HIV-1 pretreatment drug resistance negatively impacts outcomes of first-line antiretroviral treatment. (1st June 2022)

• Record Type: Journal Article
• Authors: Hermans, Lucas E.; Hofstra, Laura M.; Schuurman, Rob; Ter Heine, Rob; Burger, David M.; Talboom, Stijn A.J.; De Jong, Dorien; Tempelman, Hugo A.; Venter, Willem D.F.; Nijhuis, Monique; Wensing, Annemarie M.J.
• Is Part Of: AIDS. Volume 36:Number 7(2022)
• Page Start: 923
• Page End: 931
• Publication Date: 2022-06-01
• Subjects: antiretroviral treatment -- HIV -- pretreatment drug resistance; AIDS (Disease) -- Periodicals; Acquired Immunodeficiency Syndrome; AIDS (Disease); Periodicals; Periodicals; 616.9792005
• DOI: 10.1097/QAD.0000000000003182
• Languages: English
• ISSNs: 0269-9370

Abstract

Abstract : Introduction: Pretreatment drug resistance (PDR) prevalence in sub-Saharan Africa is rising, but evidence of its impact on efavirenz (EFV)-based antiretroviral treatment (ART) is inconclusive. We determined the impact of PDR on outcomes of EFV-based ART in a subanalysis of a randomized clinical trial comparing different ART monitoring strategies implemented at a rural treatment facility in Limpopo, South Africa. Methods: Participants initiating EFV-based first-line ART (2015–2017) were enrolled and received 96 weeks follow-up. Resistance to nucleos(t)ide reverse transcriptase inhibitors (NRTIs) and non-NRTI's (NNRTIs) was retrospectively assessed by population-based sequencing. Virological failure was defined as a viral load of at least 1000 copies/ml after at least 24 weeks of ART. Results: A total of 207 participants were included, 60.4% (125/207) of whom were female. Median age was 38.8 (interquartile range: 31.4–46.7) years. Median CD4 + cell count was 191 (interquartile range: 70–355) cells/μl. PDR was detected in 12.9% (25/194) of participants with available sequencing results; 19 had NNRTI-resistance, and six had NRTI- and NNRTI-resistance. 26.0% of participants (40/154) with sequencing results and virological follow-up developed virological failure. PDR was independently associated with failure (adjusted hazard ratio: 3.7 [95% confidence interval: 1.68.5], P = 0.002). At failure, 87.5% (7/8) of participants with PDR harboured dual-class resistant virus, versus 16.7% (4/24) of participants without PDR ( P = 0.0007). Virological resuppression after failure on first-line ART occurred in 57.7% (15/26) of participants without PDR versus 14.3% (1/7) of participants with PDR ( P = 0.09). Conclusion: PDR was detected in 13% of study participants. PDR significantly increased the risk of virological failure of EFV-based ART. Accumulation of resistance at failure and inability to achieve virological resuppression illustrates the profound impact of PDR on treatment outcomes.