Inma Ocaña

Raltegravir, etravirine, and ritonavir-boosted darunavir: a safe and successful rescue regimen for multidrug-resistant HIV-1 infection.

Background:Boosted darunavir (DRV/r) plus etravirine (ETR), in DUET trials, and raltegravir, in BENCHMRK trials, showed high rates of virologic response in patients with multidrug-resistant HIV-1 infection, particularly when associated with two more fully active antiretroviral drugs. No data from clinical trials, about this combination, are available. Patients and Methods:Thirty-two consecutive heavily pretreated patients with multidrug-resistant HIV-1 infection who started a new salvage regimen with RAL (400 mg twice daily), ETR (200 mg twice daily), and DRV/r (600/100 mg twice daily) were studied. Clinical evaluation and immunologic, virologic, and biochemical parameters were collected at baseline and at Weeks 4, 12, and 24. Results:Median baseline characteristics were age 44 years, 13 years on antiretroviral therapy, nine prior highly active antiretroviral therapy regimens, 261 CD4 cells/mL, and HIV-1 RNA 4.2 log10 copies/mL. Sixteen (50%) and 14 (44%) patients were enfuvirtide- and tipranavir-experienced, respectively. Three-class resistance mutations were present in all patients. Three patients (9%) had isolates with three ETR resistance mutations. All patients were DRV-naïve with a median of one DRV resistance mutation. At Weeks 4, 12, and 24, respectively, 63%, 81%, and 94% of patients achieved HIV1-RNA less than 50 copies/mL. Median CD4 cell count increased 30, 73, and 103 cells/mL at Weeks 4, 12, and 24, respectively. No patient had adverse events leading to discontinuation of the regimen. Conclusion:The combination of raltegravir, ETR, and DRV/r was a highly effective and well-tolerated antiretroviral salvage regimen in patients infected with multidrug-resistant HIV-1.

Adenosine deaminase activity in the diagnosis of lymphocytic pleural effusions of tuberculous, neoplastic and lymphomatous origin

We studied the activity of adenosine deaminase in 74 lymphocytic pleural effusions which were divided into four groups according to the aetiology: tuberculous (38 cases), neoplastic (17), lymphomatous (7) and miscellaneous (12). The mean enzyme value was significantly higher in the tuberculous cases (93.81 +/- 29.56 U/I) than for the other three groups and significantly higher in pleural effusions of lymphomatous origin than in the neoplastic and miscellaneous groups. Based on the lowest value of enzyme activity found in the tuberculous group (50 U/I), the test had a sensitivity of 1 and a specificity of 0.97.

Epidemiological characteristics and predictors of late presentation of HIV infection in Barcelona (Spain) during the period 2001-2009

BackgroundEarly diagnosis of HIV infection can prevent morbidity and mortality as well as reduce HIV transmission. The aim of the present study was to assess prevalence, describe trends and identify factors associated with late presentation of HIV infection in Barcelona (Spain) during the period 2001-09.MethodsDemographic and epidemiological characteristics of cases reported to the Barcelona HIV surveillance system were analysed. Late presentation was defined for individuals with a CD4 count below 350 cells/ml upon HIV diagnosis or diagnosis of AIDS within 3 months of HIV diagnosis. Multivariate logistic regression were used to identify predictors of late presentation.ResultsOf the 2,938 newly diagnosed HIV-infected individuals, 2,507 (85,3%) had either a CD4 cell count or an AIDS diagnosis available. A total of 1,139 (55.6%) of the 2,507 studied cases over these nine years were late presenters varying from 48% among men who have sex with men to 70% among heterosexual men. The proportion of late presentation was 62.7% in 2001-2003, 51.9% in 2004-2005, 52.6% in 2006-2007 and 52.1% in 2008-2009. A decrease over time only was observed between 2001-2003 and 2004-2005 (p = 0.001) but remained constant thereafter (p = 0.9). Independent risk factors for late presentation were older age at diagnosis (p < 0.0001), use of injected drugs by men (p < 0.0001), being a heterosexual men (p < 0.0001), and being born in South America (p < 0.0001) or sub-Saharan Africa (p = 0.002).ConclusionLate presentation of HIV is still too frequent in all transmission groups in spite of a strong commitment with HIV prevention in our city. It is necessary to develop interventions that increase HIV testing and facilitate earlier entry into HIV care.

Utility of week-4 viral response to tailor treatment duration in hepatitis C virus genotype 3/HIV co-infected patients.

