Drug Resistance Mutations from Whole Blood Proviral DNA Among Patients on Antiretroviral Drugs in Zimbabwe

Title:Drug Resistance Mutations from Whole Blood Proviral DNA Among Patients on Antiretroviral Drugs in Zimbabwe

Volume: 12 Issue: 5

Author(s): Benjamin Chimukangara, Lovemore Gwanzura, Rebecca Mitchell, David Katzenstein and Collen Masimirembwa

Affiliation:

Keywords: Drug resistance, genotypic testing, HIV-1 subtype C, HIV/TB treatment, proviral DNA, resource-limited settings, treatment monitoring, Zimbabwe.

Abstract: Introduction: There are more than 500 000 HIV-infected people on antiretroviral treatment (ART) in Zimbabwe with very limited laboratory monitoring. To ensure effective treatment and prevent transmission of drug resistance, affordable treatment monitoring is needed to guide individual treatment.

Methods: 125 whole blood samples from patients on first-line ART were investigated for drug resistance mutations using an in-house genotypic testing method. Patients had been on HIV reverse transcriptase inhibitors only, with some having been on both HIV and TB treatment. DNA was extracted from whole blood; amplicons were generated by nested PCR and sequenced. Drug resistance mutations were determined using the Stanford HIV drug resistance database. Exact statistics were used to investigate relationships between drug resistance and predisposing factors.

Results: From 125 samples, 108 were successfully analyzed for drug resistance mutations. 11 of the 108 sequences had drug resistance mutations; predominantly M184V and Y181C. For a 100-cell increase in CD4 count, the odds of being resistant were 61% lower than those with the baseline CD4 count (p=0.04, CI: 0.34-0.98). There was no association between concurrent HIV/TB treatment and drug resistance (p=0.41).

Discussion and Conclusion: Although plasma samples are recommended for genotypic testing, the cost of analyzing plasma RNA makes it less feasible in resource limited settings. Lower cost DNA drug resistance testing from whole blood samples was assessed as a treatment-monitoring tool among patients followed by CD4 and clinical monitoring only. The infrequent detection of resistance and higher CD4 is consistent with effective first-line treatment. Further investigation of proviral DNA as a tool to identify drug resistance mutations is warranted.

Cite this article as:

Chimukangara Benjamin, Gwanzura Lovemore, Mitchell Rebecca, Katzenstein David and Masimirembwa Collen, Drug Resistance Mutations from Whole Blood Proviral DNA Among Patients on Antiretroviral Drugs in Zimbabwe, Current HIV Research 2014; 12 (5) . https://dx.doi.org/10.2174/1570162X12666141017100733