Efficacy and tolerability of switching to a dual therapy with darunavir/ritonavir plus raltegravir in HIV-infected patients with HIV-1 RNA ≤50 cp/mL

Abstract

raltegravir (RAL) while having a viral load (VL) ≤50 copies/mL in the clinical setting. Study design Treatment-experienced HIV 1-infected patients enrolled in the ICONA Foundation Study cohort were included if they switched their current regimen to DRV/r + RAL with a HIV-RNA ≤50 copies/mL. Different definitions of virological failure (VF) and treatment failure (TF) were employed. Kaplan-Meier curves and Cox regression models were performed to estimate time to event probability. Results We included 72 HIV-infected patients, 22 (31%) of these were female, 31 (43%) men who have sex with men (MSM) amd 15 (21%) had hepatitis co-infections. Median age was 44 (IQR: 35-50) years amd CD4 count was 389 (IQR 283-606) cells/mmc. Median follow-up time for TF was 24 (IQR 9-31) months. Twenty-five discontinuations occurred (60% simplifications); only 2 (8%) were toxicity-driven (lipid elevations). The probability of VF (confirmed VL >50 copies/mL) was estimated at 7% [95% confidence interval (CI) 1-13%] by 12 and 9% (95% CI 2-16%) by 24 months. When considering TF, we found a probability of stop/intensification/single VL > 200 copies/ mL of 13% (95% CI 1-17%) and 22% (95% CI 11-33%) by 12 and 24 months. Female gender (adjusted relative hazard, ARH = 0.10; 95% CI 0.01-0.74; p = 0.024) and older age (AHR = 0.50 per 10 years older; 95% CI 0.25-0.99; p = 0.045) were associated with a lower risk of TF. A previous PI failure was strongly associated with TF (AHR = 52.6, 95% CI 3.6-779; p = 0.004). Conclusions DRV/r + RAL is a valuable NRTI-sparing option, especially in female and older patients, with a relatively low risk of VF and good tolerability after 2 years since start in an ART-experienced population. However, previous PI-failure should be a limiting factor for this strategy. AbstractBackground Nucleos(t)ide reverse transcriptase inhibitors (NRTI) toxicity may represent a threat for long-term success of combined antiretroviral therapy. Some studies have suggested a possible improvement of NRTI-related toxicity after switching to NRTI-sparing regimens. Objectives We aimed to explore the efficacy and tolerability of switching to darunavir/ritonavir (DRV/r) plus

Similar long‐term efficacy of dual therapy containing raltegravir and a boosted protease inhibitor versus standard triple therapies in pretreated HIV‐1‐infected patients in a retrospective, real‐life cohort of 14 years

“…In a study examining combinations in treatment‐experienced patients, a combination of RAL plus boosted lopinavir showed equal efficacy to two NRTIs plus boosted lopinavir and to boosted lopinavir alone in a cohort with failure on a regimen of two NRTIs plus an NNRTI, and the efficacy was 81% in the lopinavir plus RAL group . Also, in a study conducted in a resource‐rich environment, a virological efficacy of 88% at 12 months was shown for a combination of boosted darunavir plus RAL . In this retrospective analysis, the dual combination in treatment‐experienced patients showed a virological efficacy of 70.05% at 96 weeks in a noncontrolled, real‐life cohort.…”

Maintenance of virologic suppression and improvement in comorbidities after simplification to raltegravir plus boosted darunavir among treatment-experienced HIV-infected patients

“…To date, this combination had been evaluated in clinical trials in naı¨ve patients, but there were fewer data in the simplification scenario. 5,6 Calza et al 5 described 2% VF and 5% discontinuation due to adverse events (efficacy 92.7% at 48 weeks) among 82 patients who switched to this combination after more than three years of virologic suppression. Madeddu et al 6 evaluated 72 patients with this combination as a switching strategy, and as we observed in our study, the main reason for discontinuation of this dual regimen was simplification.…”

“…5,6 Calza et al 5 described 2% VF and 5% discontinuation due to adverse events (efficacy 92.7% at 48 weeks) among 82 patients who switched to this combination after more than three years of virologic suppression. Madeddu et al 6 evaluated 72 patients with this combination as a switching strategy, and as we observed in our study, the main reason for discontinuation of this dual regimen was simplification. Notably, they found a small and not statistically significant higher rate of treatment failure in patients with major mutations against PIs (two of five patients) but the number was too low to extract valid conclusions.…”

“…However, this dual regimen has been evaluated mainly in antiretroviral-naı¨ve HIV-1-infected patients, 4 and there are few data about the usefulness of this dual regimen as a simplification strategy in treatment-experienced individuals. 5,6 Thus, there are no consistent data about its efficacy in cases of previous failure with PIs or other families of drugs, or the benefits in different comorbidities. Keeping this idea in mind, we performed a large retrospective study, including those patients who switched to the dual combination of RAL plus boosted DRV, to confirm the efficacy, limitations, and additional benefits of this dual therapy as a simplification strategy in highly experienced PLWH.…”

Nucleos(t)ide reverse transcriptase inhibitor-sparing regimens in the era of standard 3-drug combination therapies for HIV-1 infection

“…In contrast, drug-drug interactions between NRTIs and other drugs are rare (6), and thus changing to another regimen is rarely reported. This could happen in the use of a booster drug such as ritonavir or cobicistat.…”