Total hip arthroplasty in HIV-infected patients: a retrospective, controlled study.

BACKGROUND: Although HIV-infected patients are at greater risk of presenting with ischaemic necrosis of the femoral head, there have been concerns about whether total hip arthroplasty (THA) may have worse outcomes than expected. METHODS: From the Orthopedic and Trauma Surgery database we identified all patients who had undergone THA because of ischaemic necrosis of the femoral head from January 2001 until March 2010. Patient's diagnosis of HIV infection was confirmed at the time of arthroplasty by cross-matching with the HIV unit database. For every THA in HIV-infected patients, two THAs in patients not known to be HIV-infected, with the same diagnosis of ischaemic necrosis of the femoral head and having undergone surgery over the same period, were randomly selected. THAs were compared in HIV- and non-HIV-infected patients for surgical procedure, in-patient stay and long-term prognosis. RESULTS: There were 18 THAs in 13 HIV-infected patients and 36 THAs in 27 non-HIV-infected patients. No significant differences were observed in the mean time spent in surgery (106 vs. 109 minutes, respectively; P = 0.66), the need for red cell transfusion (1 vs. 4, respectively; P = 0.48) or the mean duration of hospitalization (7.8 vs. 9.4 days, respectively; P = 0.48). The two groups showed similar postoperative functional results, which were maintained until the end of the follow-up period (median 3.3 years in the HIV-positive group and 5.8 years in the HIV-negative group). CONCLUSION: Our study suggests that the outcome of THA in HIV-positive patients is not worse than that of HIV-negative patients, although future research on larger numbers of patients is required to confirm this.

Evaluation of antiretroviral-related errors and interventions by the clinical pharmacist in hospitalized HIV-infected patients.

OBJECTIVES: The aim of the study was to identify antiretroviral-related errors in the prescribing of medication to HIV-infected inpatients and to ascertain the degree of acceptance of the pharmacist's interventions. METHODS: An observational, prospective, 1-year study was conducted in a 750-bed tertiary-care teaching hospital by a pharmacist trained in HIV pharmacotherapy. Interactions with antiretrovirals were checked for contraindicated combinations. Inpatient antiretroviral prescriptions were compared with outpatient dispensing records for reconciliation. Renal and hepatic function was monitored to determine the need for dose adjustments. RESULTS: The prescriptions for 247 admissions (189 patients) were reviewed. Sixty antiretroviral-related problems were identified in 41 patients (21.7%). The most common problem was contraindicated combinations (n=20; 33.3%), followed by incorrect dose (n=10; 16.7%), dose omission (n=9; 15%), lack of dosage reduction in patients with renal or hepatic impairment (n=6; 10% and n=1; 1.7%, respectively), omission of an antiretroviral (n=6; 10%), addition of an alternative antiretroviral (n=5; 8.3%) and incorrect schedule according to outpatient treatment (n=3; 5%). Fifteen out of 20 errors were made during admission. A multivariate analysis showed that factors associated with an increased risk of antiretroviral-related problems included renal impairment [odds ratio (OR) 3.95; 95% confidence interval (CI) 1.39-11.23], treatment with atazanavir (OR 3.53; 95% CI 1.61-7.76) and admission to a unit other than an infectious diseases unit (OR 2.50; 95% CI 1.28-4.88). Use of a nonnucleoside reverse transcriptase inhibitor was a protective factor (OR 0.33; 95% CI 0.13-0.81). Ninety-two per cent of the pharmacist's interventions were accepted. CONCLUSION: Antiretroviral-related errors affected more than one-in-five patients. The most common causes of error were contraindicated or not recommended drug-drug combinations and dose-related errors. A clinical pharmacist trained in HIV pharmacotherapy could help to detect errors and reduce the duration of their effect.

