Present-day treatment of tuberculosis and latent tuberculosis infection.

The major objectives of tuberculosis (TB) control are to reduce morbidity and mortality via an early and appropriate treatment of the disease, to prevent carriers of the Mycobacterium tuberculosis bacillus from transmitting it to others, and to prevent latent tuberculosis infection (LTB) sufferers from progressing to the disease. To achieve these objectives, it is imperative to start an appropriate, effective antituberculosis treatment as early as possible, as well as identify contacts of the infected TB patient and others at risk of LTB progressing to TB, in order to establish an appropriate treatment for them. Here we review the bases for treating TB and LTB infections, including those produced by strains resistant to anti-TB drugs.

Present-day treatment of tuberculosis and latent tuberculosis infection

El objetivo del control de la tuberculosis (TB) es reducir su morbilidad y mortalidad mediante el tratamientoprecoz y adecuado de la enfermedad, la prevención de la transmisión de Mycobacterium tuberculosisdesde personas bacilíferas y la prevención de la progresión a enfermedad de personas con infección latentetuberculosa (ILT). Para alcanzar estos objetivos se requieren el inicio precoz y la correcta cumplimentaciónde un tratamiento antituberculoso efectivo, y la identificación de contactos de pacientes con TB infectantey de otras personas con ILT con riesgo de progresar a enfermedad tuberculosa para establecer el tratamientoadecuado de estas personas. Revisamos las bases del tratamiento de la TB y de la ILT, incluyendo lasproducidas por cepas resistentes a los fármacos antituberculosos (AU)

The major objectives of tuberculosis (TB) control are to reduce morbidity and mortality via an early andappropriate treatment of the disease, to prevent carriers of the Mycobacterium tuberculosis bacillus fromtransmitting it to others, and to prevent latent tuberculosis infection (LTB) sufferers from progressing tothe disease. To achieve these objectives, it is imperative to start an appropriate, effective antituberculosistreatment as early as possible, as well as identify contacts of the infected TB patient and others at risk ofLTB progressing to TB, in order to establish an appropriate treatment for them. Here we review the basesfor treating TB and LTB infections, including those produced by strains resistant to anti-TB drugs (AU)

Usar rifampicina más pirazinamida en profilaxis antituberculosa no incrementa el riesgo de hepatotoxicidad grave en pacientes infectados por virus de la inmunodeficiencia humana: metaanálisis de ensayos clínicos aleatorizados y controlados / Use of rifampicin plus pyrazinamide for antituberculosis prophylaxis does not increase the risk of severe hepatotoxicity in HIV patients: Meta-analysis of randomized controlled clinical trials

Objetivo Comparar la incidencia de hepatitis grave asociada al tratamiento con rifampicina más pirazinamida (RZ) en tratamiento preventivo de tuberculosis en pacientes infectados por virus de la inmunodeficiencia humana (VIH), con pauta estándar de isoniacida (H) durante 6 (6H) o 12 (12H) meses. Pacientes y métodos Metaanálisis de ensayos clínicos de asignación aleatorizada y controlados, en los que se comparó el régimen RZ con la pauta estándar de tratamiento de la infección latente tuberculosa (6 a 12H) en pacientes infectados por VIH. Se realizó una búsqueda sistemática de la literatura médica desde 1986 hasta diciembre de 2007. Se identificaron 5 ensayos clínicos de asignación aleatorizada y controlados, realizados en España, EE. UU., Haití y Zambia. Se valoró como repuesta binaria la ausencia o presencia de hepatotoxicidad grave, definida como aquella que provocó la muerte del paciente o fue causa de retirada del tratamiento, y se estableció como medida la diferencia de riesgo de (..) (AU)

Objective To compare the incidence of severe hepatitis in HIV-infected patients receiving rifampicin plus pyrazinamide (RZ) for antituberculosis prophylaxis with that of patients receiving a conventional isoniazid-based regime for 6 to 12 months (6–12H).Methods Meta-analysis of randomized controlled trials, in which RZ was compared with 6–12H, the standard regimen for latent tuberculosis infection in HIV-infected patients. A systematic search of studies published between 1986 and 2007 was carried out, and 5 randomized clinical trials conducted in Spain (2), the USA (1), Haiti (1), and Zambia (1) were identified. The absence or presence of severe hepatoxicity, which was defined as toxicity causing the death of the patient or requiring treatment withdrawal, was assessed as a binary response, and the outcome measure was the difference in the risk of hepatotoxicity between patients receiving RZ and those receiving 6–12H (controls).Result sAmong the 5 trials retrieved, 1 was excluded from the final analysis because of incomplete data on the development of hepatotoxicity. A final total of 2657 (..) (AU)

