Antiviral potency of HAART regimens and clinical success are not strictly coupled in real life conditions: Evidence from the MASTER-1 study

G. Carosi, F. Castelli, F. Suter, F. Maggiolo, A. M. Orani, A. Pan, M. Andreoni, G. M. Vigevani, R. Maserati, F. Mazzotta, C. Tinelli, L. Tomasoni, A. Patroni, M. Migliorino, G. Castaldo, M. Nigro, G. Carnevale, A. Lingua, R. Visonà, R. CiammarughiL. T. Martelli, G. Pastore, N. Ladisa, L. Minoli, L. Scudeller, G. P. Cadeo, G. Paraninfo, D. Vangi, G. Riccio, V. Bartolacci, M. Toti, C. Nencioni, A. Chirianni, V. Montesarchio, A. Poggio, V. Mondino, F. Mazzotta, M. Di Pietro, S. Lo Caputo, S. Ranieri, G. Ballardini, S. Pauluzzi, G. Stagni, A. Colomba, G. Legnani, D. Torre, G. Pagano, A. Scalzini, F. Leoncini, F. Ghinelli, M. Moroni, P. Cadrobbi, A. Borri, F. De Lalla

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Purpose: To compare in a real clinical setting the largely unknown midterm clinical effectiveness of two protease inhibitor (PI)-based highly active antiretroviral therapy (HAART) regimens with different potency and tolerability profiles in naïve patients. Method: This study was a multicenter, open-label, randomized trial in naïve patients with less than 400 CD4+ cell count/μL, regardless of viral load. Treatment arms were hard gel capsule saquinavir (HGC-SQV)-based HAART (Arm A), with an expected more favorable tolerability profile, and indinavir (IDV)-based HAART (Arm B), with more potent virologic activity. While viro-immunological surrogate markers and World Health Organization (WHO) grade III toxicity (secondary endpoints) were regularly monitored, primary endpoints of the study were clinical and defined as any AIDS-defining event, AIDS-related death, WHO grade IV toxicity, drop outs, and protocol violations. Results: 262 consecutive patients were enrolled in the study from March 1, 1997 to December 31, 1997, in 24 different Italian clinical centers (132, Arm A; 130, Arm B). After 24 months of follow-up, patients who were enrolled in Arm B showed a significantly higher rate of virological success (75% had viremia below 500 copies/mL, CI = 12.9%, in the on-treatment analysis) and immunological gain (mean CD4+ cell count increase of 274 CD4+ cells/μL, SD = 234) when compared to patients enrolled in arm A (57%, CI = 15.5% and 223 CD4+ cells/μL, SD = 192; p = .0353 and .026, respectively). Despite the significant difference observed in surrogate markers, the number of total primary endpoints did not differ in the two groups (55 out of 132 in Arm A vs. 58 out of 130 person-years in Arm B;p = .86). Conclusion: Our results suggest that, after 24 months of follow-up in a real clinical setting, a PI-based HAART induces significant clinical benefits in naïve patients even in the absence of a complete suppression of viral replication. However, the long-term clinical impact of the possible accumulation of viral mutations in the presence of low-grade viral replication remains to be elucidated.

Original languageEnglish
Pages (from-to)399-407
Number of pages9
JournalHIV Clinical Trials
Volume2
Issue number5
Publication statusPublished - 2001

Fingerprint

Highly Active Antiretroviral Therapy
Antiviral Agents
CD4 Lymphocyte Count
Protease Inhibitors
Acquired Immunodeficiency Syndrome
Biomarkers
Saquinavir
Indinavir
Viremia
Viral Load
Capsules
Gels
Therapeutics

Keywords

  • Clinical endpoints
  • HAART
  • Real clinical setting

ASJC Scopus subject areas

  • Virology
  • Immunology

Cite this

Carosi, G., Castelli, F., Suter, F., Maggiolo, F., Orani, A. M., Pan, A., ... De Lalla, F. (2001). Antiviral potency of HAART regimens and clinical success are not strictly coupled in real life conditions: Evidence from the MASTER-1 study. HIV Clinical Trials, 2(5), 399-407.

