Drug resistance testing through remote genotyping and predicted treatment options in human immunodeficiency virus type 1 infected Tanzanian subjects failing first or second line antiretroviral therapyReport as inadecuate




Drug resistance testing through remote genotyping and predicted treatment options in human immunodeficiency virus type 1 infected Tanzanian subjects failing first or second line antiretroviral therapy - Download this document for free, or read online. Document in PDF available to download.

Introduction

Antiretroviral therapy ART has been successfully introduced in low-middle income countries. However an increasing rate of ART failure with resistant virus is reported. We therefore described the pattern of drug resistance mutations at antiretroviral treatment ART failure in a real-life Tanzanian setting using the remote genotyping procedure and thereafter predicted future treatment options using rule-based algorithm and the EuResist bioinformatics predictive engine. According to national guidelines, the default first-line regimen is tenofovir + lamivudine + efavirenz, but variations including nevirapine, stavudine or emtricitabine can be considered. If failure on first-line ART occurs, a combination of two nucleoside reverse transcriptase inhibitors NRTIs and boosted lopinavir or atazanavir is recommended.

Materials and methods

Plasma was obtained from subjects with first n = 174 or second-line n = 99 treatment failure, as defined by clinical or immunological criteria, as well as from a control group of ART naïve subjects n = 17 in Dar es Salaam, Tanzania. Amplification of the pol region was performed locally and the amplified DNA fragment was sent to Sweden for sequencing split genotyping procedure. The therapeutic options after failure were assessed by the genotypic sensitivity score and the EuResist predictive engine. Viral load was quantified in a subset of subjects with second-line failure n = 52.

Results

The HIV-1 pol region was successfully amplified from 55-174 32% and 28-99 28% subjects with first- or second-line failure, respectively, and 14-17 82% ART-naïve individuals. HIV-1 pol sequence was obtained in 82 of these 97 cases 84.5%. Undetectable or very low <2.6 log10 copies-10−3 L viral load explained 19 out of 25 76% amplification failures in subjects at second-line ART failure. At first and second line failure, extensive accumulation of NRTI 88% and 73%, respectively and NNRTI 93% and 73%, respectively DRMs but a limited number of PI DRMs 11% at second line failure was observed. First line failure subjects displayed a high degree of cross-resistance to second-generation NNRTIs etravirine ETR; 51% intermediate and 9% resistant and rilpivirine RPV; 12% intermediate and 58% resistant, and to abacavir ABC; 49% resistant which is reserved for second line therapy in Tanzania. The predicted probability of success with the best salvage regimen at second-line failure decreased from 93.9% to 78.7% when restricting access to the NRTIs, NNRTIs and PIs currently available in Tanzania compared to when including all approved drugs.

Discussion

The split genotyping procedure is potential tool to analyse drug resistance in Tanzania but the sensitivity should be evaluated further. The lack of viral load monitoring likely results in a high false positive rate of treatment failures, unnecessary therapy switches and massive accumulation of NRTI and NNRTI mutations. The introduction of regular virological monitoring should be prioritized and integrated with drug resistance studies in resource limited settings.



Author: Jenny Svärd , Sabina Mugusi, Doreen Mloka, Ujjwal Neogi, Genny Meini, Ferdinand Mugusi, Francesca Incardona, Maurizio Zazzi, And

Source: http://plos.srce.hr/



DOWNLOAD PDF




Related documents