HIV-1 Genetic Diversity and Natural Polymorphisms of the Integrase Gene in Integrase Inhibitor-Naive Patients in Harare, Zimbabwe.

Madyadi, Amanda; Dhoro, Milcah; Shamu, Tinei; Washaya, Tendai; Kouamou, Vinie; Chimukangara, Benjamin; Katzenstein, David; Manasa, Justen (2021). HIV-1 Genetic Diversity and Natural Polymorphisms of the Integrase Gene in Integrase Inhibitor-Naive Patients in Harare, Zimbabwe. AIDS research and human retroviruses, 37(12), pp. 954-961. Mary Ann Liebert 10.1089/AID.2021.0084

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Previously used as part of salvage therapy, integrase strand transfer inhibitors (INSTIs) have become part of the preferred antiretroviral therapy (ART) first-line regimen in most low- to middle-income countries. With the extensive use of dolutegravir in first-line ART, drug resistance mutations to INSTIs are inevitable. Therefore, active monitoring and surveillance of INSTI drug resistance is required. The aim of this study was to evaluate the genetic diversity of the integrase gene and determine pretreatment INSTI resistance in Harare, Zimbabwe. Forty-four HIV-1 Integrase sequences from 65 were obtained from treatment-naive individuals using a custom genotyping method. Drug resistance mutations were determined using the Stanford HIV Drug Resistance Interpretation program. Viral subtyping was done by phylogenetic analysis and the REGA HIV subtyping tool determined recombinants. Natural polymorphisms were evaluated relative to the global subtype B and C consensus sequences. One hundred ninety-two sequences from the region were accessed from GenBank to assess differences between the Zimbabwean sequences and those from neighboring countries. No major INSTI resistance mutations were detected; however, the L74I polymorphism was detected in three sequences of the 44 (6.8%). There was little genetic variability in the Integrase gene, with a mean genetic distance range of 0.053015. The subtype C consensus was identical to the global subtype C consensus and varied from the global subtype B consensus at five major positions: T124A, V201I, T218I, D278A, and S283G. This study has provided baseline sequence data on the presence of HIV-1 subtype C Integrase gene drug resistance mutations from Harare, Zimbabwe.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Social and Preventive Medicine (ISPM)

Graduate School:

Graduate School for Health Sciences (GHS)

UniBE Contributor:

Shamu, Tinei

Subjects:

600 Technology > 610 Medicine & health
300 Social sciences, sociology & anthropology > 360 Social problems & social services

ISSN:

0889-2229

Publisher:

Mary Ann Liebert

Language:

English

Submitter:

Doris Kopp Heim

Date Deposited:

14 Feb 2022 19:19

Last Modified:

03 Jan 2023 11:19

Publisher DOI:

10.1089/AID.2021.0084

PubMed ID:

34714124

Uncontrolled Keywords:

HIV-1 integrase gene Zimbabwe integrase strand transfer inhibitors natural polymorphisms pretreatment drug resistance

BORIS DOI:

10.48350/165510

URI:

https://boris.unibe.ch/id/eprint/165510

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