A randomized trial comparing the efficacy and tolerability of two HAART strategies at two years in antiretroviral naive patients / Un ensayo randomizado que compara la eficacia y tolerancia de dos estrategias de HAART a dos años en pacientes sin tratamiento antirretroviral

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-naïve 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 and 307 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 (AU)

Introducción. El uso del tratamiento antirretroviral de alta eficacia (TARGA) que combina 2 análogos de nucleósidos (NRTI) más un inhibidor de proteasas (IP) o 2 NRTI más 1 no-análogo de nucleósido (NNRTI) ha demostrado tener eficacia comparable. Este estudio fue diseñado para comparar la efectividad a largo plazo (2 años) de 2 estrategias de tratamiento antirretroviral (ARV) en pacientes no tratados previamente: empezando con un TARGA utilizando nelfinavir (NFV) y cambiando a nevirapina (NEV) en caso de fallo o de efectos adversos o viceversa. Métodos. Éste es un ensayo clínico, abierto, randomizado y multicéntrico que incluye pacientes infectados por el virus de la inmunodeficiencia humana (VIH) que nunca han recibido ARV y con menos de 500 CD4. Los pacientes fueron aleatorizados a recibir ddI mas d4T mas NFV (cambiando a ZDV más 3TC más NEV en caso de fallo o toxicidad; brazo PI-NEV) o ddI más d4T más NEV (cambiando a ZDV más 3TC más NFV en caso de fallo o toxicidad; brazo NEV-PI). El objetivo primario del estudio fue el tiempo estimado hasta el fracaso después de cambiar al segundo régimen terapéutico cuando fue necesario (considerando fracaso como 2 determinaciones de carga viral del VIH por encima de 200 copias/ml, muerte, un nuevo evento de la categoría C o toxicidad que lleve a la discontinuación del segundo régimen) después de un mínimo de seguimiento de 2 años. Resultados. Se evaluaron un total de 137 pacientes (67 y 70 en el brazo PI-NEV y NEV-PI, respectivamente). Las características basales de los pacientes fueron similares en ambos grupos. El tiempo estimado hasta el fracaso del tratamiento mediante las curvas de Kaplan-Meier no mostraron diferencias entre los 2 brazos de tratamiento ni en el análisis por tratamiento (OT) (p = 0,81) ni en el análisis por intención de tratar (p = 0,58). A los 24 meses, la proporción estimada de pacientes libres de fracaso fue del 72 y el 66%, respectivamente, en el brazo de PI-NEV y NEV-PI en el análisis OT (p = 0,54) y del 73 y el 64% en el PI-NEV y NEV-PI en el análisis ITT (p = 0,49). La diferencia en la mediana de linfocitos CD4 a los 24 meses no fue significativamente diferente entre ambos grupos: 393 y 307 CD4 células/mm3 en el grupo PI-NEV y NEV-PI, respectivamente (p = 0,167). La aparición de efectos adversos del tratamiento fue muy similar: 50 (75%) en el grupo PI-NEV y 54 (70%) en el grupo NEV-PI, así como los efectos adversos de grado 3-4 que llevaron a la discontinuación del tratamiento. Conclusión. Las estrategias de tratamiento PI-NEV frente a NEV-PI tienen una eficacia alta y comparable a los 2 años de seguimiento y en general fueron bien toleradas (AU)

Problemas de salud y la vulnerabilidad social en pacientes inmigrantes ingresados con patología infecciosa: estudio caso-control / Background. Health resources needed by immigrants have increased steadily in the last few years. Studying health problems and social vulnerability in immigrants would help to improve the health care quality

