribavirin from October 2001 to January 2006, were included in this study. All patients were taking one protease inhibitor or one non-nucleoside reverse transcriptase inhibitor and abacavir plus lamivudine or tenofovir plus lamivudine or emtricitabine as N(t)RTI backbone during HCV therapy. Sustained virological response (SVR) rates in both backbone groups were compared. RESULTS In an intention-to-treat analysis, 20 out of 70 (29%) individuals under abacavir and 83 out of 186 (45%) under tenofovir showed SVR (P = 0.02). N(t)RTI backbone containing tenofovir was an independent predictor of SVR in the multivariate analysis [adjusted odds ratio (95% CI), 2.6 (1.05-6.9); P = 0.03]. The association between abacavir use and lower SVR was chiefly seen in patients with plasma HCV-RNA load higher than 600 000 IU/mL and genotype 1 or 4. Among patients treated with ribavirin dose <13.2 mg/kg/day, 3 (20%) of those under abacavir versus 22 (52%) under tenofovir reached SVR (P = 0.03), whereas the rates were 31% and 38% (P = 0.4), respectively, in those receiving >/=13.2 mg/kg/day. CONCLUSIONS HIV-infected patients who receive abacavir plus lamivudine respond worse to pegylated interferon plus ribavirin than those who are given tenofovir plus lamivudine or emtricitabine as N(t)RTI backbone, especially in those receiving lower ribavirin doses.

Epidemiological, Clinical, and Prognostic Differences between the Diseases Caused by Mycobacterium kansasii and Mycobacterium tuberculosis in Patients Infected with Human Immunodeficiency Virus: A Multicenter Study

A multicenter, comparative study was performed to determine the epidemiological, clinical, and prognostic differences between the diseases caused by Mycobacterium tuberculosis and Mycobacterium kansasii in human immunodeficiency virus (HIV)-infected patients. From 1 January 1995 through 31 December 1999, 25 HIV-infected patients received diagnoses of M. kansasii infection, and another 75 were selected as control subjects from among patients who had M. tuberculosis infection. Variables associated with M. tuberculosis disease in the multivariate analysis were previous intravenous drug use (odds ratio [OR], 8; 95% confidence interval [CI], 1.5-41.4) and interstitial radiologic pattern (OR, 12.7; 95% CI, 1.7-94.3). Variables associated with M. kansasii were previous diagnosis of acquired immunodeficiency syndrome (OR, 15.8; 95% CI, 4.2-59.6) and concomitant opportunistic infections (OR, 14.2; 95% CI, 2-105.7). Clinical and radiologic features were similar for both groups, but epidemiological characteristics and prognosis were different. M. kansasii disease was associated more closely with level of immunosuppression and progression of HIV infection than was disease caused by M. tuberculosis.

Haemophilus influenzae Pneumonia in Human Immunodeficiency Virus-Infected Patients

Although Haemophilus influenzae is a common etiologic agent of pneumonia in patients infected with human immunodeficiency virus (HIV), the characteristics of this pneumonia have not been adequately assessed. We have prospectively studied features of H. influenzae pneumonia in 26 consecutive HIV-infected inpatients. Most of these patients were severely immunosuppressed; 73.1% had a CD4+ cell count <100/microL. A subacute clinical presentation was observed in 27% of the patients and was associated with a higher degree of immunosuppression (P=.04). Bilateral lung infiltrates were noted radiographically in 57.7% of the cases. The mortality attributable to H. influenzae pneumonia was 11.5%. Thus, pneumonia caused by H. influenzae affects mainly patients with advanced HIV disease, and since its clinical and radiological features may be diverse, this etiology should be considered when pneumonia occurs in patients with advanced HIV infection. The mortality rate associated with H. influenzae pneumonia is not higher than that occurring in the general population.

Usefulness of Sputum Culture for Diagnosis of Bacterial Pneumonia in HIV-Infected Patients

Abstract.The use of sputum culture in immunocompetent patients with community-acquired pneumonia is controversial. The usefulness of this technique in HIV-infected patients has not been evaluated. A prospective, observational, multicenter, hospital-based study of bacterial community-acquired pneumonia was carried out to analyze the value of sputum culture in HIV-infected patients. Only good-quality sputum samples were cultured. Altogether, 355 cases of bacterial community-acquired pneumonia were included. An etiological diagnosis was obtained in 190 (53.5%) cases. Sputum was cultured in 313 (88.1%) cases, being diagnostic in 108 (34.5%). The microorganism identified in sputum culture was the same as that identified in sterile samples in 26 of 27 (96.3%) cases in which both cultures were diagnostic. The microbiologic findings in sputum and bronchoscopic cultures were concordant in seven of eight (87.5%) cases in which both were positive. These results suggest that sputum culture is a useful technique, given its availability and ease of performance and its good correlation with culture of sterile samples.

