Use of Proviral DNA to Investigate Virus Resistance Mutations in HIV-infected Zimbabweans



Tutsirai V. Musingwini1, Danai T. Zhou1, 2, *, Doreen Mhandire3, Kerina Duri4, Exnevia Gomo1, Olav Oktedalen5, Benjamin Chimukangara6, Tinei Shamu7, Sandra Shawarira-Bote7, Collet Dandara8, Babill Stray-Pedersen9
1 University of Zimbabwe, College of Health Sciences, Department of Medical Laboratory Sciences, Harare, Zimbabwe
2 Institute of Clinical Medicine, University in Oslo, Oslo University Hospital, Oslo, Norway
3 University of Zimbabwe, College of Health Sciences, Department of Chemical Pathology, Harare, Zimbabwe
4 Universisty of Zimbabwe, College of Health Sciences, Department of Immunology, Harare, Zimbabwe
5 Department of Infectious Diseases, Oslo University Hospital, Oslo, Norway
6 Africa Centre for Health and Population Studies, University of KwaZulu-Natal, KwaZulu-Natal, South Africa
7 Newlands Clinic, Newlands, Harare, Zimbabwe
8 Division of Human Genetics, Department of Clinical Laboratory Sciences & Institute for Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
9 Institute of Clinical Medicine, University in Oslo and Women’s Clinic, Oslo University Hospital, Oslo, Norway


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© 2017 Musingwini et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the University of Zimbabwe, College of Health Sciences, Department of Medical Laboratory Sciences, Institute of Clinical Medicine, University in Oslo, Oslo University Hospital, Oslo, Norway; Tel: +263 4 707 707; E-mails: danaizh@yahoo.co.uk, zhoud@africau.edu


Abstract

Background:

Antiretroviral therapy (ART) to suppress HIV replication has reduced morbidity and mortality yet effectiveness of current HIV drugs is threatened by HIV drug resistance (HIVDR) mutations.

Objective:

To determine HIVDR mutations using proviral DNA from specimens of patients presenting to an HIV treatment clinic.

Methods:

DNA from 103 patients, 86 treatment-experienced, 17 treatment-naïve, were genotyped for the HIV-1C reverse transcriptase gene (RT; codons 21-304) using Sanger sequencing and sequences analyzed using Sequencher software. Resistance mutations were interpreted using Stanford HIVDR reference database.

Results:

Median age was 39 (IQR, 33-46) years and 80% of patients were female. Six-percent (n=6) had at least one HIVDR mutation, comprising NRTI-associated mutations, (M184V, T69D, T69N and V75I); NNRTI-associated mutations (G190A, K103N, V106M, Y181C) and thymidine analogue associated mutations (D67N, K70R, K219Q, L210W, M41L, T215Y). Of the six participants, with at least one HIVDR mutation, all were treatment experienced, five were on tenofovir, lamivudine and nevirapine and one was on tenofovir, lamivudine and atazanavir. There was no difference in median CD4 count and viral loads when patients were compared by presence of HIVDR mutations.

Conclusion:

We demonstrated the use of proviral DNA in HIVDR testing in adult patients and present that all the patients with various kinds of HIVDR mutations were treatment experienced, pointing to the role of drug regimens in driving viral mutations. Thus, the use of proviral DNA has potential to help provide surveillance on risk of HIVDR in HIV-infected individuals who are on treatment, which may assist in corrective treatment.

Keywords: Drug resistance, Genotyping, HIV proviral DNA, Sequencing, Zimbabwe.