[Use of rifampicin plus pyrazinamide for antituberculosis prophylaxis does not increase the risk of severe hepatotoxicity in HIV patients: meta-analysis of randomized controlled clinical trials]. / Usar rifampicina más pirazinamida en profilaxis antituberculosa no incrementa el riesgo de hepatotoxicidad grave en pacientes infectados por virus de la inmunodeficiencia humana: metaanálisis de ensayos clínicos aleatorizados y controlados.

OBJECTIVE: To compare the incidence of severe hepatitis in HIV-infected patients receiving rifampicin plus pyrazinamide (RZ) for antituberculosis prophylaxis with that of patients receiving a conventional isoniazid-based regime for 6 to 12 months (6-12H). METHODS: Meta-analysis of randomized controlled trials, in which RZ was compared with 6-12H, the standard regimen for latent tuberculosis infection in HIV-infected patients. A systematic search of studies published between 1986 and 2007 was carried out, and 5 randomized clinical trials conducted in Spain (2), the USA (1), Haiti (1), and Zambia (1) were identified. The absence or presence of severe hepatoxicity, which was defined as toxicity causing the death of the patient or requiring treatment withdrawal, was assessed as a binary response, and the outcome measure was the difference in the risk of hepatotoxicity between patients receiving RZ and those receiving 6-12H (controls). RESULTS: Among the 5 trials retrieved, 1 was excluded from the final analysis because of incomplete data on the development of hepatotoxicity. A final total of 2657 patients were included (1324 patients receiving RZ and 1333 receiving 6-12H). The development of severe hepatotoxicity was lower in the RZ group than in the 6-12H group (1.208% vs. 2.851%; P=0.0042, 95% CI: -0.028 to -0.005). The meta-analysis showed no statistical evidence of heterogeneity between the studies or publication bias. The difference in the risk of severe hepatotoxicity favored the RZ regimen in both the fixed effects model (-0.0119, 95% CI: -0.0206 to -0.0033) and random effects model (-0.0147, 95% CI: -0.0289 to -0.0006). CONCLUSIONS: The meta-analysis did not demonstrate an increased risk of severe hepatoxicity in HIV-infected patients receiving tuberculosis prophylaxis with the rifampicin/pyrazinamide combination compared to the conventional 6- or 12-month isoniazid-based regimen.

[Clinical practice guidelines from the Andalusian Society of Infectious Diseases (SAEI) for the treatment of tuberculosis]. / Guía de práctica clínica de la Sociedad Andaluza de Enfermedades Infecciosas (SAEI) sobre el tratamiento de la tuberculosis.

The therapeutic scheme for initial pulmonary tuberculosis recommended by the SAEI is as follows: Initial phase, isoniazid, rifampin and pyrazinamide given daily for 2 months. In HIV(+) patients and immigrants from areas with a rate of primary resistance to isoniazid > 4%, ethambutol should be added until susceptibility studies are available. Second phase (continuation phase): rifampin and isoniazid, given daily or intermittently for 4 months in the general population. HIV(+) patients (< or = 200 CD4) and culture-positive patients after 2 months of treatment should receive a 7-month continuation phase. A 6-month regimen is recommended for extrapulmonary tuberculosis, with the exception of tuberculous meningitis, which should be treated for a minimum of 12 months and bone/joint tuberculosis, treated for a minimum of 9 months. Treatment regimens for multidrug resistant tuberculosis are based on expert opinion. These would include a combination of still-useful first-line drugs, injectable agents, and alternative agents, such as quinolones. Patients who present a special risk of transmitting the disease or of non-adherence should be treated with directly observed therapy.

