Wellcome Trust, UK (082384/Z/07/Z). The Hlabisa HIV Treatment and Care programme was made possible by the support of the United States Agency for International Development (USAID) and the President’s Emergency Plan. Research was supported by a South African Medical Research Council (MRC) Flagship grant (MRC-RFA-UFSP-01-2013/UKZN HIVEPI) and by Brazil’s Ciencia Sem Fronteiras Project from CNPQ.Background: HTLV-1/HIV co-infection is known to elevate the CD4+ T-cell counts of treatment-naïve persons. We investigated whether HTLV-1/HIV co-infected patients continued to have elevated CD4+ T-cell counts after developing virologic failure on antiretroviral therapy (ART). Methods: The data comes from a drug resistance study located in the KwaZulu-Natal province of South Africa. All participants (N=383) presented for repeated CD4+ T-cell count and HIV viral load level testing between January 2006 and March 2014. We used a random-coefficient model to estimate the change in CD4+ T-cell count and HIV viral load level by HTLV-1/HIV co-infection status over time, adjusting for age, sex, and duration of virologic failure. Results: HTLV-1/HIV co-infected participants (n=8) had higher CD4+ T-cell counts, with a positive difference of 117.2 cells/μL at the ART initiation date (p-value=0.001), 114.7 cells/μL (p-value<0.001) 12 months after this date, and 112.3 cells/μL (p-value=0.005) 24 months after this date, holding all else constant. In contrast, there was no difference in the HIV viral load level by HTLV-1/HIV co-infected status throughout the observation period. Conclusions: We show that HTLV-1/HIV co-infected participants continued to have elevated CD4+ T-cell counts after developing virologic failure on ART, despite no difference in their HIV viral load levels when compared with HIV mono-infected participants. Our results indicate that CD4+ T-cell count testing may not be a useful strategy to monitor ART response in the presence of HTLV-1/HIV co-infection.