Juan Flores

Effects of Culture Filtrates of Rhizobacteria Isolated from Wild Lupine on Germination, Growth, and Biological Nitrogen Fixation of Lupine Seedlings

Abstract In order to select potential Plant Growth Promoting Rhizobacteria (PGPRs), a selection of strains from the predominant genera in the rhizosphere of four lupine species, based on genetic divergence criteria, carried out in a previous study, yielded 11 Aureobacterium (Aur), four Cellulomonas (Cell), two Arthrobacter (Arth), two Pseudomonas (Ps), and six Bacillus (Bc) strains. Cell‐free culture filtrates of each bacterium were assayed for effects on germination, growth, and biological nitrogen fixation (BNF) of Lupinus albus L. cv. Multolupa seeds or seedlings. Four (Aur 6, Aur 9, Aur 11, and Cell 1) of the twenty‐five strains assayed promoted germination. Aureobacterium 6 and Aur 9 also increased root surface, total nitrogen content, and BNF. As a result of the screening, and considering all the variables studied, Aur 6 can be considered a plant growth promoting rhizobacterium and is suitable for further field trials in other plants and in different production systems.

Safety of Switching Nevirapine Twice Daily to Nevirapine Once Daily in Virologically Suppressed Patients.

Background:The strategy of switching nevirapine (NVP) twice daily to once daily was evaluated. Methods:Forty-eight-week randomized, open, multicenter trial. Stable HIV-infected patients on NVP twice daily for >12-18 weeks with alanine aminotransferase (ALT) <2.5, the upper normal limit were randomized to continue their regimen or switch to NVP 400 mg once daily. Primary end point was the proportion of ALT/aspartate transaminase (AST) ≥grade 3. Results:Two hundred eighty-nine patients were included, mean CD4 620 cells per microliter. Noninferiority was demonstrated in the per protocol analysis, with 97.9% (once daily) and 99.3% (twice daily) of patients event free (difference, 1.4%; 95% confidence interval, −1.95% to 5.4%), whereas 81.8% vs. 93.8% were event free by intent-to-treat switch = toxicity analysis (difference, 12%; 95% confidence interval, 4.6% to 19.4%). Only 4 patients (3 once daily, 1 twice daily) had NVP-related grade 3/4 ALT/AST increases, but in 2 of them (once daily), transaminases decreased despite continuation with NVP. Two other once daily patients presented grade 3/4 ALT/AST increase due to well-documented acute hepatitis A virus or hepatitis C virus infection. Grade 2 ALT/AST increases occurred in 11.2% (once daily) vs. 10.3% (twice daily) of patients (P = 0.80). A larger number of once daily patients were lost to follow-up/violated protocol (15% vs. 5%). Conclusions:In patients on standard twice daily NVP-containing regimens for at least 12-18 weeks, per protocol analysis showed that switching to once daily NVP was not inferior to continued twice daily NVP in terms of the predefined noninferiority margin of 10% for hepatotoxicity.

Recomendaciones españolas sobre el uso adecuado de enfuvirtida

Enfuvirtide is a high-cost, parenterally administered drug commonly used in late phases of HIV infection, when its efficacy may be compromised. To optimize enfuvirtide use, consensus recommendations for this purpose have been formulated by 247 physicians attending patients with HIV infection in Spain. A literature review was performed in which grades of evidence and recommendations were defined according to the origin of the data (randomized clinical trials, non-randomized studies, expert opinion). Twenty-eight local consensus meetings were held between May and September 2005 to discuss the most important aspects related to the use of enfuvirtide, following a pre-established system used in all the meetings. The main conclusions were as follows: a) enfuvirtide use is often excessively delayed and is given to patients with little chance of treatment success; b) enfuvirtide is indicated in patients who require antiretroviral treatment and for whom an optimum treatment with three other fully effective drugs cannot be designed; c) the most important prognostic factor is the availability of at least one other completely active drug; d) there is no infallible method to avoid the development of local reactions, but measures are available to decrease their incidence and severity; and e) patient counseling and training for correct administration of the drug are essential to improve adherence, the repercussions of local reactions and, of course, the efficacy of the treatment.