Guía de práctica clínica de la Sociedad Andaluza de Enfermedades Infecciosas (SAEI) sobre el tratamiento de la tuberculosis / Clinical practice guidelines from the Andalusian Society of Infectious Diseases (SAEI) for the treatment of tuberculosis

El esquema terapéutico de la tuberculosis pulmonar inicial recomendado por la Sociedad Andaluza de Enfermedades Infecciosas (SAEI) es el siguiente: En la fase inicial se usa isoniacida, rifampicina y piracinamida con administración diaria durante 2 meses. En pacientes VIH(1) e inmigrantes procedentes de zonas con tasa de resistencia primaria a isoniacida superior a 4% debe añadirse etambutol hasta disponer del estudio de resistencias. La segunda fase (continuación): rifampicina e isoniacida con administración diaria o intermitente durante 4 meses en la población general y 7 meses en pacientes VIH(1) (< 200 CD4) y/o pacientes con cultivos positivos después de 2 meses de tratamiento. La pauta de 6 meses es la más recomendada para tratar la tuberculosis extrapulmonar. Las excepciones serían la meningitis cuyo tratamiento debería durar 12 meses y la tuberculosis osteoarticular que debería tratarse durante nueve. Las pautas de tratamiento de la tuberculosis resistente se basan en opiniones de expertos. Habría que utilizar una combinación de fármacos de primera línea todavía útiles, fármacos inyectables y agentes alternativos, como las quinolonas. Se recomienda el uso de tratamiento directamente observado en aquellos pacientes que presenten especial riesgo de contagiosidad o de incumplimiento del tratamiento (AU)

The therapeutic scheme for initial pulmonary tuberculosis recommended by the SAEI is as follows: Initial phase, isoniazid, rifampin and pyrazinamide given daily for 2 months. In HIV(1) patients and immigrants from areas with a rate of primary resistance to isoniazid > 4%, ethambutol should be added until susceptibility studies are available. Second phase (continuation phase): rifampin and isoniazid, given daily or intermittently for 4 months in the general population. HIV(1) patients (< 200 CD4) and culture-positive patients after 2 months of treatment should receive a 7-month continuation phase. A 6-month regimen is recommended for extrapulmonary tuberculosis, with the exception of tuberculous meningitis, which should be treated for a minimum of 12 months and bone/joint tuberculosis, treated for a minimum of 9 months. Treatment regimens for multidrug resistant tuberculosis are based on expert opinion. These would include a combination of still-useful first-line drugs, injectable agents, and alternative agents, such as quinolones. Patients who present a special risk of transmitting the disease or of non-adherence should be treated with directly observed therapy (AU)

[Randomized clinical trial investigating three chemoprophylaxis regimens for latent tuberculosis infection in HIV-infected patients]. / Ensayo clínico aleatorizado para evaluar tres pautas cortas de tratamiento de la infección latente tuberculosa en pacientes infectados por el VIH.

OBJECTIVE: To evaluate the adherence to, and safety of three chemoprophylaxis regimens for latent tuberculosis (TB) infection in HIV-infected patients with a positive tuberculin skin test. PATIENTS AND METHODS: A randomized, comparative, open clinical assay was carried out in 316 HIV-infected patients in 12 Spanish hospitals. Patients were randomly assigned to one of three regimens, 108 to isoniazid for six months (6H), 103 to rifampin and isoniazid for three months (3RH), and 105 to rifampin and pyrazinamide for two months (2RZ). After completion of treatment, patients were followed-up for two years. RESULTS: The period of observation following completion of treatment was 115, 108 and 101 person-years for 6H, 3RH and 2RZ, respectively. Twenty-seven percent of patients voluntarily abandoned chemoprophylaxis and 9.7% were withdrawn due to adverse side-effects or interactions. Seven patients were withdrawn due to hepatotoxicity (5 in 6H, 2 in 3RH and 0 in 2RZ). No appreciable differences were found among the three regimens. There were 11 cases of tuberculosis during follow-up. The TB rates (cases per 100 person-years) in the three treatment groups were 3.48 in 6H, 4.63 in 3RH and 1.98 in 2RZ. With respect to 2RZ, the relative risk for TB in the 6H and 3RH regimens was 1.76 and 2.34, respectively. CONCLUSIONS: The safety of the 2RZ regimen for prophylaxis of latent TB infection in HIV patients was similar to that of the 6H and 3RH regimens. The incidence of hepatotoxicity was not higher in patients who received 2RZ.

