Patients with a baseline viral load >100,000 copies/mL receiving abacavir (ABC) as part of the nucleoside-backbone component of their first highly active antiretroviral therapy (HAART) regimen have been reported to have a greater failure rate than those receiving tenofovir (TDF). We analyzed short-term outcomes of the use of HAART combinations that included ABC or TDF. The mean 2-8-week change in viral load was calculated using linear regression. In total, 1136 patients started ABC, and 412 started TDF. After adjustment for baseline viral load and other factors, there was no difference in the change in viral load between the patients who started ABC and those who started TDF (0.03 [95% confidence interval, -0.07 to 0.12]) log copies/mL; P = .59). Furthermore, there was no evidence that this effect differed according to baseline viral load (P = .88 for the interaction between pre-HAART viral load and nucleoside started). Likewise, there was no difference in rates of virological failure between the 2 drugs at 24-48 weeks after starting HAART.