A prospective randomized trial on abacavir/ lamivudine plus darunavir/ritonavir or raltegravir in HIV-positive drug-naïve patients with CD4<200 cells/uL (the PRADAR study)

Cristina Mussini, Enrica Roncaglia, Vanni Borghi, Stefano Rusconi, Silvia Nozza, Anna Maria Cattelan, Daniela Segala, Paolo Bonfanti, Antonio Di Biagio, Enrico Barchi, Emanuele Focà, Anna Degli Antoni, Stefano Bonora, Daniela Francisci, Silvia Limonta, Andrea Antinori, Gabriella D’Ettorre, Franco Maggiolo

Research output: Contribution to journalArticle

Abstract

Background Very few data are available on treatment in HIV Late presenter population that still represents a clinical challenge. Methods Prospective, multicenter, randomized open-label, 2 arm, phase-3 trial comparing the 48-week virological response of two different regimens: abacavir/lamivudine + darunavir/r vs abacavir/lamivudine + raltegravir in antiretroviral naive with CD4+ counts < 200/mm3 and a viral load (VL)<500,000 copies/mL. The primary Endpoint was the proportion of patients with undetectable viremia (VL<50 copies/mL) after 48 weeks. The planned sample size for this trial was 350 patients. Results In 3 years, 53 patients were screened and 46 enrolled: 22 randomized to raltegravir and 24 to darunavir/r; 7 patients were excluded, 4 because of a VL >500,000 copies/mL and 3 for HLAB5701 positivity. The snapshot analysis at 48 weeks showed a virologic success of 77.3% in raltegravir and 66.7% in darunavir/r. Time to starting treatment was 34.5 days in raltegravir and 53 days in darunavir/r. At the as treated analysis, the median CD4 counts at 48 weeks was 297 cells/μL in raltegravir and 239 cells/μL in darunavir/r. No difference in total cholesterol, while triglycerides were higher in the darunavir/r arm. No statistical analyses were performed due to the low number of patients enrolled. Conclusions Late presenter patients are frequent but very difficult to enroll in clinical trials, especially in western countries. These regimens and the conditions of many patients could not allow the test and treat strategy. The rate of virologic success was higher than 65% in both arms with a median CD4 cell count >200/μL at week 48.

Original languageEnglish
Article numbere0222650
Pages (from-to)1-11
Number of pages11
JournalPLoS One
Volume14
Issue number9
DOIs
Publication statusPublished - Jan 1 2019

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Ritonavir
HIV
drugs
CD4 Lymphocyte Count
Pharmaceutical Preparations
cells
clinical trials
triacylglycerols
cholesterol
Labels
Triglycerides
Cholesterol
Darunavir
Raltegravir Potassium
lamivudine drug combination abacavir
Clinical Trials
testing
Therapeutics
Population
methodology

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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A prospective randomized trial on abacavir/ lamivudine plus darunavir/ritonavir or raltegravir in HIV-positive drug-naïve patients with CD4<200 cells/uL (the PRADAR study). / Mussini, Cristina; Roncaglia, Enrica; Borghi, Vanni; Rusconi, Stefano; Nozza, Silvia; Cattelan, Anna Maria; Segala, Daniela; Bonfanti, Paolo; Biagio, Antonio Di; Barchi, Enrico; Focà, Emanuele; Antoni, Anna Degli; Bonora, Stefano; Francisci, Daniela; Limonta, Silvia; Antinori, Andrea; D’Ettorre, Gabriella; Maggiolo, Franco.

In: PLoS One, Vol. 14, No. 9, e0222650, 01.01.2019, p. 1-11.

Research output: Contribution to journalArticle

Mussini, C, Roncaglia, E, Borghi, V, Rusconi, S, Nozza, S, Cattelan, AM, Segala, D, Bonfanti, P, Biagio, AD, Barchi, E, Focà, E, Antoni, AD, Bonora, S, Francisci, D, Limonta, S, Antinori, A, D’Ettorre, G & Maggiolo, F 2019, 'A prospective randomized trial on abacavir/ lamivudine plus darunavir/ritonavir or raltegravir in HIV-positive drug-naïve patients with CD4<200 cells/uL (the PRADAR study)', PLoS One, vol. 14, no. 9, e0222650, pp. 1-11. https://doi.org/10.1371/journal.pone.0222650
Mussini, Cristina ; Roncaglia, Enrica ; Borghi, Vanni ; Rusconi, Stefano ; Nozza, Silvia ; Cattelan, Anna Maria ; Segala, Daniela ; Bonfanti, Paolo ; Biagio, Antonio Di ; Barchi, Enrico ; Focà, Emanuele ; Antoni, Anna Degli ; Bonora, Stefano ; Francisci, Daniela ; Limonta, Silvia ; Antinori, Andrea ; D’Ettorre, Gabriella ; Maggiolo, Franco. / A prospective randomized trial on abacavir/ lamivudine plus darunavir/ritonavir or raltegravir in HIV-positive drug-naïve patients with CD4<200 cells/uL (the PRADAR study). In: PLoS One. 2019 ; Vol. 14, No. 9. pp. 1-11.
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T1 - A prospective randomized trial on abacavir/ lamivudine plus darunavir/ritonavir or raltegravir in HIV-positive drug-naïve patients with CD4<200 cells/uL (the PRADAR study)