Simplicity and Efficacy of a Once-Daily Antiretroviral Regimen with Didanosine, Lamivudine, and Efavirenz in Naïve Patients: The VESD Study

Abstract Purpose: Our aim was to analyze the efficacy and safety of didanosine-lamivudine-efavirenz in a cohort of HIV patients starting antiretroviral therapy between January and September 2003. Method: We undertook a prospective, open-label, observational, multicenter study. Results: 163 patients were enrolled. Over a 48-week period, plasma HIV RNA levels declined sharply, with a median decrease at the end of the observation time of >4.62 log copies/mL. The proportion of patients achieving a plasma HIV RNA level below 50 copies/mL was 62.9% (intention-to-treat analysis) at the end of the study period. The mean CD4 cell count increased steadily over time by 199 cells/mL. Antiviral efficacy was similar in patients with a baseline HIV RNA level above or below 100,000 copies/mL. Overall, 57 (34.1%) patients interrupted therapy; 9 due to lack of treatment response, 18 due to adverse side-effects, and 30 patients lost to follow-up or who withdrew their consent. Adherence was very high (90%-95%) and quality of life was good or very good in 69%. Conclusion: The once-daily combination of didanosine-lamivudine-efavirenz resulted in sustained viral suppression and was well-accepted by patients under real-life conditions, even immunosuppressed patients and those with a high viral load. Associated adverse events and virological failures were few.

Efficacy and Safety of Pegylated Interferon plus Ribavirin in HIV and Hepatitis C Virus-Coinfected Patients with Advanced Immunosuppression

BACKGROUND The aim of this study was to assess the efficacy and safety of pegylated interferon (IFN) plus ribavirin (RBV) in human immunodeficiency virus (HIV) and hepatitis C virus (HCV)-coinfected patients with severe immunodeficiency in a clinical cohort. BACKGROUND. A total of 542 HIV-infected patients receiving treatment with pegylated IFN plus RBV from June 2001 through April 2007 were included in this study. The outcome variables were sustained virologic response (SVR) rate and the emergence of AIDS-defining events during HCV infection therapy. SVR rates among patients with a CD4 cell count <or=250 cells/mm(3) at baseline were compared with those among patients with CD4 cell counts >250 cells/mm(3). The association between SVR and potential predictors was analyzed. RESULTS Ten (26%) of 39 individuals with a baseline CD4 cell count 250 cells/mm(3) and 198 (39%) of 503 with baseline CD4 cell counts >or=250 CD4 cells/mm(3) achieved SVR (P = .09). In a nested case-control study with populations matched at a 1:2 ratio, the SVR rate was 26% in the CD4 cell count 250 cells/mm(3) group and 32% in the CD4 cell count >250 cells/mm(3) group (P = .5). Baseline CD4 cell count (250 cells/mm(3) vs >250 cells/mm(3)) was not associated with SVR in the multivariate analysis. Two (5%) individuals in the CD4 cell count 250 cells/mm(3) group experienced opportunistic events during follow-up. In the CD4 cell count 250 cells/mm(3) group, severe hematological toxicity and pegylated IFN or RBV dosage reductions occurred in 16 (41%) and 12 (31%) patients, respectively. In the CD4 cell count >250 cells/mm(3) group, severe hematological toxicity and pegylated IFN or RBV dosage reductions occurred in 29% (P = .1) and 20% (P = .1) of patients, respectively. CONCLUSIONS The efficacy of pegylated IFN plus RBV in HIV-HCV-coinfected patients with advanced immunosuppression is substantial and not significantly different to that observed in the overall coinfected population. HCV therapy is generally safe in the population of coinfected patients with advanced immunosuppression.

Nevirapine-based antiretroviral therapy is associated with lower plasma hepatitis C virus viral load among HIV/hepatitis C virus-coinfected patients.

1Unidad de Enfermedades Infecciosas, Hospital Universitario de Valme, Sevilla, Spain 2Servicio de Medicina Interna, Hospital Universitario de Valme, Sevilla, Spain 3Seccion de Enfermedades Infecciosas, Hospital Universitario Reina Sofia, Cordoba, Spain 4Servicio de Enfermedades Infecciosas, Hospital Universitario Virgen del Rocio, Sevilla, Spain 5Seccion de Enfermedades Infecciosas, Hospital Punta de Europa, Algeciras, Spain 6Servicio de Medicina Interna, Hospital Juan Ramon Jimenez, Huelva, Spain 7Unidad de Enfermedades Infecciosas, Servicio de Medicina Interna, Hospital Universitario Virgen de la Victoria, Malaga, Spain 8Unidad de Enfermedades Infecciosas, Hospital Universitario Virgen Macarena, Sevilla, Spain 9Unidad de Enfermedades Infecciosas, Complejo Hospitalario de Jaen, Jaen, Spain 10Grupo HEPAVIR de la Sociedad Andaluza de Enfermedades Infecciosas (SAEI)

Etiology of spontaneous pneumothorax in 105 HIV-infected patients without highly active antiretroviral therapy.

