Very High Baseline HIV viremia impairs efficacy of NNRTI-based ART: A long-term observation in treatment-naïve patients

Abstract

Background: High baseline HIV-RNA level (≥100,000 copies/ml) has been proved to be related with weaker virological response to antiretroviral therapy (ART). However, it was not completely clear whether a very high pre-therapy viral load (≥500,000 copies/ml) can further impair the virological response, especially in the long run. Methods: A retrospective study based on data from multicenter cohorts in China was performed. We enlisted untreated HIV infected adults recruited between18 and 65 years old, who received China’s first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen. All patients had baseline HIV-RNA levels over 500 copies/ml, showed good adherence, and were followed for at least 24 weeks. Virological suppression (VS) was defined as the first HIV-RNA <50 copies/ml which lasted for six months. Virological failure was defined as any of incomplete viral suppression (HIV-RNA ≥200 copies/mL with no recorded VS within 24 weeks of treatment) and viral rebound (confirmed HIV-RNA level ≥50 copies/mL after VS). Chi-square analysis was used to compare rates of VS between different HIV-RNA strata. Kaplan–Meier analysis and Cox regression model were used to compare time to virological suppression. Logistic regression was used to evaluate odds to virological failure. Results: 758 treatment-naïve HIV patients in China were enlisted. Median follow-up time (IQR) was 144 (108-276) weeks. Most patients (68.2%) were given tenofovir disoproxil fumarate (TDF) + lamivudine (3TC) + efavirenz (EFV) regimen. By week 48, rates of VS in three groups (<100,000, 100,000-500,000 and ≥500,000 copies/ml) were 94.1%, 85.0%, and 63.8%, respectively ( p <0.001). Very high baseline HIV viremia over 500,000 copies/ml were found to be independently associated with delayed VS [≥500,000 vs. <100,000, adjusted relative hazard (95% CI), 0.455 (0.32-0.65); p <0.001] as well as incomplete viral suppression [≥500,000 vs. <100,000, adjusted odds ratio (aOR) (95% CI), 6.084 (2.761-13.407); p <0.001] and viral rebound [≥500,000 vs. <100,000, aOR (95% CI), 3.671 (1.009-13.355), p =0.048]. Conclusion: Very high levels of pre-treatment HIV-RNA were significantly related with delayed efficacy of NNRTI-based ART and increased risk of treatment failure. More potent initial regimens should be considered for those with very high baseline viremia.