Antiviral potency of HAART regimens and clinical success are not strictly coupled in real life conditions : Evidence from the MASTER-1 study. / Carosi, G.; Castelli, F.; Suter, F.; Maggiolo, F.; Orani, A. M.; Pan, A.; Andreoni, M.; Vigevani, G. M.; Maserati, R.; Mazzotta, F.; Tinelli, C.; Tomasoni, L.; Patroni, A.; Migliorino, M.; Castaldo, G.; Nigro, M.; Carnevale, G.; Lingua, A.; Visonà, R.; Ciammarughi, R.; Martelli, L. T.; Pastore, G.; Ladisa, N.; Minoli, L.; Scudeller, L.; Cadeo, G. P.; Paraninfo, G.; Vangi, D.; Riccio, G.; Bartolacci, V.; Toti, M.; Nencioni, C.; Chirianni, A.; Montesarchio, V.; Poggio, A.; Mondino, V.; Mazzotta, F.; Di Pietro, M.; Lo Caputo, S.; Ranieri, S.; Ballardini, G.; Pauluzzi, S.; Stagni, G.; Colomba, A.; Legnani, G.; Torre, D.; Pagano, G.; Scalzini, A.; Leoncini, F.; Ghinelli, F.; Moroni, M.; Cadrobbi, P.; Borri, A.; De Lalla, F.

In: HIV Clinical Trials, Vol. 2, No. 5, 2001, p. 399-407.

Research output: Contribution to journalArticle

Carosi, G, Castelli, F, Suter, F, Maggiolo, F, Orani, AM, Pan, A, Andreoni, M, Vigevani, GM, Maserati, R, Mazzotta, F, Tinelli, C, Tomasoni, L, Patroni, A, Migliorino, M, Castaldo, G, Nigro, M, Carnevale, G, Lingua, A, Visonà, R, Ciammarughi, R, Martelli, LT, Pastore, G, Ladisa, N, Minoli, L, Scudeller, L, Cadeo, GP, Paraninfo, G, Vangi, D, Riccio, G, Bartolacci, V, Toti, M, Nencioni, C, Chirianni, A, Montesarchio, V, Poggio, A, Mondino, V, Mazzotta, F, Di Pietro, M, Lo Caputo, S, Ranieri, S, Ballardini, G, Pauluzzi, S, Stagni, G, Colomba, A, Legnani, G, Torre, D, Pagano, G, Scalzini, A, Leoncini, F, Ghinelli, F, Moroni, M, Cadrobbi, P, Borri, A & De Lalla, F 2001, 'Antiviral potency of HAART regimens and clinical success are not strictly coupled in real life conditions: Evidence from the MASTER-1 study', HIV Clinical Trials, vol. 2, no. 5, pp. 399-407.
Carosi, G. ; Castelli, F. ; Suter, F. ; Maggiolo, F. ; Orani, A. M. ; Pan, A. ; Andreoni, M. ; Vigevani, G. M. ; Maserati, R. ; Mazzotta, F. ; Tinelli, C. ; Tomasoni, L. ; Patroni, A. ; Migliorino, M. ; Castaldo, G. ; Nigro, M. ; Carnevale, G. ; Lingua, A. ; Visonà, R. ; Ciammarughi, R. ; Martelli, L. T. ; Pastore, G. ; Ladisa, N. ; Minoli, L. ; Scudeller, L. ; Cadeo, G. P. ; Paraninfo, G. ; Vangi, D. ; Riccio, G. ; Bartolacci, V. ; Toti, M. ; Nencioni, C. ; Chirianni, A. ; Montesarchio, V. ; Poggio, A. ; Mondino, V. ; Mazzotta, F. ; Di Pietro, M. ; Lo Caputo, S. ; Ranieri, S. ; Ballardini, G. ; Pauluzzi, S. ; Stagni, G. ; Colomba, A. ; Legnani, G. ; Torre, D. ; Pagano, G. ; Scalzini, A. ; Leoncini, F. ; Ghinelli, F. ; Moroni, M. ; Cadrobbi, P. ; Borri, A. ; De Lalla, F. / Antiviral potency of HAART regimens and clinical success are not strictly coupled in real life conditions : Evidence from the MASTER-1 study. In: HIV Clinical Trials. 2001 ; Vol. 2, No. 5. pp. 399-407.
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title = "Antiviral potency of HAART regimens and clinical success are not strictly coupled in real life conditions: Evidence from the MASTER-1 study",
abstract = "Purpose: To compare in a real clinical setting the largely unknown midterm clinical effectiveness of two protease inhibitor (PI)-based highly active antiretroviral therapy (HAART) regimens with different potency and tolerability profiles in na{\"i}ve patients. Method: This study was a multicenter, open-label, randomized trial in na{\"i}ve patients with less than 400 CD4+ cell count/μL, regardless of viral load. Treatment arms were hard gel capsule saquinavir (HGC-SQV)-based HAART (Arm A), with an expected more favorable tolerability profile, and indinavir (IDV)-based HAART (Arm B), with more potent virologic activity. While viro-immunological surrogate markers and World Health Organization (WHO) grade III toxicity (secondary endpoints) were regularly monitored, primary endpoints of the study were clinical and defined as any AIDS-defining event, AIDS-related death, WHO grade IV toxicity, drop outs, and protocol violations. Results: 262 consecutive patients were enrolled in the study from March 1, 1997 to December 31, 1997, in 24 different Italian clinical centers (132, Arm A; 130, Arm B). After 24 months of follow-up, patients who were enrolled in Arm B showed a significantly higher rate of virological success (75{\%} had viremia below 500 copies/mL, CI = 12.9{\%}, in the on-treatment analysis) and immunological gain (mean CD4+ cell count increase of 274 CD4+ cells/μL, SD = 234) when compared to patients enrolled in arm A (57{\%}, CI = 15.5{\%} and 223 CD4+ cells/μL, SD = 192; p = .0353 and .026, respectively). Despite the significant difference observed in surrogate markers, the number of total primary endpoints did not differ in the two groups (55 out of 132 in Arm A vs. 58 out of 130 person-years in Arm B;p = .86). Conclusion: Our results suggest that, after 24 months of follow-up in a real clinical setting, a PI-based HAART induces significant clinical benefits in na{\"i}ve patients even in the absence of a complete suppression of viral replication. However, the long-term clinical impact of the possible accumulation of viral mutations in the presence of low-grade viral replication remains to be elucidated.",
keywords = "Clinical endpoints, HAART, Real clinical setting",
author = "G. Carosi and F. Castelli and F. Suter and F. Maggiolo and Orani, {A. M.} and A. Pan and M. Andreoni and Vigevani, {G. M.} and R. Maserati and F. Mazzotta and C. Tinelli and L. Tomasoni and A. Patroni and M. Migliorino and G. Castaldo and M. Nigro and G. Carnevale and A. Lingua and R. Vison{\`a} and R. Ciammarughi and Martelli, {L. T.} and G. Pastore and N. Ladisa and L. Minoli and L. Scudeller and Cadeo, {G. P.} and G. Paraninfo and D. Vangi and G. Riccio and V. Bartolacci and M. Toti and C. Nencioni and A. Chirianni and V. Montesarchio and A. Poggio and V. Mondino and F. Mazzotta and {Di Pietro}, M. and {Lo Caputo}, S. and S. Ranieri and G. Ballardini and S. Pauluzzi and G. Stagni and A. Colomba and G. Legnani and D. Torre and G. Pagano and A. Scalzini and F. Leoncini and F. Ghinelli and M. Moroni and P. Cadrobbi and A. Borri and {De Lalla}, F.",
year = "2001",
language = "English",
volume = "2",
pages = "399--407",
journal = "HIV Clinical Trials",
issn = "1528-4336",
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TY - JOUR