Introducción. La necesidad de recursos sanitarios de la población inmigrante ha aumentado en los últimos años. El estudio de los problemas de salud y la vulnerabilidad social planteados durante el ingreso hospitalario de estos pacientes ayudaría a mejorar su cuidado. Pacientes y métodos. Estudio caso-control realizado en el Hospital Clínic de Barcelona. Se incluyeron pacientes inmigrantes ingresados con patología infecciosa de octubre de 2002 a septiembre de 2003. Los casos fueron apareados por edad, sexo e infección por virus de la inmunodeficiencia humana (VIH). Se evaluaron variables clínicas (visitas a Urgencias, días y número de ingresos, cantidad de procedimientos y fármacos, diagnóstico etiológico y control post alta) y de vulnerabilidad social (utilización de trabajo social, tarjeta sanitaria, cuidador de referencia, consumo de tóxicos, barrera idiomática y alta de enfermería). Resultados. Se estudiaron 102 pacientes (51 casos y 51 controles, todos varones). El 56% estaban infectados por VIH en ambos grupos. El número de procedimientos diagnósticos o terapéuticos fue mayor en el grupo de inmigrantes (p = 0,02), se llegó en menor proporción a un diagnóstico etiológico (el 82% frente al 98%, p = 0,021) y el número de visitas post alta fue inferior (el 55% frente al 77%, p = 0,04). Los pacientes inmigrantes tuvieron unos índices de vulnerabilidad social mayores que la población autóctona y en un 35% de ellos existía una barrera idiomática. Un menor número tenían tarjeta sanitaria (el 63% frente al 94%, p < 0,0001) y un número mayor tuvieron necesidad de traslado a un centro sociosanitario (el 16% frente al 2%, p = 0,01). Discusión. La vulnerabilidad social de los pacientes inmigrantes influye en una menor obtención del diagnóstico etiológico, mayor número de procedimientos durante la hospitalización y un menor seguimiento posterior al alta (AU)

Health problems and social vulnerability in immigrants admitted for an infectious disease: a case-control study Patients and methods. A case-control study performed in the Hospital Clínic of Barcelona. Immigrant patients admitted with infectious diseases from October 2002 to September 2003 were included. Controls were paired by age, gender and HIV infection. Clinical (emergency room attendance, days and number of admission to hospital, amount of clinical procedures and drugs used during the admission, etiological and microbiological diagnosis and post-admission control) and social vulnerability variables (social worker consultation, health care card, relatives or friends caregiver, drug use, language barrier and discharge document of the nurse) were analyzed. Results. One hundred and two patients (51 cases and 51 controls, all of them males) were studied. A total of 56% were HIV-1 infected in both groups. The number of diagnostic or therapeutic procedures was higher in the immigrant group (p = 0.02), a lower proportion of patients had a final etiologic diagnosis (82% vs 98%, p = 0.021) and the number of post-discharge controls was lower (55% vs 77%, p = 0.04). Immigrants had a higher social vulnerability index than the Spanish population and 35% could not speak Spanish, French or English. The number of immigrants with health care card was lower (63% vs 94%, p < 0,0001) and a higher number needed to be admitted to a social-health care center after discharge (16% vs 2%, p = 0.01). Discussion. Social vulnerability influences the etiological diagnosis, the number of diagnostic and therapeutic procedures during the admission to the hospital and post-discharge control of immigrant population (AU)

Inhibitory quotient as a prognostic factor of response to a salvage antiretroviral therapy containing ritonavir-boosted saquinavir. The CIVSA Study.

BACKGROUND: The addition of a low dose of ritonavir to protease inhibitors (PIs) has become a widespread strategy to improve PI pharmacokinetics. As resistance is a major barrier to long-term suppression, in salvage therapy genotype and/or phenotype scoring is currently used to predict the response. We evaluated the relationship between the saquinavir (SQV) inhibitory quotient (IQ) (virtual and genotypic) and virological response. METHODS: Eligible patients were on a PI-containing highly active antiretroviral therapy (HAART) regimen excluding SQV and had a viral load >5000 HIV-1 RNA copies/mL. The PI was switched to SQV/ritonavir (RTV) 1000/100 mg twice a day (bid) and the same two backbone nucleoside reverse transcriptase inhibitors (NRTIs) were maintained at least until week 4, when the resistance test results became available. Genotype and virtual phenotype were determined at baseline, while the SQV trough plasma concentration was determined at week 4. RESULTS: Fifty-three patients were included in the study. Mean baseline viral load and CD4 count were 137,693 copies/mL and 263 cells/microL, respectively, the mean number of previous PIs was 2.3 and the mean number of protease gene mutations (PGMs) was 4.1. Using an on-treatment analysis, at week 16 the mean increase in CD4 count was 70.9 cells/microL, viral load was <200 copies/mL in 17 out of 37 patients (45.9%), and 30 out of 45 patients (66.7%) were considered virological responders (VRs) (viral load <200 copies/mL or viral load declined > or =1 log(10) at week 16). Median virtual phenotype was 1.3 (0.6-6.9). Baseline differences were detected between VR and non-VR populations: the mean numbers of PGMs were 3.2 and 5.8 (P<0.05), the mean numbers of SQV-associated mutations were 2 and 3.8 (P<0.05), and the mean CD4 counts were 365.9 and 184.3 cells/microL (P<0.05), respectively. Mean SQV trough concentrations at week 4 were 1.1 and 1.0 microg/mL (not significant), and mean virtual IQs were 0.7 and 0.1 (P<0.01), respectively. Multivariate analysis showed that baseline PGMs >5 or SQV-associated mutations>5, virtual phenotype, baseline viral load >50,000 copies/mL, and virtual IQ <0.5, but not genotypic IQ, were the variables independently associated with non-VR. CONCLUSION: In heavily pretreated patients, the use of SQV virtual IQ or alternatively virtual phenotype, as well as PGMs, is a useful tool for the prediction of virological response.

