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La Neisseria meningitis es un agente causal raro de neumonía. Se describen 3 casos diagnosticados de neumonía meningocócica a lo largo de 14 años en un centro. Existen factores clínicos predisponentes para su desarrollo, como el tabaquismo, déficits inmunológicos o grupos cerrados de convivencia. El mecanismo principal de producción de la neumonía meningocócica es la aspiración de secreciones desde la nasofaringe hasta la vía aérea inferior. El meningococo dispone de proteínas en su cápsula y de endotoxinas que condicionarán el daño pulmonar, lo que ocasiona la muerte hasta en un 16% de los casos. Generalmente, el diagnóstico se realiza con el resultado de los hemocultivos ya que no se suele sospechar clínicamente; sin embargo, al ser altamente sensible a las penicilinas, el tratamiento empírico indicado suele solucionar la enfermedad tanto en los casos ambulatorios como en los hospitalizados.

Objectives The primary objective was to evaluate the improvement in neuropsychiatric symptoms attributed to an antiretroviral drug after that drug was substituted with nevirapine. The secondary objective was to evaluate the impact on patient adherence and quality of life. Methods A prospective, observational study was carried out that included patients with HIV-1 plasma suppression for whom an antiretroviral drug was substituted with nevirapine because of central nervous system (CNS) side effects, a Pittsburgh Sleep Quality Index (PSQI) score > 5 or a Hospital Anxiety and Depression Scale (HADS) score ≥ 10, and who had not initiated psychoactive drug treatment during the prior 6 weeks. Evaluations were carried out at baseline and 1 and 3 months after the switch using the PSQI, HADS, Epworth Sleepiness Scale, Medical Outcomes Study-Short Form 30 items (MOS-SF-30) and Simplified Medication Adherence Questionnaire (SMAQ). Results A total of 129 patients were included in the study. The drug substituted was mainly efavirenz (89.9%), and reasons for the switch included sleep disturbances (75.2%), anxiety (65.1%), depression (38.7%), attention disturbances (31%), and other reasons (31%), with a mean of 2.4 neuropsychiatric disturbances per patient. A statistically significant improvement was observed in all the tests evaluating neuropsychiatric symptoms and adherence at 1 and 3 months. The CD4 lymphocyte count remained stable (P = 0.096). Three (2.3%) patients had a detectable plasma HIV-1 RNA at the end of the study. Nine patients (6.9%) withdrew because of nevirapine-related toxicity (rash in seven patients and hypertransaminasaemia in two patients, none of which were > grade 2). Conclusions The switch to nevirapine from a drug causing neuropsychiatric disturbances (primarily efavirenz) in subjects with virological suppression was effective in resolving those disturbances, with an improvement in all the parameters studied. This led to better adherence to treatment and quality of life, with no detrimental effect on their immunological and virological control.

Objectives: Our aim is to describe the impact of emtricitabine (FTC)/tenofovir (TDF) versus other nucleoside reverse transcriptase inhibitor (NRTIs)-based regimens on renal function of human immunodeficiency virus (HIV) naiive patients >50 years old who started combination antiretroviral therapy (cART). Design: National, retrospective cohort analysis of patients >50 years old when they started cART (January 1, 2006-December 31, 2009). Methods: We compared renal safety (changes in estimated glomerular filtration rate [eGFR] during the first year, and time to renal events during 4 years of follow-up) in FTC/TDF versus non-FTC/TDF users. Among FTC/TDF users, we compared protease inhibitors vs non-nucleoside reverse transcriptase inhibitors and Lopinavir/ritonavir vs Efavirenz. Results: We included 103 patients: median age: 54.9 years, 84% males, median CD4 count 247 cells/mu l, median viral load 4.7 log; median follow up 18 months (max: 48 months); 73 started with FTC/TDF and 30 with other NRTIs. Change in eGFR was significantly worse for ritonavir-boosted lopinavir (LPV/r) vs efavirenz (EFV) users in the FTC/TDF group (71.2 vs 98.9 ml/min/1.73 m(2) at month 12, P= 50 years old, renal safety was similar for FTC/TDF and other NRTI-based regimens, but worse for LPV/r as compared to other regimens.

Despite having demonstrated noninferior efficacy against atazanavir/ritonavir plus coformulated tenofovir/emtricitabine (cTDF/FTC), the combination of nevirapine plus cTDF/FTC is not included among preferred regimens in some international guidelines. This combination is frequently used in Spain. We analyzed its effectiveness and safety as first-line therapy in a routine clinical practice. A retrospective, multicenter study was performed in treatment-naive HIV-1-infected subjects who started nevirapine plus cTDF/FTC as first-line therapy according to the nevirapine CD4(+) cell count threshold. The primary endpoint was the proportion of subjects with plasma HIV-1 RNA

Objective: Currently, 12% of the Spanish population is foreign-born, and a third of newly diagnosed HIV-infected patients are immigrants. We determined whether being an immigrant was associated with a poorer response to antiretroviral treatment. Methods: Historical multicenter cohort study of naive patients starting HAART. The primary endpoint was time to treatment failure (TTF) defined as virological failure (VF), death, opportunistic disease, treatment discontinuation (D/C), or missing patient. Secondary endpoints were TTF expressed as observed data (TFO; censoring missing patients) and time to virological failure (TVF; censoring missing patients and D/C not due to VF). A multivariate analysis was performed to control for confounders. Results: A total of 1090 treatment-naive HIV-infected patients (387 immigrants and 703 autochthonous) from 33 hospitals were included. Most immigrants were from Sub-Saharan Africa (28.3%) or South-Central America/Caribbean (31%). Immigrants were significantly younger (34 y vs 39 y), more frequently female (37.5% vs 24.6%), with less HCV coinfection than autochthonous patients (7% vs 31.3%). There were no differences in baseline viral load (4.95 Log(10) vs 4.98 Log(10)), CD4 lymphocyte count (193.5/mu L vs 201.5/mu L), late initiation of HAART (56.4% vs 56.0%), or antiretrovirals used. Cox-regression analysis (HR; 95%CI) did not show differences in TTF (0.89; 0.66-1.20), TFO (0.95; 0.66-1.36), or TVF (1.00; 0.57-1.78) between immigrants and autochthonous patients. Losses to follow-up were more frequent among immigrants (17.8% vs 12.1; p=0.009). Sub-Saharan African patients and immigrant females had a significantly shorter TTF. Conclusions: The response to HAART among immigrant patients was similar to that of autochthonous patients, although they had a higher rate of losses to follow-up. Sub-Saharan Africans and immigrant females may need particular measures to avoid barriers hindering antiviral efficacy. 1.923 JCR (2010) Q3, 23/33 Virology; Q4, 103/134 Immunology, 44/58 Infectious Diseases

Objetivo estudiar las caracteristicas de la infeccion por el VIH en gitanos en Espana, en comparacion con las de la mayoria caucasica no gitana (CNG). Metodos estudio transversal y de cohortes historicas en la Cohorte VACH. Clasificamos a los pacientes que acudieron a las clinicas participantes en VACH entre el 1 de junio de 2004 y el 30 de noviembre de 2004 de acuerdo a su raza y etnia, como «gitanos», «nativos espanoles CNG» u «otros» (estos, excluidos de este estudio). Comparamos sus caracteristicas sociodemograficas y clinicoepidemiologicas, asi como sus curvas de Kaplan�Meier del tiempo hasta sida, muerte o progresion de la enfermedad (cualquiera de ambos). Resultados 4819 (48%) de 10.032 casos recogidos en la base de datos de VACH fueron incluidos en el estudio: 210 (4,2%) eran gitanos y 4.252 (84,8%) eran nativos CNG. Observamos diferencias en sus distribuciones por edad, domicilio, estudios, antecedentes penales, situacion laboral y marital. La inyeccion de drogas habia sido el mecanismo de transmision del VIH mas frecuente en los dos grupos, pero mas marcadamente en los gitanos (72% frente a 50%; p

