Simplification to atazanavir/ritonavir+lamivudine in virologically suppressed HIV‐infected patients: 24‐weeks interim analysis from ATLAS‐M trial

Fabbiani, Massimiliano; Giambenedetto, Simona Di; Quirós-Roldán, Eugenia; Latini, Alessandra; Vullo, Vincenzo; Antinori, Andrea; Castagna, Antonella; Orofino, Giancarlo; Francisci, Daniela; Grilli, Elisabetta; Madeddu, G; Grima, Pierfrancesco; Rusconi, Stefano; Pin, Barbara Del; Mondi, Annalisa; Borghetti, Alberto; Focà, Emanuele; Colafigli, Manuela; Luca, Andrea De; Cauda, Roberto

doi:10.7448/ias.17.4.19808

Cited by 13 publications

(6 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Two‐drug combinations are only mentioned and considered in guidelines in specific switch circumstances. Of the currently available treatment options, PI/r plus lamivudine (3TC) dual combinations have been assessed in randomized trials in suppressed patients compared with continued triple‐drug ART . Within its recommendations on the roles of PI/r, the BHIVA considers this a possible option in the setting of virological suppression .…”

Section: Considering the Evidence For Switch – What The Guidelines Saymentioning

confidence: 99%

Switching regimens in virologically suppressed HIV‐1‐infected patients: evidence base and rationale for integrase strand transfer inhibitor (INSTI)‐containing regimens

Raffi¹,

Eßer

Nunnari

et al. 2016

HIV Medicine

View full text Add to dashboard Cite

In an era when most individuals with treated HIV infection can expect to live into old age, clinicians should proactively review their patients' current and future treatment needs and challenges. Clinical guidelines acknowledge that, in the setting of virological suppression, treatment switch may yield benefits in terms of tolerability, regimen simplification, adherence, convenience and long-term health considerations, particularly in the context of ageing. In this paper, we review evidence from six key clinical studies on switching virologically suppressed patients to regimens based on integrase strand transfer inhibitors (INSTIs), the antiretroviral class increasingly preferred as initial therapy in clinical guidelines. We review these studies and focus on the virological efficacy, safety, and tolerability of switching to INSTI-based regimens in suppressed HIV-positive individuals. We review the early switch studies SWITCHMRK and SPIRAL [assessing a switch from a ritonavir-boosted protease inhibitor (PI/r) to raltegravir (RAL)-containing regimens], together with data from STRATEGY-PI [assessing a switch to elvitegravir (EVG)-containing regimens; EVG/cobicistat (COBI)/emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) vs. remaining on a PI/r-containing regimen], STRATEGY-NNRTI [assessing a switch to EVG/COBI/FTC/TDF vs. continuation of a nonnucleoside reverse transcriptase inhibitor (NNRTI) and two nucleoside reverse transcriptase inhibitors (NRTIs)], STRIIVING [assessing a switch to a dolutegravir (DTG)-containing regimen (abacavir (ABC)/lamivudine (3TC)/DTG) vs. staying on the background regimen], and GS study 109 [assessing a switch to EVG/COBI/FTC/tenofovir alafenamide fumarate (TAF) vs. continuation of FTC/TDF-based regimens]. Switching to INSTI-containing regimens has been shown to support good virological efficacy, with evidence from two studies demonstrating superior virological efficacy for a switch to EVG-containing regimens. In addition, switching to INSTI regimens was associated with improved tolerability and greater reported patient satisfaction and outcomes in some studies. INSTI-based regimens offer an important contemporary switch option that may be tailored to meet and optimize the needs of many patients.

show abstract

Section: Considering the Evidence For Switch – What The Guidelines Saymentioning

confidence: 99%

Switching regimens in virologically suppressed HIV‐1‐infected patients: evidence base and rationale for integrase strand transfer inhibitor (INSTI)‐containing regimens

Raffi¹,

Eßer

Nunnari

et al. 2016

HIV Medicine

View full text Add to dashboard Cite

show abstract

“…The GARDEL study was the first to show non-inferiority of a dual combination of ritonavir-boosted lopinavir (LPV/r) plus 3TC, even in patients with baseline viral load (VL) above 100,000 copies/mL [6]. Other three studies showed non-inferior virologic efficacy of the same dual regimen or the combination of ritonavir-boosted atazanavir plus 3TC, all performed in virologically suppressed patients as a switch strategy [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Dolutegravir–lamivudine as initial therapy in HIV‐1 infected, ARV‐naive patients, 48‐week results of the PADDLE (Pilot Antiretroviral Design with Dolutegravir LamivudinE) study

