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Article

Detection of HIV-1 Transmission Clusters from Dried Blood Spots within a Universal Test-and-Treat Trial in East Africa

1
Ashworth Laboratories, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3FL, UK
2
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
3
Uganda Virus Research Institute, Entebbe P.O. Box 49, Uganda
4
Division of Prevention Science, Department of Medicine, University of California, San Francisco, CA 94158, USA
5
Kenya Medical Research Institute, Nairobi P.O. Box 54840-00200, Kenya
6
Division of HIV, Infectious Diseases and Global Medicine, Department of Medicine, University of California, San Francisco, CA 94110, USA
7
Usher Institute, University of Edinburgh, Edinburgh EH8 9AG, UK
8
Department of Infectious Disease Epidemiology, Faculty of Epidemiology and Population Health, LSHTM, London WC1E 7HT, UK
9
Centre for Mathematical Modelling of Infectious Diseases, LSHTM, London WC1E 7HT, UK
10
School of Medicine, Makerere University, Kampala P.O. Box 7072, Uganda
11
Division of Biostatistics, School of Public Health, University of California, Berkeley, CA 94720, USA
*
Author to whom correspondence should be addressed.
Deceased.
Academic Editor: Ana Barroso Abecasis
Viruses 2022, 14(8), 1673; https://doi.org/10.3390/v14081673
Received: 11 May 2022 / Revised: 15 July 2022 / Accepted: 25 July 2022 / Published: 29 July 2022
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. View Full-Text
Keywords: HIV; phylogenetics; phylodynamics; cluster; transmission network; molecular epidemiology HIV; phylogenetics; phylodynamics; cluster; transmission network; molecular epidemiology
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MDPI and ACS Style

Pujol-Hodge, E.; Salazar-Gonzalez, J.F.; Ssemwanga, D.; Charlebois, E.D.; Ayieko, J.; Grant, H.E.; Liegler, T.; Atkins, K.E.; Kaleebu, P.; Kamya, M.R.; Petersen, M.; Havlir, D.V.; Leigh Brown, A.J. Detection of HIV-1 Transmission Clusters from Dried Blood Spots within a Universal Test-and-Treat Trial in East Africa. Viruses 2022, 14, 1673. https://doi.org/10.3390/v14081673

AMA Style

Pujol-Hodge E, Salazar-Gonzalez JF, Ssemwanga D, Charlebois ED, Ayieko J, Grant HE, Liegler T, Atkins KE, Kaleebu P, Kamya MR, Petersen M, Havlir DV, Leigh Brown AJ. Detection of HIV-1 Transmission Clusters from Dried Blood Spots within a Universal Test-and-Treat Trial in East Africa. Viruses. 2022; 14(8):1673. https://doi.org/10.3390/v14081673

Chicago/Turabian Style

Pujol-Hodge, Emma, 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, and Andrew J. Leigh Brown. 2022. "Detection of HIV-1 Transmission Clusters from Dried Blood Spots within a Universal Test-and-Treat Trial in East Africa" Viruses 14, no. 8: 1673. https://doi.org/10.3390/v14081673

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