Mariano Matarranz

Infecciones importadas por inmigrantes y viajeros: resultados de la Red Cooperativa para el estudio de las Enfermedades Importadas por Inmigrantes y Viajeros +Redivi

INTRODUCTION Imported diseases by travellers and immigrants are a priority in the prevention of emerging infectious diseases in the 21st century. There are international records on imported diseases, but no such records are available in Spain. MATERIAL AND METHODS The cooperative network +Redivi was created in 2009 and consists of 11 national healthcare centres. +Redivi collects demographic data relating to travel/migration and infectious diseases in brief, computerised forms. RESULTS From January 2009 to October 2011, we collected 4,570 patients and recorded the main demographic data (age, sex, presence of immunosuppression), travel data (destination, duration, time between the return trip and the consultation) and data regarding the migratory process (country of origin, time between the arrival in Spain and the first consultation), as well as preventive measures that have been taken (pre-travel advice, need for malaria chemoprophylaxis, drug that was used and whether it was correct), the reason for coming to the consultation, and final diagnoses of the travellers, immigrants and immigrants-travellers. Likewise, the most frequent diagnoses of asymptomatic patients who came for a check-up are described for each of the three groups. CONCLUSIONS The +Redivi network allows us to identify and quantify the geographical origin and the type of patients affected, as well as time pattern of infections imported by migrants and travellers. Preliminary data show the significant presence of transmissible diseases and the potential reintroduction in Spain, as well as the importance of systematic screening in patients that came from tropical areas. The objective of +Redivi is to evaluate the impact of imported diseases in Spain in order to contribute to improving the care of patients, to have an influence on prevention and treatment of the most prevalent imported diseases, and to detect possible outbreaks.

Changes in Liver Steatosis After Switching From Efavirenz to Raltegravir Among Human Immunodeficiency Virus–Infected Patients With Nonalcoholic Fatty Liver Disease

Background Antiretroviral drugs with a lower potential to induce hepatic steatosis in human immunodeficiency virus (HIV) infection need to be identified. We compared the effect of switching efavirenz (EFV) to raltegravir (RAL) on hepatic steatosis among HIV-infected patients with nonalcoholic fatty liver disease (NAFLD) receiving EFV plus 2 nucleoside analogues. Methods HIV-infected patients on EFV plus tenofovir/emtricitabine or abacavir/lamivudine with NAFLD were randomized 1:1 to switch from EFV to RAL (400 mg twice daily), maintaining nucleoside analogues unchanged, or to continue with EFV plus 2 nucleoside analogues. At baseline, eligible patients should show controlled attenuation parameter (CAP) values ≥238 dB/m. Changes in hepatic steatosis at 48 weeks of follow-up over baseline levels were measured by CAP. Results Overall, 39 patients were included, and 19 of them were randomized to switch to RAL. At week 48, median CAP for the RAL group was 250 (Q1-Q3, 221-277) dB/m and 286 (Q1-Q3, 269-314) dB/m for the EFV group (P = .035). The median decrease in CAP values was -20 (Q1-Q3, -67 to 15) dB/m for the RAL arm and 30 (Q1-Q3, -17 to 49) dB/m for the EFV group (P = .011). CAP values <238 dB/m at week 48 were observed in 9 (47%) patients on RAL and 3 (15%) individuals on EFV (P = .029). Conclusions After 48 weeks, HIV-infected individuals switching EFV to RAL showed decreases in the degree of hepatic steatosis, as measured by CAP, compared with those continuing with EFV. In addition, the proportion of patients without significant hepatic steatosis after 48 weeks was greater for those who switched to RAL. Clinical Trials Registration NCT01900015.

Raltegravir plus abacavir/lamivudine in virologically suppressed HIV-1-infected patients: 48-week results of the KIRAL study

