Heffron R, et al. - Considering the observational studies suggesting increased HIV risk in correlation with self-reported use of injectable depot medroxyprogesterone acetate, researchers examined if testing blood samples for medroxyprogesterone acetate (MPA), the progestin in depot medroxyprogesterone acetate, may permit validation of self-reported data, and exploration of whether potential HIV risk is correlated with MPA levels, which are highest soon after injection. Serum from women who participated in three longitudinal studies of HIV prevention in East and southern Africa was tested in this case–control study. Women, who acquired HIV, significantly more frequently had detection of MPA at low levels close to the estimated time of HIV acquisition. This study highlights the necessity for studies exploring the biological mechanisms elicited by any MPA level and HIV risk.