T1 - Antiviral potency of HAART regimens and clinical success are not strictly coupled in real life conditions

T2 - Evidence from the MASTER-1 study

AU - Carosi, G.

AU - Castelli, F.

AU - Suter, F.

AU - Maggiolo, F.

AU - Orani, A. M.

AU - Pan, A.

AU - Andreoni, M.

AU - Vigevani, G. M.

AU - Maserati, R.

AU - Mazzotta, F.

AU - Tinelli, C.

AU - Tomasoni, L.

AU - Patroni, A.

AU - Migliorino, M.

AU - Castaldo, G.

AU - Nigro, M.

AU - Carnevale, G.

AU - Lingua, A.

AU - Visonà, R.

AU - Ciammarughi, R.

AU - Martelli, L. T.

AU - Pastore, G.

AU - Ladisa, N.

AU - Minoli, L.

AU - Scudeller, L.

AU - Cadeo, G. P.

AU - Paraninfo, G.

AU - Vangi, D.

AU - Riccio, G.

AU - Bartolacci, V.

AU - Toti, M.

AU - Nencioni, C.

AU - Chirianni, A.

AU - Montesarchio, V.

AU - Poggio, A.

AU - Mondino, V.

AU - Mazzotta, F.

AU - Di Pietro, M.

AU - Lo Caputo, S.

AU - Ranieri, S.