Short-Term Effect of Ritonavir-Boosted Atazanavir in Hepatitis B and/or C Co-infected, Treatment-Experienced HIV Patients

Abstract Objective: To describe the short-term, liver safety, immunological, and virological outcome in HIV subjects according to their hepatitis co-infection status after switching to ritonavir-boosted atazanavir (ATV/r)-based therapy. Methods: Rates of treatment discontinuation, changes in liver enzyme values, viral load, and CD4+ T-cell counts responses from patients included in the Bristol-Myers Squibb Atazanavir Early Access Program (BMS ATV EAP) were evaluated in hepatitis C and/or B co-infected patients (co-infected) and non–co-infected. Results: A total of 304 subjects with known HCV and/or HBV status from 55 centers were included in the analysis: 180 co-infected and 124 HIV non–co-infected. Accumulated follow-up until study closure was 762 and 551 person-months in the co-infected and non–co-infected subjects, respectively. The proportion of discontinuations through Month 6 was 9.4% (co-infected) and 5.6% (non–co-infected). Discontinuations due to elevated liver enzymes [1.7% (co-infected) and 0% (non–co-infected)] and due to scleral icterus/jaundice [4.4% (co-infected) and 3.2% (non–co-infected)] were low and similar between groups. Only three subjects (1%) discontinued due to virological failure. Successful virological outcome (viral load <500 copies/mL or a decrease >1 log10) was observed in 74% of subjects in each group. CD4+ T-cell count changes were +51 (co-infected) and +53 cells/mm3 (non–co-infected). Conclusions: Short-term effectiveness and liver safety in HCV and or HBV co-infected patients changing to an ATV/r-based regimen was similar to that observed in non–co-infected patients.

Abacavir/lamivudine plus darunavir/ritonavir in routine clinical practice: a multicentre experience in antiretroviral therapy-naive and -experienced patients

OBJECTIVES To present clinical experience with a regimen including abacavir/lamivudine + darunavir/ritonavir in a cohort of HIV-1-infected patients. METHODS A retrospective, multicentre cohort study, including all consecutive adult HIV-1-infected patients who started abacavir/lamivudine + darunavir/ritonavir from April 2008 to December 2010 and had at least one follow-up visit. The primary endpoint was HIV-1 viral load (VL) <40 copies/mL at week 48. RESULTS One hundred and eighty-three patients (42 naive and 141 experienced) from 19 hospitals in Spain were studied. The median follow-up was 26.7 (0.5-58.6) months, 79.8% were men, the median age was 47.1 (21.4-80.5) years, 26.2% had AIDS and 38.8% were positive for hepatitis C virus. At baseline, the median CD4 count was 246 cells/mm(3) in naive patients and 393 cells/mm(3) in experienced patients and the median VL was 4.80 and <1.59 log copies/mL, respectively. At week 48, 81.8% of naive patients and 84.2% of experienced patients receiving the regimen reached a VL <40 copies/mL, whereas at 96 weeks this occurred in 90.5% and 92.8%, respectively. CD4 cell count increases at 48 and 96 weeks were +176.5 and +283.5 cells/mm(3) in naive patients and +74.9 and +93 cells/mm(3) in experienced patients, respectively. Overall, 86 (47%) patients discontinued the study regimen, in many cases possibly related to non-medical reasons, such as drug switches to reduce cost or changes in address due to economic constraints. Three patients died of causes unrelated to therapy and 19 (10.4%) discontinued the regimen due to adverse events. CONCLUSIONS In our cohort, abacavir/lamivudine + darunavir/ritonavir was safe, well tolerated and achieved high rates of virological suppression. In a proportion of patients, discontinuation of this effective regimen was possibly due to non-medical reasons.

Genotypic tropism testing in proviral DNA to guide maraviroc initiation in aviremic subjects: 48-week analysis of the PROTEST study

In a previous interim 24‐week virological safety analysis of the PROTEST study [ 1 ], initiation of Maraviroc (MVC) plus 2 nucleoside reverse‐transcriptase inhibitors (NRTIs) in aviremic subjects based on genotypic tropism testing of proviral HIV‐1 DNA was associated with low rates of virological failure. Here we present the final 48‐week analysis of the study.

