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

Krznaric, Ivanka; Bickel, Markus; Carganico, A; Leuw, P De; Haberl, Annette; Knecht, Gaby; Koegl, C; Lauscher, Paul; Schüttfort, Gundolf; Stephan, Christoph; Wolf, Eva; Wolf, Timo

doi:10.1111/hiv.12636

Cited by 2 publications

(2 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the SPARE study, there was no significant difference between DRV/r plus raltegravir and lopinavir/ritonavir plus tenofovir/emtricitabine [9]. Several observational studies further assessed this combination and demonstrated viral success in 75.5% to 97.6% of patients [10][11][12]. The use of raltegravir, a drug with relatively low genetic barrier and twicedaily administration at that time, could have affected the overall results, as described in other studies [9].…”

Section: Discussionmentioning

confidence: 98%

Efficacy and Safety of Dolutegravir plus Boosted-Darunavir Dual Therapy among Highly Treatment-Experienced Patients

Vizcarra¹,

Fontecha²,

Monsalvo³

et al. 2018

Antiviral Therapy

View full text Add to dashboard Cite

Background: Dual therapies decrease toxicity, pill-burden and treatment-associated cost. The combination of high genetic barrier drugs such as dolutegravir plus boosteddarunavir may be suitable as simplification regimen for patients harbouring multidrug-resistant virus. Methods: Patients switched to a once-daily regimen consisting of dolutegravir plus darunavir, boosted with cobicistat or ritonavir, were included in this cohort study. The primary end point was the proportion of patients with HIV RNA viral load <37 copies/ml at week 48 (NCT02491242). Results: Overall, 51 patients were enrolled. At baseline, all patients had failed to ≥2 antiretroviral classes. Genotypic resistance profiles showed a mean of primary mutations of 1.2 for non-nucleoside reverse transcriptase inhibitors, 2.4 for nucleoside/nucleotide reverse transcriptase inhibitors and 3.5 for protease inhibitors (PIs), but they were virologically suppressed for a median of 33 months (IQR 12-60). Only five patients had reduced sensitivity to darunavir and mean genotypic susceptibility score of dual therapy was 1.95 over 2. At week 48, there were no virological failures, three patients discontinued the regimen due to neuropsychiatric adverse events, two were lost to follow-up, and therefore the efficacy was 90% (95% CI, 82, 99%, intention-to-treat analysis). Mean estimated glomerular filtration rate decreased by 8.8 ml/min/1.73 m 2 , though kidney tubular parameters, high density lipoprotein-cholesterol and triglycerides levels improved after switching to dual therapy. Conclusions: In highly treatment-experienced patients who were virologically suppressed, switching to the combination of dolutegravir plus boosted-darunavir dual therapy was effective and well tolerated, improving lipid and renal parameters.Salvage regimens with the combination of multiple antiretroviral drugs were able to fully suppress HIV replication in patients infected with multidrug-resistant virus [1,2]. Nevertheless, high pill burden and concerns about toxicity and costs made dual therapy strategies interesting options to maintain viral suppression [3], especially in patients with poor compliance or comorbidities. Dolutegravir and darunavir are potent drugs with high genetic barrier and low rates of adverse effects. The use of dolutegravir plus boosteddarunavir reduces pill-burden, avoiding the toxicity of multiple-drug regimens without compromising viral suppression. However, no or limited data are available regarding this regimen for simplification of salvage therapies [4]. Accordingly, we assessed the efficacy and safety of dual regimens containing dolutegravir plus boosted-darunavir as switching strategies in patients with history of virological failure. MethodsWe performed a Phase IV, prospective, single-arm, open-label cohort study at the HIV Unit of a tertiary university hospital from January 2015 through December 2017. Patients with previous virological failures to different classes of antiretroviral drugs, but virologically suppressed in a salvage regimen for at least 24...

show abstract

Section: Discussionmentioning

confidence: 98%

Efficacy and Safety of Dolutegravir plus Boosted-Darunavir Dual Therapy among Highly Treatment-Experienced Patients

Vizcarra¹,

Fontecha²,

Monsalvo³

et al. 2018

Antiviral Therapy

View full text Add to dashboard Cite

show abstract

“…The requirement for lifelong antiretroviral therapy (ART) to maintain viral suppression in people living with HIV (PLWH) has increased the interest in developing effective dual therapy (DT) regimens to reduce cumulative drug exposure and cost, and to simplify regimens 1,2 . Several studies have demonstrated that when compared with triple therapy (TT), DT has non‐inferior virological responses and CD4 cell recoveries when used as a switch strategy in virologically suppressed, ART‐experienced patients 3‐5 . Randomized clinical trials have demonstrated similar results in ART‐naïve patients starting treatment, when comparing DT regimens based on boosted protease inhibitors (PIs) and integrase strand transfer inhibitors (INSTIs) with similar TT regimens 6–8 .…”

Section: Introductionmentioning

confidence: 99%

The effect of protease inhibitor‐based dual antiretroviral regimens on CD4/CD8 ratio during the first year of therapy in ART‐naïve patients with HIV‐infection

et al. 2020

View full text Add to dashboard Cite

Objectives To assess the effect of protease inhibitor (PI)‐based dual therapy on CD4/CD8 ratio during the first year of therapy in antiretroviral therapy (ART)‐naïve patients using data from randomized controlled clinical trials. Methods We pooled data from the GARDEL and ANDES studies, both randomized controlled clinical trials that recruited ART‐naïve people living with HIV and randomly assigned them to receive PI‐based dual therapy (DT) or triple therapy (TT) aiming to compare viral efficacy. We compared median CD4/CD8 ratios and the proportion of patients with CD4/CD8 ratio > 1 at 48 weeks after ART initiation in both treatment arms using the Mann–Whitney U‐test and the χ2 test. We performed subgroup analysis for patients > 50 years old, with baseline CD4 counts ≤ 200 cells/μL, viral load > 100 000 HIV RNA copies/mL, and ritonavir‐boosted lopinavir‐based therapy. Results We analysed data from 571 patients: 292 on DT and 279 on TT. No differences were observed in CD4/CD8 ratio (0.632 vs. 0.617, P = 0.729) or in the proportion of patients with CD4/CD8 ratio > 1 (17.9% vs. 19.3%, P = 0.678) 48 weeks after ART initiation. Subgroup analysis showed no further differences. Conclusion The impact of PI‐based DT regimens on the CD4/CD8 ratio during the first year of treatment for ART‐naïve patients is similar to that of TT.

show abstract

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

Abstract: These data indicate that, in a real-life setting, raltegravir can be used with a high virological success rate in treatment-experienced patients, and that the different combinations analysed (2NRTIs + RAL, bPI + RAL and others) show comparable rates of virological suppression.

Cited by 2 publications

References 8 publications

Efficacy and Safety of Dolutegravir plus Boosted-Darunavir Dual Therapy among Highly Treatment-Experienced Patients

Efficacy and Safety of Dolutegravir plus Boosted-Darunavir Dual Therapy among Highly Treatment-Experienced Patients

The effect of protease inhibitor‐based dual antiretroviral regimens on CD4/CD8 ratio during the first year of therapy in ART‐naïve patients with HIV‐infection

Contact Info

Product

Resources

About