CompletedNCT01511809Updated Feb 9, 2024Results posted

Efficacy of Atazanavir/Ritonavir Monotherapy as Maintenance in Patients With Viral Suppression

A Phase 3 interventional study of Atazanavir/ritonavir monotherapy in HIV-1 Infection, sponsored by IRCCS San Raffaele. Completed at 1 site in Italy. Open to participants aged 18 Years to 90 Years. Per ClinicalTrials.gov, last updated 2024-02-09.

Sponsored by IRCCS San Raffaele · Phase 3, Interventional, and Treatment

Phase: Phase 3
Study type: Interventional
Enrollment: 117
Allocation: Randomized
Ages: 18 Years to 90 Years
Sex: All

Study summary

The study will assess whether Atazanavir/ritonavir monotherapy provides a non-inferior proportion of virological efficacy with respect to ATV/RTV + 2 NRTIs in patients with stable suppressed viremia and no prior virologic failures.

Read the detailed description

This is a randomised (1:1), multicentre, comparative, parallel-group, prospective, open label, non-inferiority controlled clinical trial.

Enrolled patients, taking an ATV/r based HAART and with stable HIV-RNA \< 50c/ml (24 weeks), will be randomized to:

continue the same regimen ATV/RTV 300mg/100mg OD plus 2 NRTIs (according to the specific dosing schedule) as backbone (HAART arm) with ATV/r
or simplify therapy to ATV/RTV 300mg/100mg OD as monotherapy (Monotherapy arm) with ATV/r The study follow up will be 96 weeks after randomization and primary objective will be evaluated at week 48.

Patients will be followed every 4 weeks for the first 16 weeks, and then every 8 weeks until week 48, then every 12 weeks until week 96 or discontinuation ; at each visit the following evaluations will be performed:

clinical assessment.
routine laboratory tests (hematological tests and hematochemistry) including creatinine, phosphorus, calcium, alkaline phosphatase, gammaGT; urine analysis, lipid profile, level of HIV-RNA and CD4 cell counts.

During follow-up, at randomization, week 48, week 96 or discontinuation, patients will additionally undergo:

Fat redistribution evaluation by DEXA (dual-energy X-ray absorptiometry
Vertebral and femoral bone mineral density evaluation by DEXA.
ECG;
Glicate haemoglobin.
Adherence assessment (questionnaire and/or pills counts).
Neurocognitive evaluation [HIV-associated neurocognitive disorders (HANDs) evaluated by validated neuropsychological tests].

In case of viral rebound (defined as 2 consecutive measurement of HIV-RNA > 50 c/ml) patients will be immediately contacted in order to perform genotypic tests. Furthermore a plasma PK analysis will also be performed. Any patients with virological rebound will be selected for a reintensification therapy with NRTIs and if not suppressed after 12 weeks they will be discontinued.

Conditions studied

HIV-1 Infection

Keywords

HIV-1

In context

Lead sponsor

IRCCS San Raffaele is the lead sponsor of 443 studies on the registry; 234 are open to participants now.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 90 Years
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

HIV infected patients
age > 18 years
On treatment with ATV/r plus 2 NRTIs for at least 48 weeks
Virological suppression (HIV-RNA\<50 c/ml) by at least 24 weeks with ATV/r plus 2 NRTIs
No virologic failure after the initiation of the first antiretroviral therapy. Previous treatment changes due to toxicity or treatment simplifications will be permitted only if occurred with documented virological suppression.
CD4 cells nadir >100 cells/µL
PPI and H2-receptor antagonists as follows: the proton-pump inhibitors should not be used; if H2-receptor antagonists are co-administered, a dose equivalent to famotidine 20 mg BID should not be exceeded.

Exclusion criteria

Exclusion Criteria:

Pregnancy and breast feeding women
AIDS defining events
Evidence of active HBV infection (HBsAg positive)
Previous virological failure
History of resistance to ATV
Use of contraindicated medications

Study design

Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 117 participants (actual)

Study arms

Experimental
Atazanavir/ritonavir monotherapy
Patients will simplify therapy to ATV/RTV 300mg/100mg OD as monotherapy
Drug: Atazanavir/ritonavir monotherapy
No intervention
Atazanavir/ritonavir triple therapy
Patients will continue the same regimen ATV/RTV 300mg/100mg OD plus 2 NRTIs as backbone

Interventions

DrugAtazanavir/ritonavir monotherapy
Monotherapy Simplification Strategy with Atazanavir/ritonavir 300/100 mg once daily for 96 weeks.
Also known as: ATV/r monotherapy

