Detection of HIV-1 Transmission Clusters from Dried Blood Spots within a Universal Test-and-Treat Trial in East Africa
| Autor: | Emma Pujol-Hodge, Jesus Salazar-Gonzalez, Deogratius Ssemwanga, Edwin Charlebois, James Ayieko, Heather Grant, Teri Liegler, Katherine Atkins, Pontiano Kaleebu, Moses Kamya, Maya Petersen, Diane Havlir, Andrew Leigh Brown |
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| Rok vydání: | 2022 |
| Předmět: |
HIV-1/genetics
Reverse Transcriptase Inhibitors/therapeutic use Anti-HIV Agents transmission network HIV Infections molecular epidemiology Microbiology Clinical Research Virology HIV Seropositivity Genetics Humans Uganda cluster HIV phylogenetics phylodynamics Uganda/epidemiology Bayes Theorem HIV Infections/diagnosis Good Health and Well Being Infectious Diseases Anti-HIV Agents/therapeutic use HIV-1 HIV/AIDS Reverse Transcriptase Inhibitors Infection |
| Zdroj: | Viruses; Volume 14; Issue 8; Pages: 1673 Viruses, vol 14, iss 8 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 2022, ' Detection of HIV-1 Transmission Clusters from Dried Blood Spots within a Universal Test-and-Treat Trial in East Africa ', Viruses, vol. 14, no. 8, 1673 . https://doi.org/10.3390/v14081673 Pujol-Hodge, E, Salazar-Gonzalez, J F, Ssemwanga, D, Charlebois, E, Ayieko, J, Grant, H, Liegler, T, Atkins, K, Kaleebu, P, Kamya, M R, Petersen, M, Havlir, D & Leigh Brown, A 2022, ' Detection of HIV-1 transmission clusters from dried blood spots within a universal test-and-treat trial in East Africa ', Viruses, vol. 14, no. 8, 1673 . https://doi.org/10.3390/v14081673 |
| ISSN: | 1999-4915 |
| DOI: | 10.3390/v14081673 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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