Santamaría Jm

Recomendaciones de GESIDA/Plan Nacional sobre el Sida respecto al tratamiento antirretroviral en pacientes adultos infectados por el VIH (octubre 2004)

Objetivo Efectuar una puesta al dia de las recomendaciones sobre el tratamiento antirretroviral (TAR) para los adultos infectados por el virus de la inmunodeficiencia humana (VIH). Metodos Estas recomendaciones se han consensuado por un comite del Grupo de Estudio de Sida (GESIDA) y del Plan Nacional sobre el Sida (PNS). Para ello se han revisado los avances en la fisiopatologia del VIH, los resultados de eficacia y seguridad de ensayos clinicos, estudios de cohortes y de farmacocinetica, publicados en revistas biomedicas o presentados en congresos en los ultimos anos. Se han definido tres niveles de evidencia segun la procedencia de los datos: estudios aleatorizados (nivel A), de cohortes o de caso-control (nivel B), u opinion de expertos (nivel C). En cada una de las situaciones se ha establecido recomendar, considerar o no recomendar el TAR. Resultados En el momento actual, el TAR con combinaciones de al menos tres farmacos constituye el tratamiento de inicio de eleccion de la infeccion cronica por el VIH. Estas pautas deben incluir dos inhibidores de la transcriptasa inversa analogos de nucleosidos (ITIAN) mas un no nucleosido (ITINN) o dos ITIAN mas un inhibidor de la proteasa (IP). En los pacientes con una infeccion por VIH sintomatica se recomienda iniciar TAR. En los pacientes asintomaticos el inicio de TAR se basara en la cifra de linfocitos CD4+/μl y en la carga viral plasmatica (CVP): a) en pacientes con linfocitos CD4+ 350 cel./μl se puede diferir el inicio del TAR. El objetivo del TAR inicial es lograr una CVP indetectable. La adherencia al TAR tiene un papel fundamental en la duracion de la respuesta antiviral. Las opciones terapeuticas en los fracasos del TAR son limitadas por la aparicion de resistencias cruzadas. Los estudios genotipicos en estos casos son de utilidad. La toxicidad es un factor limitante del TAR, aunque los beneficios superan los posibles perjuicios. Tambien se discuten los criterios de TAR de la infeccion aguda, embarazo y profilaxis postexposicion, y el manejo de la coinfeccion por el VIH y los virus de la hepatitis C y B (VHC y VHB). Conclusiones La cifra de linfocitos CD4+ es el factor de referencia mas importante para iniciar el TAR en pacientes asintomaticos. Por otra parte, el numero considerable de farmacos disponibles, los metodos de monitorizacion mas sensibles (CVP), y la posibilidad de determinar las resistencias hacen que las estrategias terapeuticas sean mucho mas individualizadas.

Recomendaciones de GESIDA/Plan Nacional sobre el Sida respecto al tratamiento antirretroviral en pacientes adultos infectados por el virus de la inmunodeficiencia humana en el año 2002

Objetivo Efectuar una puesta al dia de las recomendaciones sobre el tratamiento antirretroviral (TAR) para los adultos infectados por el virus de la inmunodeficiencia humana (VIH). Metodos Estas recomendaciones se han consensuado por un comite del Grupo de Estudio de Sida (GESIDA) y del Plan Nacional sobre el Sida (PNS). Para ello, se han revisado los avances en la fisiopatologia del VIH, los resultados de eficacia y seguridad de ensayos clinicos, estudios de cohortes y de farmacocinetica, publicados en revistas biomedicas o presentados en congresos en los ultimos anos. Se han definido tres niveles de evidencia segun la procedencia de los datos: estudios aleatorizados (nivel A), de cohortes o de caso-control (nivel B) u opinion de expertos (nivel C). En cada una de las situaciones se ha establecido recomendar, considerar o no recomendar el TAR. Resultados En el momento actual, el TAR con combinaciones de al menos 3 farmacos constituye el tratamiento de eleccion de la infeccion cronica por el VIH. En los pacientes con una infeccion por VIH sintomatica se recomienda iniciar el TAR. En los pacientes asintomaticos el inicio de TAR se basara en la cifra de linfocitos CD4+/μl y en la carga viral plasmatica (CVP): a) en pacientes con linfocitos CD4+ 350 cel./μl se puede diferir el inicio del TAR. El objetivo del TAR es lograr una CVP indetectable. La adherencia al TAR tiene un papel en la durabilidad de la respuesta antiviral. Las opciones terapeuticas en los fracasos del TAR son limitadas por la aparicion de resistencias cruzadas. Los estudios genotipicos en estos casos son de utilidad. La toxicidad es un factor limitante del TAR. Tambien se discuten los criterios de TAR de la infeccion aguda, embarazo y profilaxis postexposicion, y el manejo de la coinfeccion por el VIH y los virus de las hepatitis B y C (VHC y VHB). Conclusiones En la actualidad existe una actitud mas conservadora para iniciar el TAR que en recomendaciones previas. La cifra de linfocitos CD4+ es el factor de referencia mas importante para iniciar el TAR en pacientes asintomaticos. Por otra parte, el numero considerable de farmacos disponibles, los metodos de monitorizacion mas sensibles (CVP) y la posibilidad de determinar las resistencias hacen que las estrategias terapeuticas sean mucho mas individualizadas.

