Comparison of 48-week efficacies of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide and nucleoside/nucleotide reverse transcriptase inhibitor-sparing regimens: a systematic review and network meta-analysis

HIV Medicine ◽  
2018 ◽  
Vol 19 (8) ◽  
pp. 559-571 ◽  
Author(s):  
S Gallien ◽  
M Massetti ◽  
P Flandre ◽  
H Leleu ◽  
D Descamps ◽  
...  
Keyword(s):  
Systematic Review ◽  
Reverse Transcriptase ◽  
Meta Analysis ◽  
Transcriptase Inhibitor ◽  
Tenofovir Alafenamide ◽  
Nucleotide Reverse Transcriptase Inhibitor ◽  
Reverse Transcriptase Inhibitor

scholarly journals Clinical Impact of Pretreatment Human Immunodeficiency Virus Drug Resistance in People Initiating Nonnucleoside Reverse Transcriptase Inhibitor–Containing Antiretroviral Therapy: A Systematic Review and Meta-analysis

2020 ◽  
Author(s):  
Silvia Bertagnolio ◽  
Lucas Hermans ◽  
Michael R Jordan ◽  
Santiago Avila-Rios ◽  
Collins Iwuji ◽  
...  
Keyword(s):  
Systematic Review ◽  
Human Immunodeficiency Virus ◽  
Drug Resistance ◽  
Reverse Transcriptase ◽  
Treatment Outcomes ◽  
Meta Analysis ◽  
Transcriptase Inhibitor ◽  
Nonnucleoside Reverse Transcriptase Inhibitor ◽  
Immunodeficiency Virus ◽  
Reverse Transcriptase Inhibitor

Abstract Background Increased access to antiretroviral therapy (ART) has resulted in rising levels of pretreatment human immunodeficiency virus drug resistance (PDR). This is the first systematic review and meta-analysis to assess the impact of PDR on treatment outcomes among people initiating nonnucleoside reverse transcriptase inhibitor (NNRTI)–based ART, including the combination of efavirenz (EFV), tenofovir (TDF), and lamivudine or emtricitabine (XTC). Methods We systematically reviewed studies and conference proceedings comparing treatment outcomes in populations initiating NNRTI-based ART with and without PDR. We conducted subgroup analyses by regimen: (1) NNRTIs + 2 nucleoside reverse transcriptase inhibitors (NRTIs), (2) EFV + 2 NRTIs, or (3) EFV/TDF/XTC; by population (children vs adults); and by definition of resistance (PDR vs NNRTI PDR). Results Among 6197 studies screened, 32 were analyzed (31 441 patients). We found that individuals with PDR initiating NNRTIs across all the subgroups had increased risk of virological failure compared to those without PDR. Risk of acquisition of new resistance mutations and ART switch was also higher in people with PDR. Conclusions This review shows poorer treatment outcomes in the presence of PDR, supporting the World Health Organization’s recommendation to avoid using NNRTIs in countries where levels of PDR are high.

Low In Vitro Potential for Class-specific Toxicity of GS-9148, A Novel Nucleotide Reverse Transcriptase Inhibitor

2008 ◽  
Vol 78 (2) ◽  
pp. A27
Author(s):  
Genevieve Laflamme ◽  
Constantin Boojamra ◽  
Lijun Zhang ◽  
Hon Hui ◽  
Robyn Fisher ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Transcriptase Inhibitor ◽  
Nucleotide Reverse Transcriptase Inhibitor ◽  
Reverse Transcriptase Inhibitor

scholarly journals Diagnostic Accuracy of Pan-Degenerate Amplification and Adaptation Assay for HIV-1 Drug Resistance Mutation Analysis in Low- and Middle-Income Countries

2020 ◽  
Vol 58 (9) ◽  
Author(s):  
Vinie Kouamou ◽  
Justen Manasa ◽  
David Katzenstein ◽  
Alan M. McGregor ◽  
Chiratidzo E. Ndhlovu ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Diagnostic Accuracy ◽  
Reverse Transcriptase ◽  
Sensitivity And Specificity ◽  
Sanger Sequencing ◽  
Transcriptase Inhibitor ◽  
Middle Income ◽  
Middle Income Countries ◽  
Nucleotide Reverse Transcriptase Inhibitor ◽  
Reverse Transcriptase Inhibitor

ABSTRACT HIV drug resistance (HIVDR) is a barrier to sustained virologic suppression in low- and middle-income countries (LMICs). Point mutation assays targeting priority drug resistance mutations (DRMs) are being evaluated to improve access to HIVDR testing. In a cross-sectional study (June 2018 to September 2019), we evaluated the diagnostic accuracy of a simple and rapid HIVDR assay (the pan-degenerate amplification and adaptation [PANDAA] assay targeting the mutations K65R, K103NS, M184VI, Y181C, and G190A) compared to Sanger sequencing and next-generation sequencing (NGS). Plasma samples from adolescents and young adults (aged 10 to 24 years) failing antiretroviral therapy (viral load, >1,000 copies/ml on 2 consecutive occasions 1 month apart) were analyzed. Sensitivity and specificity of the PANDAA assay were determined by a proprietary application designed by Aldatu Biosciences. Agreement between genotyping methods was evaluated using Cohen’s kappa coefficient. One hundred fifty samples previously characterized by Sanger sequencing were evaluated using PANDAA. For all DRMs detected, PANDAA showed a sensitivity and specificity of 98% and 94%, respectively. For nucleotide reverse transcriptase inhibitor DRMs, sensitivity and specificity were 98% (95% confidence interval [CI], 92% to 100%) and 100% (94% to 100%), respectively. For non-nucleotide reverse transcriptase inhibitor DRMs, sensitivity and specificity were 100% (97% to 100%) and 76% (61% to 87%), respectively. PANDAA showed strong agreement with Sanger sequencing for K65R, K103NS, M184VI, and G190A (kappa > 0.85) and substantial agreement for Y181C (kappa = 0.720). Of the 21 false-positive samples genotyped by PANDAA, only 6 (29%) were identified as low-abundance variants by NGS. With the high sensitivity and specificity to detect major DRMs, PANDAA could represent a simple and rapid alternative HIVDR assay in LMICs.

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