Background Although efavirenz and lopinavir/ritonavir(r) are both recommended antiretroviral agents in antiretroviral-naive HIV-infected patients, there are few randomized comparisons of their efficacy and tolerability. Methods A multicenter and randomized study was performed including 126 antiretroviral-naive patients, randomly assigned to efavirenz + Kivexa ® ( n = 63) or lopinavir/r + Kivexa ® ( n = 63). Efficacy endpoints were the percentage of patients with HIV-RNA ≤50 copies/mL at week 48 and CD4 recovery. Safety was assessed by comparing toxicity and discontinuations. Statistical analyses were performed on an intention-to-treat (ITT) basis (Missing = Failure). Results At week 48, 56.7% of patients in the efavirenz and 63.2% in the lopinavir/r groups showed HIV-1 RNA P = 0.770) (intention-to-treat analysis; Missing = Failure). Only 1 (1.53%) patient from each group experienced virological failure. CD4 values increased in both groups (298 cells in the efavirenz group, P = 0.001; 249 cells in the lopinavir/r group, P = 0.002; P = 0.126 between groups). HDL-cholesterol only increased in the efavirenz group (from 39 ± 12 mg/dL to 49 ± 11; P = 0.001). Discontinuations were more frequent in the lopinavir/r group (36.5% versus 28.5%; P = 0.193), but more patients with efavirenz interrupted due to toxicity (11.1% versus 6.3%); most of them were attributed to hypersensitivity reaction. Conclusions Similar virological efficacy was observed for efavirenz and lopinavir/r, when administered with Kivexa ® in antiretroviral-naive patients, while immunological improvement was slightly superior for efavirenz. The higher rate of discontinuation due to toxicity in the efavirenz group was related to a higher incidence of hypersensitivity reaction. Nowadays, the use of the new formulation of lopinavir/r and the HLA-B*5701 genotype test before starting abacavir should improve the safety profiles of these regimens.

Background: Mitochondrial damage of HIV and antiretrovirals, especially nucleoside-analogue interference on mitochondrial DNA (mtDNA) replication, is reported to underlay highly active antiretroviral therapy (HAART)-related hyperlactatemia, but scarce approaches have been performed to correlate clinical manifestations and mitochondrial abnormalities. Methods: We obtained lymphocytes and monocytes of 26 HIV-infected and treated patients who developed hyperlactatemia and after recovery, 28 nonhyperlactatemic HIV subjects on HAART, 31 naive individuals, and 20 uninfected controls. Mitochondrial replication and transcription analysis were performed by quantitative real-time PCR, mitochondrial translation quantification by western blot and mitochondrial enzymatic activities by spectrophotometry. Results: Mitochondrial parameters decreased during hyperlactatemia and improved at recovery. Mitochondrial replication and transcription species were reduced (P = 0.16 and P = 0.71), but the most significant decay was observed on mitochondrial protein content (P < 0.05) and mitochondrial complexes III and IV activities (P < 0.01 and P < 0.001). During hyperlactatemia lactate level correlated complexes III and IV function (P < 0.05). After recovery mitochondrial parameters achieved values of nonhyperlactatemic HIV individuals, which were lower than ranges of naive subjects and uninfected controls. Conclusions: HIV and HAART-related hyperlactatemia is associated with a general mitochondrial impairment which reverts after recovery. Mitochondrial biochemistry show a better correlation with lactate levels than mitochondrial genetics suggesting that mitochondrial function could be a better marker of hyperlactatemia development than mtDNA content.

Because of the increased cardiovascular risk (CVR) in HIV-positive patients, preventive measures are essential, requiring algorithms for risk estimation, such as the Framingham risk equation, the Prospective Cardiovascular Munster Study (PROCAM) algorithm and the Systematic Coronary Risk Evaluation (SCORE) chart. Classical cardiovascular risk factors (CVRF) are closely related to CVR in HIV-infected patients but whether this risk is comparable to that in the general population is unknown. Therefore, these algorithms probably underestimate the risk in these patients. Currently, application of the same strategies as those used in the general population is recommended, without forgetting the specific characteristics of HIV positive patients or the importance of their inflammatory status, which can accelerate the development of arteriosclerosis and lead to an increase in cardiovascular morbidity and mortality. Therefore, in addition to traditional CVRF, biological markers of inflammation could help to identify the patients most at risk of a cardiovascular event. These markers, as well as the diverse techniques for assessment of subclinical atherosclerosis that could help in the early identification of at-risk patients, are reviewed in the present study. Lifestyle changes (healthy diet, smoking cessation, maintaining a healthy weight and daily physical exercise) reduce the probability of a coronary event by up to 80% in the general population. Traditional therapeutic measures (dyslipidemia, hypertension, diabetes mellitus) and those specific to HIV infection (viral suppression, discontinuous treatment, etc.) are reviewed.

Objectives: The aim of this study was to assess the influence of hepatitis B virus or hepatitis C virus co-infection and the extent of liver fibrosis on saquinavir and ritonavir pharmacokinetics in HIV-infected subjects without liver function impairment. Methods: A cross-sectional, comparative study enrolling HIV-infected adults receiving saquinavir/ ritonavir 1000/100 mg twice daily or 1500/100 mg once daily was conducted. Patients with chronic viral hepatitis (HEP+) were grouped as having advanced liver fibrosis (HEP+/FIB+) or not (HEP+/FIB-) based on the FIB-4 index. Saquinavir and ritonavir trough concentrations (C trough ) in plasma were determined by HPLC. The geometric mean ratio (GMR) was used to compare saquinavir and ritonavir C trough between HEP― and HEP+ patients, and the influence of the extent of liver fibrosis on saquinavir and ritonavir pharmacokinetics was explored using analysis of variance. Results: One hundred and thirty-eight patients on twice-daily saquinavir/ritonavir (67 HEP―, 71 HEP+) and 36 patients on once-daily saquinavir/ritonavir (12 HEP―, 24 HEP+) were included. Saquinavir C trough was comparable between HEP― and HEP+ patients receiving either saquinavir/ritonavir 1000/ 100 mg twice daily [GMR 0.91, 95% confidence interval (CI) 0.60―1.37; P=0.655] or 1500/100 mg once daily (GMR 0.88, 95% CI 0.39―1.97; P=0.752). Similarly, ritonavir C trough was also comparable between HEP― and HEP+ patients. The extent of liver fibrosis was not significantly related to saquinavir or ritonavir C trough in patients receiving either of the two studied doses. Conclusions: Saquinavir C trough was not increased in HIV-infected patients with chronic viral hepatitis in the absence of liver function impairment. These results confirm that no specific dose modification of saquinavir/ritonavir should be recommended in this setting.

Preliminary data suggest that a once-daily combination of lamivudine, didanosine and efavirenz is an effective alternative regimen for antiretroviral-naive HIV-1-infected patients. However, data from randomized trials comparing this combination versus standard first-line regimens are not available yet. In an observational study, we analyse the efficacy and tolerability of didanosine plus lamivudine and efavirenz versus zidovudine plus lamivudine and efavirenz in a cohort of therapy naive patients. We performed an observational study on prospectively collected data from patients participating in a multicentre Spanish treatment-naive cohort (VACH cohort). Efficacy was assessed comparing time to therapeutic failure and CD4 cell recovery. Safety was analysed comparing the proportion of patients who discontinued therapy for toxicity or any other reason. Overall, 219 patients treated with once-daily didanosine/lamivudine/efavirenz and 409 patients receiving twice-daily zidovudine/lamivudine (Combivir((R))) plus efavirenz were evaluated. By intent-to treat analysis (non-completers and therapeutic change = failure), time to treatment failure was similar in both groups of treatment: 40.0 months (95% CI 23.3-56.8 months) among patients on didanosine/lamivudine/efavirenz and 33.3 months (95% CI 25.6-41.1 months) in patients treated with zidovudine/lamivudine/efavirenz (P = 0.253). The risk of failure due to treatment change was almost double among patients treated with zidovudine/lamivudine/efavirenz compared with those who received didanosine/lamivudine/efavirenz. Our data suggest that didanosine/lamivudine/efavirenz is a combination with an efficacy comparable to zidovudine/lamivudine/efavirenz as first-line therapy for HIV infection. The risk of treatment change was significantly higher among patients treated with zidovudine/lamivudine/efavirenz than in those starting therapy with didanosine/lamivudine/efavirenz.

