Long-term effectiveness of recommended boosted protease inhibitor-based antiretroviral therapy in Europe. HIV Medicine
Santos et al. on behalf of the EuroSIDA study group aimed to evaluate the long-term effectiveness of different protease inhibitor (PI) containing regimens initiated at various stages during participants’ antiretroviral therapy (ART) history and the factors associated with virological failure (VF), treatment discontinuation, and CD4 cell count recovery in a large European cohort of HIV-1-infected patients. Data were analysed for 5’678 EuroSIDA-enrolled patients starting a darunavir/ritonavir (DRV/r)-, atazanavir/ritonavir (ATZ/r)- or lopinavir/ritonavir (LPV/r)-containing regimen between 1 January 2000 and 30 June 2013. VF was defined as two consecutive viral load measurements >200 copies/mL ≥24 weeks after PI/r initiation.
Of these 5678 patients, a total of 431 (8%) were ART-naïve patients of whom 220 (51%) were receiving LPV/r, 119 (28%) were on ATZ/r, and 92 (21%) were on DRV/r-based regimens. The median (IQR) time of follow-up was 28 (11–57) months. The time to VF favoured DRV/r over ATZ/r, and both were superior to LPV/r (log-rank test; P < 0.02) in all analyses. Nevertheless, the risk of VF in ART-naïve patients was similar regardless of the PI/r initiated after controlling for potential confounders. The risk of VF in both treatment-experienced groups was lower for DRV/r than for ATZ/r, which, in turn, was lower than for LPV/r-based ART. Injecting drug use, higher HIV-1 RNA at baseline, black ethnicity, having historic genotyping tests available, and a higher number of prior failures on non-PI-based ART were independent predictors of an increased hazard of VF. The risk of PI/r discontinuation for any reason was > 2.5 times higher in patients who started LPV/r-based ART than in those initiating a DRV/r-based ART, while no significant difference was observed when ATZ/r and DRV/r regimens were compared.
In summary, assuming no unmeasured confounding factors, the long-term effectiveness of boosted PI-containing regimens in ART-experienced subjects appears to be greater in people receiving DRV/r than in those receiving ATZ/r and LPV/r. The same tendency was observed in ART-naïve patients, although the analysis was likely to be underpowered in this population. Strategies to improve clinical care and treatment response continue to be necessary in some subsets of the HIV-infected population such as women, injecting drug users, hepatitis virus-coinfected patients and ethnic minorities.