Ensayo clínico aleatorizado para evaluar tres pautas cortas de tratamiento de la infección latente tuberculosa en pacientes infectados por el VIH / Randomized clinical trial investigating three chemoprophylaxis regimens for latent tuberculosis infection in HIV-infected patients

Objetivo. Evaluar la adherencia y seguridad de 3 pautas cortas de tratamiento de la infección latente tuberculosa (ILT) en pacientes infectados por el virus de la inmunodeficiencia humana (VIH). Pacientes y métodos. Ensayo clínico, aleatorizado, multicéntrico, comparativo y abierto, realizado en 12 hospitales españoles. Los pacientes se distribuyeron de forma aleatoria a una de las siguientes 3 pautas de tratamiento, isoniazida durante 6 meses (6H) y rifampicina más isoniazida durante 3 meses (3RH) y rifampicina más pirazinamida durante 2 meses (2RZ). Tras finalizar el tratamiento los pacientes fueron seguidos durante un período de 2 años. Resultados. Se incluyeron en el estudio 316 pacientes, 105 en la pauta 2RZ, 103 en la pauta 3RH y 108 en la pauta 6H. El período de observación tras la finalización del tratamiento fue de 115, 108 y 101 personas/año, respectivamente, para 6H, 3RH y 2RZ. El 27% de los pacientes abandonaron voluntariamente el estudio antes de finalizar el tratamiento al que fueron asignados y el 9,7% abandonaron el mismo por reacciones adversas o interacciones. Se produjeron 7 retiradas del estudio por hepatotoxicidad, cinco en el grupo 6H y dos en 3RH. No se observaron retiradas por hepatotoxicidad en el brazo 2RZ. Se produjeron 11 casos de tuberculosis durante el seguimiento. Las tasas de tuberculosis (casos por 100 personas/año) en los distintos grupos de tratamiento fueron de 3,48 en 6H, 4,63 en 3RH y 1,98 en 2RZ, con un riesgo relativo para tuberculosis en las pautas 6H y 3RH de 1,76 y 2,34, respectivamente, respecto a 2RZ. Conclusiones. En nuestro estudio la seguridad de la pauta 2RZ en el tratamiento de la ILT de la pauta 2RZ fue similar a la observada con las pautas 6H y 3RH, no observándose una mayor incidencia de hepatotoxicidad en pacientes que recibieron 2RZ (AU)

Objective. To evaluate the adherence to, and safety of three chemoprophylaxis regimens for latent tuberculosis (TB) infection in HIV-infected patients with a positive tuberculin skin test. Patients and methods. A randomized, comparative, open clinical assay was carried out in 316 HIV-infected patients in 12 Spanish hospitals. Patients were randomly assigned to one of three regimens, 108 to isoniazid for six months (6H), 103 to rifampin and isoniazid for three months (3RH), and 105 to rifampin and pyrazinamide for two months (2RZ). After completion of treatment, patients were followed-up for two years. Results. The period of observation following completion of treatment was 115, 108 and 101 person-years for 6H, 3RH and 2RZ, respectively. Twenty-seven percent of patients voluntarily abandoned chemoprophylaxis and 9.7% were withdrawn due to adverse side-effects or interactions. Seven patients were withdrawn due to hepatotoxicity (5 in 6H, 2 in 3RH and 0 in 2RZ). No appreciable differences were found among the three regimens. There were 11 cases of tuberculosis during follow-up. The TB rates (cases per 100 person-years) in the three treatment groups were 3.48 in 6H, 4.63 in 3RH and 1.98 in 2RZ. With respect to 2RZ, the relative risk for TB in the 6H and 3RH regimens was 1.76 and 2.34, respectively. Conclusions. The safety of the 2RZ regimen for prophylaxis of latent TB infection in HIV patients was similar to that of the 6H and 3RH regimens. The incidence of hepatotoxicity was not higher in patients who received 2RZ (AU)

IL-2 increased RANTES production and CD25 expression in cultured PBMCs only from antiretroviral treated HIV-1+ patients with detectable viral loads.

In order to better understand the possible beneficial effects of intermittent IL-2 treatment as complement of antiretroviral therapy in HIV-1+ patients, we have measured the levels of RANTES in the supernatants and the CD25 expression in cultured PBMCs obtained from HIV-1+ individuals in presence of IL-2. The results showed a significant increases in RANTES production and in the expression of CD25+ in the cultures with IL-2 of PBMC obtained from HIV-1+ patients with a detectable viral load in comparison with both, HIV-1+ patients with no detectable viral loads and with healthy individuals. These results suggest that therapeutic IL-2 administered in addition to highly active anti-retroviral therapy (HAART) may contribute to increase the effect of this therapy by rising both RANTES production and CD25 expression only in HIV-1+ patients with detectable viral loads.

