Low Multiplicity of HIV-1 Infection and No Vaccine Enhancement in VAX003 Injection Drug Users

Overview

Journal Open Forum Infect Dis

Specialty Infectious Diseases

Date 2015 Mar 4

PMID 25734126

Citations 16

Authors

Sarah Sterrett

Gerald H Learn

Paul T Edlefsen

Barton F Haynes

Beatrice H Hahn

George M Shaw

Katharine J Bar

Affiliations

Soon will be listed here.

Abstract

Background: We performed human immunodeficiency virus type 1 (HIV-1) transmitted/founder (T/F) virus analysis of the VAX003 vaccine efficacy trial participants to characterize the transmission bottleneck and test for vaccine-associated reduction or enhancement of infection in this injection drug user (IDU) cohort.

Methods: We performed single genome sequencing of plasma vRNA from 50 subjects sampled in early HIV infection. Sequences were analyzed phylogenetically, T/F viruses enumerated, and a sieve analysis performed.

Results: Eight of 19 (42%) placebo recipients were productively infected by more than 1 virus (range 1-5, median 1, mean 1.7). This frequency of multiple virus transmission was greater than reported for heterosexual cohorts (19%, P = .03) but not statistically different from vaccine recipients (22.6%, P > .05), where the range was 1-3, median 1, and mean 1.3 (P > .05 for all comparisons). An atypical sieve effect was detected in Env V2 but was not associated with reduction or enhancement of virus acquisition.

Conclusions: The number of T/F viruses in IDUs was surprising low, with 95% of individuals infected by only 1-3 viruses. This finding suggests that a successful vaccine or other prevention modality generally needs to protect against only one or a few viruses regardless of risk behavior. T/F analysis identified an atypical genetic sieve in the V2 region of Envelope and found no evidence for vaccine-mediated enhancement in VAX003.

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