Objective:To investigate the utility of a week-4 virological response for sustained response prediction in hepatitis C virus (HCV) genotype 3/HIV-co-infected patients treated with interferon and ribavirin for 24 weeks. Methods:Using a real-time polymerase chain reaction-based quantitative assay (COBAS AmpliPrep-COBAS-TaqMan 48; Roche Diagnostics) we retrospectively analysed samples obtained at baseline and weeks 4 and 12 from a subset of 35 HCV genotype 3-HIV co-infected patients enrolled in a randomized comparative trial of peginterferon α-2b versus interferon α-2b both in combination with ribavirin. Results:In an intention-to-treat analysis, 78% of patients treated with peginterferon and 53% of those receiving standard interferon achieved a sustained virological response (SVR) Overall, at 4 weeks, 49% of patients had HCV RNA < 50 IU/ml and 63% had < 600 IU/ml. Of these rapid responders 88 and 86% achieved a SVR, respectively, with only one patient relapsing among end-of-treatment responders. In contrast, only 44 and 31% of patients with a week-4 HCV RNA ≥ 50 or ≥ 600 IU/ml achieved an SVR, respectively, with relapse rates of 33 and 50%, respectively. In multivariate logistic regression analysis a serum HCV RNA level below 600 IU/ml at week 4 was the strongest independent predictor of SVR (odds ratio, 11.3; 95% confidence interval, 1.7 to 75.0; P = 0.012). Conclusion:Monitoring early viral response may be useful to tailor the duration of treatment among patients with HCV genotype 3/HIV-co-infection. Patients whose HCV RNA falls below 600 IU/ml at 4 weeks are at low risk of relapse after 24 weeks of combination therapy.

Diagnostic value of ascites gamma interferon levels in tuberculous peritonitis. Comparison with adenosine deaminase activity

The value of ascites gamma interferon concentration and ascites adenosine deaminase activity in distinguishing tuberculosis from other causes of ascites was examined in a prospective study of 86 patients with ascites, including 16 with tuberculous peritonitis. Gamma interferon concentration was higher in tuberculous peritonitis than in the other causes of ascites (p less than 0.0001), and a cut-off between 3 and 9 u/ml reached a sensitivity and a specificity of 100%. The mean (+/- SD) gamma interferon level in tuberculous ascites was 39.3 +/- 18.3 u/ml in patients seronegative for HIV and 14.2 +/- 4.7 u/ml in patients with AIDS (p = 0.01). Adenosine deaminase activity in tuberculous ascites was also higher than in the other causes of ascites (p less than 0.0001), and a cut-off of 40 u/l reached a sensitivity of 100% and a specificity of 97%. The two false positives for adenosine deaminase test were true negatives for the gamma interferon test. There was no significant correlation between gamma interferon concentration and adenosine deaminase activity either in tuberculous ascitis or in any other group. This study suggests that ascites gamma interferon determination may be very useful in the screening of tuberculous peritonitis, but its cost makes it advisable to use adenosine deaminase activity as a routine test, at least in areas where tuberculosis is endemic.

Response-Guided Therapy for Chronic Hepatitis C Virus Infection in Patients Coinfected with HIV: A Pilot Trial

BACKGROUND To study the feasibility of a response-guided therapy for chronic hepatitis C virus (HCV) infection in patients coinfected with human immunodeficiency virus (HIV) in a tertiary care hospital. METHODS Treatment duration was individualized on the basis of week 4 and week 12 virologic response. Sixty patients were enrolled and received pegylated interferon alfa-2b (1.5 microg/kg per week) plus weight-based ribavirin (800-1400 mg/day). Patients who achieved a rapid virologic response, defined as viral load <50 IU/mL at treatment week 4, completed 24 weeks of therapy. Patients who did not achieve a rapid virologic response were reassessed at treatment week 12. Patients with a complete early virologic response, defined as an HCV RNA level <600 IU/mL, were treated for 48 weeks. Patients with a partial response, defined as a decrease in the viral load > or = 2 log10 and an HCV RNA level > or = 600 IU/mL, who attained an undetectable viral load at week 24 were treated for 60 weeks. The primary efficacy end point was sustained virologic response, defined as HCV RNA <50 IU/mL, 24 weeks after the end of treatment. RESULTS Overall, 33 (55%) of 60 patients achieved a sustained virologic response: 11 (44%) of 25 patients with HCV genotype 1, 3 (27%) of 11 patients with genotype 4, and 19 (79%) of 24 patients with genotype 3. One-third of patients showed a rapid virologic response. Of patients with genotype 1, there was a rapid virologic response in 4 (16%) of 25; with genotype 4, in 1 (9%) of 11; and with genotype 3, in 14 (58%) of 24. Of the 19 patients with a rapid virologic response, 17 (89.5%) eradicated the virus after 24 weeks of therapy. The rate of sustained virologic response was significantly higher among patients with genotype 3 and low pretreatment HCV RNA levels. A high relapse rate (46%) after 48 weeks of therapy occurred among patients infected with genotypes 1 or 4 who first achieved undetectable viral load at treatment week 12. CONCLUSION A response-guide therapy is feasible and may be useful to optimize the individual outcome of HCV treatment in patients coinfected with HIV.

