Impacto de la viremia de bajo grado en el riesgo de fallo virológico en pacientes con infección por VIH-1 / Impact of low-grade viremia on the risk of virological failure in patients with HIV-1 infection on antiretroviral therapy

Resumen Introducción: Cargas virales (CV) entre 20-200 copias/mL se consideran cargas virales de bajo grado (CVBG). Su implicancia clínica y manejo no han sido definidos. Objetivo: Evaluar el impacto de CVBG en el riesgo de desarrollo posterior de fallo virológico (FV). Pacientes y Métodos: Se incluyeron pacientes ≥ 18 años, desde enero de 2009 a diciembre de 2019, con infección por VIH-1 con CV< 20 copias/mL, por un mínimo de seis meses y/o en dos muestras consecutivas bajo tratamiento anti-retroviral . Se realizó seguimiento de las CV estrati ficándolas: CV < 20 copias/mL, CVBG (20-50 copias/mL y 51-200 copias/mL) y FV. Mediana de seguimiento 25 meses (IQR 15-31). Resultados: Fueron incluidos 1.416 pacientes con CV < 20 copias/ mL bajo TARV. De ellos, 797 permanecieron con CV< 20 copias/mL durante el seguimiento, 144 presentaron CV entre 20-50 copias/mL, 384 entre 51-200 copias/mL y 91 presentaron FV sin CVBG previa. De los 528 pacientes que tuvieron CVBG, 110 (20,1%) fallaron, riesgo 3,45 veces superior respecto a los que no tuvieron CVBG previa. El riesgo de FV fue 3,27 mayor para aquellos que tuvieron CVBG entre 51-200 copias/mL vs 20-50 copias/mL. Discusión: El estudio permite relacionar la CVBG con el FV posterior, siendo el mayor riesgo CVBG entre 51-200 copias/mL.

Abstract Background: Viral loads (VL) between 20-200 copies/mL are considered low-grade viral loads (LGVL). Its clinical implications and management have not been defined. Aim: To evaluate the impact of LGVL on the risk of subsequent development of virological failure (VF). Methods: Patients ≥ 18 years, with HIV-1 infection who had VL < 20 copies/mL for at least six months and/or in two consecutive samples under antiretroviral therapy (ART) were included, between January 1st, 2009 and December 31, 2019. Follow-up of the VLs was carried out stratifying them in VL < 20 copies/mL, LGVL (20-50 copies/mL and 51-200 copies/mL) and VF. Median follow-up 25 months (IQR 15-31). Results: 1,416 patients were included who reached VL < 20 copies/ml under ART, 797 patients remained with CV < 20 copies/mL during follow-up, 144 patients had VL between 21-50 copies/mL, 384 between 51-200 copies/mL and 91 had VF without previous LGVL. Out of 528 patients who had LGVL, 110 failed, risk 3.45 times higher than those who had no previous LGVL. Risk 3.27 times higher of VF for those who had LGVL between 51-200 copies/mL compared to 20-50 copies/mL. Discussion: The study allows to relate the LGVL with VF. This association was observed more frequently with LGVL between 51-200 copies/mL

Excreção e transmissão do vírus da diarréia viral bovina por bezerros persistentemente infectados / Shedding and transmission of bovine viral diarrhea virus by persistently infected calves

Bezerros persistentemente infectados (PI) nascidos de vacas infectadas com amostras não-citopáticas do vírus da diarréia viral bovina (BVDV) se constituem nos principais reservatórios do vírus na natureza. Este trabalho relata uma investigação do padrão de excreção e transmissão viral por cinco bezerros PI produzidos experimentalmente pela inoculação de vacas prenhes com isolados brasileiros do BVDV. Cinco bezerros que sobreviveram a infecção intrauterina nasceram saudáveis, soronegativos e com a presença de vírus no sangue. Após o desmame - e desaparecimento dos anticorpos colostrais - os bezerros PI foram monitorados semanalmente durante 150 dias para a presença de vírus e títulos virais no soro e em secreções (ocular, oral, nasal e genital). Os títulos virais no soro de cada animal apresentaram pequenas variações durante o período (com exceção de um animal que apresentou um aumento de título tardiamente), mas os títulos variaram amplamente entre os animais (entre 10² e 10(6)TCID50/ml). O vírus também foi excretado continuamente nas secreções de todos os animais, com pequenas variações de título entre as coletas. Os maiores títulos virais foram geralmente detectados nas secreções nasais e oculares (títulos de 10(4) a 10(6)TCID50/mL), enquanto as secreções orais e genitais usualmente continham títulos virais baixos (10² a 10³TCID50/mL). Com o objetivo de avaliar a dinâmica de transmissão viral, um bezerro PI foi introduzido em um grupo de 10 bezerros soronegativos, mantido com uma alta densidade animal e submetido a manejo diário para simular as condições de manejo semi-intensivo. Após 30 dias de convívio com o bezerro PI, todos os demais animais haviam soroconvertido ao BVDV. Para investigar a transmissão viral sob condições extensivas, outro bezerro PI foi incorporado a um rebanho de 48 animais mantido a campo, com baixa densidade animal e submetido a manejo extensivo. Dentre estes animais, 8/48 (16,6 por cento) foram soropositivos ...

Persistently infected (PI) calves born to cows infected with non-cytopathic bovine virus diarrhea virus (BVDV) represent the main reservoir of the virus in nature. We herein report an investigation on the patterns of virus shedding and transmission by five PI calves produced experimentally through inoculation of pregnant cows with Brazilian BVDV isolates. Five calves that survived intrauterine infection were born healthy, lacking neutralizing antibodies to BVDV and harboring virus in the blood. After weaning - and following the disappearance of colostral antibodies - PI calves were monitored for virus in serum and body secretions (ocular, oral, nasal and genital) at weekly intervals for up to 150 days. For each animal, the virus titers in serum showed minor variations throughout the collections (with one exception that presented an increase late in infection), yet the titers varied widely among animals (from 10² to 10(6)TCID50/mL). Virus shedding in secretions was detected steadily during all the observation period with minor titer variations for each particular animal. The highest titers were generally detected in nasal and ocular secretions (titers 10(4) to 10(6)TCID50mL) whereas genital and oral secretions usually contained low amount of virus (10² to 10³TCID50mL). To evaluate the kinetics of virus transmission by these animals, one PI was introduced on a group of 10 seronegative calves maintained with a high animal density simulating the conditions of an intensive management. All 10 contact calves seroconverted to BVDV by day 30. Another PI calf was introduced into a 48-head herd kept under a low animal density, extensive grass management. Among these animals, 8/48 (16.6 percent) seroconverted by day 10, 26/48 (54.1 percent) by day 40 and 37/48 (77 percent) were seropositive at day 100, when the monitoring was discontinued. These results show that continuous viremia and virus shedding in high titers in secretions by PI animals assure ...