P14-07. Offering new prevention modalities in HIV vaccine trials: experience with male circumcision in the Phambili trial

Background: New prevention options will be added to the 'standard of prevention' offered in HIV vaccine efficacy trials as new methods prove effective. The HVTN503/Phambili trial was initiated in January 2007, shortly after results from 3 randomized controlled trials of male circumcision (MC) demonstrated that MC reduces the risk of HIV acquisition. Thus, HVTN503 investigators made plans to offer MC at no cost to enrolled male participants. Methods: All participants were informed of the benefits of MC as a component of HIV risk reduction counseling, including how and where MC could be accessed. One site offered on-site MC and the others provided referral to local services for men who requested MC. We present data on uptake of MC post-enrollment. Results: Prior to discontinuation of enrolment, 441 men joined the trial, of whom 312 (70.7%) were uncircumcised. Of these, 82 (26.3% of uncircumcised men) requested MC after enrolment. Uptake varied by site, being lower (70%) at the eThekwini site, the site with lowest baseline MC prevalence. Among 3 sites with intermediate baseline MC prevalence, uptake varied from 3.3 to 37.6%, being highest at the site providing MC on site. Uptake was similar in vaccine and placebo arms of the trial [42 (26.1%) vs. 40 (26.5%)]. There was no significant difference by arm in the timing of circumcision relative to randomization assignment being provided to participants following release of the STEP trial results [post-unblinding, vaccine 18 (42.9%) vs. placebo 13 (32.5%), p = 0.37]. Conclusion: MC, a new prevention modality, was offered as part of HIV prevention services in HVTN503. Uptake varied by provision of care model and inversely with baseline MC prevalence, but did not differ between treatment arms, and remained similar even after provision of treatment

Re: Comparison of single photon emission computed tomography findings in cases of healthy adults and solvent-exposed adults

No abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34818/1/19_ftp.pd

Continued Follow-Up of Phambili Phase 2b Randomized HIV-1 Vaccine Trial Participants Supports Increased HIV-1 Acquisition among Vaccinated Men.

CAPRISA, 2015.Abstract available in pdf

Safety and Immunogenicity of an HIV-1 Gag DNA Vaccine with or without IL-12 and/or IL-15 Plasmid Cytokine Adjuvant in Healthy, HIV-1 Uninfected Adults

DNA vaccines are a promising approach to vaccination since they circumvent the problem of vector-induced immunity. DNA plasmid cytokine adjuvants have been shown to augment immune responses in small animals and in macaques.We performed two first in human HIV vaccine trials in the US, Brazil and Thailand of an RNA-optimized truncated HIV-1 gag gene (p37) DNA derived from strain HXB2 administered either alone or in combination with dose-escalation of IL-12 or IL-15 plasmid cytokine adjuvants. Vaccinations with both the HIV immunogen and cytokine adjuvant were generally well-tolerated and no significant vaccine-related adverse events were identified. A small number of subjects developed asymptomatic low titer antibodies to IL-12 or IL-15. Cellular immunogenicity following 3 and 4 vaccinations was poor, with response rates to gag of 4.9%/8.7% among vaccinees receiving gag DNA alone, 0%/11.5% among those receiving gag DNA+IL-15, and no responders among those receiving DNA+high dose (1500 ug) IL-12 DNA. However, after three doses, 44.4% (4/9) of vaccinees receiving gag DNA and intermediate dose (500 ug) of IL-12 DNA demonstrated a detectable cellular immune response.This combination of HIV gag DNA with plasmid cytokine adjuvants was well tolerated. There were minimal responses to HIV gag DNA alone, and no apparent augmentation with either IL-12 or IL-15 plasmid cytokine adjuvants. Despite the promise of DNA vaccines, newer formulations or methods of delivery will be required to increase their immunogenicity.Clinicaltrials.gov NCT00115960 NCT00111605