Genotypic tropism testing of proviral DNA to guide maraviroc initiation in aviraemic subjects: 48‐week analysis of results from the PROTEST study

Maraviroc (MVC) is a suitable drug for aviraemic subjects on antiretroviral treatment (ART) developing toxicity. Its prescription requires prior tropism testing. It is unknown if proviral DNA genotypic tropism testing is reliable for guiding MVC initiation in aviraemic subjects, so this study was carried out to address this issue.

Interferon-free therapy for treating HCV in difficult-to-treat HIV-coinfected patients as implemented in routine medical practice

Background/aims: Data regarding the use of all-oral direct-acting antivirals in HIV/hepatitis C virus (HCV)-coinfected patients with advanced liver fibrosis are required, because they are generally under-represented in clinical trials. This study sought to evaluate the use of these drugs in a cohort of coinfected patients, mostly with factors that have previously been recognized as predictors of treatment failure. Methods: COINFECOVA-2 is an observational, multicenter study conducted in Eastern Spain. Data of all HIV/HCV-coinfected patients treated with direct-acting antiviral under real-life conditions were retrospectively collected, and factors associated with treatment success or safety were analysed. Results: Among 515 included patients, 96% were on antiretroviral therapy and 89.5% had an HIV-RNA less than 50 copies/ml. HCV genotype (G) distribution was 47% G-1a, 20% G-4, 14.4% G-1b, and 12.8% G-3. Patients with cirrhosis were 54.2%, and 46% failed to prior HCV-therapies. Overall, 92.8% patients (95% confidence interval: 90.2–94.9) achieved sustained virologic response (SVR12). Cirrhosis was the only factor associated with treatment failure, and SVR12 rate was significantly lower in patients with liver stiffness at least 21 kPa. Adverse events were reported in 36.7%, but only two patients (0.4%) discontinued treatment because of adverse events. The bivariate analysis showed an association between ribavirin use and an increased risk of adverse events (odds ratio 2.84; 95% confidence interval: 1.95–4.1; P ⩽ 0.0001). Conclusion: This heterogeneous cohort of coinfected patients showed a high rate of SVR12. Among cirrhotic patients, those with a liver stiffness at least 21 kPa had a higher probability of treatment failure. Ribavirin use seems to increase the appearance of adverse events.BACKGROUND/AIMS Data regarding the use of all-oral direct-acting antivirals (DAA) in HIV/HCV-coinfected patients with advanced liver fibrosis are required, because they are generally under-represented in clinical trials. This study sought to evaluate the use of these drugs in a cohort of coinfected patients, mostly with factors that have previously been recognised as predictors of treatment failure. METHODS COINFECOVA-2 is an observational, multicenter study conducted in Eastern Spain. Data of all HIV/HCV-coinfected patients treated with DAA under real-life conditions were retrospectively collected, and factors associated with treatment success or safety were analysed. RESULTS Among 515 included patients, 96% were on antiretroviral therapy and 89.5% had an HIV-RNA < 50 copies/mL. HCV genotype (G) distribution was: 47% G-1a, 20% G-4, 14.4% G-1b, and 12.8% G-3. Patients with cirrhosis were 54.2%, and 46% failed to prior HCV-therapies. Overall, 92.8% patients (95% CI: 90.2-94.9) achieved sustained virologic response (SVR12). Cirrhosis was the only factor associated with treatment failure, and SVR12 rate was significantly lower in patients with liver stiffness ≥ 21 kPa. Adverse events (AEs) were reported in 36.7%, but only two patients (0.4%) discontinued treatment because of AEs. The bivariate analysis showed an association between ribavirin use and an increased risk of AEs (OR 2.84; 95%CI: 1.95-4.1; p ≤ 0.0001). CONCLUSIONS This heterogeneous cohort of coinfected patients showed a high rate of SVR12. Among cirrhotic patients, those with a liver stiffness ≥ 21 kPa had a higher probability of treatment failure. Ribavirin use seem to increase the appearance of AEs.

Telaprevir or boceprevir in HIV/HCV-1 co-infected patients in a real-life setting. Interim analysis (24 weeks). COINFECOVA-SEICV study

In general, HIV co‐infected patients included in clinical trials evaluating the hepatitis C virus (HCV) therapy with telaprevir (TVR) or boceprevir (BOC) with advanced fibrosis, are scarce. We analyze data concerning the use of these drugs in a real‐life clinical setting with patients affected by a more advanced degree of fibrosis in a Spanish cohort.