Impact of Baseline NNRTI Resistance in Antiretroviral-naïve Patients with HIV in A Large Urban Clinic

Background: Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are prone to baseline resistance and potential early treatment failure. We investigated the NNRTI resistance profiles of antiretroviral therapy (ART)–naive patients with HIV in a large urban clinic and assessed their response to initial ART.

Materials and Methods: This was a retrospective cohort study of ART-naive patients, who had baseline genotypes, starting ART prior to July 16, 2015. Cox regression was used to determine the impact on time to viral suppression with baseline NNRTI resistance as the primary covariate of interest. Of those who achieved virologic suppression, Cox regression was used to determine the impact on viral rebound [viral load (VL) ≥ 200 copies/mL or two VLs at least two weeks apart ≥ 50 copies/mL].

Results: Of the 1220 included, 84 (6.9%) had baseline NNRTI resistance (34-103N, 19-138A/G/K, 15-181C, 16-17D/E, and 7-101E/H/P). Of the 84, 7 had 184V, 20 had other NRTI mutations and 6 had PI mutations. Patients without NNRTI mutations were most commonly started on NNRTI-based regimens (41%), followed by PI-based (30%) and then integrase inhibitor (INI)-based regimens (11%). Patients with baseline NNRTI resistance were most commonly started on PI-based regimens (42%), followed by INI-based regimens (19%). Overall 83% with NNRTI mutations achieved viral suppression as compared to 84% without NNRTI mutations. In multivariable analysis, adjusting for age, gender, baseline VL and CD4 count, duration of HIV and baseline PI mutations, the presence of NNRTI mutations did not impact virologic suppression (aHR=0.96; 95%CI=0.74-1.23). For virologic rebound, after adjusting for the same covariates, the presence of NNRTI mutations did not impact virologic rebound (aHR=1.10; 95%CI=0.67-1.81).

Conclusions: Despite having baseline NNRTI mutations, the majority of the patients reached viral suppression and did not experience virologic rebound. It’s reassuring to clinicians that those with baseline NNRTI mutations still respond well to ART.