Rilpivirine plus boosted-darunavir (RPV + bDRV) dual therapy may be effective and safe in patients with advanced HIV infection and previous virologic failure according to a study recently published in BMC Infectious Diseases.
With the effectiveness and good tolerability of antiretroviral therapy (ART), the life expectancy of individuals infected with HIV is approaching that of the general population. However, there are rising concerns about ART and drug-related toxicity, especially over the long term. For example, nonucleotide reverse transcriptase inhibitors (NRTIs), included in the classic triple therapy, increase the potential toxicity. Therefore, nucleos(t)ide-sparing regimens that do not include one or both NRTIs, have been developed to prevent and reduce ART-related toxicity. With the creation of novel and highly effective ART drugs with a high genetic barrier against developing drug resistance (like protease inhibitors [PI]), treatments can be simplified with fewer drugs administrated. Many studies have found that the efficacy of PI monotherapy and dual therapy is not inferior to the classic triple therapy regimens, but few data are available on the application of dual therapy in patients with a less favorable profile, including advanced HIV infection, long ART exposure, history of virologic failure, and long-term toxicity. The dual therapy of RPV + bDRV is an attractive nucleos(t)ide-sparing regimen that combines both efficacy and genetic barrier with a lower pill burden and good toxicity profile. Therefore, this observational, retrospective study analyzed the effectiveness and safety of dual therapy RPV + bDRV in real-life patients by calculating the proportion of patients with virologic success.
In total, 161 patients with HIV from 15 hospitals who had received RPV + bDRV for 24 weeks to optimize/simplify their previous ART were included. The percentage of patients without virologic failure (2 consecutive viral loads >50 copies/mL) at 24 weeks of treatment was calculated. Virologic success was defined as 24 weeks of follow up without virologic failure.
Baseline characteristics of the patients included median age of 49 years, previous AIDS stage and median CD4+ lymphocyte nadir of 170 cells/uL in 29.3%, median HIV diagnosis of 17 years, and ART duration for a median of 14 years with 5 previous treatment combinations. There was a history of virologic failure in 36.6% of participants. Of the included patients, the reason for the switch to dual therapy included simplification/optimization (49.7%), toxicity/intolerance (17.4%), or inadequate effectiveness of previous ART (1.06%).
Results showed that dual therapy with RPV + bDRV may be an acceptable alternative to triple therapy in those who have disease suppression or who have stable HIV disease with a less favorable profile (history of ART exposure, severe immunodepression, virologic failure, toxicity associated with antiretroviral drugs). The dual therapy was able to achieve and maintain viral suppression in >90% of the studied patient population. The virologic load at baseline of 50 to 1000 copies/mL was recorded in 25.5% of patients. In the “intention-to-treat” analysis at 24 weeks, 87.6% patients continued the study treatment without virologic failure criteria. In the “on treatment” analysis, which excluded patients who discontinued dual therapy treatment for any reason other than virologic failure, the efficacy was 94.6%. In addition, dual therapy was well tolerated with no severe adverse effects reported.
Overall, the study authors concluded that, “Dual therapy with RPV + bDRV in the clinical setting has proven to be effective, even in patients with advanced HIV infection, extended exposure to ART, low CD4 lymphocyte nadir, history of VF [virological failure], and/or previous non-suppressive ART.”
Pasquau J, de Jesus SE, Arazo P, et al. Effectiveness and safety of dual therapy with rilpivirine and boosted darunavir in treatment-experienced patients with advanced HIV infection: a preliminary 24 week analysis (RIDAR study).BMC Infect Dis. 2019;19:207.