Background Long-term combination antiretroviral therapy often results in toxicity/tolerability problems, which are one of the main reasons for switching treatment. Despite the favorable profile of raltegravir (RAL), data on its combination with abacavir/lamivudine (ABC/3TC) are scarce. Based on clinical data, we evaluated this regimen as a switching strategy. Design Multicenter, non-controlled, retrospective study including all virologically suppressed HIV-1-infected patients who had switched to RAL+ABC/3TC. Methods We evaluated effectiveness (defined as maintenance of HIV-1-RNA <50 copies/mL at 48 weeks) safety, tolerability, laboratory data, and CD4+ count at week 48 of this switching strategy. Results The study population comprised 467 patients. Median age was 49 years (IQR: 45–53). Males accounted for 75.4%. Median CD4+ count at baseline was 580 cells/μL (IQR, 409). The main reasons for switching were toxicity/tolerability problems (197; 42.2%) and physician’s criteria (133; 28.5%). At week 48, HIV-1 RNA remained at <50 copies/mL in 371/380 (97.6%; 95%CI: 96.4–99.0) when non-virological failure was censured. Virological failure was recorded in 1.9% patients and treatment failure in 20.5% of patients (96/467 [95%CI, 16.9–24.2]). The main reasons for treatment failure included switch to fixed-dose combination regimens (31; 6.6%), toxicity/poor tolerability (27; 5.8%), and physician’s decision (17; 3.6%). A total of 73 adverse events were detected in 64 patients (13.7%). These resolved in 43 patients (67.2%). Of the 33 cases related or likely related to treatment, 30 were Grade-1 (90.9%). CD4+ count and renal, hepatic, and lipid profiles remained clinically stable over the 48 weeks. Conclusions Our findings suggest that RAL+ABC/3TC could be an effective, safe/tolerable, and low-toxicity option for virologically suppressed HIV-1-infected patients.

Effects of Immunonutrition in Advanced Human Immunodeficiency Virus Disease: A Randomized Placebo-controlled Clinical Trial (Promaltia Study)

Background While nutritional interventions with prebiotics and probiotics seem to exert immunological effects, their clinical implications in human immunodeficiency virus (HIV)-infected subjects initiating antiretroviral therapy (ART) at advanced HIV disease remain unclear. Methods This was a pilot multicenter randomized, placebo-controlled, double-blind study in which 78 HIV-infected, ART-naive subjects with <350 CD4 T cells/μL or AIDS were randomized to either daily PMT25341 (a mixture of synbiotics, omega-3/6 fatty acids and amino acids) or placebo for 48 weeks, each in combination with first-line ART. Primary endpoints were changes in CD4 T-cell counts and CD4/CD8 ratio from baseline to week 48 and safety. Secondary endpoints were changes in markers of T-cell activation, bacterial translocation, inflammation, and α and β microbiota diversity. Results Fifty-nine participants completed the follow-up with a mean CD4+ T-cell count of 221 ± 108 cells/μL and mean CD4/CD8 ratio of 0.26 ± 0.19. PMT25341 was well tolerated, without grade 3-4 adverse effects attributable to the intervention. While most of the assessed biomarkers improved during the follow-up in both arms, PMT25341-treated subjects did not experience any significant change, compared to placebo-treated subjects, in mean CD4+ T-cell count change (278 vs 250 cells/μL, P = .474) or CD4/CD8 ratio change (0.30 vs 0.32, P = .854). Similarly, we did not detect differences between treatment arms in secondary endpoints. Conclusions In HIV-infected patients initiating ART at advanced disease, the clear immunological benefits of ART were not enhanced by this nutritional intervention targeting the gut-associated lymphoid tissue and microbiota. Clinical Trials Registration NCT00870363.

Efectividad y seguridad de darunavir a largo plazo

Los estudios de cohortes observacionales ofrecen un diseño de investigación complementario al proporcionar información sobre la efectividad comparativa de las diferentes pautas de tratamiento antirretroviral utilizadas en la práctica clínica. Estos estudios permiten comparaciones de estrategias utilizadas en la vida real que no son evaluadas por los ensayos clínicos. La efectividad, durabilidad y tolerabilidad de los antirretrovirales sigue siendo poco estudiada en el contexto de la práctica clínica habitual. Darunavir ha demostrado buenos resultados en ensayos clínicos, tanto en pacientes previamente no tratados como en terapia de rescate, pero existen pocos datos de su efectividad, durabilidad y seguridad a largo plazo en la vida real. Darunavir potenciado con ritonavir (DRV/r) puede alcanzar una efectividad y seguridad en la práctica clínica similar a la observada en los ensayos clínicos, con una durabilidad de la supresión viral prolongada, tanto como pauta de primera línea como pauta de rescate en pacientes con fracaso virológico. Las discontinuaciones del tratamiento debido a una respuesta virológica insuficiente o por intolerancia son poco frecuentes. El perfil de tolerabilidad de las pautas con DRV/r en la vida real es bueno y similar al descrito en los ensayos clínicos controlados. DRV/r es una opción de tratamiento seguro, tanto en pacientes naïve como en aquellos previamente tratados o con fracaso virológico.