Background. The clinical relevance of ultrasensitive human immunodeficiency virus type 1 (HIV-1) genotypic
resistance testing in antiretroviral treatment (ART)-experienced individuals remains unknown.
Methods. This was a retrospective, multicentre, cohort study in ART-experienced, HIV-1-infected adults who initiated
salvage ART ...»»»»
Background. The clinical relevance of ultrasensitive human immunodeficiency virus type 1 (HIV-1) genotypic
resistance testing in antiretroviral treatment (ART)-experienced individuals remains unknown.
Methods. This was a retrospective, multicentre, cohort study in ART-experienced, HIV-1-infected adults who initiated
salvage ART including, at least 1 ritonavir-boosted protease inhibitor, raltegravir or etravirine. Presalvage ART
Sanger and 454 sequencing of plasma HIV-1 were used to generate separate genotypic sensitivity scores (GSS) using the
HIVdb, ANRS, and REGA algorithms. Virological failure (VF) was defined as 2 consecutive HIV-1 RNA levels ≥200
copies/mL at least 12 weeks after salvage ART initiation, whereas subjects remained on the same ART. The ability of
Sanger and 454-GSS to predict VF was assessed by receiver operating characteristic (ROC) curves and survival analyses.
Results. The study included 132 evaluable subjects; 28 (21%) developed VF. Using HIVdb, 454 predicted VF better
than Sanger sequencing in the ROC curve analysis (area under the curve: 0.69 vs 0.60, Delong test P = .029). Time toVF
was shorter for subjects with 454-GSS < 3 vs 454-GSS ≥ 3 (Log-rank P = .003) but not significantly different between
Sanger-GSS < 3 and ≥3. Factors independently associated with increased risk of VF in multivariate Cox regression were
a 454-GSS < 3 (HR = 4.6, 95 CI, [1.5, 14.0], P = .007), and the number of previous antiretrovirals received (HR = 1.2 per
additional drug, 95 CI, [1.1, 1.3], P = .001). Equivalent findings were obtained with the ANRS and REGA algorithms.
Conclusions. Ultrasensitive HIV-1 genotyping improves GSS-based predictions of virological outcomes of salvage
ART relative to Sanger sequencing. Thismay improve the clinical management of ART-experienced subjects living with
HIV-1.
Clinical Trials Registration. NCT01346878.
Keywords. HIV-1; antiretroviral drug resistance; deep sequencing; salvage antiretroviral therapy; genotypic
susceptibility score.^^^^
