How can you control DR virus?

1. How can you control DR virus? ARV Therapy Pharmacological Control Mutation Reversion Prevent viral DR mutation Enhance immune responses Immune Control CTL Response

2. Peptide design and Elispot assay • 49 patients • 218 peptides • 140 pairs (WT Vs. DR) • Protease and Reverse Transcriptase • Epitopes overlapping DR mutations sites were selected.

3. High-magnitudeELISpot responses bothto WT and DR variants Higher recognition of DR Higher recognition of WT DR - WT

4. Mostrecognizedpeptides. (>20%) WT WT DR DR Peptides with DR mutations were frequently recognized. WT DR DR DR

5. Summary • Peptides including DR mutations could be considered as immunogens in therapeutic CTL vaccines directed towards immunological-pharmacological strategies to control HIV. • Therapeutic CTL vaccines could prevent selection of DR variants in places where continuous medication supply has not been achieved. • Therapeutic CTL vaccines could control viremia in patients with failure to multiple ART schemes. • 217 from the 218 peptides tested were recognized by at least 1 patient. • The median of patients recognizing each peptide was 5 (0-15). • The most frequently recognized peptides (twice the median) are shown in Table 1, along with the DR mutations they overlap and the associated HLA. • More cornering than escape cases were found among total responses (one patient recognizing either WT or DR mutation peptide). • We found four HLA alleles (B*35, B*08, A*11 and A*02) associated with responses with the highest average magnitude (SFC/106 PBMC/#responses). • No differences were found between the average magnitude of response for WT peptides and DR mutation peptides, or by comparing HLA alleles against each other or each HLA allele against all other HLA alleles.

6. IrsiCaixa Institut de Recerca de la Sida Abstract number: WEPDA0102