Background The aim of this study was to analyze the incidence of new cases, survival of HIV-1-infected patients with progressive multifocal leukoencephalopathy (PML), and the characteristics of PML-associated immune reconstitution inflammatory syndrome (IRIS). Methods Multicenter observational cohort study of all HIV-1-infected patients newly diagnosed of PML in 7 hospitals in Barcelona (Spain) from 2002 to 2006. The annual incidence of PML was calculated. Survival was estimated using the Kaplan-Meier method. IRIS was defined as new onset or rapid worsening of PML shortly after initiation of highly active antiretroviral therapy together with a decline in HIV-1 viral load and rising of CD4 lymphocytes. Results Sixty-one new cases of PML were diagnosed. The mean survival time was 15 months [95% confidence interval (CI), 11 to 19]. The Kaplan-Meier estimates of the probability of survival were 47.7% (95% CI, 35 to 59) at 6 months, 38.6% (95% CI, 25 to 51) at 12 months, 35.1% (95% CI, 22 to 48) at 24 months, and 25.1% (95% CI, 10 to 40) at 36 months. IRIS was diagnosed in 14 (23%) cases. Mortality was similar in patients with and without IRIS. Conclusions PML continues to be one of the deadliest opportunistic infections in acquired immunodeficiency syndrome patients. The development of PML-associated IRIS has no influence on prognosis.

We evaluated a single-class quadruple nucleoside/nucleotide regimen in a 96-week prospective one-arm pilot study in adult HIV-infected naive patients with CD4100 cells/microl. Standard zidovudine/lamivudine/abacavir and tenofovir doses were given. Virologic efficacy was evaluated by intent-to-treat (ITT), switch = failure and on-treatment (OT) analyses. A total of 54 patients were included (median CD4 count 254 cells/microl, VL 79,706 copies/ml). A median drop in VL of 2 log at 14 days and3 log since week 12 was observed. A total of 34/54 (63%) patients (ITT) and 34/39 (87%) patients (OT) had VL50 copies/ml at 96 weeks. Four (7%) patients switched therapy due to adverse events, 5 (9%) had virologic failure, and 1 died. Similar efficacy results were observed irrespective of baseline VL (or5 log) or CD4 cells (or250/microl). A median CD4 gain of +223 cells/microl was achieved. K65R + 41L + 219Q were detected in one patient at virologic failure. Only two patients presented fat loss on clinical evaluation. A decrease in total cholesterol (p = 0.007) and LDLc (p = 0.016) was observed. Our data suggest that zidovudine/lamivudine/abacavir plus tenofovir is a simple, effective, and well-tolerated NNRTI/PI-sparing regimen, even for patients with high viral loads. Larger trials comparing this option with standard initial antiretroviral regimens should be conducted.

Background The use of HAART combining 2 nucleoside analogues reverse transcriptase inhibitors (NRTIs) plus one protease inhibitor (PI) or 2 NRTIs + 1 non-nucleoside reverse transcriptase inhibitor (NNRTI) has shown comparable efficacy. The study was designed to compare long term (2 years) effectiveness of two antiretroviral (ARV) treatment strategies in patients not previously treated: starting with a nelfinavir based HAART switching to nevirapine in case of failure or side effects or the reverse sequence. Methods This multicenter, randomized, open label clinical trial enrolled ARV-naive HIV patients with CD4 counts below 500 cells/mm3. They were randomly assigned to start ddI + d4T + nelfinavir (switching to ZDV + 3TC + NEV in case of failure or toxicity) (PI-NEV arm) or ddI + d4T + nevirapine, switching to ZDV + 3TC + NFV in case of failure or toxicity (NEV-PI arm). The primary study endpoint was the Kaplan-Meier estimates of the time to failure after switching to second regimen if necessary (considering failure as two consecutive plasma HIV-1 RNA determinations above 200 copies/mL, death, a new category C event or toxicity leading to treatment discontinuation of the second regimen) after a minimum follow-up of two years. Results A total of 137 patients were evaluable (67 and 70 in the PI-NEV and NEV-PI arms respectively). Baseline characteristics did not differ among groups. Kaplan-Meier estimates of time to failure did not show differences between the two arms neither in the on-treatment (OT) analysis (log rank test, p = 0.81) nor in the intent-to-treat (ITT) analysis (p = 0.58). At 24 months, the estimated proportion of patients free of failure were 72% and 66% respectively in the PI-NEV and NEV-PI arms OT analysis (p = 0.54) and 73% and 64% in the PI-NEV and NEV-PI arms in the ITT analysis (p = 0.49). The difference in the median in CD4+ lymphocyte count at 24 months was not significantly different in the two groups: 393 and307 CD4 cells/mm3 in the PI-NEV and NEV-PI arms respectively (p = 0.167). The incidence of adverse events (AEs) in the two arms was very similar: 50 (75%) in the PI-NEV and 54 (70%) in the NEV-PI group, as it was for grade 3-4 AEs leading to drug switching. Conclusion At two years both treatments strategies (PI-NEV vs NEV-PI) had a high and comparable efficacy and were generally well tolerated.

Fundamento y objetivo La estavudina (d4T) ha demostrado ser un farmaco bien tolerado y eficaz a corto y largo plazo. Sin embargo, su uso se ha asociado a una serie de toxicidades que han condicionado su prescripcion actual. Se evalua la eficacia inmunovirologica y seguridad de pautas antirretrovirales con d4T a dosis reducidas. Pacientes y metodo Se ha realizado un estudio retrospectivo y multicentrico, en el que se incluyo a pacientes tratados con d4T a dosis habituales (peso > 60 kg: 40 mg/12 h; peso 60 kg: 30 mg/12 h; peso Resultados Se incluyo a 982 pacientes. La prevencion de la toxicidad fue el principal motivo de reduccion de la dosis (76%). A los 6 meses el 97% y el 84% de los pacientes tenian menos de 400 y de 50 copias/ml, respectivamente y hubo un incremento significativo de 38 linfocitos/μl. No se observaron cambios significativos en los parametros lipidicos en la lipodistrofia ni en la neuropatia periferica el periodo de 6 meses de seguimiento. Conclusiones La reduccion de dosis de d4T no compromete su eficacia en una poblacion inmunovirologicamente estable. Para corroborar si esta estrategia conlleva una menor toxicidad se necesitan estudios con seguimientos mas prolongados.

Fundamento y objetivo Los documentos de voluntades anticipadas (DVA) permiten conocer y respetar los deseos del enfermo en materia de salud cuando este no es competente para decidir. El estudio pretende valorar el conocimiento de estos documentos en pacientes infectados por el virus de la inmunodeficiencia humana (VIH) y el conocimiento de la propia enfermedad y de sus complicaciones. Pacientes y metodo Pacientes con infeccion por el VIH controlados en el Hospital de Mataro y en el Hospital de Granollers, a los que se les administro una entrevista estructurada como un cuestionario que valora el conocimiento de la propia enfermedad, la satisfaccion con la informacion medica recibida, los deseos de participar en la toma de decisiones medicas, la disposicion a tolerar diferentes estados hipoteticos de salud y el conocimiento de los DVA. Se valoran los factores asociados al conocimiento de la enfermedad y al conocimiento de los DVA. Resultados El 74,3% de los entrevistados mostro un buen conocimiento de la enfermedad, circunstancia que se relaciono con el hecho de ser joven, presentar un peor nivel funcional segun la escala de Karnofsky, percepcion subjetiva de mayor gravedad, no haber ingresado en la unidad de cuidados intensivos, tener hepatopatia cronica y haber sido adicto a drogas por via parenteral. Asimismo se relaciono con no estar dispuesto a vivir conectado a un respirador ni dependiendo de otra persona y no sentirse incomodo hablando de estos temas. El conocimiento de los DVA fue del 31,1%, y se relaciono con ser mujer (el 42,0 frente al 26,8%; p = 0,024), con mayor nivel de estudios (el 55,1 frente al 25,5%; p Conclusiones El conocimiento de la enfermedad y sus complicaciones puede considerarse aceptable en la poblacion infectada por el VIH. Una tercera parte de esta poblacion conoce los DVA, circunstancia que se relaciona con el hecho de ser mujer, tener mayor nivel de estudios y desear implicarse en las decisiones medicas.

