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Background Reports on the impact of some antiretrovirals against SARS-CoV-2 infection and disease severity are conflicting. Objectives We evaluated the effect of tenofovir as either tenofovir alafenamide/emtricitabine (TAF/FTC) or tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) against SARS-CoV-2 infection and associated clinical outcomes among people living with HIV (PLWH). Methods We conducted a propensity score-matched analysis in the prospective PISCIS cohort of PLWH (n = 14 978) in Catalonia, Spain. We used adjusted Cox regression models to assess the association between tenofovir and SARS-CoV-2 outcomes. Results After propensity score-matching, SARS-CoV-2 diagnosis rates were similar in TAF/FTC versus ABC/3TC recipients (11.6% versus 12.5%, P = 0.256); lower among TDF/FTC versus ABC/3TC recipients (9.6% versus 12.8%, P = 0.021); and lower among TDF/FTC versus TAF/FTC recipients (9.6% versus 12.1%, P = 0.012). In well-adjusted logistic regression models, TAF/FTC was no longer associated with reduced SARS-CoV-2 diagnosis [adjusted odds ratio (aOR) 0.90; 95% confidence interval (CI), 0.78–1.04] or hospitalization (aOR 0.93; 95% CI, 0.60–1.43). When compared with ABC/3TC, TDF/FTC was not associated with reduced SARS-CoV-2 diagnosis (aOR 0.79; 95% CI, 0.60–1.04) or hospitalization (aOR 0.51; 95% CI, 0.15–1.70). TDF/FTC was not associated with reduced SARS-CoV-2 diagnosis (aOR 0.79; 95% CI, 0.60–1.04) or associated hospitalization (aOR 0.33; 95% CI, 0.10–1.07) compared with TAF/FTC. Conclusions TAF/FTC or TDF/FTC were not associated with reduced SARS-CoV-2 diagnosis rates or associated hospitalizations among PLWH. TDF/FTC users had baseline characteristics intrinsically associated with more benign SARS-CoV-2 infection outcomes. Tenofovir exposure should not modify any preventive or therapeutic SARS-CoV-2 infection management.

Summary Background Factors affecting outcomes of SARS-CoV-2 infection in people living with HIV are unclear. We assessed the factors associated with SARS-CoV-2 diagnosis and severe outcomes among people living with HIV. Methods We did a retrospective cohort study using data from the PISCIS cohort of people with HIV in Catalonia (Spain) between March 1 and Dec 15, 2020. We linked PISCIS data with integrated health-care, clinical, and surveillance registries through the Public Data Analysis for Health Research and Innovation Program of Catalonia (PADRIS) to obtain data on SARS-CoV-2 diagnosis, chronic comorbidities, as well as clinical and mortality outcomes. Participants were aged at least 16 years in care at 16 hospitals in Catalonia. Factors associated with SARS-CoV-2 diagnoses and severe outcomes were assessed using univariable and multivariable Cox regression models. We estimated the effect of immunosuppression on severe outcomes (hospital admission for >24 h with dyspnoea, tachypnoea, hypoxaemia, asphyxia, or hyperventilation; or death) using Kaplan-Meier survival analysis. Findings We linked 20 847 (72·8%) of 28 666 participants in the PISCIS cohort with PADRIS data; 13 142 people had HIV. 749 (5·7%) people with HIV were diagnosed with SARS-CoV-2: their median age was 43·5 years (IQR 37·0–52·7), 131 (17·5%) were female, and 618 (82·5%) were male. 103 people with HIV (13·8%) were hospitalised, seven (0·9%) admitted to intensive care, and 13 (1·7%) died. SARS-CoV-2 diagnosis was more common among migrants (adjusted hazard ratio 1·55, 95% CI 1·31–1·83), men who have sex with men (1·42, 1·09–1·86), and those with four or more chronic comorbidities (1·46, 1·09–1·97). Age at least 75 years (5·2, 1·8–15·3), non-Spanish origin (2·1, 1·3–3·4), and neuropsychiatric (1·69, 1·07–2·69), autoimmune disease (1·92, 1·14–3·23), respiratory disease (1·84, 1·09–3·09), and metabolic disease (2·59, 1·59–4·23) chronic comorbidities were associated with increased risk of severe outcomes. A Kaplan-Meier estimator showed differences in the risk of severe outcomes according to CD4 cell count in patients with detectable HIV RNA (p=0·039) but no differences were observed in patients with undetectable HIV RNA (p=0·15). Interpretation People living with HIV with detectable HIV viraemia, chronic comorbidities, and some subpopulations could be at increased risk of severe outcomes from COVID-19. These groups should be prioritised in clinical management and SARS-CoV-2 vaccination programmes. Funding Fundacio "la Caixa". Translations For the Catalan, Spanish and Russian translations of the Summary see Supplementary Materials section.

