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Boosted tipranavir versus darunavir in treatment-experienced patients: observational data from the randomized POTENT trial.

Elgadi MM, Piliero PJ - Drugs R D (2011)

Bottom Line: Total observation time was 32 weeks.TPV/r- and DRV/r-based regimens showed similar short-term safety and efficacy.These data support the use of next-generation PIs such as tipranavir or darunavir with novel class antiretroviral agents (integrase inhibitors, CCR5 antagonists, or fusion inhibitors).

View Article: PubMed Central - PubMed

Affiliation: Clinical Development and Medical Affairs, Boehringer Ingelheim (Canada) Ltd., Burlington, ON, Canada. mabrouk.elgadi@boehringer-ingelheim.com

ABSTRACT

Background: The POTENT trial compared the safety and efficacy of tipranavir/ritonavir (TPV/r) to darunavir/ritonavir (DRV/r), each with an optimized background regimen (OBR) in triple-class experienced HIV-1-infected patients with resistance to more than one protease inhibitor (PI).

Methodology/principal findings: POTENT was a prospective, open-label study of triple-class (PI, non-nucleoside reverse transcriptase inhibitors [NNRTI], nucleoside reverse transcriptase inhibitors [NRTI]), treatment-experienced, HIV-positive patients. Subjects were randomized to either TPV/r (500/200 mg twice daily) or DRV/r (600/100 mg twice daily) on a genotype-guided, investigator-selected OBR. CD4+ counts and HIV viral loads were assayed at key timepoints. The primary endpoint was time to virologic failure (viral load ≥500copies/mL). POTENT was prematurely terminated due to slow enrollment. Thirty-nine patients were treated with either TPV/r (n = 19) or DRV/r (n = 20); 82% were male, 77% White, with mean age of 43.6 years. Mean baseline HIV RNA was 3.9 log(10) copies/mL. Median prior antiretrovirals was 11, with no prior raltegravir or maraviroc exposure. Raltegravir was the most common novel class agent in the OBRs (n = 14 TPV/r; n = 12 DRV/r). In both groups, patients achieved mean viral load decreases ≥2 log(10) copies/mL by week 8, and by week 12 mean CD4+ counts rose by 40-50 cells/mm3. Total observation time was 32 weeks. Drug-related adverse events were reported in 21% (TPV/r) and 25% (DRV/r) of patients.

Conclusions/significance: TPV/r- and DRV/r-based regimens showed similar short-term safety and efficacy. These data support the use of next-generation PIs such as tipranavir or darunavir with novel class antiretroviral agents (integrase inhibitors, CCR5 antagonists, or fusion inhibitors).

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Related in: MedlinePlus

Changes in log10 viral load from baseline. Log10 HIV viral loads were measured at each study visit (see Methods section), and individual patient values were normalized to their corresponding baseline (BL) values. Mean log10 declines for each treatment group at each timepoint are depicted in the graph. The table at the bottom presents the number of patients in each treatment arm at each timepoint. DRV/r=darunavir/ritonavir; TPV/r= tipranavir/ritonavir.
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Fig2: Changes in log10 viral load from baseline. Log10 HIV viral loads were measured at each study visit (see Methods section), and individual patient values were normalized to their corresponding baseline (BL) values. Mean log10 declines for each treatment group at each timepoint are depicted in the graph. The table at the bottom presents the number of patients in each treatment arm at each timepoint. DRV/r=darunavir/ritonavir; TPV/r= tipranavir/ritonavir.

Mentions: Observed log10 changes in VL (figure 2) indicated a drop in VL >1.5 log10 copies/mL for both treatment arms by week 2, with mean reductions of ∼2 log10 copies/mL by week 8, indicating short-term potent virologic activity for both TPV/r- and DRV/r-containing regimens in these treatment-experienced patients. At no timepoint were the changes in log10 HIV VL found to be different between the two treatment groups.


