[Infrequent deletion in 67 codon in HIV reverse transcriptase in antiretroviral treatment failure]. / Deleción infrecuente en el codón 67 del gen de la transcriptasa reversa de HIV en falla al tratamiento antirretroviral.

We present a clinical case of antiretroviral treatment failure with appearance of mutations demonstrated by genotyping. We also show the evolution of the pattern of mutations that confers resistance to protease and reverse transcriptase inhibitors along with changes in the scheme of drugs indicated to the patient. A deletion was found in codon 67 of the TR gen, along with a novel resistance model to AZT pointing out the benefits of the detection of antiviral resistance by sequencing (genotyping).

Deleción infrecuente en el codón 67 del gen de la transcriptasa reversa de HIV en falla al tratamiento antirretroviral. / [Infrequent deletion in 67 codon in HIV reverse transcriptase in antiretroviral treatment failure]

We present a clinical case of antiretroviral treatment failure with appearance of mutations demonstrated by genotyping. We also show the evolution of the pattern of mutations that confers resistance to protease and reverse transcriptase inhibitors along with changes in the scheme of drugs indicated to the patient. A deletion was found in codon 67 of the TR gen, along with a novel resistance model to AZT pointing out the benefits of the detection of antiviral resistance by sequencing (genotyping).

Regression of AIDS-related Kaposi's sarcoma following combined antiretroviral treatment.

The aim of the study was to assess regression of Kaposi's sarcoma (KS) in AIDS patients in Argentina. Eighteen male AIDS patients with human immunodeficiency virus (HIV)-associated Kaposi's sarcoma at different clinical stages received KS specific treatment and/or anti-retroviral therapy. Triple anti-retroviral therapy was given to most of the patients with the exception of four who received zidovudine (ZDV) in combination with another nucleoside analogue but no protease inhibitors. Plasma viral load and CD4+ T lymphocyte number were measured in two blood samples (before and after treatment). Complete remission was found in all patients (five) at KS stage I, three out of eight patients at stage II but in none at stages III and IV. Two out of three patients at KS stage IV did not respond to treatments at all. Three patients at KS stages I and II showed complete remission of sarcoma with only anti-retroviral therapy suggesting that anti-retroviral therapy and non-KS specific chemotherapy can successfully control KS.

Regression of AIDS-related Kaposis sarcoma following combined antiretroviral treatment.

The aim of the study was to assess regression of Kaposis sarcoma (KS) in AIDS patients in Argentina. Eighteen male AIDS patients with human immunodeficiency virus (HIV)-associated Kaposis sarcoma at different clinical stages received KS specific treatment and/or anti-retroviral therapy. Triple anti-retroviral therapy was given to most of the patients with the exception of four who received zidovudine (ZDV) in combination with another nucleoside analogue but no protease inhibitors. Plasma viral load and CD4+ T lymphocyte number were measured in two blood samples (before and after treatment). Complete remission was found in all patients (five) at KS stage I, three out of eight patients at stage II but in none at stages III and IV. Two out of three patients at KS stage IV did not respond to treatments at all. Three patients at KS stages I and II showed complete remission of sarcoma with only anti-retroviral therapy suggesting that anti-retroviral therapy and non-KS specific chemotherapy can successfully control KS.

HIV-1 viral load: comparative evaluation of three commercially available assays in Argentina.

Viral load (HIV-RNA copies per milliliter of plasma) has good correlation to prognosis considering progression to AIDS. The evaluation of commercial kits to measure viral load has become a need to find the most specific, sensitive and reproducible procedure to follow up HIV-infected patients. Hereby, a comparative analysis was done by using three different assays available in Argentina for quantitation of HIV-RNA in plasma. A plasma panel: 20 from HIV-1 infected individuals (9 asymptomatic and 11 symptomatic) and 9 from HIV-1 seronegative individuals was studied. Samples were run by Amplicor HIV-1 Monitor (Roche Diagnostic System, USA) Quantiplex HIV-1 RNA 2.0 Assay (Chiron Corporation, USA) and NASBA HIV-1 RNA QT (Organon Teknika, Holland). RNA was extracted from 0.2 ml of plasma for Amplicor, 0.1 ml and 1 ml of plasma for NASBA and, duplicates of 1 ml of plasma was centrifuged and pellet was used for bDNA assay no RNA extraction step. For a given specimen, a log difference of < 0.5 between assays was considered as concordant result. All seronegative samples were bellow the detection limit for all assays (Amplicor 200 c/ml, NASBA 400 c/ml and Quantiplex (bDNA) 500 c/ml). Two samples from asymptomatic patients were not detectable by NASBA (Sensitivity: 90%) Sensitivity was increased to 100% by using 1 ml of plasma. All samples were detectable by the other assays (sensitivity: 100%). For NASBA-bDNA, 74% samples were concordant, 35% for Amplicor-bDNA and 53% for NASBA-Amplicor. By using 1 ml of plasma from asymptomatic patients, concordance was 65% for NASBA-bDNA and 60% for NASBA Amplicor. Comparing samples from asymptomatic patients, only 22% was concordant in both cases. Reproducibility of NASBA was low (33% with differences lower than 0.5 Log) when 0.1 and 1 ml were used. Due to the levels of concordance of these results, it would be suggested to use always the same technique to follow up HIV-1 infection. The reproducibility of the assays should be tested by every laboratory and for every technician in charge of the assay in order to have confidence in the results specially to follow up HIV-infected patients or to monitor anti-viral therapies.

