Virologic and immunologic outcomes of treatment with integrase inhibitors in a real-world setting: The RESPOND cohort consortium. PLoS One
Neesgaard et al. for The RESPOND study group aimed to compare virologic and immunologic outcomes of integrase inhibitor (INSTI)-containing, contemporary boosted protease inhibitor (PI/b)-containing and non-nucleotide reverse transcriptase inhibitor (NNRTI)-containing regimens in a real-life setting.
Virologic and immunologic outcomes of INSTI use were compared to outcomes of PI/b or NNRTI treatment 12 months after treatment start or switch, for participants in the RESPOND cohort consortium. A composite treatment outcome (cTO) was used, defining success as viral load (VL) <200 copies/mL and failure as at least one of: ≥200 copies/mL, unknown VL in the time window, any changes of antiretroviral therapy (ART) regimen, AIDS, or death. In addition, on-treatment analysis including only individuals with known VL and no regimen changes was performed. Favorable immunologic response was defined as a 25% increase in CD4 count or as reaching ≥750 CD4 cells/μL.
Between January 2012 and January 2019, 13’703 (33.0% ART-naïve) individuals were included, of whom 7’147 started/switched to a regimen with an INSTI, 3’102 to a PI/b and 3’454 to an NNRTI-containing regimen. The main reason for cTO failure in all treatment groups were changes in ART regimen. Compared to INSTIs, the adjusted odds ratio (aOR) of cTO success was significantly lower for PI/b (0.74 [95% confidence interval, CI 0.67–0.82], p <0.001), but similar for NNRTIs (1.07 [CI 0.97–1.17], p = 0.11). On-treatment analysis and sensitivity analyses using a VL cut-off of 50 copies/mL were consistent. Compared to INSTIs, the aORs of a 25% increase in CD4 count were lower for NNRTIs (0.80 [CI 0.71–0.91], p<0.001) and PI/b (0.87 [CI 0.76–0.99], p = 0.04).
In conclusion, this large, real-world based analysis of a heterogeneous population of PLWH seen in routine clinical care showed that treatment with INSTI and NNRTI-containing regimes was preferable to PI/b with regard to virologic outcomes, although the potential for residual confounding cannot be fully excluded. Favorable immunologic responses were more likely with INSTI-containing regimens than with NNRTI-containing regimens, and to a lesser degree with PI/b-containing regimens. Crude numbers did not reveal any major differences in the occurrence of AIDS or death. These data supports the use of INSTI treatment and suggest that 12 months efficacy and durability of INSTIs are independent of prior treatment status and on-going viremia.