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Unassigned Complex Unique Recombinant Forms Related to CRF36_cpx in Children Identified in an HIV-1 Outbreak in Pakistan.

ABSTRACT: In 2019, an outbreak of HIV infection predominantly affecting children occurred in Larkana district, Pakistan. This is the largest outbreak ever reported in this age group in Pakistan. In this study, we report two HIV-1 unique recombinant forms identified during the outbreak. Blood samples were collected from HIV-positive children as part of a case-control study to investigate the outbreak. The pol gene was sequenced and used to detect HIV subtype/recombinant forms using subtype, recombination, and phylogenetic analyses. Drug resistance mutation (DRM) analysis was performed to characterize the DRMs in each sequence. We observed the emergence of two unassigned unique recombinant forms related to CRF36_cpx in 15 individuals of the 344 samples collected. Genotype analysis revealed the presence of multiple DRMs associated with resistance to reverse transcriptase inhibitors. The discovery of these unassigned unique recombinant forms in our population highlights the need for comprehensive molecular epidemiological studies to fully understand the distribution and drug resistance patterns to aid control efforts.

SUBMITTER: Abidi SH

PROVIDER: S-EPMC7614887 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Unassigned Complex Unique Recombinant Forms Related to CRF36_cpx in Children Identified in an HIV-1 Outbreak in Pakistan.

Abidi Syed Hani SH Siddiqui Dilsha D Mahmood Syed Faisal SF Siddiqui Amna Rehana AR Nathwani Apsara Ali AA Hotwani Aneeta A Shah Sharaf Ali SA Khan Palwasha P Ferrand Rashida Abbas RA Mir Fatima F

AIDS research and human retroviruses 20220726 10

In 2019, an outbreak of HIV infection predominantly affecting children occurred in Larkana district, Pakistan. This is the largest outbreak ever reported in this age group in Pakistan. In this study, we report two HIV-1 unique recombinant forms identified during the outbreak. Blood samples were collected from HIV-positive children as part of a case-control study to investigate the outbreak. The pol gene was sequenced and used to detect HIV subtype/recombinant forms using subtype, recombination, ...[more]

PMID: 35778855

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Project description:Intersubtype recombinants classified as circulating recombinant forms (CRFs) or unique recombinant forms (URFs) have been shown to play an important role in the complex and dynamic Brazilian HIV/AIDS epidemic. Previous pol region studies (2003-2013) in 828 patients from six states from Central Western, Northern and Northeastern Brazil reported variable rates of BF1, F1CB, BC, and CF1 mosaics. In this study HIV-1 subtype diversity BF1, F1CB, BC, and CF1 recombinants in pol were analyzed. Full/near-full/partial genome sequences were generated from F1CB and BF1 recombinants. Genomic DNA extracted from whole blood was used in nested-PCR to amplify four overlapping fragments encompassing the full HIV-1 genome. Phylogenetic trees were generated using the neighbor-joining/NJ method (MEGA 6.0). The time of the most recent common ancestor (TMRCA) of F1CB and BF1 clades was estimated using a Bayesian Markov Chain Monte Carlo approach (BEAST v1.8; BEAGLE). Bootscanning was used for recombination analyses (Simplot v3.5.1); separate NJ phylogenetic analysis of fragments confirmed subtypes. The phylogenetic analyses of protease/reverse-transcriptase sequences in 828 patients revealed 76% subtype B (n = 629), 6.4% subtype C (n = 53), 4.2% subtype F1 (n = 35), 13.4% intersubtype recombinants: 10.5% BF1 (n = 87), 2.3% BC (n = 19), 0.4% F1CB (n = 3), and 0.2% CF1 (n = 2). Two full and one partial BF1C genomes allowed the characterization of the CRF81_cpx that has 9 breakpoints dividing the genome into 10 subregions. Basic Local Alignment Search Tool searches (Los Alamos HIV Sequence Database) identified six other sequences with the same recombination profile in pol, five from Brazil, and one from Italy. The estimated median TMRCA of CRF81_cpx was 1999 (1992-2003). CRF60_BC-like sequences, originally described in Italy, were also found. Two full and one near full-length BF1 genomes led to the characterization of the new CRF99_BF1 that has six recombination breakpoints dividing the genome into seven subregions. Two new URFs BF1, with six recombination breakpoints and seven subregions were also characterized. The description of the first Brazilian BF1C CRF81_cpx and of the new CRF99_BF1 corroborate the important role of CRFs in the HIV/AIDS epidemic throughout Brazil. Our data also highlight the value of HIV-1 full-genome sequence studies in order to fully reveal the complexity of the epidemic in a huge country as Brazil.

Dataset Information

Unassigned Complex Unique Recombinant Forms Related to CRF36_cpx in Children Identified in an HIV-1 Outbreak in Pakistan.

Publications

Unassigned Complex Unique Recombinant Forms Related to CRF36_cpx in Children Identified in an HIV-1 Outbreak in Pakistan.

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