Vincenzo Spagnuolo1, Laura Galli1, Alba Bigoloni1, Silvia Nozza1, Antonella d'Arminio Monforte2, Andrea Antinori3, Antonio Di Biagio4, Stefano Rusconi5, Giovanni Guaraldi6, Simona Di Giambenedetto7, Adriano Lazzarin1, Antonella Castagna1. 1. Department of Infectious Diseases, IRCCS San Raffaele Hospital, Milan, Italy. 2. Clinic of Infectious and Tropical Diseases, S Paolo Hospital, University of Milan, Milan, Italy. 3. Clinical Department, National Institute for Infectious Diseases IRCCS Lazzaro Spallanzani, Rome, Italy. 4. Division of Infectious Diseases, Azienda Ospedaliera San Martino, Genoa, Italy. 5. Division of Infectious Diseases, Ospedale Luigi Sacco, University of Milan, Milan, Italy. 6. Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy. 7. Institute of Clinical Infectious Diseases, Catholic University of the Sacred Heart, Rome, Italy.
Abstract
INTRODUCTION: The 48-week interim analysis of the MODAT study showed that confirmed virologic failure (CVF) was more frequent in patients simplifying to ATV/r monotherapy compared to maintaining ATV/r-based triple therapy. The DSMB recommended stopping study enrollment but continuing follow-up of enrolled patients. We present the 96-week efficacy analysis. MATERIAL AND METHODS: Multicentre, randomized, open-label, non-inferiority trial (non-inferiority margin -10%). Treatment failure (TF) was defined as CVF (two consecutive HIV-RNA >50 cp/mL) or discontinuation for any cause. In the monotherapy arm, patients with CVF re-introduced their previous NRTIs and remained in the study if HIV-RNA <50 copies/mL within 12 weeks of re-intensification. RESULTS:101 patients evaluated (Figure 1): 85% males, 21% HCV-positive, median (IQR) age of 42 (36-48) years, baseline CD4+ 576 (447-743) cells/µL. In the 96-week analysis (ITT; TF=failure), efficacy was 64% (32/50) in the monotherapy arm and 63% (32/51) in the triple-therapy arm (difference +1.3%, 95% CI -17.5-20.1). Fourteen patients in monotherapy and two in triple-therapy arm had CVF; median HIV-RNA was 136 (72-376) copies/mL. In monotherapy arm, no PI or NRTI associated resistance mutations were observed at CVF. All patients who re-intensified re-suppressed. In monotherapy arm, TF was more frequent in HCV-co-infected patients (64% vs 28%; p=0.041). In the secondary analysis (ITT; re-intensification=success), 82% (41/50) in monotherapy arm and 63% (32/51) in triple-therapy arm were on study at week 96 (difference +19.3%, 95% CI 2.2-36.3). SAEs occurred in four (8%) patients in the monotherapy arm (one left basal pneumonia, one acute coronary stenosis, one traumatic lesion, one nephrolithiasis) and two (4%) in the triple therapy arm (one sepsis, one renal failure). Drug-related adverse events (AEs) leading to discontinuation were three (6%) in the monotherapy arm (two AEs occurred in patients after successful re-intensification) and 12 (23.5%) in the triple-therapy (p=0.023). CONCLUSIONS: Despite the small sample size, the primary 96-week analysis showed that simplification to ATV/r monotherapy showed inferior efficacy to maintaining ATV/r triple-therapy but appeared to be superior when re-intensification was considered success.
RCT Entities:
INTRODUCTION: The 48-week interim analysis of the MODAT study showed that confirmed virologic failure (CVF) was more frequent in patients simplifying to ATV/r monotherapy compared to maintaining ATV/r-based triple therapy. The DSMB recommended stopping study enrollment but continuing follow-up of enrolled patients. We present the 96-week efficacy analysis. MATERIAL AND METHODS: Multicentre, randomized, open-label, non-inferiority trial (non-inferiority margin -10%). Treatment failure (TF) was defined as CVF (two consecutive HIV-RNA >50 cp/mL) or discontinuation for any cause. In the monotherapy arm, patients with CVF re-introduced their previous NRTIs and remained in the study if HIV-RNA <50 copies/mL within 12 weeks of re-intensification. RESULTS: 101 patients evaluated (Figure 1): 85% males, 21% HCV-positive, median (IQR) age of 42 (36-48) years, baseline CD4+ 576 (447-743) cells/µL. In the 96-week analysis (ITT; TF=failure), efficacy was 64% (32/50) in the monotherapy arm and 63% (32/51) in the triple-therapy arm (difference +1.3%, 95% CI -17.5-20.1). Fourteen patients in monotherapy and two in triple-therapy arm had CVF; median HIV-RNA was 136 (72-376) copies/mL. In monotherapy arm, no PI or NRTI associated resistance mutations were observed at CVF. All patients who re-intensified re-suppressed. In monotherapy arm, TF was more frequent in HCV-co-infectedpatients (64% vs 28%; p=0.041). In the secondary analysis (ITT; re-intensification=success), 82% (41/50) in monotherapy arm and 63% (32/51) in triple-therapy arm were on study at week 96 (difference +19.3%, 95% CI 2.2-36.3). SAEs occurred in four (8%) patients in the monotherapy arm (one left basal pneumonia, one acute coronary stenosis, one traumatic lesion, one nephrolithiasis) and two (4%) in the triple therapy arm (one sepsis, one renal failure). Drug-related adverse events (AEs) leading to discontinuation were three (6%) in the monotherapy arm (two AEs occurred in patients after successful re-intensification) and 12 (23.5%) in the triple-therapy (p=0.023). CONCLUSIONS: Despite the small sample size, the primary 96-week analysis showed that simplification to ATV/r monotherapy showed inferior efficacy to maintaining ATV/r triple-therapy but appeared to be superior when re-intensification was considered success.
Authors: Sang Ah Lee; Shin Woo Kim; Hyun Ha Chang; Hyejin Jung; Yoonjung Kim; Soyoon Hwang; Sujeong Kim; Han Ki Park; Jong Myung Lee Journal: Infect Chemother Date: 2018-09