Académique Documents
Professionnel Documents
Culture Documents
Even a vaccine with low efficacy and limited coverage can impact the epidemic and play a role in preventing future infections
Stover J, et al. The impact of an AIDS Vaccine in Developing Countries: A New Model and Initial Results. Health Affairs 26(4):1147-1158 (2007)
Length of Study
3.5 y
1% TDF gel
(Caprisa, Karim et al.)
2.5 y
1.2 y
TDF/FTC PrEP
(iPrEx, Grant et al 2010)
Circumcision
(Orange Farm, Rakai, Kisumu)
0% 10 20 30 40 50 60 70 80 90 100%
Efficacy
Slide: Glenda Gray, HVTN Conference, Nov 2010; modified by Jerome Kim, 2010 Siegfried N et al. Male circumcision preventing heterosexual acquisition of HIV in men. Int J Epidemiol 2010; 39: 968-972
HVTN 505
Phase 2, Randomized, Placebo-Controlled Trial to Evaluate the Safety and Effect on Post-HIV Acquisition Viremia of a Multiclade HIV-1 DNA Plasmid Vaccine Followed by a Multiclade HIV-1 Recombinant Adenoviral Vector Vaccine in HIV-Uninfected, Adenovirus Type 5 Neutralizing Antibody Negative, Circumcised Men and Male-to-Female Transgender Persons, Who Have Sex with Men
(Version 2.0 December 21, 2009)
rAd5
Env A Env B Env C gag/pol B
Infection Dx
Primary endpoint
Definition of VL setpoint
Average of all values at week 10 through week 20 post-infection diagnosis study visit VL values prior to ART initiation 20% is an upper bound for censored VL endpoints
FPI to FPI
Revisions per Version 2.0 of DAIDS EAE Manual Updated references to DAIDS AE grading table SICF sections 5-8 reordered and rewritten
Based upon results from these human and NHP HIV vaccine studies, HVTN 505 has added a third primary objective:
Assessing whether the 505 vaccines might protect against HIV infection. Study size was increased from 1350 to 2200 participants in 2011.
1. Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, et al. Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N Engl J Med. 2009;361:2209-2220. 2. Koup RA. Antibody responses to the VRC vaccine: Implications for HVTN 505. HVTN Full Group Meeting, Washington, DC, May 5, 2010. 3. Letvin NL, Rao SS, Montefiori DC, et al. Immune and Genetic Correlates of Vaccine Protection Against Mucosal Infection by SIV in Monkeys. Sci Transl Med. 2011;3:81ra36.
Microbicides
CAPRISA 004: topical PrEP (Tenofovir gel)
HVTN 505: Opportunity to adapt and incorporate results as other non-vaccine and vaccine prevention studies emerge
Knowledge and attitudes towards use of ARTs for prophylaxis are evolving
Distinction between pre- and post-exposure prophylaxis may become less clear
Emerging data about optimal timing and frequency of dosing around exposure
HVTN 505: Rationale for Behavioral and Biological Monitoring of Prophylactic ART
ART used as prophylaxis may influence
HIV incidence Post-infection disease course Study participation, risk behavior over time, and perception of risk
Important opportunity to ask a number of questions and monitor prophylactic ART use in 505
Lessons can be applied broadly to vaccine field and prevention field
Increased sample size to enable evaluation of HIV-1 acquisition Modified inclusion and exclusion criteria anticipating increased use of prophylactic ART Opportunity to evaluate self reported use in correlation with objective measures of drug levels Opportunity for further education and risk reduction counseling of participants
Analysis of samples
Chosen retrospectively to capture levels on HIV negative individuals reporting ART use Random sampling of HIV negative individuals who do not report prophylactic ART At HIV diagnosis visit and visit with earliest evidence of infection
40
40
8 144 (120:24)
Total
Social Science
Social research is the systematic observation of social life for the purpose of finding and understanding patterns among what is observed
(Earl Babbie, sociologist)
HVTN.org/Science/HVTNews
Informs readers about the science of the HVTN, the management of the Networks many multilateral collaborations, and our outstanding clinical sites. Current issue includes articles on Epitope Mapping, Adaptive Trial Design, and Exploring Barriers and Facilitators in the Recruitment of Transgender Women.
Acknowledgements
Magda Sobieszczyk 505 Protocol Team HVTN 505 Sites, Staff and Participants HVTN Community Education & Communications Team HVTN 505 PrEP Monitoring Working Groups
PK substudy Working Group
John Hural, Peter Gilbert, Carter Bently, Shelly Karuna, Magda Sobieszczyk, Scott Hammer, Adam Sherwat, Angela Kashuba, Jim Rooney, HVTN Lab Jonathan Fuchs, Beryl Koblin. Ken Mayer, Susan Buchbinder, Al Liu, Michele Andrasik