Generation of Human Monoclonal Antibodies from HIV-Infected Individuals / Generación de anticuerpos monoclonales humanos a partir de individuos infectados por VIH

Recently, the protective role of anti-HIV-1 neutralising antibodies has been «re-discovered». Few broadly protective epitopes on the HIV envelope proteins are known, which were defined by few human monoclonal antibodies (mAbs) derived many years ago from non-progressor HIV-infected individuals. It is of interest to try to generate new neutralising human mAbs both to identify new protective epitopes for vaccine design and as potential passive immunotherapy agents. In addition, it is now known that rather than recognising HIV envelope proteins, some neutralising antibodies might be autoantibodies directed to the receptor (CD4) or co-receptors (CCR5 or CXCR4) on the HIV target cells. In that context, we attempted to generate neutralising human mAbs from few HIV-1-infected individuals who, after structured antiretroviral therapy interruptions, showed good virologic and immunologic responses, including serum HIV neutralising activity. We employed the classical heterohybridoma technology and found that the best screening strategy is a primary selection of IgG-producing hybridomas, followed by secondary screenings with different antigens and assays such as HIV neutralisation activity, direct binding to HIV components, binding to HIV target cells, and to cell lines transfected with human HIV receptors and co-receptors. From a single subject, 61 IgG-producing hybridomas out of 5,760 primary wells were obtained, and preliminary data indicate the presence of six (out of 23 tested) neutralising antibodies of the X4 strain, eight anti-p24 antibodies and two antibodies that bind to the MT-2 cell line, the target of X4 strains. None of the 61 mAbs obtained reacted with cells expressing CD4, CXCR4 or CCR5. Other screening tests such as neutralisation assay with the R5 strain, binding to HIV gp120-CD4 covalent complex, and to whole chemically (aldrithiol-2)-inactivated HIV are in progress. The screening strategy is also a means to “open” the repertoire of IgG antibodies of circulating B cells in HIV-infected individuals permitting to assess the frequency of HIV-related IgG antibodies and the IgV genes encoding them, an issue largely unknown (AU)

