In April 2015, the Spanish National Health System (SNHS) developed a national strategic plan for the diagnosis, treatment, and management of hepatitis C virus (HCV). Our aim was to analyze the impact of this on human immunodeficiency virus (HIV)-infected patients included in the HERACLES cohort during the first 6 months of its implementation. The HERACLES cohort (NCT02511496) was set up in March 2015 to evaluate the status and follow-up of chronic HCV infection in patients co-infected with HIV in the south of Spain. In September 2015, the data were analyzed to identify clinical events (death, liver decompensation, and liver fibrosis progression) and rate of treatment implementation in this population. The study population comprised a total of 3474 HIV/HCV co-infected patients. The distribution according to liver fibrosis stage was: 1152 F0-F1 (33.2 %); 513 F2 (14.4 %); 641 F3 (18.2 %); 761 F4 (21.9 %); and 407 whose liver fibrosis was not measured (12.3 %). During follow-up, 248 patients progressed by at least one fibrosis stage [7.1 %; 95 % confidence interval (CI): 6.3-8 %]. Among cirrhotic patients, 52 (6.8 %; 95 % CI: 5.2-8.9 %) developed hepatic decompensation. In the overall population, 50 patients died (1.4 %; 95 % CI: 1.1-1.9 %). Eight hundred and nineteen patients (23.56 %) initiated interferon (IFN)-free treatment during follow-up, of which 47.8 % were cirrhotic. In our study, during 6 months of follow-up, 23.56 % of HIV/HCV co-infected patients included in our cohort received HCV treatment. However, we observed a high incidence of negative short-term outcomes in our population. ; Journal Article; Ethical approval The study coordinator presented the study protocol (protocol code: FIBICO-0015/01017-2015) to the Coordinating Ethics Committee for Biomedical Research in Andalusia for evaluation and obtained approval (240-2819-05/15). ; This work was supported by the Ministerio de Sanidad (RD12/0017/0012 and PI15/01017) integrated in the Plan Nacional de I + D + I and cofinanced by the ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER). A.R.-J. was the recipient of a Post-Doctoral Research Extension Grant from the Fundación Progreso y Salud (0024-RH-2013 Consejería de Salud, Innovación y Ciencia de la Junta de Andalucia). The HEPAVIR group was the recipient of a Research Network Support Grant from the Fundación Progreso y Salud (Consejería de Salud, Innovación y Ciencia de la Junta de Andalucia; AC-0095-2013, AYUDAS A GRUPOS DE INVESTIGACION).