Long-Term Efficacy and Safety of Fosamprenavir plus Ritonavir Versus Lopinavir/Ritonavir in Combination with Abacavir/Lamivudine over 144 Weeks

Pulido, Federico; Estrada, Vicente; Baril, Jean-Guy; Logue, Ken; Schewe, Knud; Plettenberg, Andreas; Duiculescu, Dan; Yau, Linda; Vavro, Cindy; Lim, Michael; Pharo, Cristina

doi:10.1310/hct1002-76

Cited by 28 publications

(16 citation statements)

References 6 publications

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“…Other long‐term studies involving treatment‐naïve patients have compared other PIs with LPV/r. The 144‐week KLEAN study demonstrated noninferiority in virological response (HIV‐1 RNA < 50 copies/mL; ITT‐TLOVR) of fosamprenavir/r plus an optimized background regimen (OBR) compared with LPV/r plus an OBR. The 96‐week CASTLE study compared atazanavir (ATV/r) 300/100 mg once daily with LPV/r 400/100 mg twice daily (both with fixed‐dose TDF/FTC 300/200 mg once daily), where ATV/r was shown to be noninferior to LPV/r in virological response (HIV‐1 RNA < 50 copies/mL; ITT‐TLOVR).…”

Section: Discussionmentioning

confidence: 99%

“…The statistical superiority, demonstrated at week 192, does also appear to have been influenced by better tolerability and fewer discontinuations in the DRV/r treatment arm, thus showing safety to be an important contributor to outcome, in addition to antiviral activity. The percentage of self-reported adherent patients (> 95% adherent to PI use) ranged from 82.0 to 89.4% for [12] demonstrated noninferiority in virological response (HIV-1 RNA < 50 copies/mL; ITT-TLOVR) of fosamprenavir/r plus an optimized background regimen (OBR) compared with LPV/r plus an OBR. The 96-week CASTLE study [13] compared atazanavir (ATV/r) 300/100 mg once daily with LPV/r 400/100 mg twice daily (both with fixed-dose TDF/FTC 300/200 mg once daily), where ATV/r was shown to be noninferior to LPV/r in virological response (HIV-1 RNA < 50 copies/mL; ITT-TLOVR).…”

Section: Discussionmentioning

confidence: 99%

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Final 192‐week efficacy and safety of once‐daily darunavir/ritonavir compared with lopinavir/ritonavir in HIV‐1‐infected treatment‐naïve patients in the ARTEMIS trial

et al. 2012

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ObjectiveThis paper presents the final analysis of once-daily darunavir/ritonavir (DRV/r) vs. lopinavir/ritonavir (LPV/r) in treatment-naïve HIV-1-infected adults. Methods ARTEMIS (AntiRetroviral Therapy with TMC114 ExaMinedIn naïve Subjects; NCT00258557) was a randomized, open-label, phase-III, 192-week trial. Patients were stratified by baseline HIV-1 RNA and CD4 count, and randomized to once-daily DRV/r 800/100 mg or LPV/r 800/200 mg total daily dose (either once or twice daily) plus tenofovir/emtricitabine. ResultsOf 689 randomized patients receiving treatment (DRV/r: 343; LPV/r: 346), 85 and 114 patients in the DRV/r and LPV/r arms, respectively, had discontinued by week 192. Noninferiority was shown in the primary endpoint of virological response (HIV-1 RNA < 50 copies/mL) [DRV/r: 68.8%; LPV/r: 57.2%; P < 0.001; intent to treat (ITT)/time to loss of virological response; estimated difference in response 11.6% (95% confidence interval 4.4-18.8%)]. Statistical superiority in virological response of DRV/r over LPV/r was demonstrated for the primary endpoint (P = 0.002) and for the ITT non-virological-failure-censored analysis (87.4% vs. 80.8%, respectively; P = 0.040). No protease inhibitor (PI) primary mutations developed and only low levels of nucleoside reverse transcriptase inhibitor (NRTI) resistance developed in virological failures in both groups. Significantly fewer discontinuations because of adverse events were observed with DRV/r (4.7%) than with LPV/r (12.7%; P = 0.005). Grade 2-4 treatment-related diarrhoea was significantly less frequent with DRV/r than with LPV/r (5.0% vs. 11.3%, respectively; P = 0.003). DRV/r was associated with smaller median increases in total cholesterol and triglyceride levels than LPV/r. Changes in low-and high-density lipoprotein cholesterol were similar between groups. Similar increases in aspartate aminotransferase and alanine aminotransferase for DRV/r and LPV/r were observed. ORIGINAL RESEARCH 49 ConclusionOver 192 weeks, once-daily DRV/r was noninferior and statistically superior in virological response to LPV/r, with a more favourable gastrointestinal profile, demonstrating its suitability for long-term use in treatment-naïve patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Final 192‐week efficacy and safety of once‐daily darunavir/ritonavir compared with lopinavir/ritonavir in HIV‐1‐infected treatment‐naïve patients in the ARTEMIS trial