Boosted tipranavir versus darunavir in treatment-experienced patients: observational data from the randomized POTENT trial.

Elgadi MM, Piliero PJ - Drugs R D (2011)

Changes in log10 viral load from baseline. Log10 HIV viral loads were measured at each study visit (see Methods section), and individual patient values were normalized to their corresponding baseline (BL) values. Mean log10 declines for each treatment group at each timepoint are depicted in the graph. The table at the bottom presents the number of patients in each treatment arm at each timepoint. DRV/r=darunavir/ritonavir; TPV/r= tipranavir/ritonavir.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3585832&req=5

Fig2: Changes in log10 viral load from baseline. Log10 HIV viral loads were measured at each study visit (see Methods section), and individual patient values were normalized to their corresponding baseline (BL) values. Mean log10 declines for each treatment group at each timepoint are depicted in the graph. The table at the bottom presents the number of patients in each treatment arm at each timepoint. DRV/r=darunavir/ritonavir; TPV/r= tipranavir/ritonavir.
Mentions: Observed log10 changes in VL (figure 2) indicated a drop in VL >1.5 log10 copies/mL for both treatment arms by week 2, with mean reductions of ∼2 log10 copies/mL by week 8, indicating short-term potent virologic activity for both TPV/r- and DRV/r-containing regimens in these treatment-experienced patients. At no timepoint were the changes in log10 HIV VL found to be different between the two treatment groups.

Bottom Line: Total observation time was 32 weeks.TPV/r- and DRV/r-based regimens showed similar short-term safety and efficacy.These data support the use of next-generation PIs such as tipranavir or darunavir with novel class antiretroviral agents (integrase inhibitors, CCR5 antagonists, or fusion inhibitors).

View Article: PubMed Central - PubMed

Affiliation: Clinical Development and Medical Affairs, Boehringer Ingelheim (Canada) Ltd., Burlington, ON, Canada. mabrouk.elgadi@boehringer-ingelheim.com

ABSTRACT

Background: The POTENT trial compared the safety and efficacy of tipranavir/ritonavir (TPV/r) to darunavir/ritonavir (DRV/r), each with an optimized background regimen (OBR) in triple-class experienced HIV-1-infected patients with resistance to more than one protease inhibitor (PI).

Methodology/principal findings: POTENT was a prospective, open-label study of triple-class (PI, non-nucleoside reverse transcriptase inhibitors [NNRTI], nucleoside reverse transcriptase inhibitors [NRTI]), treatment-experienced, HIV-positive patients. Subjects were randomized to either TPV/r (500/200 mg twice daily) or DRV/r (600/100 mg twice daily) on a genotype-guided, investigator-selected OBR. CD4+ counts and HIV viral loads were assayed at key timepoints. The primary endpoint was time to virologic failure (viral load ≥500copies/mL). POTENT was prematurely terminated due to slow enrollment. Thirty-nine patients were treated with either TPV/r (n = 19) or DRV/r (n = 20); 82% were male, 77% White, with mean age of 43.6 years. Mean baseline HIV RNA was 3.9 log(10) copies/mL. Median prior antiretrovirals was 11, with no prior raltegravir or maraviroc exposure. Raltegravir was the most common novel class agent in the OBRs (n = 14 TPV/r; n = 12 DRV/r). In both groups, patients achieved mean viral load decreases ≥2 log(10) copies/mL by week 8, and by week 12 mean CD4+ counts rose by 40-50 cells/mm3. Total observation time was 32 weeks. Drug-related adverse events were reported in 21% (TPV/r) and 25% (DRV/r) of patients.

Conclusions/significance: TPV/r- and DRV/r-based regimens showed similar short-term safety and efficacy. These data support the use of next-generation PIs such as tipranavir or darunavir with novel class antiretroviral agents (integrase inhibitors, CCR5 antagonists, or fusion inhibitors).

Show MeSH
Related in: MedlinePlus