Detection of HIV-1 Transmission Clusters from Dried Blood Spots within a Universal Test-and-Treat Trial in East Africa
Emma Pujol-Hodge,
Jesus F. Salazar-Gonzalez,
Deogratius Ssemwanga,
Edwin D. Charlebois,
James Ayieko,
Heather E. Grant,
Teri Liegler,
Katherine E. Atkins,
Pontiano Kaleebu,
Moses R. Kamya,
Maya Petersen,
Diane V. Havlir,
Andrew J. Leigh Brown
Affiliations
Emma Pujol-Hodge
Ashworth Laboratories, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3FL, UK
Jesus F. Salazar-Gonzalez
Medical Research Council (MRC)/Uganda Virus Research Institute (UVRI) and London School of Hygiene and Tropical Medicine (LSHTM) Uganda Research Unit, Entebbe P.O. Box 49, Uganda
Deogratius Ssemwanga
Medical Research Council (MRC)/Uganda Virus Research Institute (UVRI) and London School of Hygiene and Tropical Medicine (LSHTM) Uganda Research Unit, Entebbe P.O. Box 49, Uganda
Edwin D. Charlebois
Division of Prevention Science, Department of Medicine, University of California, San Francisco, CA 94158, USA
James Ayieko
Kenya Medical Research Institute, Nairobi P.O. Box 54840-00200, Kenya
Heather E. Grant
Ashworth Laboratories, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3FL, UK
Teri Liegler
Division of HIV, Infectious Diseases and Global Medicine, Department of Medicine, University of California, San Francisco, CA 94110, USA
Katherine E. Atkins
Usher Institute, University of Edinburgh, Edinburgh EH8 9AG, UK
Pontiano Kaleebu
Medical Research Council (MRC)/Uganda Virus Research Institute (UVRI) and London School of Hygiene and Tropical Medicine (LSHTM) Uganda Research Unit, Entebbe P.O. Box 49, Uganda
Moses R. Kamya
School of Medicine, Makerere University, Kampala P.O. Box 7072, Uganda
Maya Petersen
Division of Biostatistics, School of Public Health, University of California, Berkeley, CA 94720, USA
Diane V. Havlir
Division of HIV, Infectious Diseases and Global Medicine, Department of Medicine, University of California, San Francisco, CA 94110, USA
Andrew J. Leigh Brown
Ashworth Laboratories, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3FL, UK
The Sustainable East Africa Research in Community Health (SEARCH) trial was a universal test-and-treat (UTT) trial in rural Uganda and Kenya, aiming to lower regional HIV-1 incidence. Here, we quantify breakthrough HIV-1 transmissions occurring during the trial from population-based, dried blood spot samples. Between 2013 and 2017, we obtained 549 gag and 488 pol HIV-1 consensus sequences from 745 participants: 469 participants infected prior to trial commencement and 276 SEARCH-incident infections. Putative transmission clusters, with a 1.5% pairwise genetic distance threshold, were inferred from maximum likelihood phylogenies; clusters arising after the start of SEARCH were identified with Bayesian time-calibrated phylogenies. Our phylodynamic approach identified nine clusters arising after the SEARCH start date: eight pairs and one triplet, representing mostly opposite-gender linked (6/9), within-community transmissions (7/9). Two clusters contained individuals with non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance, both linked to intervention communities. The identification of SEARCH-incident, within-community transmissions reveals the role of unsuppressed individuals in sustaining the epidemic in both arms of a UTT trial setting. The presence of transmitted NNRTI resistance, implying treatment failure to the efavirenz-based antiretroviral therapy (ART) used during SEARCH, highlights the need to improve delivery and adherence to up-to-date ART recommendations, to halt HIV-1 transmission.
