For the VOICE Study Team: Tenofovir-Centered Preexposure Prophylaxis for HIV Contamination among African Women.. Jeanne M. Marrazzo, M.D., Gita Ramjee, Ph.D., Barbra A. Richardson, Ph.D., Kailazarid Gomez, M.P.A., Nyaradzo Mgodi, M.Med., Gonasagrie Nair, M.B., Ch.B., M.P.H., Thesla Palanee, Ph.D., Clemensia Nakabiito, M.Med., Ariane van der Straten, Ph.D., Lisa Noguchi, M.S.N., Craig W. Hendrix, M.D., James Y. Dai, Ph.D., Shayhana Ganesh, M.Med., Baningi Mkhize, M.B., Ch.B., Marthinette Taljaard, B.S., Urvi M. Parikh, Ph.D., Jeanna Piper, M.D.D., Cynthia Grossman, Ph.D., James Rooney, M.D., L Jill. Schwartz, M.D., Heather Watts, M.D., Mark A. Marzinke, Ph.D., Sharon L.Ali, Ph.D. The encoded retinoid isomerase converts all-trans retinyl esters to 11-cis retinal for the regeneration of visual pigment after contact with light. RPE65 deficiency causes photoreceptor-cell dysfunction and impaired eyesight from birth. The function of cone photoreceptor cells, which mediate eyesight in daylight, is relatively preserved in childhood because cones get access to an choice source of 11-cis retinal.2 However, progressive degeneration of both rod and cone photoreceptor cells, in association with regional accumulation of toxic retinyl esters,3 outcomes in severe sight impairment by early adulthood. Augmentation of Rpe65 in animal types of Rpe65 deficiency can improve visual and retinal function, as assessed through electroretinography and observation of vision-guided behavior, respectively.4-6 We and others have previously reported that gene-augmentation therapy for RPE65 deficiency may improve areas of sight in human being participants.7-10 However, the magnitude and durability of benefit reported up to now in humans do not match those seen in animal models.11 Species-specific differences in the outcomes of gene therapy are largely unexplained, however they may reflect differences in pathophysiological mechanisms, vector tropism, or both.