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Overview of STEP and Phambili trial results: two phase IIb test-of-concept studies investigating the efficacy of MRK adenovirus type 5 gag/pol/nef subtype B HIV vaccine

Gray, Glendaa; Buchbinder, Susanb; Duerr, Annc

Current Opinion in HIV and AIDS: September 2010 - Volume 5 - Issue 5 - p 357–361
doi: 10.1097/COH.0b013e32833d2d2b
HIV vaccines after STEP: Edited by Susan P. Buchbinder and Lawrence Corey and James Kublin

Purpose of review Two phase IIb test-of-concept studies evaluated the replication-defective adenovirus type 5 (Ad5) vaccine MRK gag/pol/nef HIV vaccine to prevent infection or decrease early plasma viral load in disparate populations. The STEP study enrolled men and women in the Americas, Caribbean and Australia; the Phambili trial enrolled men and women in South Africa, where the modes of sexual transmission and HIV-1 risk, subtypes of HIV-1, and background Ad5 seroprevalence differed.

Recent findings Vaccination in both studies were stopped, after the first interim efficacy analysis of the STEP study crossed predetermined nonefficacy boundaries. Neither trial demonstrated a decrease in HIV acquisition nor decreased early plasma viral load in vaccinees compared with placebo recipients. Post-hoc analyses of men enrolled in the STEP study showed a larger number of HIV infections in the subgroup of vaccinated men who were Ad5-seropositive and uncircumcised compared with a comparable placebo group. This was not demonstrated in the Phambili study, in which most men were heterosexual, whereas most in STEP were homosexual/bisexual. Further analysis of the STEP study has yet to explain the effect of Ad5 seroprevalence on increased HIV-1 susceptibility in men receiving the vaccine. However, promising vaccine effects on early viral control were seen, and the possibility of effects on early viral load set-point in women in Phambili was seen.

Summary These trials have provided a number of lessons about the importance of clinical trials in the HIV vaccine discovery process, and insight into the type and level of immune response that will be required for control of viral replication.

aPerinatal HIV Research Unit, University of the Witwatersrand, Johannesburg, South Africa

bSan Francisco Department of Public Health and University of California, San Francisco, California, USA

cHIV Vaccine Clinical Trials Network, Fred Hutchinson Cancer Research, University of Washington, Seattle, Washington, USA

Correspondence to Glenda Gray, Perinatal HIV Research Unit, PO Box 114, Diepkloof, Soweto 1864, South Africa E-mail:

© 2010 Lippincott Williams & Wilkins, Inc.