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Abstract
IntroductionIn April 2019, an HIV-1 outbreak among children occurred in Larkana, Pakistan, affecting more than a thousand children. It was assumed that the outbreak originated from a single source, namely a doctor at a private health facility. In this study, we performed subtype distribution, phylogenetic and drug-resistance analysis of HIV-1 sequences from 2019 outbreak in Larkana, Pakistan.MethodsA total of 401 blood samples were collected between April–June 2019, from children infected with HIV-1 aged 0–15 years recruited into a case-control study to investigate the risk factors for HIV-1 transmission. Partial HIV-1 pol sequences were generated from 344 blood plasma samples to determine HIV-1 subtype and drug resistance mutations (DRM). Maximum-likelihood phylogenetics based on outbreak and reference sequences was used to identify transmission clusters and assess the relationship between outbreak and key population sequences between and within the determined clusters. Bayesian analysis was employed to identify the time to the most recent common recent ancestor (tMRCA) of the main Pakistani clusters.ResultsThe HIV-1 circulating recombinant form (CRF) 02_AG and subtype A1 were most common among the outbreak sequences. Of the treatment-naïve participants, the two most common mutations were RT: E138A (8%) and RT: K219Q (8%). Four supported clusters within the outbreak were identified, and the median tMRCAs of the Larkana outbreak sequences were estimated to 2016 for both the CRF02_AG and the subtype A1 clusters. Furthermore, outbreak sequences exhibited no phylogenetic mixing with sequences from other high-risk groups of Pakistan.ConclusionThe presence of multiple clusters indicated a multi-source outbreak, rather than a single source outbreak from a single health practitioner as previously suggested. The multiple introductions were likely a consequence of ongoing transmission within the high-risk groups of Larkana, and it is possible that the so-called Larkana strain was introduced into the general population through poor infection prevention control practices in healthcare settings. The study highlights the need to scale up HIV-1 prevention programmes among key population groups and improving infection prevention control in Pakistan.
Highlights
In April 2019, an HIV-1 outbreak among children occurred in Larkana, Pakistan, affecting more than a thousand children
This study was embedded in an individually matched casecontrol study that recruited 401 cases defined as children aged 0–15 years who registered for HIV-1 care at the Paediatric Treatment Center at Shaikh Zayed Children’s Hospital (Siddiqui et al, 2020)
The ART regimen comprised of zidovudine, lamivudine, and nevirapine
Summary
In April 2019, an HIV-1 outbreak among children occurred in Larkana, Pakistan, affecting more than a thousand children. We performed subtype distribution, phylogenetic and drug-resistance analysis of HIV-1 sequences from 2019 outbreak in Larkana, Pakistan. One of the characteristic features of HIV-1 is its high mutation rate and recombination rate within and between hosts, leading to the emergence of distinct subtypes and circulating recombinant forms (CRFs) (Taylor et al, 2008; van Zyl et al, 2018). Mutations may lead to resistance to anti-retroviral drugs (van Zyl et al, 2018). Certain immune- or drug-escape mutations may facilitate rapid transmission (van Zyl et al, 2018)
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