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

Collet Dandara,Tutsirai V. Musingwini,Benjamin Chimukangara,Babill Stray-Pedersen,Tinei Shamu,Sandra Shawarira-Bote,Exnevia Gomo,Kerina Duri,Danai T. Zhou,Olav Oktedalen,Doreen Mhandire

doi:10.2174/1874285801711010045

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.

Highlights

The human immunodeficiency virus (HIV) has infected nearly 78 million people and close to 39 million have died of acquired immunodeficiency syndrome (AIDS), to date [1, 2]
A total of 103 patient samples were analyzed for drug resistance mutations in this study
Time since diagnosis was longer for patients receiving antiretroviral treatment (ART) than those who were ART-naïve (p=0.02) (Table 3)

Summary

Introduction

The human immunodeficiency virus (HIV) has infected nearly 78 million people and close to 39 million have died of acquired immunodeficiency syndrome (AIDS), to date [1, 2]. Ritonavir-boosted protease inhibitors (bPIs) are preferred in second-line regimens, in place of NNRTIs [4, 5]. In line with these recommendations, the Zimbabwean government through the Ministry of Health and Child Care (MOHCC) first introduced the national antiretroviral treatment (ART) program in 2004, which was providing approximately 581 801 adults with ART by 2012 [5, 6]. With the rapid scale up of ART over the years, the emergence of antiretroviral (ARV) drug resistance mutations in Zimbabwe has been inevitable as in any other settings [7, 8]. 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

Methods

Results

Discussion

Conclusion