Recientemente se ha «re-descubierto» el carácter protectivo de los anticuerpos anti-VIH neutralizantes. Se conocen sólo unos pocos epitopos protectivos en las proteínas de la envoltura del VIH definidos gracias a unos pocos anticuerpos monoclonales humanos (mAbs) generados hace ya tiempo en pacientes infectados asintomáticos. Tiene interés intentar generar otros mAbs humanos neutralizantes que puedan definir nuevos epitopos protectivos para el diseño de vacunas, y ser útiles en inmunoterapia pasiva. Además, actualmente está claro que podrían existir anticuerpos neutralizantes que en vez de ir dirigidos contra la envoltura del VIH, reconocieran al receptor (CD4) o coreceptores (CCR5 o CXCR4) en la membrana de las células diana del VIH. En este contexto, hemos intentado obtener mAbs neutralizantes a partir de aquellos pacientes VIH+ que, tras un protocolo de interrupciones estructuradas de la terapia antiretroviral, mostraron buena respuesta virológica e inmunológica, con aumento de actividad sérica neutralizante. Utilizamos la metodología de heterohybridomas convencional y hallamos que la mejor estrategia de escrutinio es la selección primaria de hibridomas secretores de IgG, y luego el escrutinio con distintos ensayos para actividad neutralizante, unión a proteínas víricas, unión a la membrana de las células diana y a células transfectadas con receptores y co-receptores del VIH. A partir de un paciente, de 5.760 microcultivos primarios, se obtuvieron 61 hibridomas productores de IgG entre los que, según datos preliminares, hay seis mAbs (de 23 probados) neutralizantes contra cepas X4, ocho anti-p24 del VIH, y dos que se unen a la componentes de la membrana de la línea MT-2, diana de las cepas X4. Ningún mAb de los 61 obtenidos se unía a CCR5, CD4 o CXCR4. Hay otros escrutinios en curso como neutralización frente a cepa R5, la unión a complejo covalente gp120-CD4 y a VIH total inactivado químicamente con aldritiol-2. El escrutinio utilizado es también un modo de abrir el repertorio de anticuerpos IgG de los linfocitos B circulantes en individuos VIH+ y averiguar la frecuencia de los anticuerpos de especificidad relacionada con el VIH y los genes IgV que los codifican, un aspecto apenas estudiado (AU)

La respuesta de células t frente a antígenos de toxoplasma gondii (tg) discrimina los individuos sanos con y sin infección crónica por tg. su interés para evaluar la reconstitución de células t cd4+ específicas de tg en pacientes con sida co-infectados por tg que reciben tratamiento antirretroviral / T-cell response to Toxoplasma gondii (Tg) antigens discriminates healthy individuals with and without chronic infection. Its interest to evaluate the reconstitution of Tg-specific CD4+ T cells in Tgcoinfected AIDS patients receiving antiretroviral therapy

La demostración de que entre las nuevas células T CD4 circulantes que aparecen tras la terapia antirretrovial de alta actividad (TARGA) en los pacientes con SIDA co-infectados con Toxoplasma gondii (Tg), se hallan también aquéllas específicas de antígenos solubles del Tg, es una información que sería de gran importancia para decidir la seguridad de interrumpir la profilaxis primaria y sobre todo la secundaria de la Encefalitis Toxoplásmica (ET). No está claro si la respuesta de células T frente a extractos de antígenos solubles de Tg (SATg) puede discriminar entre las células T específicas y las activadas policlonalmente por el SATg. Este estudio ha abordado esta cuestión comparando la respuesta linfoproliferativa y la producción de citocinas de células mononucleares sanguíneas frente a SATg y a proteínas recombinantes de Tg (rTg), SAG-1, SAG3, ROP-2, de individuos sanos Tg-seropositivos (n=12) y Tgs e ronegativos (n=12).La respuesta linfoproliferativa frente a S ATg fue claramente superior en los individuos Tg-seropositivos (p=0,003), con índices de estimulación (SI) 10 en el 92 por ciento de estos casos, y 50 UI/ml. La producción de IFN- , pero no la de IL-12p40, frente a SATg (p=0,05), así como la de ambas citocinas (p=0,02, p=0,03, respectivamente ) frente a las rTg fue superior en los Tg-seropositivos. Estos datos indican que la respuesta de células T frente a antígenos solubles de Tg permite identificar a la mayoría de individuos normales que controlan la infección crónica por Tg, y sugiere que estas pruebas podrían ser útiles para evaluar si, tras la TARGA, se restauran las células T CD4+ anti-Tg en individuos con SIDA que reciben profilaxis contra la ET (AU)

Historia Natural de sida / The natural history of AIDS

No disponible

Tratamiento antirretroviral en el 2001 / Antiretroviral treatment on 2001

No disponible

Avanzando hacia la erradicación del VIH-1 o hacia el control de la infección sin tratamiento / Advancing towards the eradication of HIV-1 or towards the control of the infection

No disponible