H I V / A I D S M A J O R A R T I C L E
A Randomized Noninferiority Trial of Standard
Versus Enhanced Risk Reduction and Adherence
Prophylaxis Following Sexual Exposures to HIV
Michelle E. Roland,1,aTorsten B. Neilands,2Melissa R. Krone,3Thomas J. Coates,aKarena Franses,1Margaret
A. Chesney,aJames S. Kahn,1and Jeffrey N. Martin1,2,3
1Positive Health Program, Department of Internal Medicine, San Francisco General Hospital;2Center for AIDS Prevention Studies, and3Department of
Epidemiology and Biostatistics, University of California, San Francisco, California
Intensive risk reduction and adherence counseling appear to be effective but are resource intensive. Identifying
simpler interventions that maximize the HIV prevention potential of PEP is critical.
Methods. A randomized noninferiority study comparing 2 (standard) or 5 (enhanced) risk reduction
counseling sessions was performed. Adherence counseling was provided in theenhanced arm.We measuredchanges
in unprotected sexual intercourse acts at 12 months, compared with baseline; HIV acquisition; and PEP adherence.
Outcomes were stratified by degree of baseline risk.
Results. We enrolled 457 individuals reporting unprotected intercourse within 72 h with an HIV-infected or
at-risk partner. Participants were 96% male and 71% white. There were 1.8 and 2.3 fewer unprotected sex acts in the
standard and enhanced groups. The maximum potential risk difference, reflected by the upper bound of the 95%
confidence interval, was 3.9 acts. The difference in the riskier subset may have been as many as 19.6 acts. The
incidence of HIV seroconversion was 2.9% and 2.6% among persons randomized to standard and enhanced
counseling, respectively, with a maximum potential difference of 3.4%. The absolute and maximal HIV
seroconversion incidence was 9.9% and 20.4% greater in the riskier group randomized to standard, compared with
enhanced, counseling. Adherence outcomes were similar, with noninferiority in the lower risk group and
concerning differences among the higher-risk group.
Conclusions. Risk assessment is critical at PEP initiation. Standard counseling is only noninferior for
individuals with lower baseline risk; thus, enhanced counseling should be targeted to individuals at higher risk.
The National HIV/AIDS Strategy proposes to scale-up post-exposure prophylaxis (PEP).
The United States 2010 National HIV/AIDS Strategy
includes scale-up of access to post-exposure prophylaxis
(PEP) . Despite uncertain efficacy in preventing
infection, PEP with risk reduction and medication ad-
herence counseling is recommended after potential
HIV risk behaviors and support PEP adherence maxi-
mize the potential impact of PEP services. Although
they appear to be effective, the 5-session HIV risk
reduction counseling strategy and intensive adherence
interventions previously evaluated are resource intensive
[5, 6]. Developing simpler, effective interventions is
a priority .
Received 17 September 2010; accepted 2 February 2011.
aPresent affiliation: Office of AIDS, Center for Infectious Diseases, California
Department of Public Health (M. E. R.); University of California, Los Angeles
(T. J. C.); Osher Center for Integrative Medicine, University of California, San
Francisco, California (M. A. C.).
Presented in part: 13th Conference on Retroviruses and Opportunistic Infections,
San Francisco, CA, February 2006 (abstract 902).
Correspondence: Michelle E. Roland, MD, Office of AIDS, Center for Infectious
Diseases, California Department of Public Health, PO Box 997426, MS7700,
Sacramento, CA 95899-7426 (firstname.lastname@example.org).
Clinical Infectious Diseases
? The Author 2011. Published by Oxford University Press on behalf of the Infectious
Diseases Society of America. All rights reserved. For Permissions, please e-mail:
d CID 2011:53 (1 July)
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