AU - Ballardini, G.

AU - Pauluzzi, S.

AU - Stagni, G.

AU - Colomba, A.

AU - Legnani, G.

AU - Torre, D.

AU - Pagano, G.

AU - Scalzini, A.

AU - Leoncini, F.

AU - Ghinelli, F.

AU - Moroni, M.

AU - Cadrobbi, P.

AU - Borri, A.

AU - De Lalla, F.

PY - 2001

Y1 - 2001

N2 - Purpose: To compare in a real clinical setting the largely unknown midterm clinical effectiveness of two protease inhibitor (PI)-based highly active antiretroviral therapy (HAART) regimens with different potency and tolerability profiles in naïve patients. Method: This study was a multicenter, open-label, randomized trial in naïve patients with less than 400 CD4+ cell count/μL, regardless of viral load. Treatment arms were hard gel capsule saquinavir (HGC-SQV)-based HAART (Arm A), with an expected more favorable tolerability profile, and indinavir (IDV)-based HAART (Arm B), with more potent virologic activity. While viro-immunological surrogate markers and World Health Organization (WHO) grade III toxicity (secondary endpoints) were regularly monitored, primary endpoints of the study were clinical and defined as any AIDS-defining event, AIDS-related death, WHO grade IV toxicity, drop outs, and protocol violations. Results: 262 consecutive patients were enrolled in the study from March 1, 1997 to December 31, 1997, in 24 different Italian clinical centers (132, Arm A; 130, Arm B). After 24 months of follow-up, patients who were enrolled in Arm B showed a significantly higher rate of virological success (75% had viremia below 500 copies/mL, CI = 12.9%, in the on-treatment analysis) and immunological gain (mean CD4+ cell count increase of 274 CD4+ cells/μL, SD = 234) when compared to patients enrolled in arm A (57%, CI = 15.5% and 223 CD4+ cells/μL, SD = 192; p = .0353 and .026, respectively). Despite the significant difference observed in surrogate markers, the number of total primary endpoints did not differ in the two groups (55 out of 132 in Arm A vs. 58 out of 130 person-years in Arm B;p = .86). Conclusion: Our results suggest that, after 24 months of follow-up in a real clinical setting, a PI-based HAART induces significant clinical benefits in naïve patients even in the absence of a complete suppression of viral replication. However, the long-term clinical impact of the possible accumulation of viral mutations in the presence of low-grade viral replication remains to be elucidated.

AB - Purpose: To compare in a real clinical setting the largely unknown midterm clinical effectiveness of two protease inhibitor (PI)-based highly active antiretroviral therapy (HAART) regimens with different potency and tolerability profiles in naïve patients. Method: This study was a multicenter, open-label, randomized trial in naïve patients with less than 400 CD4+ cell count/μL, regardless of viral load. Treatment arms were hard gel capsule saquinavir (HGC-SQV)-based HAART (Arm A), with an expected more favorable tolerability profile, and indinavir (IDV)-based HAART (Arm B), with more potent virologic activity. While viro-immunological surrogate markers and World Health Organization (WHO) grade III toxicity (secondary endpoints) were regularly monitored, primary endpoints of the study were clinical and defined as any AIDS-defining event, AIDS-related death, WHO grade IV toxicity, drop outs, and protocol violations. Results: 262 consecutive patients were enrolled in the study from March 1, 1997 to December 31, 1997, in 24 different Italian clinical centers (132, Arm A; 130, Arm B). After 24 months of follow-up, patients who were enrolled in Arm B showed a significantly higher rate of virological success (75% had viremia below 500 copies/mL, CI = 12.9%, in the on-treatment analysis) and immunological gain (mean CD4+ cell count increase of 274 CD4+ cells/μL, SD = 234) when compared to patients enrolled in arm A (57%, CI = 15.5% and 223 CD4+ cells/μL, SD = 192; p = .0353 and .026, respectively). Despite the significant difference observed in surrogate markers, the number of total primary endpoints did not differ in the two groups (55 out of 132 in Arm A vs. 58 out of 130 person-years in Arm B;p = .86). Conclusion: Our results suggest that, after 24 months of follow-up in a real clinical setting, a PI-based HAART induces significant clinical benefits in naïve patients even in the absence of a complete suppression of viral replication. However, the long-term clinical impact of the possible accumulation of viral mutations in the presence of low-grade viral replication remains to be elucidated.

KW - Clinical endpoints

KW - HAART

KW - Real clinical setting

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