Background and objectives: The standard of care for HIV treatment is a three-drug regimen consisting of two nucleoside reverse transcriptase inhibitors (NRTIs) and either a non-nucleoside reverse transcriptase inhibitor, a protease inhibitor (PI) or an integrase strand transfer inhibitor. Darunavir boosted with ritonavir (DRV/r) is the only preferred PI in the US Department of Health and Human Services (DHHS) HIV treatment guidelines for antiretroviral-naïve patients, recommended in combination with tenofovir/emtricitabine for antiretroviral-naïve patients. For treatment-experienced and certain antiretroviral-naïve patients, abacavir and lamivudine (ABC/3TC) in combination with DRV/r is considered an effective and tolerable alternative, despite limited research on the effectiveness of this particular combination. This study evaluated virologic outcomes in treatment-experienced patients taking ABC/3TC + DRV/r compared to treatment-experienced patients taking ABC/3TC with any other PI.
Methods: Treatment-experienced HIV-infected patients initiating their first regimen containing ABC/3TC in combination with any PI in the year 2005 or later were selected from the Observational Pharmaco-Epidemiology Research and Analysis (OPERA®) cohort, a prospective observational cohort reflecting routine medical care. Viral load measurements taken during follow-up were compared between patients taking ABC/3TC + DRV/r and ABC/3TC with a PI other than DRV/r. Logistic regression models were fit to assess the association between regimen exposure and viral load suppression.
Results: A total of 151 patients initiating ABC/3TC + DRV/r and 525 patients initiating ABC/3TC + a non-darunavir PI were included. Patients in both treatment groups had comparable clinical indicators (viral load, CD4) at baseline. A regimen of ABC/3TC + DRV/r was more likely to be prescribed in the later years of the study period, leading to a shorter median follow-up in the DRV/r treatment group (as-treated analysis: 14 vs. 17 months, p = 0.04; intent-to-treat analysis: 33 vs. 68 months, p < 0.001). Multivariable logistic regression models accounting for year of regimen initiation, among other factors, indicated no statistically significant differences in achieving an undetectable viral load for patients taking DRV/r with ABC/3TC compared with other PIs, both in the as-treated (odds ratio [95 % confidence interval]: 0.84 [0.53-1.34]) and intent-to-treat analyses (0.82 [0.48-1.40]). Patients in both treatment groups also showed similar reductions in viral load (median darunavir vs. non-darunavir: -23.0 vs. -23.0 copies/mL; p = 0.72) and gains in CD4 T cell counts (median darunavir vs. non-darunavir: 106 vs. 108 cells/mm3; p = 0.59] while being treated with the regimen of interest.
Conclusions: Patients receiving ABC/3TC + DRV/r appear to experience similar treatment benefit to patients taking ABC/3TC with other PIs in terms of achieving suppression, as well as absolute reductions in viral load and CD4 lymphocyte gains.