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Phylogenetic and Drug-Resistance Analysis of HIV-1 Sequences From an Extensive Paediatric HIV-1 Outbreak in Larkana, Pakistan

Abidi, Syed Hani ; Nduva, George Makau LU ; Siddiqui, Dilsha ; Rafaqat, Wardah ; Mahmood, Syed Faisal ; Siddiqui, Amna Rehana ; Nathwani, Apsara Ali ; Hotwani, Aneeta ; Shah, Sharaf Ali and Memon, Sikander , et al. (2021) In Frontiers in Microbiology 12.
Abstract

Introduction: In 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. Methods: A 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... (More)

Introduction: In 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. Methods: A 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. Results: The 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. Conclusion: The 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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
drug resistance, HIV-1, outbreak investigation, paediatric [MeSH], phylogenetic analysis
in
Frontiers in Microbiology
volume
12
article number
658186
publisher
Frontiers Media S. A.
external identifiers
  • pmid:34484134
  • scopus:85114299359
ISSN
1664-302X
DOI
10.3389/fmicb.2021.658186
language
English
LU publication?
yes
id
80eda2f3-98c3-4200-ba6b-e53d1be2a7e4
date added to LUP
2021-09-30 13:44:14
date last changed
2024-06-15 17:06:58
@article{80eda2f3-98c3-4200-ba6b-e53d1be2a7e4,
  abstract     = {{<p>Introduction: In 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. Methods: A 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. Results: The 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. Conclusion: The 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.</p>}},
  author       = {{Abidi, Syed Hani and Nduva, George Makau and Siddiqui, Dilsha and Rafaqat, Wardah and Mahmood, Syed Faisal and Siddiqui, Amna Rehana and Nathwani, Apsara Ali and Hotwani, Aneeta and Shah, Sharaf Ali and Memon, Sikander and Sheikh, Saqib Ali and Khan, Palwasha and Esbjörnsson, Joakim and Ferrand, Rashida Abbas and Mir, Fatima}},
  issn         = {{1664-302X}},
  keywords     = {{drug resistance; HIV-1; outbreak investigation; paediatric [MeSH]; phylogenetic analysis}},
  language     = {{eng}},
  month        = {{08}},
  publisher    = {{Frontiers Media S. A.}},
  series       = {{Frontiers in Microbiology}},
  title        = {{Phylogenetic and Drug-Resistance Analysis of HIV-1 Sequences From an Extensive Paediatric HIV-1 Outbreak in Larkana, Pakistan}},
  url          = {{http://dx.doi.org/10.3389/fmicb.2021.658186}},
  doi          = {{10.3389/fmicb.2021.658186}},
  volume       = {{12}},
  year         = {{2021}},
}