HIV-1 drug resistance testing at second-line regimen failure in Arua, Uganda: avoiding unnecessary switch to an empiric third-line.

OBJECTIVES: The number of patients on second-line antiretroviral therapy is growing, but data on HIV drug resistance patterns at failure in resource-constrained settings are scarce. We aimed to describe drug resistance and investigate the factors associated with extensive resistance to nucleoside/nucleotide reverse transcriptase inhibitors (NRTI), in patients failing second-line therapy in the HIV outpatient clinic at Arua Regional Referral Hospital, Uganda. METHODS: We included patients who failed on second-line therapy (two consecutive viral loads ≥1000 copies/mm3 by SAMBA-1 point-of-care test) and who had a drug resistance test performed between September 2014 and March 2017. Logistic regression was used to investigate factors associated with NRTI genotypic sensitivity score (GSS) ≤1. RESULTS: Seventy-eight patients were included: 42% female, median age 31 years and median time of 29 months on second-line therapy. Among 70 cases with drug resistance test results, predominant subtypes were A (47%) and D (40%); 18.5% had ≥1 major protease inhibitor mutation; 82.8% had ≥1 NRTI mutation and 38.5% had extensive NRTI resistance (NRTI GSS ≤1). A nadir CD4 count ≤100/ml was associated with NRTI GSS ≤1 (OR 4.2, 95% CI [1.3-15.1]). Thirty (42.8%) patients were switched to third-line therapy, composed of integrase inhibitor and protease inhibitor (60% darunavir/r) +/- NRTI. A follow-up viral load was available for 19 third-line patients at 12 months: 84.2% were undetectable. CONCLUSIONS: Our study highlights the need for access to drug resistance tests to avoid unnecessary switches to third-line therapy, but also for access to third-line drugs, in particular integrase inhibitors. Low nadir CD4 count might be an indicator of third-line drug requirement for patients failing second-line therapy.

Resistencias de Mycobacterium tuberculosis en el área del Hospital de Sagunto desde 1999 al 2004 / Anti-tuberculosis drug resistance of Mycobacterium tuberculosis in the area of the Hospital de Sagunto from 1999 to 2004

Objetivo. La finalidad del estudio fue conocer los patrones de sensibilidad a antimicrobianos de Mycobacterium tuberculosis, en particular la resistencia primaria a isoniacida, en el área del Hospital de Sagunto, así como estudiar las características clínicas y factores de riesgo asociadas a los mismos. Material y métodos. Se incluyeron todos los pacientes con diagnóstico de tuberculosis desde enero de 1999 a diciembre de 2004, en los que se aislaron cepas de M. tuberculosis en cultivo de una muestra clínica y se realizó estudio de resistencias a los fármacos antituberculosos de primera línea. Se recogieron de la historia clínica los factores de riesgo y las características clínicas de los pacientes. Resultados. El total de cepas aisladas fue de 77, con una tasa global de resistencias del 14,1%. La frecuencia de resistencias primarias fue del 12%, siendo las secundarias del 27%. No se detectó ningún caso de multirresistencia. Las resistencias primarias fueron: 3% a isoniacida, 3% a rifampicina, 3% a piracinamida, 4,5% a etambutol y 3% a estreptomicina. La resistencia adquirida fue del 9,1% para isoniacida y del 27% para estreptomicina, no encontrando resistencias para el resto de los fármacos testados. Conclusiones. La baja frecuencia de resistencias primarias a isoniacida hace que podamos tratar los casos nuevos en población autóctona con tres fármacos. Los factores de riesgo asociados a resistencias en nuestra área fueron el tabaquismo y el alcoholismo. Aunque todos los pacientes con resistencias presentaban formas pulmonares, las diferencias no fueron estadísticamente significativas, y sí lo fue la mayor frecuencia de derrame pleural en pacientes con resistencias (AU)

Objectives. This study aimed to know the drug resistance patterns of Mycobacterium tuberculosis, specifically primary drug resistance to isoniazid, in the area of the Hospital de Sagunto and to study the clinical characteristics and the risk factors associated with them. Material and methods. Patients included were those who were diagnosed of tuberculosis and whose M. tuberculosis strains were isolated in culture of a clinical sample and in whom a susceptibility test against the first line anti-tuberculosis drugs was performed from January 1999 to December 2004. Risk factors and clinical characteristics of the patients were gathered from the case- history. Results. The total number of strains isolated was 77 and the global rate of resistance was 14.1%. Rate of primary drug resistance was 12.1%, and acquired 27%. No multidrug resistant case was detected. Primary drug resistance was 3% to isoniazid, 3% to rifampin, 3% to pyrazinamid, 4.5% to ethambutol and 3% to streptomycin. Acquired drug resistance was 9.1% against isoniazid and 27% against streptomicin, no resistance against the other drugs tested being found. Conclusions. The low level of primary drug resistance against isoniazid allows us to start treatment with three-drug regimes in new cases of native population. In our hospital area, the risk factors associated with drug resistances were smoking habit and alcoholism. Although all patients with drug resistance presented pulmonary disease, the differences were not statistically significant. However, the higher rate of pleural effusion in patients with drug resistance was statistically significant (AU)

[Anti-tuberculosis drug resistance of Mycobacterium tuberculosis in the area of the Hospital de Sagunto from 1999 to 2004]. / Resistencias de Mycobacterium tuberculosis en el área del Hospital de Sagunto desde 1999 al 2004.

OBJECTIVES: This study aimed to know the drug resistance patterns of Mycobacterium tuberculosis, specifically primary drug resistance to isoniazid, in the area of the Hospital de Sagunto and to study the clinical characteristics and the risk factors associated with them. MATERIAL AND METHODS: Patients included were those who were diagnosed of tuberculosis and whose M. tuberculosis strains were isolated in culture of a clinical sample and in whom a susceptibility test against the first line anti-tuberculosis drugs was performed from January 1999 to December 2004. Risk factors and clinical characteristics of the patients were gathered from the case- history. RESULTS: The total number of strains isolated was 77 and the global rate of resistance was 14.1%. Rate of primary drug resistance was 12.1%, and acquired 27%. No multidrug resistant case was detected. Primary drug resistance was 3% to isoniazid, 3% to rifampin, 3% to pyrazinamid, 4.5% to ethambutol and 3% to streptomycin. Acquired drug resistance was 9.1% against isoniazid and 27% against streptomicin, no resistance against the other drugs tested being found. CONCLUSIONS: The low level of primary drug resistance against isoniazid allows us to start treatment with three-drug regimes in new cases of native population. In our hospital area, the risk factors associated with drug resistances were smoking habit and alcoholism. Although all patients with drug resistance presented pulmonary disease, the differences were not statistically significant. However, the higher rate of pleural effusion in patients with drug resistance was statistically significant.