HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study.

BACKGROUND: In resource-limited settings, multi-experienced HIV infected patients are often prescribed raltegravir for salvage therapy. Patients failing raltegravir-containing regimens require other drugs including other integrase inhibitors. In this context, real-life data about the resistance and cross-resistance pathways between integrase inhibitors is limited. The aim of this study was to investigate integrase resistance pathways in a cohort of Mexican multi-experienced patients failing of a raltegravir-containing salvage regimen. METHODS: Twenty-five plasma samples from subjects failing antiretroviral regimens which included raltegravir were obtained from various healthcare centres from 2009 to 2017 in Mexico. Antiretroviral history and demographics were collected. Samples were processed for integrase resistance genotyping testing by sequencing. The viral sequences were analysed with the Stanford HIV drug resistance database algorithm. Data was analysed with SPSS Statistics software. RESULTS: We found a mean viral load of 4.17 log10 c/mL (SD 1.11) at the time of virologic failure. Forty-eight percent of the samples were raltegravir resistant. The Y143R/H/C substitutions were the most prevalent, followed by the N155H, and both Q148H/K and G140S/A in the same proportion. The Q148 + G140 combination was found in (12%) of the samples. Cross-resistance to elvitegravir was found in 83.3% and in 18.2% for both dolutegravir and bictegravir. Thirteen samples (52%) were susceptible to the four integrase strand-transfer inhibitors. CONCLUSIONS: Our findings suggest a high occurrence of resistance and cross-resistance to other integrase inhibitors among multi-experienced subjects failing raltegravir. We found a modestly lower proportion of cross-resistance to dolutegravir than data from clinical trials. Likely this drug could be used for salvage therapy. Explanations for the absence of mutations in half of the samples, other than reduced adherence, should be further investigated. Close surveillance is needed.

[Enteropathogens responsible for gastrointestinal disorders in HIV patients]. / Agentes patógenos responsables de trastornos gastrointestinales en sujetos infectados con VIH.

Gastrointestinal disorders or GID are debilitating conditions common in individuals infected by the human immunodeficiency virus (HIV), capable of leading to death. Numerous etiological agents and pathophysiological mechanisms have been involved in this status. Although the use of highly active antiretroviral therapy (HAART) in many countries has greatly reduced the prevalence of gastrointestinal infections, enteric pathogens such as bacteria, parasites, fungi and viruses may still act as opportunist agents in these patients. Cytomegalovirus, adenovirus, calicivirus, astrovirus, rotavirus, enterovirus, picobirnavirus and some more recently described, like bocavirus and Aichi virus, have been detected in HIV patients. However, except for cytomegalovirus, which is an established etiological agent of GID in these patients, the role of the other viruses remains unclear. Several species of Cryptosporidium, microsporidia, Salmonella, atipical mycobacteria and Campylobacter jejuni, have also been recognized as important causes of GID in HIV patients. The progressive incorporation of increasingly sensitive immunological and molecular assays for antigen, antibody and pathogens detection from faeces, has improved the diagnosis of diarrhea and contributed to clarify the etiological significance of some microorganisms in immunocompetent patients. In Venezuela, some information is available about the prevalence of enteric pathogens in immunocompromised patients infected with HIV. The identification of the etiologic agent responsible for this condition may be useful for the management and treatment of these patients, for whom viral enteritis is a disease, which reduces their quality of life and causes a high public health spending.

Agentes patógenos responsables de trastornos gastrointestinales en sujetos infectados con VIH / Enteropathogens responsible of gastrointestinal disorders in HIV patients

Los trastornos gastrointestinales o TGI son afecciones debilitantes muy comunes en individuos infectados con el virus de inmunodeficiencia humana (VIH), que pueden conducir a muerte. Numerosos agentes etiológicos y mecanismos patofisiológicos han sido propuestos causar esta afección. A pesar del uso de terapia antirretroviral, que ha reducido enormemente la prevalencia de TGI en estos pacientes, patógenos entéricos como virus, bacterias, parásitos y hongos logran actuar todavía como agentes oportunistas. Citomegalovirus, adenovirus, calicivirus, astrovirus, rotavirus, enterovirus, picobirnavirus y algunos más recientemente descritos, como bocavirus y Aichi virus han sido detectados en pacientes con VIH. Sin embargo, a excepción del citomegalovirus, hay muy poca certeza acerca del papel que juegan algunos de ellos en estas afecciones. Varias especies de Criptosporidium, microsporidos, Salmonella, micobacterias atípicas y Campylobacter jejuni han sido reconocidos también como una importante causa de TGI en estos pacientes. La progresiva incorporación de técnicas inmunoenzimáticas y moleculares, cada vez más sensibles para la detección de antígenos, anticuerpos y agentes patógenos en heces ha mejorado el diagnóstico de las diarreas y contribuido a esclarecer la importancia etiológica de algunos microorganismos en los pacientes inmunocompetentes. En Venezuela existen algunos datos acerca de la prevalencia de patógenos entéricos en pacientes inmunodeficientes infectados con VIH. La identificación del agente etiológico responsable de TGI podría ser de gran utilidad para el manejo y tratamiento de estos pacientes, para quienes la enteritis viral es una manifestación morbosa que reduce la calidad de vida y ocasiona un elevado gasto en salud pública.

Gastrointestinal disorders or GID are debilitating conditions common in individuals infected by the human immunodeficiency virus (HIV), capable of leading to death. Numerous etiological agents and pathophysiological mechanisms have been involved in this status. Although the use of highly active antiretroviral therapy (HAART) in many countries has greatly reduced the prevalence of gastrointestinal infections, enteric pathogens such as bacteria, parasites, fungi and viruses may still act as opportunist agents in these patients. Cytomegalovirus, adenovirus, calicivirus, astrovirus, rotavirus, enterovirus, picobirnavirus and some more recently described, like bocavirus and Aichi virus, have been detected in HIV patients. However, except for cytomegalovirus, which is an established etiological agent of GID in these patients, the role of the other viruses remains unclear. Several species of Cryptosporidium, microsporidia, Salmonella, atipical mycobacteria and Campylobacter jejuni, have also been recognized as important causes of GID in HIV patients. The progressive incorporation of increasingly sensitive immunological and molecular assays for antigen, antibody and pathogens detection from faeces, has improved the diagnosis of diarrhea and contributed to clarify the etiological significance of some microorganisms in immunocompetent patients. In Venezuela, some information is available about the prevalence of enteric pathogens in immunocompromised patients infected with HIV. The identification of the etiologic agent responsible for this condition may be useful for the management and treatment of these patients, for whom viral enteritis is a disease, which reduces their quality of life and causes a high public health spending.