Deep-sequence phylogenetics to quantify patterns of HIV transmission in the context of a universal testing and treatment trial – BCPP/ Ya Tsie trial

Background: Mathematical models predict that community-wide access to HIV
testing-and-treatment can rapidly and substantially reduce new HIV
infections. Yet several large universal test-and-treat HIV prevention
trials in high-prevalence epidemics demonstrated variable reduction in
population-level incidence. Methods: To elucidate patterns of HIV spread
in universal test-and-treat trials we quantified the contribution of
geographic-location, gender, age and randomized-HIV-intervention to HIV
transmissions in the 30-community Ya Tsie trial in Botswana (estimated
trial population: 175,664). Results: Deep-sequence phylogenetic analysis
revealed that most inferred HIV transmissions within the trial occurred
within the same or between neighboring communities, and between
similarly-aged partners. Transmissions into intervention communities from
control communities were more common than the reverse post-baseline (30%
[12.2 – 56.7] versus 3% [0.1 – 27.3]) than at baseline (7% [1.5 – 25.3]
versus 5% [0.9 – 22.9]) compatible with a benefit from
treatment-as-prevention. Conclusion: Our findings suggest that population
mobility patterns are fundamental to HIV transmission dynamics and to the
impact of HIV control strategies. Funding: This study was supported by the
National Institute of General Medical Sciences (U54GM088558); the Fogarty
International Center (FIC) of the U.S. National Institutes of Health (D43
TW009610); and the President’s Emergency Plan for AIDS Relief through the
Centers for Disease Control and Prevention (CDC) (Cooperative agreements
U01 GH000447 and U2G GH001911).