Using a multicenter, cross-sectional, observation study, the long-term safety, metabolic profile, and viral efficacy of nevirapine (NVP)-based approaches in HIV-1-infected patients treated for at least 2 years were assessed. For 4 months, all consecutive HIV-1-infected patients who had been receiving an NVP-containing regimen for at least 2 years were recruited. A total of 613 patients were included with a median follow-up period of 43 months (IQR: 31-51). At baseline, 24.5% (150 patients) were treatment naive, 41.5% (254 patients) switched for simplification purposes, and 34% (209 patients) were failing HAART. Increases by five times or more in AST/ALT values were observed in fewer than 2% of patients. Only 5.7% of all adverse events reported during the investigation were attributable to NVP. The percentage of patients with normal HDL cholesterol levels rose from 17.7% at baseline to 35.4% at the last visit. At the latest time point available for analysis, 76% of naive and 74% of those who had switched had HIV-1 RNA loads of50 copies/ml, while 59% of salvage patients achieved this level of viral suppression. Factors associated with viral suppression at the latest visit were adequate adherence (OR: 2.58, 95% CI: 0.85-7.78, p0.001), first-line treatment (OR: 3.02, 95% CI: 1.52-6.00, p = 0.002), and baseline CD4 cells400 cells/microl (OR: 2.34, 95% CI: 1.22-4.47, p = 0.010). Exposure to nevirapine for up to 4 years is safe. Liver toxicity is infrequent and generally mild. HDL cholesterol levels consistently increase over time and viral suppression is maintained.

Objetivo Efectuar una puesta al dia de las alteraciones metabolicas y morfologicas presentes en los pacientes con infeccion por virus de la inmunodeficiencia humana (VIH), ahondando en su manejo clinico y tratamiento. Metodos Estas recomendaciones han sido consensuadas por un comite de expertos en alteraciones metabolicas y en la atencion al paciente con VIH, bajo los auspicios de la Secretaria del Plan Nacional sobre el Sida (PNS). Para ello se han revisado los ultimos avances clinicos, epidemiologicos y fisiopatologicos resenados en estudios publicados en las revistas medicas y/o presentados en los congresos. Resultados Las alteraciones metabolicas que con mayor frecuencia aparecen en los pacientes con infeccion por VIH y en tratamiento antirretroviral (TAR) son la dislipidemia con perfil aterogenico y las alteraciones del metabolismo hidrocarbonado/resistencia a la insulina. Se ha descrito una elevada prevalencia de factores de riesgo cardiovascular, especialmente el tabaquismo. Para su manejo se han utilizado los mismos criterios que para la poblacion general, con matices especificos. La dieta y el ejercicio deben ser la primera recomendacion terapeutica. En los pacientes con dislipidemia y necesidad de tratamiento farmacologico, estarian indicadas las estatinas y/o los fibratos. En el tratamiento de la resistencia a la insulina las glitazonas han demostrado su eficacia. El abordaje del reparto anomalo de la grasa sigue siendo controvertido. El cambio de TAR, la cirugia reparadora, el soporte psicologico y los cambios de estilo de vida son las bases para abordar este problema en el momento actual. La acidosis lactica es una complicacion infrecuente pero muy grave, siendo la primera actitud terapeutica la retirada del TAR. En cuanto a las alteraciones del metabolismo oseo son fundamentales la prevencion y la deteccion precoz, especialmente en mujeres perimenopausicas y ninos. La disfuncion sexual es un problema frecuente tanto en varones como en mujeres; la diversidad de causas obliga a un tratamiento individualizado. Conclusiones La prevalencia de alteraciones metabolicas y morfologicas ha aumentado desde la introduccion del tratamiento antirretroviral de gran actividad (TARGA). Es fundamental el conocimiento de los diversos aspectos relacionados con su diagnostico y tratamiento para una correcta atencion de los pacientes con infeccion por VIH.

Background and Objectives: The influence of the polymorphisms of the CX3CR1 chemokine receptor gene on the natural history of HIV-1 infection is controversial. This study aimed to determine whether functionally active CX3CR1 genetic variants are associated with long-term nonprogressive infection of > 15 years in HIV-1-infected Spanish patients. Patients and Methods: Two single-nucleotide polymorphisms, V249I (G > A) and T280M (C > T), of the CX3CR1 gene were assessed in 271 Spaniards. These included 60 HIV-1-infected patients who were long-term nonprogressors (LTNPs) of > 15 years, 109 HIV-1-infected patients who were usual progressors (UPs), and 102 control subjects. The CCR5Δ32 was also assessed. Genotyping was performed using polymerase chain reaction and automatic sequencing analysis methods on white cell DNA. Genotype and allele frequencies were compared by the χ 2 test and the Fisher exact test. Results: The frequencies of the 249I variant allele were 42% for LTNPs, 24.5% for UPs, and 35% for healthy controls; the differences between LTNPs and UPs were significant (odds ratio 0.46; 95% CI: 0.27 to 0.75; P = 0.0017). For 280M the distribution was 16% for LTNPs, 14% for UPs, and 17% for healthy controls (P = NS). The haplotype 249I280T was significantly more common in LTNPs than in UPs (P = 0.0007). These results persisted after excluding from the analysis the individuals carrying the CCR5Δ32. Conclusions: CX3CR1 249I variant allele is more frequent in Spanish HIV-1-infected LTNPs of > 15 years. This effect is independent of the presence of the CCR5Δ32 allele.

BackgroundIn vitro studies have reported controversial effects of protease inhibitors (PIs) on mitochondrially driven apoptosis. Additionally, since PIs in the clinical setting are almost always given in combination with nucleoside analogues, which may have negative effects on mitochondrial DNA (mtDNA), the impact of PI-containing highly active antiretroviral therapy (HAART) on apoptosis and mtDNA content is unclear.Patients and methodsA cross-sectional study was performed including 20 HIV-negative (HIV-) patients, 16 HIV-positive, antiretroviral-naive (HIV+) patients and 17 HIV-positive patients receiving the PI nelfinavir (NFV) plus zidovudine and lamivudine (AZT+3TC) or didanosine and stavudine (ddI+d4T) - collectively known as HIV+PI - as first-line antiretroviral treatment for at least 12 months. Peripheral blood mononuclear cells (PBMCs) were isolated. BCL2 expression (anti-apoptotic) and the levels of the cleaved, active form of caspase-9 (pro-apoptotic) were determined by western blot. An index of mitochondrially driven apoptotic activation was estimated calculating the ratio caspase-9:BCL2. Mitochondrial DNA content was measured by real-time PCR.ResultsBCL2 expression was lower in HIV+ than in HIV-patients ( PConclusionsNFV-based PI-containing HAART regimens may exert some beneficial effects counteracting the increased mitochondrially driven apoptosis present in HIV-infected people.

Objective To assess the baseline factors associated with haematological toxicity that lead to ribavirin or pegylated interferon (peginterferon) dosage reductions in hepatitis C and human immunodeficiency virus (HCV/HIV)-coinfected patients. Design Multicentre, prospective, observational study. Setting Eleven hospitals in Spain during the period 2002–2003. Subjects and methods One-hundred and forty-two HIV/HCV-coinfected patients received peginterferon-α2a plus ribavirin. Baseline characteristics and haematological parameters were recorded at baseline, week 4, 8, 12, 24 and 48. Cox's regression model was used to study the factors associated with the appearance of a haemoglobin level below 10g/dl (haemoglobin-endpoint), a neutrophil count below 750/mm3 (neutrophil-endpoint) and a platelet count below 50,000/mm3 (platelet-endpoint). Results Nineteen patients (13.4%) reached the haemoglobin-endpoint, 22.5% the neutrophil-endpoint and 7% the platelet-endpoint. Mean time of follow-up was 8 months (±3.5). A baseline haemoglobin level below 14g/dl [hazard ratio (HR): 3.65; 95% confidence interval (CI): 1.46–9.06] and treatment with zidovudine (HR: 3.25; 95% CI: 1.31–8.11) were the independent factors associated with the appearance of the haemoglobin-endpoint. A baseline neutrophil below 2050/mm3 (HR: 3.59; 95% CI: 1.77–7.28) and baseline weight 3 decrease) (HR: 1.074; 95% CI: 1.04-1.11) was independently associated with the appearance of the platelet-endpoint. Conclusions Baseline factors allow the identification of a subset of HIV/HCV-coinfected patients who are prone to experience haematological toxicity during HCV antiviral therapy.