INTRODUCTION Spontaneous pneumothorax (SP) is a frequent complication in non-treated HIV-infected patients as a complication of opportunistic infections and tumours. OBJECTIVE To analyse the aetiology of SP in non-treated HIV patients. PATIENTS AND METHODS Observational study of SP cases observed in a cohort of 9831 of non-treated HIV-infected patients attended in seven Spanish hospitals. RESULTS 105 patients (1.06%) developed SP. The aetiological cause was identified in 89 patients. The major causes identified were: bacterial pneumonia (36 subjects, 34.3%); Pneumocystis jiroveci pneumonia (PJP) (31 patients, 29.5%); and pulmonary tuberculosis (17 cases, 15.2%). The most common cause of SP in drugs users was bacterial pneumonia (40%), whereas PJP was more common (65%) in sexual transmitted HIV-patients. The most common cause of bilateral SP was PJP (62.5%) whereas unilateral SP was most commonly associated with bacterial pneumonia (40.2%). The most common cause of SP in patients with a CD4+ lymphocyte count >200 cells/ml and in patients without AIDS criteria was bacterial pneumonia. PJP was the more common cause in patients with a CD4+ lymphocyte count <200 cells/ml or with AIDS. CONCLUSION The incidence of SP in non-treated HIV-infected patients was 1.06%. The aetiology was related to the patients risk practices and to their degree of immunosuppression. Bacterial pneumonia was the most common cause of SP.

Prognostic Evaluation of Bacteremia and Fungemia in Patients with Acquired Immunodeficiency Syndrome

Abstract.The incidence of bacterial infections in general and of bacteremia in particular is high among patients with acquired immunodeficiency syndrome (AIDS). The factors influencing the prognosis of bacteremia in these patients are not well known. In order to better define those factors associated with a poor prognosis, all episodes of bacteremia or fungemia in patients with AIDS who were hospitalized in four general hospitals between 1 September 1987 and 31 December 1996 were studied prospectively. Among 1,390 patients diagnosed with AIDS, 238 (17.1%) developed 274 episodes of bacteremia or fungemia. Mortality related to bacteremia was 21.3%. Variables associated with high mortality were fungemia (odds ratio [OR], 6.19; 95% confidence interval [CI], 1.99–19.28), hypotension (OR, 19.65; 95%CI, 7.42–52.07), inappropriate antimicrobial treatment (OR, 16.94; 95%CI, 4.92–58.32), and unknown origin of bacteremia (OR, 3.93; 95%CI, 1.58–9.76). The mortality rate among patients with at least one of these factors was 46.7%, whereas in patients without any of these factors, the rate was 4.9% (P<0.001). Bacteremic episodes of unknown origin were significantly more frequently associated with community acquisition (P=0.001), inappropriate antimicrobial treatment (P=0.04), and etiology by gram-negative microorganisms or fungi (P<0.001) and were significantly less frequently associated with the presence of a previous intravenous catheter (P=0.004), resulting in peculiar etiologic and epidemiological profiles. The factors that influence the outcome of AIDS patients who develop bacteremia are sometimes avoidable or known during the first days after admission. Therefore, knowledge about these factors could improve the prognosis of bloodstream infections in this population.

Antimicrobial therapy for anthrax

Kaya et al. [1] performed an interesting study of 132 patients diagnosed with cutaneous anthrax. They asserted that penicillin is the therapy of choice for anthrax. However, recent evidence and recommendations indicate this is not entirely so, particularly for patients with severe forms of the disease. In a recent update from the Centers for Disease Control and Prevention (Atlanta, GA, USA) [2] it was reported that even naturally occurring strains of Bacillus anthracis may produce inducible cephalospirinases and penicillinases. In a series of 10 cases of inhalational anthrax, possibly related to bioterrorism, six patients were cured [3]. This survival rate, which was higher than that described previously [4, 5], was attributed to the use of combined therapy with a fluoroquinolone plus another antimicrobial agent active against the respective strains. In 2001, Mayer et al. [6] described two patients diagnosed with inhalational anthrax who were cured after being treated with ciprofloxacin, rifampin and clindamycin soon after admission. The rationale for this regimen was as follows: (i) ciprofloxacin was considered to be the therapy of choice against Bacillus anthracis; (ii) the intracellular action of rifampin was considered valuable; and (iii) clindamycin was thought to have potential additional value due to its antitoxin activity. The last point has previously been demonstrated for streptococcal infections [7]. Thus, ciprofloxacin or doxycycline have recently been recommended as the antimicrobial agents of choice for cases of inhalational anthrax or for other forms with systemic involvement, and one or two antimicrobial agents active against the isolated strains should be added [2, 8]. In such cases, monotherapy with penicillin is not currently recommended [2]. To illustrate this point, a farmer who was admitted to a hospital in Spain with meningitis and cutaneous anthrax was treated with penicillin G (24 millionU/day) and died 1 week later. Afterwards, grampositive bacilli were shown in leptomeninges as well as in both lungs [9]. Thus, although nonsevere cases of cutaneous anthrax may be cured with penicillin, the agents ciprofloxacin or doxycycline should also be recommended as options for initial treatment [2, 8].