et al. 2012

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“…Data were pooled from four recent GlaxoSmithKline‐sponsored HIV trials in adult subjects naïve to antiretroviral treatment (studies: ARIES, HEAT, KLEAN and APV109141 ). Discontinuations were categorised as: Treatment‐related/‘unavoidable’: defined as withdrawal due to adverse event, protocol‐defined virologic failure, insufficient viral load response, disease progression, or ‘potentially avoidable’: defined as lost to follow‐up, subject decision, non‐compliance, protocol violation, other.…”

Section: Methodsmentioning

confidence: 99%

The statistician's role in the prevention of missing data

Hughes¹,

Harris²,

Flack

et al. 2012

Pharmaceutical Statistics

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Considerable statistical research has been performed in recent years to develop sophisticated statistical methods for handling missing data and dropouts in the analysis of clinical trial data. However, if statisticians and other study team members proactively set out at the trial initiation stage to assess the impact of missing data and investigate ways to reduce dropouts, there is considerable potential to improve the clarity and quality of trial results and also increase efficiency. This paper presents a Human Immunodeficiency Virus (HIV) case study where statisticians led a project to reduce dropouts. The first step was to perform a pooled analysis of past HIV trials investigating which patient subgroups are more likely to drop out. The second step was to educate internal and external trial staff at all levels about the patient types more likely to dropout, and the impact this has on data quality and sample sizes required. The final step was to work collaboratively with clinical trial teams to create proactive plans regarding focused retention efforts, identifying ways to increase retention particularly in patients most at risk. It is acknowledged that identifying the specific impact of new patient retention efforts/tools is difficult because patient retention can be influenced by overall study design, investigational product tolerability profile, current standard of care and treatment access for the disease under study, which may vary over time. However, the implementation of new retention strategies and efforts within clinical trial teams attests to the influence of the analyses described in this case study.

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“…Head-to-head trials of ritonavir-boosted PIs demonstrate noninferiority, fewer side effects, and lower pill burden with atazanavir (ATV), fosamprenavir (FPV), and darunavir (DRV) when compared with lopinavir (LPV) [23][24][25]. Once-daily dosing in the ARTnaïve subject offers an added benefit, and provides the adolescent with several simple regimen options.…”

Section: Initial Art Regimen Considerationsmentioning

confidence: 99%

The HIV-Infected Adolescent

Ross

Camacho-González

Henderson

et al. 2010

Curr Infect Dis Rep

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HIV-infected adolescents represent a unique, yet diverse, population requiring specialized medical and psychosocial HIV care. Perinatally infected and behaviorally infected adolescents often have differing therapeutic needs, but may share common difficulties, including medication nonadherence, high-risk sexual behavior, psychosocial stressors, and concomitant psychiatric disorders. Addressing these needs within a culturally sensitive framework and in the context of a population-specific approach to treatment is paramount to optimizing care. Harm reduction for this group to maximize their health and limit HIV transmission to others is also critical with respect to the rising incidence of newly diagnosed HIV-positive adolescents. Implementing a formal, multidisciplinary program that involves individual youths and their families for improved transition to adult HIV care will afford such adolescents a better chance for a healthy adulthood.

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Long-Term Efficacy and Safety of Fosamprenavir plus Ritonavir Versus Lopinavir/Ritonavir in Combination with Abacavir/Lamivudine over 144 Weeks

Abstract: The findings of the KLEAN study extension (48 to 144 weeks) support durable viral suppression with both FPV/r and LPV/r treatment regimens when used in combination with ABC/3TC irrespective of viral load at baseline. Both regimens were well tolerated and had similar safety profiles.

Cited by 28 publications

References 6 publications

Final 192‐week efficacy and safety of once‐daily darunavir/ritonavir compared with lopinavir/ritonavir in HIV‐1‐infected treatment‐naïve patients in the ARTEMIS trial

Final 192‐week efficacy and safety of once‐daily darunavir/ritonavir compared with lopinavir/ritonavir in HIV‐1‐infected treatment‐naïve patients in the ARTEMIS trial

The statistician's role in the prevention of missing data

The HIV-Infected Adolescent

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