New targets and new drugs in the treatment of HIV.

Antiretroviral treatment has modified the course of human immunodeficiency virus (HIV) infection transforming it into a chronic disease. However, as treatment is conceived "for life", more effective and safety drugs, overcoming the growing resistance of the virus are required. New molecules may block the known viral targets or other new ones. The mechanism of the virus union and entrance to the cell includes the new therapeutic targets that are studied more frequently. Although studies with substances that efficiently block the virus-CD4 receptors union are in very early phases, other studies of molecules capable to block the entrance co-receptors are in more advanced phases (II or III), and enfuvirtide, a substance that blocks membrane fusion, the last phase of virus entrance, has been recently marketed. Another very promising pharmacological target is the integration of the proviral DNA as we know some substances that in vitro block HIV integrase. Besides this, new drugs are increasing the three classic antiretroviral families. Among nucleoside analogs emtricitabine (recently marketed) and amdoxovir are the more prominent. Capravirine and TMC-125 are the non-nucleoside analogs whose studies are more advanced. And atazanavir, fos-amprenavir, tipranavir and TMC-114 are the new protease inhibitors recently marketed or near to be.

Nuevas dianas y nuevos fármacos en el tratamiento de la infección por el VIH / New targets and new drugs in the treatment of HIV

El tratamiento antirretroviral ha modificado el curso de la infección por el virus de la inmunodeficiencia humana (VIH) hasta convertirla en una enfermedad crónica. Sin embargo, dado que el tratamiento se concibe de por vida, se requieren nuevos fármacos que sean más eficaces, tengan menos efectos adversos y, además, que superen la resistencia creciente del virus. Estas nuevas moléculas pueden actuar tanto sobre las dianas virales conocidas como sobre otras nuevas. Los mecanismos de unión y entrada del virus a la célula incluyen las nuevas dianas terapéuticas más estudiadas. A pesar de que los estudios con sustancias que bloqueen eficazmente la unión del virus al receptor CD4 están en fases muy precoces, ya están en fases avanzadas (II o III) estudios de algunas moléculas que bloquean los correceptores de la entrada y recientemente se ha comercializado la enfuvirtida, que actúa bloqueando la fusión de membranas, fase última de la entrada del virus. Otro punto de actuación farmacológico muy prometedor es la integración del ADN proviral, ya que se están encontrando sustancias capaces de bloquear la integrasa in vitro. Por otra parte se siguen incorporando nuevos fármacos a las tres familias clásicas de antirretrovirales. Entre los inhibidores de la transcriptasa inversa análogos de nucleósidos destacan la emtricitabina (recientemente comercializada) y el amdoxovir. La capravirina y el TMC-125 son los no análogos en fase más avanzada de desarrollo. Mientras que atazanavir, fosamprenavir, tipranavir y TMC-114 son nuevos inhibidores de la proteasa ya comercializados o próximos a estarlo

Antiretroviral treatment has modified the course of human immunodeficiency virus (HIV) infection transforming it into a chronic disease. However, as treatment is conceived "for life", more effective and safety drugs, overcoming the growing resistance of the virus are required. New molecules may block the known viral targets or other new ones. The mechanism of the virus union and entrance to the cell includes the new therapeutic targets that are studied more frequently. Although studies with substances that efficiently block the virus-CD4 receptors union are in very early phases, other studies of molecules capable to block the entrance co-receptors are in more advanced phases (II or III), and enfuvirtide, a substance that blocks membrane fusion, the last phase of virus entrance, has been recently marketed. Another very promising pharmacological target is the integration of the proviral DNA as we know some substances that in vitro block HIV integrase. Besides this, new drugs are increasing the three classic antiretroviral families. Among nucleoside analogs emtricitabine (recently marketed) and amdoxovir are the more prominent. Capravirine and TMC-125 are the non-nucleoside analogs whose studies are more advanced. And atazanavir, fos-amprenavir, tipranavir and TMC-114 are the new protease inhibitors recently marketed or near to be

[Spanish GESIDA/Nacional AIDS Plan Recommendations for antiretroviral therapy in HIV-infected Adults (October 2004)]. / Recomendaciones de GESIDA/Plan Nacional sobre el Sida respecto al tratamiento antirretroviral en pacientes adultos infectados por el VIH (octubre 2004).