[Abstract] A percentage of hepatitis C virus (HCV)-infected patients fail direct acting antiviral (DAA)-based treatment regimens, often because of drug resistance-associated substitutions (RAS). The aim of this study was to characterize the resistance profile of a large cohort of patients failing DAA-based treatments, and investigate the relationship between HCV subtype and failure, as an aid to optimizing management of these patients. A new, standardized HCV-RAS testing protocol based on deep sequencing was designed and applied to 220 previously subtyped samples from patients failing DAA treatment, collected in 39 Spanish hospitals. The majority had received DAA-based interferon (IFN) α-free regimens; 79% had failed sofosbuvir-containing therapy. Genomic regions encoding the nonstructural protein (NS) 3, NS5A, and NS5B (DAA target regions) were analyzed using subtype-specific primers. Viral subtype distribution was as follows: genotype (G) 1, 62.7%; G3a, 21.4%; G4d, 12.3%; G2, 1.8%; and mixed infections 1.8%. Overall, 88.6% of patients carried at least 1 RAS, and 19% carried RAS at frequencies below 20% in the mutant spectrum. There were no differences in RAS selection between treatments with and without ribavirin. Regardless of the treatment received, each HCV subtype showed specific types of RAS. Of note, no RAS were detected in the target proteins of 18.6% of patients failing treatment, and 30.4% of patients had RAS in proteins that were not targets of the inhibitors they received. HCV patients failing DAA therapy showed a high diversity of RAS. Ribavirin use did not influence the type or number of RAS at failure. The subtype-specific pattern of RAS emergence underscores the importance of accurate HCV subtyping. The frequency of “extra-target” RAS suggests the need for RAS screening in all three DAA target regions. Ministerio de Economía y Empresa; IDI-20151125 Ministerio de Ciencia, Innovación y Universidades; SAF SAF 2017-87846-R

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. 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. 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 mu g/mL. 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.

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.

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.

Introducción En España algunos pacientes con VIH no reciben tratamiento antirretroviral (TAR), aun teniendo indicaciones para ello. Nuestro objetivo es identificar las barreras de inicio del TAR en pacientes con indicación para recibirlo. Métodos Encuesta transversal en 19 hospitales en España en 2012, incluyendo todos los pacientes que no recibían tratamiento y tenían al menos una indicación según las recomendaciones de Gesida/2011. Las posibles barreras se agruparon así (categorías no excluyentes): a) el médico considera que la indicación no es absoluta; b) el paciente no quiere iniciarlo; c) el médico considera que debe iniciarlo pero existe alguna limitación o contraindicación; y d) el paciente tiene viremia indetectable en ausencia de tratamiento. Resultados Se incluyeron 256 pacientes de los 784 programados; 84% hombres, mediana de edad 39 años; 57% homosexuales, 24% heterosexuales, 16% UDI. Mediana de tiempo desde el diagnóstico: 3 años, CD4: 501 células/mm3, carga viral 4,4 log. Indicaciones de TAR más frecuentes: CD4

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.

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.

In Spain, HIV treatment guidelines are well known and generally followed. However, in some patients there are no plans to initiate ART despite having treatment indications. The current barriers to ART initiation are presented.A cross-sectional survey including every HIV infected patient in care in 19 hospitals across Spain in 2012, with ≥1 indication to start ART according to 2011 national treatment guidelines, who had not been scheduled for ART initiation. Reasons for deferring treatment were categorized as follows (non-exclusive categories): a) The physician thinks the indication is not absolute and prefers to defer it; b) The patient does not want to start it; c) The physician thinks ART must be started, but there is some limitation to starting it, and d) The patient has undetectable viral load in absence of ART.A total of 256 patients, out of 784 originally planned, were included. The large majority (84%) were male, median age 39 years, 57% MSM, 24% heterosexuals, and 16% IDUs. Median time since HIV diagnosis was 3 years, median CD4 count, 501 cells/mm3, median viral load 4.4 log copies/ml. Main ART indications were: CD4 count500 cells/mm(3), 48%; having an uninfected sexual partner, 28%, and hepatitis C coinfection, 23%. Barriers due to, the physician, 55%; the patient, 28%; other limitations, 23%; and undetectable viral load, 6%.The majority of subjects with ART indication were on it. The most frequent barriers among those who did not receive it were physician-related, suggesting that the relevance of the conditions that indicate ART may need reinforcing.