[Detection of the viral load and its use as a virological marker in the follow-up of HIV-1-positive patients]. / Detección de la carga viral y su uso como marcador virológico en el seguimiento de pacientes HIV-1 positivos.

The evaluation of viral load as virological marker and its clinical and immunological correlation are presented. The first viral load studies were performed during 1996 at the National Reference Center for AIDS in Argentina in HIV-1 positive patients derived from different Hospitals in Buenos Aires. The study included 216 HIV-1 positive patients, 49 females and 167 males. Plasma was used for evaluating viral load and a second sample was obtained in 25 of the 216 patients for their monitoring. Viral load was performed using bDNA technique (Quantiplex HIV RNA assay 2.0, Chiron Corporation, USA). Other parameters such as CD4 count determined by flow cytometry and clinical stages according to CDC classification were obtained in order to correlate clinical and immunological status of the patients. When CD4 count was compared with viral load, the results showed a trend of viral RNA increase in plasma along with a decrease in CD4+ lymphocytes. This trend was also observed to correlate with the progression to AIDS disease. In all groups of patients, considering either CD4 counts or clinical status, ranges of viral load values were broad. Thus, as shown by percentiles 25 and 75, patients with CD4 counts < 200/ml, presented viral load values between 18,395 c/ml to 215,425 c/ml and patients with > 200/ml viral RNA showed values from < 10,000 to 35,180 c/ml. Patients with CDC's A and B stages presented values from < 10,000 to 45,160 c/ml and 87,000 c/ml respectively, while patients classified as C had 10,582 to 215,000 c/ml. Results of two consecutive samples in the 25 patients showed the usefulness of this technique for monitoring antiretroviral therapy. Nevertheless, despite the tendency of viral load to increase along with the progression of the disease, the broad range of values suggested the importance of using both virological and immunological parameters for the management of HIV infected patients.

Detección de la carga viral y su uso como marcador virológico en el seguimiento de pacientes HIV-1 positivos / Viral load detection and its role as virological marker for the monitoring of HIV-1 positive patients

Se realizaron los primeros estudios de carga viral en pacientes HIV-1 positivos provenientes de diferentes instituciones asistenciales de la Ciudad de Buenos Aires. Se evaluó la carga viral como marcador virológico y su correlación con la clínica y el recuento de los linfocitos CD4+ para 216 pacientes HIV-1 positivos. La técnica utilizada fue bDNA (Quantiplex HIV RNA 2.0 assay, Chiron Corporation). Se observó una tendencia al aumento de la carga viral en los pacientes con menor cantidad de linfocitos CD4+ y en los estadíos clínicos con sintomatología. En pacientes que no recibieron ninguna terapia antirretroviral se encontraron valores desde < 10000 copias de ARN viral/ml de plasma hasta 48995 c/ml. En aquéllos que recibieron terapia antirretroviral se observó mayor variación en los valores de la carga viral como lo mostró un rango de < 10000 c/ml hasta 96605 c/ml. Se obtuvieron muestras consecutivas en 25 pacientes y se observaron diferencias entre ambas muestras que permitieron corroborar la utilidad de la técnica en el seguimiento de los pacientes infectados con HIV

Detección de la carga viral y su uso como marcador virológico en el seguimiento de pacientes HIV-1 positivos / Viral load detection and its role as virological marker for the monitoring of HIV-1 positive patients

Se realizaron los primeros estudios de carga viral en pacientes HIV-1 positivos provenientes de diferentes instituciones asistenciales de la Ciudad de Buenos Aires. Se evaluó la carga viral como marcador virológico y su correlación con la clínica y el recuento de los linfocitos CD4+ para 216 pacientes HIV-1 positivos. La técnica utilizada fue bDNA (Quantiplex HIV RNA 2.0 assay, Chiron Corporation). Se observó una tendencia al aumento de la carga viral en los pacientes con menor cantidad de linfocitos CD4+ y en los estadíos clínicos con sintomatología. En pacientes que no recibieron ninguna terapia antirretroviral se encontraron valores desde < 10000 copias de ARN viral/ml de plasma hasta 48995 c/ml. En aquéllos que recibieron terapia antirretroviral se observó mayor variación en los valores de la carga viral como lo mostró un rango de < 10000 c/ml hasta 96605 c/ml. Se obtuvieron muestras consecutivas en 25 pacientes y se observaron diferencias entre ambas muestras que permitieron corroborar la utilidad de la técnica en el seguimiento de los pacientes infectados con HIV (AU)