Efficacy, safety and pharmacokinetics of 900/100 mg of darunavir/ritonavir once daily in treatment-experienced patients

OBJECTIVES To evaluate the virological efficacy, safety, tolerability and pharmacokinetics of a regimen containing 900/100 mg of ritonavir-boosted darunavir once daily in patients with antiretroviral experience but no darunavir resistance. PATIENTS AND METHODS An observational, prospective, multicentre study was conducted. Patients were included if 900/100 mg of darunavir/ritonavir once daily and at least one other active drug had been started due to virological failure, simplification or toxicity. Minimum follow-up was 24 weeks, or less if there was premature discontinuation of any drug or loss to follow-up. In a subgroup of patients, a complete 24 h pharmacokinetic study was performed by HPLC. RESULTS One hundred and three patients (47 switch strategies, 56 early salvage therapies) were included. After 6 months, 85/103 (83%; 95% CI: 74%-89%) and 85/93 (91%; 95% CI: 84%-97%) patients had <50 copies/mL HIV-RNA by intention-to-treat and on-treatment analyses, respectively. The respective values were 42/47 (89%; 95% CI: 72%-96%) and 42/43 (98%; 95% CI: 88%-100%) in switch therapy, and 43/56 (77%; 95% CI: 64%-87%) and 43/50 (86%; 95% CI: 73%-94%) in salvage therapy. There was a significant increase in CD4 cell counts [+73 cells/mm(3) (95% CI: 43%-102%), P<0.001]. There were no interruptions due to rash or liver toxicity. Significant decreases in cholesterol and triglycerides were seen in patients with abnormal lipids at baseline. Ten patients discontinued antiretrovirals (5 were lost to follow-up and 5 due to side effects). Twenty-five patients were included in the pharmacokinetic study. All patients had trough plasma concentrations >0.05 μg/mL. CONCLUSIONS Darunavir/ritonavir at 900/100 mg once daily is highly effective, safe and well tolerated in treatment-experienced patients with no darunavir resistance, both in early salvage and switch strategies. Adequate drug plasma levels were achieved in all patients.

Neurological opportunistic infections and neurological immune reconstitution syndrome: impact of one decade of highly active antiretroviral treatment in a tertiary hospital.

Despite the reported decrease in the incidence and mortality rates of central nervous system (CNS) infections after the introduction of highly active antiretroviral therapy (HAART), few studies have focused on the global incidence and the relationship of these diseases with immune reconstitution inflammatory syndrome (IRIS) in the developed world.

Epidemiology and long-term survival in HIV-infected patients with Pneumocystis jirovecii pneumonia in the HAART era: experience in a university hospital and review of the literature.

AbstractAs highly active antiretroviral treatment (HAART) is widely available, the incidence of Pneumocystis jirovecii pneumonia (PJP) has decreased significantly but still represents a significant cause of morbidity and mortality in developed countries.We analyzed all the cases with PJP in human immunodeficiency virus (HIV)-infected patients from 2000 to 2013 in a university hospital in Barcelona, Spain, and conducted a systematic literature review to evaluate data regarding incidence, mortality, and long-term survival after PJP in developed settings.One hundred thirty-six episodes of PJP were analyzed. During the study period, the incidence decreased significantly (from 13.4 cases/1000 patients-year to 3.3 cases/1000 patients-year, P < 0.001). Oppositely, median age of the patients increased from 34 years in 2000 to 45 in 2013 (P = 0.024). PJP preceded HIV diagnosis in nearly 50% of the cases. Fifteen (11%) patients died during the PJP episode. The main risk factor for in-hospital mortality in our cohort was age >50 years (odds ratio 4.96, 95% confidence interval [CI] 1.45–15.14). Patients who survived were followed-up during a mean time of 44 months. Overall 5-year survival of patients after hospital discharge was 73%. Survival likelihood was 54% higher (88% [95% CI 81–96]) among HAART-adherent patients.Mean age and the proportion of patients with unknown HIV infection at the time of PJP diagnosis have increased in developed countries in the HAART era. Although the incidence has decreased, in-hospital mortality remains stable in this setting. Long-term survival is very high among HAART-adherent patients.

The effectiveness of electrocautery ablation for the treatment of high-grade anal intraepithelial neoplasia in HIV-infected men who have sex with men.

Electrocautery is one of the main treatment options for high‐grade anal intraepithelial neoplasia (HGAIN). However, data regarding its efficacy are scarce. The aim of the study was to evaluate the effectiveness of electrocautery for the treatment of HGAIN.