Estimating the impact of plasma HIV-1 RNA reductions on heterosexual HIV-1 transmission risk.
BACKGROUND
The risk of sexual transmission of HIV-1 is strongly associated with the level of HIV-1 RNA in plasma making reduction in HIV-1 plasma levels an important target for HIV-1 prevention interventions. A quantitative understanding of the relationship of plasma HIV-1 RNA and HIV-1 transmission risk could help predict the impact of candidate HIV-1 prevention interventions that operate by reducing plasma HIV-1 levels, such as antiretroviral therapy (ART), therapeutic vaccines, and other non-ART interventions.


RESULTS
We use prospective data collected from 2004 to 2008 in East and Southern African HIV-1 serodiscordant couples to model the relationship of plasma HIV-1 RNA levels and heterosexual transmission risk with confirmation of HIV-1 transmission events by HIV-1 sequencing. The model is based on follow-up of 3381 HIV-1 serodiscordant couples over 5017 person-years encompassing 108 genetically-linked HIV-1 transmission events. HIV-1 transmission risk was 2.27 per 100 person-years with a log-linear relationship to log(10) plasma HIV-1 RNA. The model predicts that a decrease in average plasma HIV-1 RNA of 0.74 log(10) copies/mL (95% CI 0.60 to 0.97) reduces heterosexual transmission risk by 50%, regardless of the average starting plasma HIV-1 level in the population and independent of other HIV-1-related population characteristics. In a simulated population with a similar plasma HIV-1 RNA distribution the model estimates that 90% of overall HIV-1 infections averted by a 0.74 copies/mL reduction in plasma HIV-1 RNA could be achieved by targeting this reduction to the 58% of the cohort with plasma HIV-1 levels ≥4 log(10) copies/mL.


CONCLUSIONS
This log-linear model of plasma HIV-1 levels and risk of sexual HIV-1 transmission may help estimate the impact on HIV-1 transmission and infections averted from candidate interventions that reduce plasma HIV-1 RNA levels.
Lingappa
Jairam R
JR
Department of Global Health, University of Washington, Seattle, Washington, United States of America. lingappa@uw.edu
Hughes
James P
JP
Wang
Richard S
RS
Baeten
Jared M
JM
Celum
Connie
C
Gray
Glenda E
GE
Stevens
Wendy S
WS
Donnell
Deborah
D
Campbell
Mary S
MS
Farquhar
Carey
C
Essex
M
M
Mullins
James I
JI
Coombs
Robert W
RW
Rees
Helen
H
Corey
Lawrence
L
Wald
Anna
A
D000351:Africa, Eastern; D000353:Africa, Southern; D019380:Anti-HIV Agents / Q000627:therapeutic use; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy / Q000517:prevention & control* / Q000635:transmission* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification* / Q000502:physiology; D020010:Heterosexuality; D006801:Humans; D008297:Male; D012367:RNA, Viral / Q000097:blood* / Q000235:genetics; D012307:Risk Factors; D012747:Sexual Partners; D019562:Viral Load
D019380:Anti-HIV Agents; D012367:RNA, Viral