Infecciones por levaduras: agentes causales y su resistencia a antifúngicos en pacientes pediátricos hospitalizados y en adultos HIV positivos / Yeast infections: etiologic agents and antifungal resistance in hospitalized pediatric patients and in HIV positive adult patients

Se realizó un estudio retrospectivo de las candidiasis en pacientes pediátricos hospitalizados y en adultos HIV positivos provenientes de 5 instituciones de la ciudad de Bunnos Aires, ciudad de La Plata y partidos del conurbano bonaerense, durante el período 1993-1995. Se determinó la frecuencia de aparición de las especies de levaduras y su perfil de sensibilidad a los antifúngicos de uso sistémico con el objeto de obtener datos actualizados de esta patología. Candida albicans fue el agente etiológico en el 87 o/o de los 214 pacientes adultos HIV positivos con candidiasis orofaríngeas estudiados y en el 50 o/o de los 209 pacientes pediátricos hospitalizados. En este último grupo el 28 o/o de estas infecciones se debió a Candida parapsilosis y el 18 o/o a Candida tropicalis, mientras que sólo el 2 y el 4 o/o de las candidiasis orales fueron causadas por estos microorganismos. La recuperación de Candida krusei y Candida glabrata, especies intrínsecamente resistentes a los azoles, se vio incrementada en la población expuesta al tratamiento con fluconazol. En ambos grupos se observó un bajo número de levaduras resistentes a la anfotericina B, en cambio para las drogas azólicas se detectó un mayor porcentaje de aislamientos resistentes, en especial al fluconazol: 13 o/o en los pacientes pediátricos y 34 o/o en los pacientes HIV positivos

Infecciones por levaduras: agentes causales y su resistencia a antifúngicos en pacientes pediátricos hospitalizados y en adultos HIV positivos / Yeast infections: etiologic agents and antifungal resistance in hospitalized pediatric patients and in HIV positive adult patients

Se realizó un estudio retrospectivo de las candidiasis en pacientes pediátricos hospitalizados y en adultos HIV positivos provenientes de 5 instituciones de la ciudad de Bunnos Aires, ciudad de La Plata y partidos del conurbano bonaerense, durante el período 1993-1995. Se determinó la frecuencia de aparición de las especies de levaduras y su perfil de sensibilidad a los antifúngicos de uso sistémico con el objeto de obtener datos actualizados de esta patología. Candida albicans fue el agente etiológico en el 87 o/o de los 214 pacientes adultos HIV positivos con candidiasis orofaríngeas estudiados y en el 50 o/o de los 209 pacientes pediátricos hospitalizados. En este último grupo el 28 o/o de estas infecciones se debió a Candida parapsilosis y el 18 o/o a Candida tropicalis, mientras que sólo el 2 y el 4 o/o de las candidiasis orales fueron causadas por estos microorganismos. La recuperación de Candida krusei y Candida glabrata, especies intrínsecamente resistentes a los azoles, se vio incrementada en la población expuesta al tratamiento con fluconazol. En ambos grupos se observó un bajo número de levaduras resistentes a la anfotericina B, en cambio para las drogas azólicas se detectó un mayor porcentaje de aislamientos resistentes, en especial al fluconazol: 13 o/o en los pacientes pediátricos y 34 o/o en los pacientes HIV positivos (AU)

[Yeast infections: causative agents and their antifungal resistance in hospitalized pediatric patients and HIV-positive adults]. / Infecciones por levaduras: agentes causales y su resistencia a antifúngicos en pacientes pediátricos hospitalizados y en adultos HIV positivos.

Candidiasis has increased its frequency over the last decade, particularly among hospitalized patients where it is accompanied with high rates of mortality, and in patients with AIDS who are predisposed to oropharyngeal or esophageal candidiasis. The aim of this study was to determine the frequency of appearance of different yeast species and the resistance profile to current antifungal drugs in hospitalized pediatric patients and adult HIV patients from 5 institutions of Buenos Aires City and suburbs, and La Plata City, during the period 1993-1995, in order to obtain local and updated information. Candida albicans was the etiologic agent recovered in 87% of the 214 HIV positive patients with oropharyngeal candidosis, and in 50% of the 209 hospitalized pediatric patients. In the latter group 28% of these infections were due to Candida parapsilosis and 18% to Candida tropicalis, but only 2% and 4% of oral candidosis were caused by these organisms. Detection of Malassezia furfur and Hansenula anomala, responsible of systemic infections, and Trichosporon beigelii, isolated from a burn patient, were considered remarkable since these organisms appear to be emerging pathogens. Azole resistant species as Candida krusei and C. glabrata were mostly recovered from HIV positive patients, exposed to fluconazole treatment. A very low number of amfotericin B "resistant" yeasts (n = 9) were observed in both groups. However, resistance to azole drugs, particularly to fluconazole, was found in pediatric patients (13%) and in HIV infected adults (34%).

