BACKGROUND AND AIMS: In Peru, the estimated prevalence of human immunodeficiency virus (HIV) and human T-lymphotropic virus-1 (HTLV-1) co-infection has been reported to be as high as 18%. Despite the endemicity of HTLV-1 in Peru, few studies have assessed the impact of HIV/HTLV-1 co-infection. Our study compared socio-demographic and clinical characteristics, and mortality rates between HIV-infected and HIV/HTLV-1 co-infected patients. METHODS: We reviewed the medical records of patients aged 18 years and older belonging to the HIV and HTLV-1 cohorts in Lima during a 30-year period: 1989-2019. Each HIV/HTLV-1 co-infected patient was randomly matched with two HIV-infected patients with similar characteristics (same sex, age ± 5 years, and same year of HIV diagnosis). Allegedly co-infected patients without a confirmatory diagnosis of HIV and HTLV-1 were excluded. Most of the patients in the HIV-infected group did not have a negative test result for HTLV-1 infection, so we used two probabilistic sensitivity analysis models to correct for potential HTLV-1 exposure misclassification bias in the group of HIV-infected patients. RESULTS: Of 162 patients enrolled, 54 were HIV/HTLV-1 co-infected and 108 were HIV-infected. The median age was 42 years (IQR = 34-51 years) and the majority were male (61.1%), single (44.4%), heterosexual (71%), born in Lima (58%), educated at the secondary school level (55.6%), and receiving antiretroviral treatment (91.4%). HIV/HTLV-1 co-infection was associated with an increased risk of death (HR: 11.8; 95% CI: 1.55-89.00; p = 0.017) while antiretroviral treatment was associated with a decreased risk of death (HR: 0.03; 95% CI: 0.003-0.25; p = 0.001). The overall mortality rate was 13.6 per 100 persons and the survival time for co-infected patients (median = 14.19 years) was significantly shorter than that of HIV-infected patients (median = 23.83 years) (p < 0.001). CONCLUSIONS: HIV/HTLV-1 co-infected patients had a significantly shorter survival time compared to HIV-infected patients, suggesting that the immune alterations caused by HTLV-1 in CD4 cell count may have contributed to late initiation of antiretroviral treatment and prophylaxis against opportunistic infections over the decades, and thus reducing their benefits in these patients.