Objective Investigate the metabolic and mitochondrial effects of switching a highly active antiretroviral therapy (HAART) regimen with a high mitochondrial toxicity profile to a HAART with a theoretically low mitochondrial toxicity. Patients and Methods Six consecutive HAART-experienced patients receiving at least one dideoxy-nucleoside reverse transcriptase inhibitor (NRTI) switched to enfuvirtide plus tenofovir plus saquinavir/ritonavir (T20+TDF+SQV/r). Blood samples were collected at baseline, 12 and 24 weeks after the switch, and viral load (VL) and lymphocyte CD4+ T-cell count were determined. Metabolic parameters consisted of fasting serum triglycerides, cholesterol (total and fractions), glucose, insulin, C-peptide and lactate. Mitochondrial assessment consisted on mitochondrial DNA (mtDNA) quantification, COX-II mitochondrial protein expression rate, mitochondrial respiratory chain complex III and IV activities, and oxygen consumption in peripheral blood mononuclear cells. For baseline mitochondrial comparisons, we included six HIV-infected patients naive for ART. Results Switched patients exhibited a mean increase of 26 CD4+ T-cells/mm3 and a mean decrease of 1.1 log in VL ( P=NS for both). Lactate, lipids and glycaemia remained stable during the study; only insulin levels increased significantly ( PConclusion Switching a HAART-containing dideoxy-NRTI to T20+TDF+SQV/r minimally alters metabolic parameters and exerts beneficial effects on mitochondrial function at 24 weeks. Mitochondrial improvement should be considered as an additional advantage of this rescue therapy.

Fundamento y objetivo: Conocer la efectividad de un tratamiento para la hiperlactatemia sintomatica y la acidosis lactica secundarias al tratamiento con antirretrovirales dirigido a corregir la toxicidad mitocondrial. Pacientes y metodo: Se recluto de forma consecutiva a pacientes infectados por el virus de la inmunodeficiencia humana (VIH) a los que se les diagnostico hiperlactatemia secundaria o acidosis lactica. Se considero hiperlactatemia con concentraciones por encima de 2,2 mmol/l. El tratamiento consistia en la administracion diaria de L-carnitina, tiamina, vitamina B6, hidroxicobalamina y vitamina C, ademas de interrumpir la administracion de glucosa intravenosa y el tratamiento antirretroviral de forma inmediata. Resultados: Se incluyo a 9 pacientes, a los que se les diagnostico de hiperlactatemia sintomatica (n = 4) o acidosis lactica (n = 5) entre enero de 2001 y septiembre de 2002. Todos eran pacientes con sida y habian recibido inhibidores de la transcriptasa inversa analogos de los nucleosidos (ITIAN) durante una media de 5 anos: 7 habian recibido didanosina, 5 estavudina, 3 zidovudina, 2 lamivudina y 1 abacavir. Los sintomas que mas frecuentemente se presentaron fueron taquipnea, febricula, dolor abdominal, nauseas, vomitos y diarreas. Todos los pacientes tuvieron un buen pronostico tras administrar L-carnitina y el complejo vitaminico descrito, asi como tras la interrupcion del tratamiento antirretroviral y de la perfusion de glucosa. Los sintomas desaparecieron a los 7 dias. Despues de una media (desviacion estandar) de 15 (5) meses de seguimiento, no se ha observado recurrencia de esta complicacion. Conclusion: La administracion de L-carnitina, tiamina, vitamina B6, hidroxicobalamina y vitamina C junto a la suspension del tratamiento antirretroviral podria desempenar un papel en el tratamiento de la acidosis lactica por ITIAN en pacientes infectados por VIH.

To investigate the effects of HIV infection on mitochondrial DNA (mtDNA) content and other mitochondrial parameters, we used peripheral blood mononuclear cells (PBMCs) from 25 asymptomatic antiretroviral-naive human immunodeficiency virus (HIV)-infected patients and from 25 healthy control subjects. HIV-infected patients had significant decreases in mtDNA content (decrease, 23%; P

IntroductionAlternation of antiretroviral drug regimens has been proposed as a novel treatment strategy for HIV infection. However, some concerns persist regarding antiviral efficacy, adherence, toxicity and resistance evolution in the long term.MethodsA total of 161 antiretroviral-naive HIV-1-infected patients were randomized to receive stavudine/ didanosine/efavirenz (group A) or zidovudine/lamivudine/ nelfinavir (group B) or to alternate between the two regimens every 3 months starting with regimen A (group C). Antiviral efficacy, adherence, safety and tolerability were analysed every 12 weeks.ResultsAfter 96 weeks, time to virological failure was significantly delayed in the alternating regimen compared with the standards of care regimens. Virological suppression was seen in 46%, 48% and 58% of patients in groups A, B and C, respectively, in the intention-to-treat analysis and in 75%, 76% and 97% in the on-treatment analysis (A vs C: P=0.014; B vs C: P=0.016; A vs B: P=0.849). At the end of the study, 94% of patients in group A and 92% in groups B and C reported an adherence greater than 95%. Alternating therapy was associated with a similar impact on CD4+ counts in comparison with the standards of care regimens, as well as a lower mitochondrial DNA/nuclear DNA (mtDNA/nDNA) ratio decrease in the mitochondrial substudy performed on 37 patients. The frequency and intensity of adverse events in the alternating group decreased during subsequent cycles.DiscussionOur results favour the hypothesis that proactive therapy switching may delay the accumulation of resistance mutations. Moreover, the alternating regimen was well tolerated and adherence remained comparably high in all treatment groups. The lower mtDNA/nDNA ratio decrease observed in this group may imply a lower impact on mitochondrial toxicity than in standard regimens.

The aim of the study was to assess differences in health-related quality of life (HRQoL) in HIV-infected naive patients treated with two HAART regimens at 12 months.The MOS-HIV questionnaire was used to measure HRQoL in a subgroup of 127 patients included in the COMBINE study, which was an open-label, randomized, multicenter study comparing zidovudine (ZDV) and lamivudine (3TC) plus nelfinavir (NFV) or nevirapine (NVP) regimens in HIV-infected naive patients. 63 patients were included in the ZDV/3TC/NFV arm and 64 in the ZDV/3TC/NVP arm.No statistically significant differences were observed at baseline in demographic and clinical variables and HRQoL scores between treatment groups, except that the proportion of homosexual men was higher in the ZDV/3TC/NVP arm. There were no statistically significant differences in HRQoL scores between arms at 12 months and over time; only ZDV/3TC/NVP patients showed statistically significant improvement in Physical Health Summary score (p.01) and a trend toward a better profile in Mental Health Summary score (p =.07). Overall, patients who were treated with ZDV/3TC/NVP showed greater changes in physical dimensions and patients who were treated with ZDV/3TC/NFV showed greater changes in mental health.Differences in HRQoL between study groups at 1 year follow-up were not detected. Nevertheless, a trend toward improvement was observed in summary health scores in ZDV/3TC/NVP-treated patients.

We assessed the strategy of substituting nevirapine, efavirenz, or abacavir for a protease inhibitor in patients infected with human immunodeficiency virus type 1 (HIV-1) in whom virologic suppression had been achieved.We randomly assigned 460 adults who were taking two nucleoside reverse-transcriptase inhibitors and at least one protease inhibitor and whose plasma HIV-1 RNA levels had been less than 200 copies per milliliter for at least the previous six months to switch from the protease inhibitor to nevirapine (155 patients), efavirenz (156), or abacavir (149). The primary end point was death, progression to the acquired immunodeficiency syndrome, or an increase in HIV-1 RNA levels to 200 copies or more per milliliter.At 12 months, the Kaplan-Meier estimates of the likelihood of reaching the end point were 10 percent in the nevirapine group, 6 percent in the efavirenz group, and 13 percent in the abacavir group (P=0.10 according to an intention-to-treat analysis). HIV-1 RNA could be amplified in 21 of the 29 patients in whom virologic failure developed during treatment with study medication (72 percent), and resistance mutations to the study medication and to at least one of the nucleoside reverse-transcriptase inhibitors in the regimen that failed were detected in all but 1 of the 21 patients. Twenty-three of the 29 patients with virologic failure during treatment with study medication had received prior suboptimal therapy with nucleoside reverse-transcriptase inhibitors. Fewer patients in the abacavir group (6 percent) than in the nevirapine group (17 percent) or the efavirenz group (17 percent) discontinued the study medication because of adverse events (P=0.01). The proportion of patients with fasting lipid levels warranting therapeutic intervention decreased significantly in the abacavir group, but the prevalence of clinical lipodystrophy did not change significantly in the three groups.When therapy was switched from a protease inhibitor to nevirapine, efavirenz, or abacavir in patients with virologic suppression, there was a trend toward a higher rate of virologic failure among those given abacavir.