[Cryptococcosis in acquired immunodeficiency syndrome (AIDS)]. / Criptococosis en el síndrome de inmunodeficiencia adquirida (SIDA).

Cryptococcus neoformans is an infrequent but important cause of severe disease in immunodepressed patients, especially in those with AIDS. We refer the case of a 45 year old patient with clinical, epidemiological and serological patterns of HIV-induced infection in the course of which the patient suffered a subacute neurologic syndrome with fatal evolution. The diagnosis was made by isolation of Cryptococcus neoformans in CSF and in palpable lymph nodes by fine-needle aspiration biopsy. Cryptococcal antigen titer of CSF was 1:2560. Treatment was standardized in the administration of amphotericin B (0.3 mg/kg/day) and 5-fluocytosine (150 mg/kg/day) for a period of six weeks. Factors that suggested poor prognosis were: a positive india ink preparation before treatment, a high initial CSF antigen titer, low CSF leukocyte count and the presence of Cryptococcus neoformans at an extraneural site. Since diagnosis of cryptococcosis was made when prominent localizing symptoms and signs were found, an intensive culture and serologic screening would be necessary in every patient with AIDS in order to establish an earlier diagnosis.

Criptococosis en el sindrome de inmunodeficiencia adquirida (SIDA) / Cryptococcosis in the acquired immunodeficiency syndrome (AIDS)

El Cryptococcus neoformans es un hongo de haja patogenicidad que actúa habitualmente como oportunista en pacientes con alteraciones de la inmunidad celular. Se presenta el caso de un paciente de 45 años, con criterios epidemiológicos, clínicos y serológicos de infección por HIV, quien padeció, durante su evolución, una criptococosis meníngea y ganglionar. El diagnóstico se realizó por el hallazgo del hongo tanto en LCR como en ganglio linfático. Si bien el cuadro clínico no difirió mayormente de aquel que presentan los enfermos con inmunodepresión de otra etiología, se destaca la dificultad de su reconocimiento precoz. Es por este motivo que se hace necesario efectuar, en todo paciente portador de SIDA, un exhaustivo relevamiento micológico que incluya pancultivos y serología seriada, a fin de lograr un diagnóstico temprano de esta asociación morbosa

Criptococosis en el síndrome de inmunodeficiencia adquirida (SIDA). / [Cryptococcosis in acquired immunodeficiency syndrome (AIDS)]

Cryptococcus neoformans is an infrequent but important cause of severe disease in immunodepressed patients, especially in those with AIDS. We refer the case of a 45 year old patient with clinical, epidemiological and serological patterns of HIV-induced infection in the course of which the patient suffered a subacute neurologic syndrome with fatal evolution. The diagnosis was made by isolation of Cryptococcus neoformans in CSF and in palpable lymph nodes by fine-needle aspiration biopsy. Cryptococcal antigen titer of CSF was 1:2560. Treatment was standardized in the administration of amphotericin B (0.3 mg/kg/day) and 5-fluocytosine (150 mg/kg/day) for a period of six weeks. Factors that suggested poor prognosis were: a positive india ink preparation before treatment, a high initial CSF antigen titer, low CSF leukocyte count and the presence of Cryptococcus neoformans at an extraneural site. Since diagnosis of cryptococcosis was made when prominent localizing symptoms and signs were found, an intensive culture and serologic screening would be necessary in every patient with AIDS in order to establish an earlier diagnosis.

Criptococosis en el sindrome de inmunodeficiencia adquirida (SIDA) / Cryptococcosis in the acquired immunodeficiency syndrome (AIDS)

El Cryptococcus neoformans es un hongo de haja patogenicidad que actúa habitualmente como oportunista en pacientes con alteraciones de la inmunidad celular. Se presenta el caso de un paciente de 45 años, con criterios epidemiológicos, clínicos y serológicos de infección por HIV, quien padeció, durante su evolución, una criptococosis meníngea y ganglionar. El diagnóstico se realizó por el hallazgo del hongo tanto en LCR como en ganglio linfático. Si bien el cuadro clínico no difirió mayormente de aquel que presentan los enfermos con inmunodepresión de otra etiología, se destaca la dificultad de su reconocimiento precoz. Es por este motivo que se hace necesario efectuar, en todo paciente portador de SIDA, un exhaustivo relevamiento micológico que incluya pancultivos y serología seriada, a fin de lograr un diagnóstico temprano de esta asociación morbosa (AU)