Atypical scabies in HIV-positive patients

Five cases of Norwegian or keratotic scabies in HIV-positive patients are described. One of these patients was the source of an outbreak in a hospital, ultimately involving 72 persons. Three of our patients had a markedly pruritic eruption. This is unusual in crusted scabies in which pruritus is usually slight or absent. Two of the five patients had unusual CD4 counts of more than 200 cells per cubic millimeter. All our patients responded to lindane and keratolytic agents. When generalized papular, crusted, or eczematoid lesions are observed in HIV-positive patients, particularly if the CD4 count is less than 200/mm3, scabies should be included in the differential diagnosis.

HIV-1 transmission cluster with T215D revertant mutation among newly diagnosed patients from the Basque Country, Spain.

Objective:To determine the introduction of HIV-1 genetic forms and to examine transmission clusters and resistance to antiretroviral inhibitors among newly diagnosed patients from the Basque Country, Spain, during 2004-2007. Methods:A total of 261 samples, corresponding to 47.5% heterosexuals, 37.9% men who have sex with men (MSM), and 11.1% intravenous drug users were analyzed in protease and reverse transcriptase to examine phylogenetic relationships and drug resistance-associated mutations. Results:Subtype B was detected in 220 (84.3%) samples and non-B subtype variants in 41 (15.7%) samples. Nearly half (47%) of the sequences grouped in transmission clusters. One of these comprised 14 individuals, 12 of them MSM, with the T215D revertan mutation. In largest transmission clusters, the percentage of MSM was higher than heterosexuals (P < 0.001). Resistance mutations were detected in 29 (11.1%) patients: 20 (7.6%) of them to nucleoside reverse transcriptase inhibitor; 6 (2.3%) to nonnucleoside reverse transcriptase inhibitor (NNRTI); and 1 each to protease inhibitors, protease inhibitor plus NNRTI, and nucleoside reverse transcriptase inhibitor plus NNRTI, respectively. Conclusions:Our findings underscore recommendations for HIV-1 genotyping in newly diagnosed patients not only to provide information on transmitted drug resistance as an issue in public health and as a guide to future therapy but also to document transmission clusters and to increase the necessary preventive measures.

Didanosine, Lamivudine, and Efavirenz versus Zidovudine, Lamivudine, and Efavirenz for the Initial Treatment of HIV Type 1 Infection : Final Analysis (48 Weeks) of a Prospective, Randomized, Noninferiority Clinical Trial, GESIDA 3903

BACKGROUND The combination of didanosine, lamivudine, and efavirenz (ddI/3TC/EFV) for the initial treatment of human immunodeficiency virus type 1 (HIV-1) infection has been insufficiently analyzed in clinical trials. METHODS We conducted an open-label, randomized study to compare the noninferiority of ddI/3TC/EFV with the lamivudine-zidovudine tablet and EFV (COM/EFV), both administered with food to improve tolerability and convenience. Patients were stratified by HIV-1 RNA level of <5.0 log(10) or > or =5.0 log(10) copies/mL. The primary end point was the percentage of patients with an HIV-1 RNA level of <50 copies/mL at week 48, determined by intention-to-treat analysis. RESULTS Three hundred sixty-nine patients were randomized: 186 for ddI/3TC/EFV treatment and 183 for COM/EFV treatment. Both groups were well matched in terms of baseline characteristics; 19.3% of patients received a Centers for Disease Control and Prevention assessment of clinical category C, median HIV RNA level was 5.0 log(10) copies/mL, and median CD4(+) cell count was 208 cells/microL. At week 48, by intention-to-treat analysis, 70% of patients in the ddI/3TC/EFV group and 63% of patients in the COM/EFV group had an HIV-1 RNA level of <50 copies/mL (treatment difference, 7.1%; 95% confidence interval, -2.39% to 16.59%). Fourteen patients (8%) in the ddI/3TC/EFV arm (not the COM/EFV arm) and 26 patients (14%) in the COM/EFV arm (not the ddI/3TC/EFV arm) [corrected] discontinued the study medication because of adverse events (P = .046). One patient (1%) in the ddI/3TC/EFV arm and 11 patients (6%) in the COM/EFV arm discontinued medication because of hematological toxicity (P = .003). CONCLUSIONS At week 48, ddI/3TC/EFV administered once per day with food did not have results inferior to those of COM/EFV treatment. A statistically significantly higher proportion of patients in the COM/EFV arm than in the ddI/3TC/EFV arm discontinued therapy because of adverse events, mainly because of hematological toxicity. CLINICAL TRIALS REGISTRATION NCT00256828.