AU - Mussini, Cristina

AU - Roncaglia, Enrica

AU - Borghi, Vanni

AU - Rusconi, Stefano

AU - Nozza, Silvia

AU - Cattelan, Anna Maria

AU - Segala, Daniela

AU - Bonfanti, Paolo

AU - Biagio, Antonio Di

AU - Barchi, Enrico

AU - Focà, Emanuele

AU - Antoni, Anna Degli

AU - Bonora, Stefano

AU - Francisci, Daniela

AU - Limonta, Silvia

AU - Antinori, Andrea

AU - D’Ettorre, Gabriella

AU - Maggiolo, Franco

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background Very few data are available on treatment in HIV Late presenter population that still represents a clinical challenge. Methods Prospective, multicenter, randomized open-label, 2 arm, phase-3 trial comparing the 48-week virological response of two different regimens: abacavir/lamivudine + darunavir/r vs abacavir/lamivudine + raltegravir in antiretroviral naive with CD4+ counts < 200/mm3 and a viral load (VL)<500,000 copies/mL. The primary Endpoint was the proportion of patients with undetectable viremia (VL<50 copies/mL) after 48 weeks. The planned sample size for this trial was 350 patients. Results In 3 years, 53 patients were screened and 46 enrolled: 22 randomized to raltegravir and 24 to darunavir/r; 7 patients were excluded, 4 because of a VL >500,000 copies/mL and 3 for HLAB5701 positivity. The snapshot analysis at 48 weeks showed a virologic success of 77.3% in raltegravir and 66.7% in darunavir/r. Time to starting treatment was 34.5 days in raltegravir and 53 days in darunavir/r. At the as treated analysis, the median CD4 counts at 48 weeks was 297 cells/μL in raltegravir and 239 cells/μL in darunavir/r. No difference in total cholesterol, while triglycerides were higher in the darunavir/r arm. No statistical analyses were performed due to the low number of patients enrolled. Conclusions Late presenter patients are frequent but very difficult to enroll in clinical trials, especially in western countries. These regimens and the conditions of many patients could not allow the test and treat strategy. The rate of virologic success was higher than 65% in both arms with a median CD4 cell count >200/μL at week 48.

AB - Background Very few data are available on treatment in HIV Late presenter population that still represents a clinical challenge. Methods Prospective, multicenter, randomized open-label, 2 arm, phase-3 trial comparing the 48-week virological response of two different regimens: abacavir/lamivudine + darunavir/r vs abacavir/lamivudine + raltegravir in antiretroviral naive with CD4+ counts < 200/mm3 and a viral load (VL)<500,000 copies/mL. The primary Endpoint was the proportion of patients with undetectable viremia (VL<50 copies/mL) after 48 weeks. The planned sample size for this trial was 350 patients. Results In 3 years, 53 patients were screened and 46 enrolled: 22 randomized to raltegravir and 24 to darunavir/r; 7 patients were excluded, 4 because of a VL >500,000 copies/mL and 3 for HLAB5701 positivity. The snapshot analysis at 48 weeks showed a virologic success of 77.3% in raltegravir and 66.7% in darunavir/r. Time to starting treatment was 34.5 days in raltegravir and 53 days in darunavir/r. At the as treated analysis, the median CD4 counts at 48 weeks was 297 cells/μL in raltegravir and 239 cells/μL in darunavir/r. No difference in total cholesterol, while triglycerides were higher in the darunavir/r arm. No statistical analyses were performed due to the low number of patients enrolled. Conclusions Late presenter patients are frequent but very difficult to enroll in clinical trials, especially in western countries. These regimens and the conditions of many patients could not allow the test and treat strategy. The rate of virologic success was higher than 65% in both arms with a median CD4 cell count >200/μL at week 48.

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