OBJECTIVE: This consensus document is an update of antiretroviral therapy (ART) recommendations for adult patients infected with the human immunodeficiency virus (HIV). METHODS: To formulate these recommendations, a panel composed of members of the Grupo de Estudio de Sida (GESIDA; AIDS Study Group) and the Plan Nacional sobre el Sida (PNS; Spanish AIDS Plan) reviewed the advances in current understanding of the pathophysiology of HIV, the safety and efficacy findings from clinical trials, and the results from cohort and pharmacokinetic studies published in biomedical journals or presented at scientific meetings over the last years. Three levels of evidence were defined according to the source of the data: randomized studies (level A), cohort or case-control studies (level B), and expert opinion (level C). The decision to recommend, consider or not recommend ART was established in each of these situations. RESULTS: ART consisting of at least three drugs is currently the initial treatment of choice for chronic HIV infection. These regimens should include 2 NRTI + 1 NNRTI or 2 NRTI + 1 PI. Initiation of ART is recommended in patients with symptomatic HIV infection. In asymptomatic patients, initiation of ART is recommended on the basis of CD4+ lymphocyte counts per L and plasma viral load, as follows: 1) Therapy should be started in patients with CD4+ counts of < 200 cells/microL; 2) Therapy should be started in most patients with CD4+ counts of 200-350 cells/microL, although it can be delayed when CD4+ count persists at around 350 cells/microL and viral load is low; and 3) Initiation of therapy can be delayed in patients with CD4+ counts of > 350 cells/microL. The initial objective of ART is to achieve an undetectable viral load. Adherence to therapy plays an essential role in maintaining the antiviral response. Because of the development of cross resistance, therapeutic options are limited when ART fails. Genotype studies are useful in these cases. Toxicity is a limiting factor in the use of ART, although the benefits outweigh the risks. In addition, the criteria for the use of ART are discussed in situations of acute infection, pregnancy, and post-exposure prophylaxis, and in the management of co-infection of HIV with HCV or HBV. CONCLUSIONS: CD4+ lymphocyte count is the most important reference factor for initiating ART in asymptomatic patients. The large number of available drugs, the increased sensitivity of tests to monitor viral load, and the possibility to determine viral resistance is leading to a more individualized approach to therapy.

Tuberculosis in the transplant candidate: importance of early diagnosis and treatment.

BACKGROUND: Transplantation is contraindicated in candidates with active tuberculosis. The present study was undertaken to determine the clinical manifestations of tuberculosis in the transplant candidate and the prognosis of cases that inadvertently undergo transplantation. METHODS: This study was a retrospective study of tuberculosis cases diagnosed among 3,889 transplant candidates. All cases were diagnosed from respiratory or tissue samples obtained in the pretransplant period or during transplantation. RESULTS: We observed 7 cases (0.18%) of active tuberculosis among 3,889 candidates. Two patients had a history of tuberculosis. Tuberculosis was frequently asymptomatic. Three patients had extrapulmonary tuberculosis. Chest radiographs showed residual fibrotic lesions in three patients and noncavitated consolidation in two patients. All of the patients in which the purified protein derivative test was performed were anergic. All patients that inadvertently underwent transplantation were cured. CONCLUSIONS: Aggressive management is required to prevent tuberculosis in transplant candidates. Patients that inadvertently undergo transplantation can be effectively treated when diagnosed early.

HAART induces the expression of HLA-G on peripheral monocytes in HIV-1 infected individuals.

The aim of this work is to analyze if the highly active antiretroviral therapy (HAART) has any effect in the number of peripheral monocytes expressing the tolerogenic molecule human leukocyte antigen G (HLA-G) in HIV-1 infected individuals. In this sense, expression of HLA-G was measured by flow cytometry on peripheral monocytes from HIV-1 antiretroviral-receiving and antiretroviral naïve patients and in HIV-1 patients at different times after the antiretroviral treatments were removed. It was found an increment of monocytes expressing HLA-G in HIV-1 infected individuals receiving HAART, whereas monocytes from untreated HIV-1 patients did not change. When the HLA-G was measured on monocytes after antiretroviral treatment was removed, the number of peripheral monocytes expressing HLA-G was progressively decreasing. These data suggest that antiretroviral therapy is able to induce the expression of the tolerogenic molecule HLA-G on peripheral monocytes from HIV-1 seropositive individuals.

