Dual HIV Regimen Equaled Triple Even After Treatment Failure
NOVEMBER 25, 2018
Kenneth Bender, PharmD, MA
Timo Wolf, MDA "dual" combination of raltegravir (Isentress) plus boosted protease inhibitor was comparable to triple combination regimens with raltegravir for HIV in treatment-experienced patients, including those with previous treatment failure, in a retrospective study with real-world cohort.
Timo Wolf, MD, Infectious Diseases Division, Department of Internal Medicine, HIV Center, University Hospital Frankfurt, Frankfurt, Germany, and colleagues point out that raltegravir has been commonly used in second- and later-generation treatment regimens in real-world practice with both treatment-experienced and treatment-naive patients, despite limited clinical trial data to support raltegravir as an antiretroviral switch option.
Although raltegravir has been shown to have a low genetic barrier to resistance, they suggest that its use, particularly if baseline resistance is ruled out, has been a successful strategy to spare the relatively greater toxicity and potential adverse drug interactions inherent in nucleoside reverse transcriptase inhibitor (NRTI)-based regimens.
"Dual regimens were recently explored thoroughly in a number of controlled studies," Wolf told MD Magazine®. "The data provided have demonstrated that raltegravir was safely used in dual regimen even earlier, provided that the resistance pattern allowed their use. This may, however, be reasonably extrapolated to patients naive to either of the dual components, raltegravir or boosted protease inhibitor."
To further examine the efficacy of different raltegravir-based combinations in treatment-experienced patients, the investigators reviewed records for 897 patients from 3 observational cohort studies conducted in 52 sites in Germany between March 2000 and January 2014. Treatment regimens were stratified into 3 groups: dual regimen of boosted protease inhibitor plus raltegravir (bPI+RAL), the "triple" regimen of 2 nucleoside reverse transcriptase inhibitors (NRTIs) and raltegravir, and other raltegravir-based combinations. Virological responses were compared at weeks 24, 48, 72, and 96.
The cohort included 90 (10%) who were previously untreated, and 67 (7.5%) with unknown previous treatment status who were not included in the pretreatment sub-analysis. Of the 740 (82.5%) who had received other treatment prior to commencing a raltegravir combination regimen, treatment failure was the cause to switch in 11.02% of those on bPI+RAL, 6.27% of those on 2 NRTIs+RAL and 21.4% of those starting other raltegravir combinations. The most common reason for switching to an raltegravir-based regimen, however, was intolerance of the prior therapy.
The investigators reported that the overall rate of virological suppression to <50 HIV-1 RNA copies/ml was 69.5%. Although the baseline rate of virological suppression had been higher for the group on 2NRTIs+RAL, the rates of suppression were similar for all 3 groups at weeks 24, 48, 72, and 96. Importantly, the comparable results were achieved despite a substantial number of subjects in each group with previous treatment failure.
"The 'dual treatment' group receiving bPI+RAL, in particular, showed a higher rate of virological failure of previous therapies at baseline, but still achieved a comparable virological response rate," Wolff and colleagues indicated. "This suggests that dual bPI+RAL combinations may be a feasible option for the management of treatment failure if applied in a resistance-guided manner."
The retrospective study, “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,” was published in HIV Medicine.