Características clinicoepidemiológicas de los nuevos diagnósticos de infección por el virus de la inmunodeficiencia humana

Fundamento Describir las caracteristicas de las personas recientemente diagnosticadas de infeccion por el virus de la inmunodeficiencia humana. Pacientes y Metodo Serie de 126 nuevos casos de infeccion por VIH diagnosticados en un Servicio de Enfermedades Infecciosas. Resultados La transmision sexual fue la mas frecuente (74%). El 15% eran mayores de 50 anos y un 16% inmigrantes. El diagnostico tardio (estadio C) ocurrio en el 36% de los casos y se asocio con tener mas de 50 anos ( odds ratio [OR]: 5,1; intervalo de confianza [IC] del 95%: 1,6-16,8). Conclusiones Es necesario implantar sistemas de notificacion de infecciones por VIH y mejorar los servicios preventivos.

Two Lymphogranuloma Venereum Cases in a Heterosexual Couple in Bilbao (spain)

LYMPHOGRANULOMA VENEREUM (LGV) WAS AN unusual disease in industrialized countries until 4 years ago; before this when it did appear, it had generally been acquired in some endemic area (Africa, Asia, South America, or the Caribbean Islands). In December 2003, an outbreak of LGV was detected in Rotterdam, Netherlands.1 Since then, more than 1000 cases have been reported in the Netherlands, France, the United Kingdom, Germany, Belgium, Switzerland, Sweden, Portugal, Denmark, and Spain.2–10 In the United States and Canada, the first cases were recorded in 2004 and between then and November 2006, 85 cases were reported in Canada.1,11 All these cases had remarkably uniform characteristics: men who have sex with men (MSM), a high rate of HIV seropositivity and frequent concurrent infection with other STIs. Most of them had rectal symptoms and only a few inguinal lymphadenopathy or classic genital ulcers.12 All confirmed cases were of the genotype L2. There was no evidence that this infection had extended beyond these nuclear groups, until 3 LGV cases were reported among Portuguese women during 2007.9 The aim of this article is to describe the first LGV cases diagnosed in a heterosexual couple in Bilbao (Spain). We directly documented sexual transmission by identifying genital Chlamydia trachomatis type L2 infection in both patients. The results also suggest that primary classic LGV can take the form of urethritis and cervicitis, without genital ulceration. A further 2 cases of LGV had previously been recorded in Spain, but both of them were in MSM.10 In June 2006, a 33-year-old Spanish man came to see us complaining of 2 months of gradually progressive and painful right inguinal lymphadenopathy (swelling). The onset of swelling was accompanied by radiating low back pain, myalgia in the lower extremities, and dysuria. He denied any history of previous genital ulceration, inguinal buboes, fever, malaise, proctitis, or urethral discharge. His general practitioner had treated him with an antibiotic and antiinflammatory drug whose name he did not know. Dysuria remitted with treatment but the swelling did not. The patient reported multiple unprotected heterosexual contacts during the previous year but he had not traveled abroad. He also denied having had sexual intercourse with men or immigrants. Physical examination revealed bilateral inguinal lymph nodes of firm consistency, those on the right being bigger. Urethral, rectal, and pharyngeal samples were taken for microbiologic diagnosis. Samples for direct fluorescent antibody and culture for C. trachomatis were negative. So were culture for Neisseria gonorrhoeae and herpes simplex virus. There was no serological evidence of syphilis or HIV infection. The laboratory extracted DNA from all samples using the Amplicor CT/NG extraction kit and tested them for C. trachomatis using an in-house TaqMan real-time PCR assay, which targeted the cryptic plasmid. C. trachomatis PCR was positive in the urethral sample and negative in other sites. Ultrasound-guided fine needle aspiration of the right lymph node was performed during a second visit in July 2006. The material obtained was processed in the same way as described above and C. trachomatis PCR was positive. Urethral and lymph node DNA samples were tested for LGV using a TaqMan based real-time PCR that used the polymorphic membrane protein H gene as a PCR target.13 The results of this assay were positive. Both samples were identified as LGV serovar 2 and not L2b genovar, by sequencing an ompA segment spanning variable segments 1 and 2 using an ABI Genetic Analyzer 3130 and Big Dye Terminator kit version 3.1 according to the manufacturer’s protocol. The man’s partner, a 29 year-old Spanish woman, described a history of painful bilateral inguinal swellings. She was 8-weeks pregnant and denied any sexual contact other than with her partner over the previous 2 years. Examination found painless bilateral inguinal nodes of firm consistency. Vaginal, endocervical, and Correspondence: Dr. Josefina López de Munain, Hospital de Basurto, Servicio de Enfermedades Infecciosas, Avenida de Montevideo 18, 48013 Bilbao, Spain. E-mail: josefina.lopezdemunain@osakidetza.net. Received for publication October 22, 2007, and accepted May 2, 2008. From the *Infectious Diseases Service, and the Clinical Microbiology Service, Basurto Hospital, Basque Health Service, Bilbao, Spain Sexually Transmitted Diseases, November 2008, Vol. 35, No. 11, p.918–919 DOI: 10.1097/OLQ.0b013e31817e9228 Copyright

