This article is part of the supplement: AIDS Vaccine 2009

Oral presentation

OA01-06 LB. HIV-1 plasma RNA and risk of HIV-1 transmission

JR Lingappa^1*, JP Hughes¹, D Donnel², JM Baeten¹, JI Mullins¹, MS Campbell¹, GE Gray³, M Essex⁴, C Farquhar¹, H Rees³, A Wald¹, L Corey¹ and C Celum¹

• * Corresponding author: JR Lingappa

Author Affiliations

¹ University of Washington, Seattle, Washington, USA

² Fred Hutchinson Cancer Research Centre, Seattle, USA

³ University of the Witwatersrand, Johannesburg, South Africa

⁴ Harvard University, Boston, USA

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Retrovirology 2009, 6(Suppl 3):O12 doi:10.1186/1742-4690-6-S3-O12

The electronic version of this article is the complete one and can be found online at: http://www.retrovirology.com/content/6/S3/O12

Published:

22 October 2009

© 2009 BioMed Central Ltd.

Background

Non-sterilizing HIV-1 vaccines may provide public health benefits if they significantly reduce plasma HIV-1 RNA, thus potentially reducing infectiousness. Quantification of reduction in plasma HIV-1 RNA needed to decrease HIV-1 transmission is useful for design of efficacy trials of candidate HIV-1 vaccines. We modeled the relationship between plasma HIV-1 RNA and HIV-1 transmission using data from a prospective study of African heterosexual HIV-1 serodiscordant couples.

Methods

3408 HIV-1-infected participants with CD4 counts ≥250 cells/mm3 enrolled in the Partners in Prevention HSV/HIV Transmission Study and their partners were followed for ≤24 months. HIV-1 transmission events were assessed for viral genetic linkage within the enrolled partnership by determining HIV-1 env and gag sequences from partners. The relationship between plasma HIV-1 RNA over time and risk of genetically linked HIV-1 transmission was evaluated with a Cox model with a natural cubic spline.

Results

84 post-enrollment linked HIV-1 transmissions were observed. HIV-1 incidence increased rapidly and non-linearly with higher plasma HIV-1: from 0.53 transmissions per 100 person-years for plasma HIV-1 RNA <10,000 copies/mL to 6.2 for HIV-1 RNA >1,000,000 copies/mL (p<0.0001). Baseline HIV-1 RNA in men was, on average, 0.4 log10 higher than in women; no significant difference in risk of transmission for a given HIV-1 level was observed between men and women (p = 0.17). Given the distribution of plasma HIV-1 RNA in this population of stable cohabiting couples, our modeling predicts that a 0.74 log10 reduction in average plasma HIV-1 RNA in the population would be required for a 50% reduction in HIV-1 transmission risk.

Conclusion

This analysis provides a detailed description of the relationship between plasma HIV-1 RNA and risk of heterosexual HIV-1 transmission. These findings suggest targets for reduction in HIV-1 RNA for use in evaluating non-sterilizing HIV-1 vaccine candidates in HIV-1 infected persons to reduce risk of heterosexual HIV-1 transmission.