V3 variation in HIV-seropositive patients receiving a V3-targeted vaccine

Objective: To analyze V3 loop sequences of HIV-1 in three seropositive indi viduals who exhibited declines in viremia while receiving a V3-targeted vac cine. Design: Retrospective analysis of case series at an HIV Clinic, University of Tel Aviv. Patients: Three HIV-1-seropositive, PPD-DTHR-positive (PPD, Siebert purifie d protein derivative of tuberculin; DTHR, delayed type hypersensitivity rea ction) individuals who had been inoculated with a mixture of PPD-cross-link ed V3 peptides from five HIV strains and then exhibited declines in HIV-1 v iremia during the course of vaccination in the absence of combination antir etroviral therapy and whose virus levels resurged once vaccine boosting was discontinued. Results: Declines in viremia were observed even when the viral V3 sequences of the patients' HIV differed by at least one or two amino acid residues f rom those of the five peptides in the vaccine. Although viral mutants with amino acid substitutions within V3 appeared during vaccination, plasma viru s loads remained at low levels for several months after these variants appe ared. About a year after boosting was discontinued, anti-V3 peptide antibod ies in the patients had declined and plasma virus returned to the prevaccin ation levels or higher. Compared with the isolates that predominated during the course of vaccination, the resurgent viruses contained zero to six ami no acid residue differences in the V3 loop but few synonymous substitutions . Conclusions: Viruses with altered V3 sequences did emerge but did not resul t in increased viremia during the course of vaccination. In two individuals where V3 mutations were absent in the virus that re-emerged after vaccine boosting ceased, resurgence could not have been a consequence of V3 changes . (C) 2001 Lippincott Williams & Wilkins.