Resumen Objetivo Actualizar las recomendaciones sobre alteraciones metabolicas y riesgo cardiovascular en pacientes con infeccion por el VIH. Metodos Este documento ha sido consensuado por un panel de expertos de GEAM, de la SPNS y de GESIDA tras revisar los resultados de eficacia y seguridad de ensayos clinicos, estudios de cohortes y de farmacocinetica publicados en revistas biomedicas (PubMed y Embase) o presentados a congresos. La fuerza de la recomendacion y la gradacion de su evidencia se basan en los criterios del sistema GRADE. Resultados Se recomienda un estilo de vida saludable, no fumar y realizar al menos 30 min de ejercicio aerobico al dia. En los pacientes diabeticos se recomienda utilizar el mismo algoritmo terapeutico que en la poblacion no VIH. Los pacientes VIH con dislipidemia deben ser considerados como minimo de alto riesgo cardiovascular, por lo que su objetivo terapeutico sera cLDL menor de 100 mg/dl. Los antihipertensivos de las familias IECA y ARA II son los mejor tolerados y con menor riesgo de interacciones. Se recomienda descartar esteatosis hepatica en pacientes diabeticos o con sindrome metabolico y con elevacion de transaminasas sin etiologia definida. Se actualizan asi mismo las recomendaciones de actuacion en alteraciones hormonales. Conclusiones En este nuevo documento se actualizan las recomendaciones previas respecto a todas las alteraciones metabolicas que intervienen en el riesgo cardiovascular. Asi mismo se incluyen las alteraciones hormonales y su manejo, y la repercusion hepatica de las alteraciones metabolicas.

The importance of the metabolic disorders and their impact on patients with HIV infection requires an individualized study and continuous updating. HIV patients have the same cardiovascular risk factors as the general population. The HIV infection per se increases the cardiovascular risk, and metabolic disorders caused by some antiretroviral drugs are added risk factors. For this reason, the choice of drugs with a good metabolic profile is essential. The most common metabolic disorders of HIV infected-patients (insulin resistance, diabetes, hyperlipidemia or osteopenia), as well as other factors of cardiovascular risk, such as hypertension, should also be dealt with according to guidelines similar to the general population, as well as insisting on steps to healthier lifestyles. The aim of this document is to provide a query tool for all professionals who treat HIV-patients and who may present or display any metabolic disorders listed in this document. (C) 2014 Elsevier Espana, S.L.U. and Sociedad Espanola de Enfermedades Infecciosas y Microbiologia Clinica. All rights reserved.

ObjectivesEx vivo analysis of mitochondrial function may reveal HIV progression and the impact of ART. We propose a mitochondrial and apoptotic in vitro model using Jurkat T cells incubated with plasma. The objectives of this study were to evaluate mitochondrial and apoptotic lesions in this model in relation to HIV progression, and to assess the effect of >1 year of standard non-thymidine-containing therapy.MethodsThis was a cross-sectional comparison among three age- and gender-matched groups (n = 19 × 3): healthy non-HIV-infected participants, HIV-infected long-term non-progressors (LTNPs) and standard antiretroviral-naive chronically infected patients [standard progressors (Sps)], longitudinally evaluated before (Sp1) and after (Sp2) >1 year of efavirenz + tenofovir + emtricitabine therapy. We analysed mitochondrial DNA content by RT–PCR, mitochondrial function by spectrophotometry, mitochondrial protein synthesis by western blot analysis, mitochondrial dynamics by western blot analysis (MFN2), apoptotic transition pore formation by western blot analysis (VDAC-1) and mitochondrial membrane potential and annexin V/propidium iodide fluorescence by flow cytometry.ResultsThere was a decreasing non-significant trend towards lower mitochondrial parameters for HIV-infected values with respect to uninfected control reference values. HIV progression (LTNP versus Sp1) was associated with decreased mitochondrial genetic, functional and translational parameters, which partially recovered after treatment intervention (Sp2). Mitochondrial fusion showed a trend to decrease non-significantly in Sp patients compared with LTNP patients, especially after therapy. All apoptotic parameters showed a trend to increase in Sp1 with respect to LTNP, followed by recovery in Sp2.ConclusionsWe proposed an in vitro model for mitochondrial and apoptotic assessment to test the effects of HIV infection and its therapy, resembling in vivo conditions. This model could be useful for clinical research purposes.

Survey in 349 HIV infected subjects in 19 Spanish Hospitals in 2010-2011, to assess the reasons for antiretroviral treatment change. Simplification was the most frequent reason for change (37%), followed by toxicity (30%) and treatment failure (21%). There were statistically significant differences according to treatment line and transmission category. In conclusion, in many patients treatment is changed in order to obtain the benefits of a regimen easier to follow.

This consensus document is an update of metabolic disorders and cardiovascular risk (CVR) guidelines for HIV-infected patients.This document has been approved by an expert panel of GEAM, SPNS and GESIDA after reviewing the results of efficacy and safety of clinical trials, cohort and pharmacokinetic studies published in biomedical journals (PubMed and Embase) or presented in medical scientific meetings. Recommendation strength and the evidence in which they are supported are based on the GRADE system.A healthy lifestyle is recommended, no smoking and at least 30min of aerobic exercise daily. In diabetic patients the same treatment as non-HIV infected patients is recommended. HIV patients with dyslipidemia should be considered as high CVR, thus its therapeutic objective is an LDL less than 100mg/dL. The antihypertensive of ACE inhibitors and ARAII families are better tolerated and have a lower risk of interactions. In HIV-patients with diabetes or metabolic syndrome and elevated transaminases with no defined etiology, the recommended is to rule out a hepatic steatosis Recommendations for action in hormone alterations are also updated.These new guidelines update previous recommendations regarding all those metabolic disorders involved in CVR. Hormone changes and their management and the impact of metabolic disorders on the liver are also included.

Background Non-nucleoside reverse transcriptase inhibitor-containing regimens may be a valid alternative to protease inhibitor-containing regimens for initial antiretroviral therapy, but to date few studies comparing these two strategies have been performed. Objective To evaluate the efficacy and safety of nelfinavir or nevirapine associated to zidovudine/lamivudine in HIV-infected naive patients. Design Randomized, open-label, multicentre trial. Setting Twelve centres in Spain (9) and Argentina (3). Patients One hundred and forty-two HIV-infected naive patients without AIDS. Interventions Patients received combivir (zidovudine 300 mg/lamivudine 150 mg, twice-daily) plus either nelfinavir (1250 mg) twice-daily (zidovudine/lamivudine/nelfinavir, n=70) or nevirapine (200 mg) twice-daily (zidovudine/lamivudine/nevirapine, n=72), and were followed for 12 months. The primary endpoint was the proportion of patients with a plasma HIV-1 RNA (pVL) of less than 200 copies/ml by PCR at 12 months. pVL of less than 20 copies/ml (PCR), changes in CD4 counts, clinical progression and adverse events were also evaluated. Efficacy was assessed using intent-to-treat (ITT) (missing=failure) and on-treatment analysis. Results At 12 months in the ITT analysis the proportion of patients with pVL below 200 copies/ml was 60% (95% CI 48.5–71.5) in the zidovudine/lamivudine/nelfinavir arm and 75% (95% CI 65–85) in the zidovudine/lamivudine/nevirapine arm ( P=0.06), and the proportion below 20 copies/ml was 50% (95% CI 38.3–61.7) and 65% (95% CI 54.2–76.2), respectively ( P=0.06). No differences were found when comparing the subgroup of patients with baseline pVL of more than 100 000 copies/ml. A gain of +173 and +162 CD4 cells/mm3, respectively, was observed. Zidovudine/lamivudine/nelfinavir was discontinued in 21% of patients, and zidovudine/lamivudine/ nevirapine in 25%, due to toxicity ( P>0.2). Conclusions Our results suggest that zidovudine/ lamivudine/nevirapine is at least as effective as zidovudine/lamivudine/nelfinavir as first-line therapy for HIV disease.