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.

Stavudine (d4T) has shown a favourable short and long-term tolerability profile. Nevertheless, its usage is currently decreasing due to some safety concerns. We aimed to evaluate the efficacy and safety of d4T low-dose-based regimens.This was a multicenter and retrospective review chart of patients receiving standard doses of d4T foror = 6 months (weight60 kg: 40 mg/12 h; weight60 kg: 30 mg/12 h) and having undetectable viral load for at least 3 months before the d4T dose reduction (weight60 kg: 30 mg/12 h; weight60 kg: 20 mg/12 h). Immunological and viral parametres, lipid profile and side effects were determined.A total of 982 patients were included. The main reason for reducing the dose was prevention of toxicity (76%). After 6 months of follow-up, 97% and 84% patients had less than 400 and 50 cp/ml, respectively, and the CD4 cell count increased by 38 cel/ml. Lipids, lipodystrophy and peripheral polineuropathy improved but there was no statistical significance.A d4T dose reduction in an immuno-virologically stable population does not affect treatment efficacy. Longer follow-ups are required to confirm improvements in the safety profile.

Mitochondrial parameters in peripheral blood mononuclear cells (PBMC) and their relationship with mitochondrially- driven PBMC apoptosis were investigated in a group of HIV-1-infected long-term nonprogressors (LTNP) and compared with untreated asymptomatic HIV-1 infected typical progressors (TP) and uninfected healthy controls (HC). Twenty-six LTNP, 27 TP and 31 HC were evaluated. Studies were performed in PBMCs. Mitochondrial DNA content (mtDNA) was assessed by quantitative real-time PCR. Activities of mitochondrial respiratory chain complexes (MRC) II, III and IV were determined by spectrophotometry. Caspase-3 activity was assessed by fluorimetry, and caspase-9 activation and Bcl-2 levels were assessed by immunoblotting. mtDNA abundance (p < 0.05), MRC complex II (p < 0.001), complex III (p < 0.01) and complex IV (p=0.01) were lower in the TP group than in the HC group. In the LTNP group these parameters were similar to those of the HC group except for complex II, which was decreased (p < 0.01). The PBMC of TP showed the highest overall apoptotic activation, since their caspase-3 activity was greater than that of HC (p < 0.05) and LTNP. In the case of LTNP, however, the difference was non-significant. Caspase-9 and the caspase-9/Bcl-2 ratio were both over-expressed in TP compared to HC (p < 0.01) and LTNP (p < 0.05). Both of these measurements indicate that mitochondrially- driven apoptosis in TP is greater than in LTNP and HC. A relationship between mitochondrial damage and apoptotic activation was found in TP. Mitochondrial damage is associated with increased PBMC apoptosis in patients with active HIV-1 replication (TP). These abnormalities are slight or not present in LTNP.

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.

We investigated atorvastatin effectiveness and tolerance in HIV patients with hypercholesterolemia related to antiretroviral treatment.Prospective study that included HIV+ patients under antiretroviral treatment who displayed secondary dyslipemia and medical treatment criteria (according to NCEP-III). These patients were given 10 mg/day atorvastatin and hygienic-dietetic measures. If the therapeutic objectives were not achieved, the dose of atorvastatin was increased to 20 mg/day. Patients were followed up for 6 months.32 patients were included. In 5 cases it was necessary to increase the dose from 10 mg atorvastatin to 20 mg. The therapeutic objective was obtained in 62% cases, with a good clinical tolerance. Only one adverse effect was noticed, which forced the removal of the drug.In our study atorvastatin was effective for the treatment of dyslipemia in HIV patients, and it was safe and well tolerated.

Patients on methadone maintenance therapy who are administered nelfinavir show a decrease in methadone plasma levels. However, the clinical relevance of this fact is seldom significant because it does not correlate with the appearance of opioid withdrawal symptoms (OWS). The objective of this study was to assess the clinical and pharmacokinetic interactions between methadone and nelfinavir.A prospective multicenter study of human immunodeficiency virus (HIV) positive patients on stable methadone therapy who initiated nelfinavir was performed. To determine the presence of OWS, 2 questionnaires, objective and subjective, were administered at weeks 1, 2, 3 and 4. A pharmacokinetic study measuring the minimal plasmatic concentration of methadone was done at baseline and at week 4.29 patient were included. In 7 patients who underwent pharmacokinetic studies, the minimal plasmatic concentration of methadone decreased after 4 weeks of nelfinavir treatment from 6.889 ng/ml to 4.354 ng/ml (37%; p = 0.046). However the results of the questionnaires did not show the significant OWS, which precluded an increase in the dose of methadone.In patients under stable methadone treatment, antiretroviral therapy including nelfinavir does not require any significant modification of methadone dose. The decrease in methadone plasmatic levels does not correlate with OWS.