Eligibility for and outcome of treatment of latent tuberculosis infection in a cohort of HIV-infected people in Spain

BackgroundPrevious studies have demonstrated the efficacy of treatment for latent tuberculosis infection (TLTBI) in persons infected with the human immunodeficiency virus, but few studies have investigated the operational aspects of implementing TLTBI in the co-infected population.The study objectives were to describe eligibility for TLTBI as well as treatment prescription, initiation and completion in an HIV-infected Spanish cohort and to investigate factors associated with treatment completion.MethodsSubjects were prospectively identified between 2000 and 2003 at ten HIV hospital-based clinics in Spain. Data were obtained from clinical records. Associations were measured using the odds ratio (OR) and its 95% confidence interval (95% CI).ResultsA total of 1242 subjects were recruited and 846 (68.1%) were evaluated for TLTBI. Of these, 181 (21.4%) were eligible for TLTBI either because they were tuberculin skin test (TST) positive (121) or because their TST was negative/unknown but they were known contacts of a TB case or had impaired immunity (60). Of the patients eligible for TLTBI, 122 (67.4%) initiated TLTBI: 99 (81.1%) were treated with isoniazid for 6, 9 or 12 months; and 23 (18.9%) with short-course regimens including rifampin plus isoniazid and/or pyrazinamide. In total, 70 patients (57.4%) completed treatment, 39 (32.0%) defaulted, 7 (5.7%) interrupted treatment due to adverse effects, 2 developed TB, 2 died, and 2 moved away. Treatment completion was associated with having acquired HIV infection through heterosexual sex as compared to intravenous drug use (OR:4.6; 95% CI:1.4-14.7) and with having taken rifampin and pyrazinamide for 2 months as compared to isoniazid for 9 months (OR:8.3; 95% CI:2.7-24.9).ConclusionsA minority of HIV-infected patients eligible for TLTBI actually starts and completes a course of treatment. Obstacles to successful implementation of this intervention need to be addressed.

The Safety of Pyrimethamine and Sulfadoxine for the Prevention of Pneumocystis carinii Pneumonia

The medical records of 157 patients taking pyrimethamine-sulfadoxine for Pneumocystis carinii pneumonia prophylaxis were reviewed for assessment of safety and tolerance. 11 patients had experienced side effects, 7 (1 each: neutropenia, Stevens-Johnson, hepatic abnormalities; 2 each: subjective and hypersensitivity reactions) leading to a discontinuation of the drugs.

Estudio transversal sobre las características clínicas y epidemiológicas de la infección por el virus de la inmunodeficiencia humana en gitanos y otras minorías en Bilbao

BACKGROUND: The health status and needs of gypsies have been insufficiently studied. PATIENTS AND METHOD: We studied the clinicoepidemiological characteristics of all HIV-1 infected patients attending in our outpatients clinic and hospitalized who were classified according to their ethnic origin as >, > (Caucasian non-gypsy Spanish natives) or >. RESULTS: Overall, there were 563 patients out of 674 previously appointed (83%). Intravenous drug use (IVDU) was the HIV acquisition mechanism in 70%, 95% and 25% (p < 0.000) and attendance was considered regular in 89%, 48% and 89% payos, gypsies and immigrants (p < 0.01), respectively. CONCLUSIONS: IVDU as the HIV transmission mechanism and lower clinic attendance rates were the most relevant differences observed between gypsy and payo subjects.