Smoking is the most important modifiable cardiovascular risk factor. Bupropion administration is an effective method to achieve smoking cessation (SC), but the drug is metabolized by the cytochrome P450 enzyme system and this might cause interactions with antiretroviral drugs. We present a prospective study of bupropion SC therapy in HIV-positive patients under antiretroviral treatment. A total of 21 patients were studied; 38% of them stopped smoking for more than one year. No clinically significant drug interactions were found. Bupropion SC therapy was effective in HIV-positive patients and did not cause significant clinical interactions with antiretroviral drugs.

Fundamento y objetivo Conocer la utilidad clinica del tratamiento hipolipemiante con atorvastatina en pacientes infectados por el virus de la inmunodeficiencia humana (VIH) con hipercolesterolemia asociada al tratamiento antirretroviral, asi como su tolerabilidad. Pacientes y metodo Estudio observacional, prospectivo y no controlado que incluye a pacientes infectados por el VIH en tratamiento antirretroviral que presentan dislipemia secundaria con criterios de tratamiento medico segun el National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III). La intervencion terapeutica realizada fue atorvastatina a dosis de 10 mg/dia y medidas higienico-dieteticas. Si a los 3 meses de tratamiento no se alcanzaba los objetivos terapeuticos, se aumentaba la dosis de atorvastatina a 20 mg/dia. Se realizo un seguimiento clinico y analitico durante 6 meses. Resultados Se incluyo a 32 pacientes. En 5 casos se preciso aumentar la dosis de 10 a 20 mg de atorvastatina al dia. En un 62% de los casos se consiguio el objetivo terapeutico con buena tolerancia clinica. Se observo un efecto adverso que obligo a retirar el farmaco. Conclusion En este estudio, la atorvastatina ha resultado ser eficaz y bien tolerada para el tratamiento de la dislipemia en la poblacion infectada por el VIH+.

Fundamento y objetivo En los pacientes tratados con nelfinavir y metadona disminuyen los valores plasmaticos de esta, lo que clinicamente no suele ser importante, ya que no aparecen sintomas de abstinencia a opiaceos (SAO). Nuestro objetivo ha sido evaluar las interacciones clinicas y farmacocineticas entre la metadona y el nelfinavir. Pacientes y metodo Estudio prospectivo y multicentrico con pacientes infectados por el virus de la inmunodeficiencia humana en tratamiento estable con metadona que iniciaban nelfinavir. La presencia de SAO se averiguo mediante sendos cuestionarios, objetivo y subjetivo, en las semanas 1, 2, 3 y 4. En un subgrupo de pacientes se midio la concentracion minima plasmatica de metadona basalmente y a la cuarta semana de tratamiento. Resultados Se incluyo a 29 pacientes y en 7 se realizo estudio farmacocinetico. La concentracion minima plasmatica de metadona disminuia a la cuarta semana de recibir nelfinavir desde 6,889 hasta 4,354 ng/ml (37%; p = 0,046). Los cuestionarios no detectaron SAO de forma significativa, por lo que no fue necesario cambiar significativamente las dosis de metadona. Conclusiones La administracion de nelfinavir en pacientes en tratamiento estable con metadona no precisa de modificaciones significativas de la dosis de esta, ya que el descenso producido en sus valores plasmaticos no provoca la aparicion de SAO.

Highly-active antiretroviral therapy (HAART) can induce a characteristic lipodystrophy syndrome characterized by peripheral fat wasting and central adiposity, usually associated with hyperlipidaemia and insulin resistance [1,2]. Indirect data have led some authors to propose that mitochondrial dysfunction could play a role in this syndrome [3,4].To date, as recently outlined by Kakuda et al. [5] in this journal, HIV-infected patients developing lipodystrophy have not been studied for mitochondrial changes or respiratory chain capacity...

Summary Zidovudine (ZDV), a nucleoside analogue which inhibits viral replication, is currently used in the treatment of type 1 human immunodeficiency virus (HIV-1) infection. It has been considered to be the cause of an acquired form of myopathy associated with a depletion of mitochondrial DNA (mtDNA) in muscle fibres, although the fact that the patients previously studied were clearly symptomatic, and the theoretical difficulty in differentiating an HIV-related myopathy from the effects of ZDV, led to a controversy on the possible deleterious effect of ZDV on muscle fibres. We studied the muscle biopsy taken from 42 HIV-1 infected patients, regardless of their medical complaints, and two series of controls: 12 HIV-negative patients suffering from diverse neuromuscular diseases and 10 normal patients who underwent orthopaedic surgery. Whole DNA was extracted following standard procedures and analysed by means of Southern blotting and polymerase chain reaction (PCR). We found that mtDNA was only depleted in HIV-1 infected patients treated with ZDV, but not in controls or patients untreated with this antiretroviral drug. Moreover, the depletion was more marked in patients who either presented weakness, myalgia, raised serum creatine kinase (CK), or ragged-red fibres. Mitochondrial DNA deletions were found in low proportion in all groups of patients, regardless of their HIV infection or ZDV status, but not in normal controls. We conclude that ZDV treatment in HIV-1 positive patients produces depletion of muscle mtDNA. The depletion can be demonstrated even in asymptotic patients, but is more marked in patients with clinical symtoms or abnormalities in their muscle biopsies. Other mtDNA abnormalities such as deletions seemed to be more related to other circumstances concurring in HIV-1 infected patients than to the effects of ZDV.

Currently, 2',3'-dideoxyinosine (ddI) is used in AIDS therapy. To investigate the possible myotoxicity of ddI in patients infected with human immunodeficiency virus (HIV), we examined the effect of ddI in vitro in tissue cultures of skeletal muscles of rats exposed to ddI at doses equivalent to plasma ddI levels obtained in the treatment of HIV patients. Control cultures were exposed to normal saline and zidovudine (AZT). After 4 weeks no changes were noted in the ddI and normal saline cultures, but AZT cultures showed abnormal accumulation of mitochondria. The creatine kinase values in culture supernatants were all normal. We also reviewed the clinical, nutritional and biological parameters, AZT and ddI dosage, and histochemical findings in muscle specimens of 14 HIV patients receiving ddI therapy. All patients had previously received AZT. The mean cumulative dose of ddI was 91.6 gm. Two patients had myalgia, 9 muscle atrophy, and 13 weakness. All patients were malnourished. Five patients had mitochondrial myopathy related to AZT, 4 had ddI-associated neuropathy and 2 patients had only selective type 2 fiber atrophy. One patient had necrotizing vasculitis, one had scattered necrotic fibers and type 2 fiber atrophy and 2 had a normal muscle biopsy. On the basis of the results, we have been unable to implicate ddI as a cause of skeletal myopathy.

Objectives: Current antiretroviral guidelines state that being older than 50 to 55 years of age is an indication to start antiretroviral therapy (ART), regardless of CD4 status. However, no references to the preferred combination ART (cART) for these patients have been described. Our study compares emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) versus other nucleoside reverse transcriptase inhibitor (NNRTI) regimens in HIV ART-naive patients who are >= 50 years. Design: National, retrospective cohort analysis of patients who were >= 50 years old when they began the first cART (January 1, 2006 to December 31, 2009). Methods: We compared safety, effectiveness, and persistence of treatment in FTC/TDF versus non-FTC/TDF users. Among FTC/TDF users, we compared protease inhibitor (PI) versus NNRTI users and lopinavir/r versus efavirenz users. Results: We included 161 patients: median age was 54.6 years, 83% were men, median CD4 count was 191 cells/mu L, median viral load was 4.7 log, and median follow-up was 19 months (maximum, 48 months). Of these participants, 112 started with FTC/TDF and 49 with other nucleotide reverse transcriptase inhibitors (NRTIs). During follow-up, 21.9% of subjects developed at least one laboratory event >= grade 3, 5.6% interrupted cART due to adverse events, 19.3% had virologic failure, and 49.1% modified cART. There were no statistically significant differences between FTC/TDF and non-FTC/TDF users for any output except for persistence: The proportion of subjects who changed cART was 71.4% for non-FTC/TDF users and 38.6% for FTC/TDF users (log rank 0.001; adjusted hazard ratio, 2.10; 95% Cl, 1.34-3.29). Conclusions: In a population of HIV-infected subjects who were years old, our study suggests that the use of FTC/TDF is generally safe and effective, with a longer persistence as compared to other regimens.