We intended to find out the effectiveness of lactic acidosis therapy for mitochondrial toxicity.HIV-patients receiving nucleoside reverse transcriptase inhibitors (NRTIs), hospitalized with lactic acidosis or symptomatic hyperlactatemia. Venous hyperlactatemia was considered at2.2 mmol/l. Treatment consisted of a daily vitamin regime of L-carnitine, thiamine, vitamin B6, hydroxicobalamine, and vitamin C; any glucose intake was discontinued. NRTIs treatment was stopped immediately.Nine patients on current therapy were identified who had symptomatic hyperlactatemia (n = 4) or lactic acidosis (n = 5) from 1/2001 to 9/2002. All were patients with AIDS, receiving NRTIs with a mean duration of 5 years: ddI (n = 7), d4T (n = 5), AZT(n = 3), 3TC (n = 2), abacavir (n = 1). Most common symptoms were tachypnea, slight fever, abdominal pain, nausea, vomiting and diarrhea. All patients had a favourable prognosis after administration of L-carnitine and vitamin complexes, with discontinuation of NRTIs and glucose intake. Clinical features lasted 7 days. After 15 (5) months of follow up, none had a recurrence of the syndrome.The application of this therapy could play a role in the treatment of NRTI - related lactic acidosis.

To find out the type of emergency consultations made by users at a substance abuse treatment center (SATC).Prospective study of emergency consultations made during six months by patients controlled at a SATC.333 patients were followed up; 27 (8%) of them consulted and 9 (33%) were found to have an HIV infection. Heroin addicts consulted more times and repeated visits more commonly than cocaine addicts (p0.04 and 0.03). Patients enrolled in the methadone maintenance programme consulted less commonly than patients included in other programmes (p0.01). 35% of visited patients did not need treatment and 75% were discharged.We have detected two different types of consultations: those owing to a psychiatric/drug disorder in patients followed-up for less than 1 year, which are resolved after just one visit, without need of hospitalization; and those consultations caused by medical disorders, frequently related to HIV, which are generated by patients submitted to longer follow-up periods; these patients use to repeat the consultations and are commonly admitted.

Material and Methods: To evaluate the influence of nevirapine on atazanavir trough concentrations (C trough ) in a group of HIV-infected patients, we performed an open-label pilot study enrolling patients receiving 300/100 mg atazanavir/ritonavir once daily for 2 weeks or longer. Nevirapine was added at a dose of 200 mg once daily from Days 0 to 14 and 200 mg twice daily from Days 14 to 28. Atazanavir and nevirapine plasma C troughs were determined at Days 0 and 28. Atazanavir C troughs were compared between Days 0 and 28. Atazanavir and nevirapine C troughs at Day 28 were compared with historical controls receiving either 400 mg atazanavir once daily or 200 mg nevirapine twice daily. Results: Fourteen patients were enrolled and 11 completed the study. The geometric mean (range) atazanavir C trough decreased from 0.631 mg/L (range, 0.235-1.87 mg/L) at Day 0 to 0.316 mg/L (range, 0.142-1.109 mg/L) at Day 28 to give a geometric mean ratio of 0.59 (95% confidence interval, 0.38-0.80; P = 0.026); nonetheless, the atazanavir C trough remained higher than the minimum effective concentration in 80% of the participants and higher than the median concentration in the control subjects receiving 400 mg atazanavir once daily without ritonavir (geometric mean ratio, 3.20; 95% confidence interval, 1.65-6.22; P = 0.001). The nevirapine C trough at Day 28 was slightly higher than in the historical controls on 200 mg nevirapine twice daily without atazanavir (geometric mean ratio, 1.46; 95% confidence interval, 1.04-2.06; P = 0.030). Conclusion: We conclude that coadministration of 300/100 mg atazanavir/ritonavir once daily plus 200 mg nevirapine twice daily was safe and well tolerated but resulted in a decrease of atazanavir C trough by nearly half. Therefore, monitoring atazanavir C trough is recommended in patients treated with this drug combination, and increasing the atazanavir dose might be necessary.