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

Clinical Trial

. 2022 Jul 29;14(8):1673.

doi: 10.3390/v14081673.

Jesus F Salazar-Gonzalez 2, Deogratius Ssemwanga 2 3, Edwin D Charlebois 4, James Ayieko 5, Heather E Grant 1, Teri Liegler 6, Katherine E Atkins 7 8 9, Pontiano Kaleebu 2 3, Moses R Kamya 10, Maya Petersen 11, Diane V Havlir 6, Andrew J Leigh Brown 1

Affiliations

Clinical Trial

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

Emma Pujol-Hodge et al. Viruses. 2022.

Abstract

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.

Keywords: HIV; cluster; molecular epidemiology; phylodynamics; phylogenetics; transmission network.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1

Figure 1

SEARCH community point locations (n = 32) across the three geographically separate SEARCH trial regions: Western Uganda (in red, n = 10), Eastern Uganda (in orange, n = 10), and Western Kenya (in gold, n = 12).

Figure 2

Figure 2

Sequencing intensity dot plot of the control (top) and intervention (bottom) arms of the SEARCH trial, with distinction between incident (dark) and prevalent (light) infections. Screening frequency differed between the intervention and control arms: yearly screening in intervention communities; baseline and year 3 screening only in control communities. Two incident infections were detected during rounds of baseline testing; most prevalent infections were detected at baseline, with the remaining picked up in later rounds.

Figure 3

Figure 3

(A) SEARCH sequenced participants in <1.5% pairwise genetic distance (GD) clusters (n = 30 sequences) and (B) participants in SEARCH-incident, phylodynamic clusters (n = 19 sequences). Nodes representing participants from control communities are in orange, intervention communities are in green; circles represent prevalent infections, squares incident infections; nodes are labelled with the gender (M = male, F = female) and age (years, in brackets) for each participant; turquoise-highlighted clusters are inferred inter-community transmissions, gold-highlighted sequences are NNRTI resistant.

References

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