Prevalence of drug resistance mutations in HAART patients infected with HIV‐1 CRF06_cpx in Estonia

Abstract

HIV-1 drug resistance mutations (DRMs) and substitutions were assessed after the failure of the first line non-nucleoside reverse transcriptase inhibitors (NNRTIs) + 2 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) treatment regimens (efavirenz [EFV] + lamivudine[3TC] + zidovudine [ZDV] vs. EFV + 3TC + ddI) among the HIV-1 CRF06_cpx infected subjects in Estonia. HIV-1 genomic RNA was sequenced; DRMs and amino acid substitutions were compared in 44 treatment naïve and 45 first-line NNRTI + 2 NRTI treatment failed patients consisting of EFV + 3TC + ZDV (n = 17) and EFV + 3TC + didanosine[ddI] (n = 21) therapy failed sub-populations. At least one DRM was found in 78% of treatment experienced patients. The most common NRTI mutations were M184V (80%), L74V (31%), L74I (17%), K219E (9%), and M184I (9%), NNRTI mutations were K103N (83%), P225H (14%), L100I (11%), and Y188L (11%), reflecting generally the similar pattern of DRMs to that seen in treatment failed subtype B viruses. Sub-population analysis revealed that EFV + 3TC + ddI failed patients had more DRMs compared to EFV + 3TC + ZDV failed patients, especially the ddI DRM L74IV and several additional NNRTI DRMs. Additionally, CRF06_cpx specific mutation E179V and substitutions R32K, K122E, and V200AE were also detected in treatment experienced population. After the failure of the first-line EFV + 3TC + ddI therapy HIV-1 CRF06_cpx viruses develop additional NRTI and NNRTI mutations compared to EFV + 3TC + ZDV regimen. Therefore the usage of EFV + 3TC + ddI in this subtype decreases the options for next regimens containing abacavir, and NNRTI class agents.

Prevalence of Pretreatment and Acquired HIV-1 Mutations Associated with Resistance to Lamivudine or Rilpivirine: A Systematic Review

“…Africa had the highest number of articles identified in the search of any region (n=30) . However, the European region had the highest number of participants for analysis of pretreatment resistance mutations (n=33,957 for NRTI-associated mutations; n=34,201 for NNRTI-associated mutations) [43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60], and Southeast Asia had the highest number of participants for analysis of acquired resistance mutations (n=26,772 for NRTI-associated mutations; 26,568 for NNRTI-associated mutations) [61][62][63][64][65][66][67][68][69].…”

“…The estimated global prevalence of pretreatment DRMs was 4% (n=2,719/60,567; range, 2% [Asia Pacific] to 6% [North America]) for those associated with NRTI resistance [16,18,25,28,[30][31][32][35][36][37][38]40,43,44,46,48,49,[51][52][53][54][55][56][57][58][59][60] and 6% (n=3,605/61,402; range, 3% [Asia Pacific] to 8% [Africa and North America]) for those associated with resistance to any NNRTI (Figure 1) [16,18,25,28,[30][31][32][33][34][35][36][37][38][39]41,[70][71][72][73][74][75]…”

“…Among reports with available data, 77% (n=702/917) and 80% (n=730/908) had acquired DRMs conferring resistance to the NRTI and NNRTI classes, respectively. The most frequent acquired 3TC/FTC DRMs were at position M184 (70%; n=2,255/3,240); the most frequent acquired RPV DRMs were at position Y181 (19%; n=611/3,191).Regional prevalence estimates: EuropeIn European studies, there were 33,957 people with data related to pretreatment NRTI-associated DRMs and 34,201 people with data on NNRTI-associated DRMs (Supplemental Tables6 and 7in Additional file 1)[43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60]. Pretreatment DRMs with NRTI ance to NRTIs was observed in 70% (n=1,846/2,633), whereas resistance to NNRTIs was observed in 52% (n=1,382/2,633).…”