HIV-1-infected patients with osteoporosis were randomly assigned to alendronate 70 mg once-weekly plus dietary counselling (n = 11) or diet counselling alone (n = 14). At week 96, 27% of patients on alendronate versus 96% of controls presented with osteoporosis. Spine bone mineral density (BMD) increases were detected at week 48, and progressed thereafter. Improvements in trochanter BMD were obtained after 2 years. Once-weekly oral alendronate may be an effective and safe treatment for HIV-1-associated osteoporosis.