Fundamento y objetivo Averiguar el tipo deconsultas urgentes que realizan los usuariosde un centro de atencion y seguimiento dedrogodependencias (CAS). Pacientes y metodo Estudio prospectivo de consultasurgentes realizadas durante 6 meses porpacientes controlados en un CAS. Resultados Se siguio a 333 pacientes, de loscuales 27 (8%) consultaron; de estos, 9 (33%)se hallaban infectados por el virus de la inmunodeficienciahumana (VIH). Los heroinomanos realizaronmas consultas y las reiteraron mas quelos cocainomanos (p Conclusiones Se diferencian dos tipos de consulta:la motivada por trastornos psiquiatricos odrogas, solucionada con una visita, sin ingresoy realizada por pacientes con menos de un anode seguimiento, y la causada por motivos medicos(frecuentemente relacionada con el VIH),generada por pacientes con mayor seguimientoque suelen repetirla e ingresar.

Objectives: Primary - evaluate the improvement in psychiatric symptoms attributable to changing the antiretroviral drug responsible for such symptoms to nevirapine (NVP). The tools used were a sleep test (the Pittsburgh Sleep Quality Index [PSQI]) and the Hospital Anxiety and Depression Scale (HADS). Secondary - determine the neuropsychiatric disorders and evaluate adherence to treatment and quality of life. Methods : Prospective, observational post-authorisation study that included HIV-1 patients from 36 Spanish hospitals who satisfied the following criteria: age over 18 years; change of antiretroviral treatment to NVP due to CNS side-effects; a PSQI score >5 (significant sleep disturbance); a HADS score ≥10 on the day of starting NVP treatment; and no psychoactive drug treatment initiated during the 6 weeks prior to starting treatment with NVP. Other data gathered from the patients included clinical and demographic details and administration of the Epworth somnolence scale, the Medical Outcomes Study-short form 30 items (MOS-SF-30) quality of life scale and the Simplified Medication Adherence Questionnaire (SMAQ). Evaluations were performed at baseline, 1 and 3 months after the change. Results : 129 patients were included (73.6% men; mean age, 43.2 ± 9.8 years; 36.5% homosexual, 30.2% heterosexual; 28.7% drug users; 38% AIDS; 33.3% co-infection). The drug changed was efavirenz in 89.9% of cases. The reason for the change was sleep disturbances in 75.2%, anxiety in 65.1%, other psychiatric disturbances in 38.7%, attention disturbances in 31%, and other reasons in 31%; a mean of 2.4 neuropsychiatric disturbances were detected in each patient. CD4 rose from 582 ± 261 to 619 ± 299 (non-significant difference). Only three patients had developed an HIV viral load at the end of the study. The differences produced by the change are shown in Table 1. 29 patients withdrew from the study, for the following reasons: 9 for NVP-related toxicity (7 cases of rash and 2 of hepatitis); 7 for loss to follow-up; 4 for voluntary withdrawal; 9 for other reasons. Discussion : The study shows that the change to NVP from a drug that is causing neuropsychiatric disturbances (principally, efavirenz) is effective in resolving those disturbances, with an improvement in all the parameters studied (quality of sleep, anxiety/depression and somnolence). This leads to better adherence and a better quality of life with no detriment to their immunological and virological control. (Published: 11 November 2012) Citation: Abstracts of the Eleventh International Congress on Drug Therapy in HIV Infection Pedrol E et al. Journal of the International AIDS Society 2012, 15 (Suppl 4):18347 http://www.jiasociety.org/index.php/jias/article/view/18347 | http://dx.doi.org/10.7448/IAS.15.6.18347

The new European Guidelines of Dislipidemia Management of the European Societies of Cardiology and Arteriosclerosis consider HIV+ as patients at high risk of developing cardiovascular events and deaths. The objective of the study was to evaluate cardiovascular events and deaths in a series of HIV+ patients. Observational, cross-sectional study, including a cohort of HIV+ and HIV- patients from 2008. CVR was calculated using the SCORE-CVR chart. Variation on lipid profile and incidence of cardiovascular events, cardiovascular death or death related to any cause were recorded. Data was analyzed using SPSS version 20.0 for MAC. 154 HIV+ and 155 HIV- patients were included. Mean age: 44.8±9.5 vs 55.2±14.3 y and 69.5% vs 49% males respectively (p

Background : Until the past decade, immune/viral failure was the main reason for antiretroviral treatment changes. After HAART generalization the management of antiretroviral treatment toxicities was the most prevalent reason for treatment modification. Today, with the advent of new more potent and less toxic drugs as well as more convenient combinations may have changed the situation. We aim to describe the main reasons that today leads to ART changes in HIV+ patients in Spain in the current clinical practice. Methods : Multicentre, national, cross-sectional epidemiological study. Eligible patients had to be HIV+, >18 years old and under current ART that was going to be changed by any reason. Patients did sign inform consent. The study consisted in a single visit (change of treatment) in which data on social and demographic characteristics, HIV disease and ARV treatment were collected. Results : 349 patients were included; mean age: 43.7±8.9 y, 70.5% male and 89.1% Caucasian. Main transmission categories were IVDU (36.4%) and heterosexual (36.4%). Mean time from HIV diagnosis was 11.3±7.6 y. 59.5% were CDC C category. Median CD4 nadir was: 155 cells/mm 3 and median CD4 at the time of switching was 467 cells/mm 3 . 64.1% had undetectable viral load (

The major antiretroviral guidelines recommend starting ART in patients >50 y of age, regardless of CD4 cell count. However, no references to the preferred cART for these patients have been described. The combination FTC/TDF is one of the cornerstones of combined antiretroviral therapy (cART) in naive patients. We studied the persistence of coformulated FTC/TDF in this scenario. National, retrospective cohort analysis of HIV-infected patients >50 y at the time they began the first cART regimen (January 1, 2006 - December 31, 2009). Patients were selected in a proportion 2:1 to FTC/TDF vs. other NRTI regimens (no-TDF). We compared the persistence of treatment in FTC/TDF users vs. no-TDF (main groups). Among TDF users, we compared the persistence in PI vs. NNRTI users and in lopinavir/r vs. efavirenz users. Persistence was defined as the duration of the initial treatment; we analyzed time to any change or discontinuation according to initial regimen. We included 161 patients: median age: 54.6 y, 83% males, median CD4 count 191 cells/μl, median viral load 4.7 log, follow up: median 19 months, max 48 months. Of them, 112 started with FTC/TDF (53 with PIs, 57 with NNRTIs); and 49 with other NRTIs (no-TDF) (22 with PI, 23 NNRTI). During the follow-up period 79 patients (49%) modified their treatment, with statistically significant differences among groups, as shown in Table 1. In our study (antiretroviral-naive patients > 50 y), the persistence of FTC/TDF regimens was significantly higher than other NRTI regimens. According to the third agent, there was a trend to a higher persistence with NNRTI vs. PI. This reaches statistical significance when we compare EFV vs. LPV/r. In the absence of randomized clinical trials, our data may contribute to a better understanding on how cART works in this ageing population, which is progressively increasing. (Published: 11 November 2012) Citation: Abstracts of the Eleventh International Congress on Drug Therapy in HIV Infection Pedrol E et al. Journal of the International AIDS Society 2012, 15 (Suppl 4):18292 http://www.jiasociety.org/index.php/jias/article/view/18292 | http://dx.doi.org/10.7448/IAS.15.6.18292