Cahn

Rolón

Figueroa

et al. 2017

Journal of the International AIDS Society

View full text Add to dashboard Cite

Introduction: A proof-of-concept study was designed to evaluate the antiviral efficacy, safety and tolerability of a two-drug regimen with dolutegravir 50 mg once daily (QD) plus lamivudine 300 mg once daily as initial highly active antiretroviral therapy (HAART) among antiretroviral (ARV)-naive patients.Methods: PADDLE is a pilot study including 20 treatment-naive adults. To be selected, participants had no IAS-USA-defined resistance, HIV-1 RNA ≤100,000 copies/mL at screening and negative HBsAg. Plasma viral load (pVL) was measured at baseline; days 2, 4, 7, 10, 14, 21 and 28; weeks 6, 8 and 12; and thereafter every 12 weeks up to 96 weeks. Primary endpoint was the proportion of patients with HIV-1 RNA <50 copies/mL in an intention to treat (ITT)-exposed analysis at 48 weeks (the FDA snapshot algorithm).Results: Median HIV-1 RNA at entry was 24,128 copies/mL (interquartile range (IQR): 11,686–36,794). Albeit as per protocol, all patients had pVL ≤100,000 copies/mL at screening as required by inclusion criteria, four patients had ≥100,000 copies/mL at baseline. Median baseline CD4+ T-cell count was 507 per cubic millimetre (IQR: 296–517). A rapid decline in pVL was observed (median VL decay from baseline to week 12 was 2.74 logs). All patients were suppressed at week 8 onwards up to week 24. At week 48, 90% (18/20) reached the primary endpoint of a pVL <50 copies/mL. Median change in CD4 cell count between baseline and week 48 was 267 cells/mm3 (IQR: 180–462). No major tolerability/toxicity issues were observed. Nineteen patients completed 48 weeks of the study, and one patient (with undetectable VL at last visit) committed suicide. One patient presented a low-level protocol-defined confirmed virological failure at week 36, being the only observed failure. This patient had pVL <50 copies/mL at the end-of-study visit without having changed the two-drug regimen. Observed failure rate was 5%. This is the first report of integrase strand transfer inhibitor/lamivudine dual regimen in ARV-naive patients.Conclusions: This novel dual regimen of dolutegravir and lamivudine warrants further clinical research and consideration as a potential therapeutic option for ARV-therapy-naive patients.ClinicalTrials.gov Identifier: NCT02211482.

show abstract

“…This result is surprising as some other ART regimen showed lipid-lowering effects, such as tenofovir [38]. In our study, this may be due to ritonavir stopping when switching to dual therapy [39]. …”

Section: Discussionmentioning

confidence: 75%

Switch to Ritonavir-Boosted versus Unboosted Atazanavir plus Raltegravir Dual-Drug Therapy Leads to Similar Efficacy and Safety Outcomes in Clinical Practice

et al. 2016

View full text Add to dashboard Cite

ObjectivesTo assess immunovirological response, safety and pharmacokinetic of NRTI-sparing regimen dual therapy of atazanavir (ATV) and raltegravir (RAL) in maintenance strategy.MethodsA retrospective analysis was conducted on a cohort of HIV-infected adults followed in French centers (Dat’AIDS cohort), comparing the proportions of virological and therapeutic failures between ATV + RAL and ATV/ritonavir + RAL dual therapy regimens.Results283 patients were assessed: 185 switched for ATV + RAL and 98 for ATV/ritonavir + RAL dual therapy. Virological failure rate at week 96 was 13.8% (95% CI, 9.8–17.8), without difference between the two groups (Log-rank Test, p = 0.87). The cumulative percentages of patients remaining free of therapeutic failure at week 24, 48 and 96 of dual therapy were 74.9% (95% CI, 69.9–80.0), 65.4% (95% CI, 59.8–70.9) and 53.4% (95% CI, 47.5–59.2), respectively. Four out of 39 confirmed virological failures developed RAL resistance. By multivariate analysis, virological failure was associated with high HIV-1 RNA zenith (p = 0.02), low CD4+ T-cell count at baseline (p<0.001) and short duration on antiretroviral therapy (p<0.001). Before week 96, dual therapy was discontinued in 44 patients (16%) because of various adverse events, with no difference between the two groups. Minimal plasma levels were targeted in 84% and 87% of patients for ATV and RAL, respectively, and both were significantly higher in ritonavir-boosted regimen.ConclusionsEmerging RAL-resistance and discontinuations for adverse events resulted in moderate efficacy rates of ATV and RAL dual therapy in heavily pretreated patients.

show abstract

Simplification to atazanavir/ritonavir+lamivudine in virologically suppressed HIV‐infected patients: 24‐weeks interim analysis from ATLAS‐M trial

Cited by 13 publications

References 0 publications

Switching regimens in virologically suppressed HIV‐1‐infected patients: evidence base and rationale for integrase strand transfer inhibitor (INSTI)‐containing regimens

Switching regimens in virologically suppressed HIV‐1‐infected patients: evidence base and rationale for integrase strand transfer inhibitor (INSTI)‐containing regimens

Dolutegravir–lamivudine as initial therapy in HIV‐1 infected, ARV‐naive patients, 48‐week results of the PADDLE (Pilot Antiretroviral Design with Dolutegravir LamivudinE) study

Switch to Ritonavir-Boosted versus Unboosted Atazanavir plus Raltegravir Dual-Drug Therapy Leads to Similar Efficacy and Safety Outcomes in Clinical Practice

Contact Info

Product

Resources

About