[Randomized trial of three regimens to prevent tuberculosis in HIV-infected patients with anergy]. / Ensayo clínico aleatorizado de tres aputas de quimioprofilaxis para prevenir la tuberculosis en pacientes infectados por el VIH con anergia cutánea.

INTRODUCTION: To evaluate the efficacy of three regimens of prophylactic therapy for tuberculosis in HIV-infected patients with anergy. METHODS: Prospective, multi-center, randomized, comparative, and open clinical trial. Anergy was defined as absence of induration in response to three antigens (PPD, Candida albicans and parotiditis antigen) applied by the Mantoux method. Patients were randomized into one of the following prophylactic treatment groups: isoniazid for six months (6H), rifampin plus isoniazid for three months (3RH), rifampin plus pyrazinamide for two months (2RZ) or no treatment (NT). After completion of treatment, patients were followed up for two years. RESULT: A total of 319 patients were included in the study, 83 in the 6H regimen, 82 in 3RH, 77 in 2RZ and 77 in NT. The observation period following treatment was 88, 96, 81 and 126 person-years, respectively, for 6H, 3RH, 2RZ and NT. There were 11 cases of tuberculosis during the follow-up period. The tuberculosis rates (cases per 100 person-years) were 3.4, 3.1, 1.2 and 3.1 for 6H, 3RH, 2RZ and NT respectively, with relative risks in regimens 6H, 3RH and 2RZ with respect to NT of 1.07 (0.24-4.80), 0.98 (0.22-4.4) and 0.39 (0.04-3.48), all statistically non-significant. Twenty-nine patients died during the follow-up period, none due to tuberculosis, and no appreciable differences were found among the groups. CONCLUSIONS: The results showed no significant decrease in the risk of developing tuberculosis with any of the evaluated regimens and, therefore, do not support the use of antituberculosis chemoprophylaxis in anergic HIV-infected patients.

Ensayo clínico aleatorizado de tres pautas de quimioprofilaxis para prevenir la tuberculosis en pacientes infectados por el VIH con anergia cutánea / Randomized trial of three regimens to prevent tuberculosis in HIV-infected patients with anergy

INTRODUCCIÓN. Evaluar la eficacia de tres pautas de quimioprofilaxis antituberculosa en pacientes infectados por el virus de la inmunodeficiencia humana (VIH) con anergia cutánea. MÉTODOS. Ensayo clínico prospectivo, multicéntrico, aleatorizado, comparativo y abierto. La anergia cutánea se definió por la ausencia de reactividad a 3 antígenos aplicados por la técnica de Mantoux (PPD, candidina y parotiditis). Los pacientes se distribuyeron de forma aleatoria a uno de los siguientes grupos de tratamiento: isoniacida durante 6 meses (6H), rifampicina más isoniacida, 3 meses (3RH), rifampicina más piracinamida, 2 meses (2RZ) o sin tratamiento (NT). Tras finalizar la quimioprofilaxis los pacientes fueron seguidos 2 años. ESULTADOS. Se incluyeron en el estudio 319 pacientes, 83 en la pauta 6H, 82 en 3RH, 77 en 2RZ y 77 en NT. El período de observación tras el tratamiento fue de 88, 96, 81 y 126 personas años, respectivamente para 6H, 3RH, 2RZ y NT. Se produjeron 11 casos de tuberculosis durante el seguimiento. Las tasas de tuberculosis (casos por 100 personas/año) fueron respectivamente de 3,4, 3,1, 1,2 y 3,1 para 6H, 3RH, 2RZ y NT, con un riesgo relativo en las pautas 6H, 3RH y 2RZ respecto a NT de 1,07 (0,24-4,80), 0,98 (0,22-4,4) y 0,39 (0,04-3,48), estadísticamente no significativo. Durante el seguimiento fallecieron 29 pacientes, ninguno de ellos por tuberculosis, sin que se apreciaran diferencias entre grupos. CONCLUSIONES. Nuestro estudio no demuestra una reducción significativa del riesgo de tuberculosis en ninguna de las 3 pautas evaluadas y, por tanto, no apoya el empleo de quimioprofilaxis antituberculosa en pacientes con anergia cutánea (AU)

Tumoración lumbar en un paciente con sida / Lumbar tumor in apatient with AIDS

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