What researchers measure

Primary outcomes

Proportion of Patients With Treatment Failure (TF)
Proportion of patients with treatment failure defined as having one of the following events: confirmed viral rebound (CVR) or treatment discontinuation for any cause. CVR was established when 2 consecutive viral load values (HIV-1 RNA)\>50 copies/mL occurred within 2 weeks during follow-up. In case of CVR, patients treated with atazanavir/ritonavir monotherapy had to re-introduce their previous 2NRTIs (re-intensification) and, if not suppressed (HIV-1 RNA \<50 copies /ml) after 12 weeks, discontinued from the study. Re-intensification was considered as treatment failure in the primary analysis conducted according to the intention-to-treat principle (intention-to-treat analysis with re-intensification equal failure, ITT=Failure) while it was not in the secondary analysis (intention-to-treat analysis with re-intensification equal success, ITT=Success).
Time frame: Up to week 48

Secondary outcomes

Efficacy and Safety
Proportion of pts with confirmed virological and treatment failure at w96. Change in CD4 cell counts. Occurrence of viral resistance to atazanavir in pts with confirmed virologic failure. Proportion of pts with adverse events, with ≥grade 2 adverse events or abnormal laboratory tests, proportion of pts with side effects leading to discontinuation. Body fat redistribution and vertebral and femoral bone mineral density. Adherence changes; changes in HIV-associated neurocognitive disorders. Difference in levels of activated Tcells and pro-inflammatory cytokines between treatment groups.
Time frame: week 96

Results

Posted Nov 24, 2014

Participant flow

Participant flow — Overall Study
Milestone	Atazanavir/Ritonavir Monotherapy	Atazanavir/Ritonavir Triple Therapy
Started	58	59
Completed	51	52
Not completed	7	7

Outcome measures

PrimaryProportion of Patients With Treatment Failure (TF)

Proportion of patients with treatment failure defined as having one of the following events: confirmed viral rebound (CVR) or treatment discontinuation for any cause. CVR was established when 2 consecutive viral load values (HIV-1 RNA)\>50 copies/mL occurred within 2 weeks during follow-up. In case of CVR, patients treated with atazanavir/ritonavir monotherapy had to re-introduce their previous 2NRTIs (re-intensification) and, if not suppressed (HIV-1 RNA \<50 copies /ml) after 12 weeks, discontinued from the study. Re-intensification was considered as treatment failure in the primary analysis conducted according to the intention-to-treat principle (intention-to-treat analysis with re-intensification equal failure, ITT=Failure) while it was not in the secondary analysis (intention-to-treat analysis with re-intensification equal success, ITT=Success).

Time frame:: Up to week 48
Reported as:: Number · percentage of patients

Proportion of Patients With Treatment Failure (TF)
percentage of patients	Atazanavir/Ritonavir Monotherapy	Atazanavir/Ritonavir Triple Therapy
ITT=Failure analysis	27.5	15.4
ITT=Success analysis	7.9	15.4

Statistical analysis

Atazanavir/Ritonavir Monotherapy vs Atazanavir/Ritonavir Triple Therapy · Difference between tf proportions: 15

SecondaryEfficacy and Safety

Proportion of pts with confirmed virological and treatment failure at w96. Change in CD4 cell counts. Occurrence of viral resistance to atazanavir in pts with confirmed virologic failure. Proportion of pts with adverse events, with ≥grade 2 adverse events or abnormal laboratory tests, proportion of pts with side effects leading to discontinuation. Body fat redistribution and vertebral and femoral bone mineral density. Adherence changes; changes in HIV-associated neurocognitive disorders. Difference in levels of activated Tcells and pro-inflammatory cytokines between treatment groups.

Time frame:: week 96

Results for this outcome have not been posted.

Adverse events

Collected over Up to week 48. Non-serious events are listed at a 2% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Atazanavir/Ritonavir Monotherapy	—	2/51 (3.9%)	1/51 (2%)
Atazanavir/Ritonavir Triple Therapy	—	0/52 (0%)	7/52 (13.5%)

Most frequent serious events

Most frequent serious events
Event	Atazanavir/Ritonavir Monotherapy	Atazanavir/Ritonavir Triple Therapy
acute coronary stenosisCardiac disorders	1/51	0/52
left basal pneumoniaRespiratory, thoracic and mediastinal disorders	1/51	0/52

Most frequent other events

Most frequent other events
Event	Atazanavir/Ritonavir Monotherapy	Atazanavir/Ritonavir Triple Therapy
nephrolitiasisRenal and urinary disorders	0/51	2/52
gross haematuria with proteinuriaRenal and urinary disorders	0/51	2/52
acute hepatitisHepatobiliary disorders	1/51	1/52
cholecystitis due to cholelithiasisHepatobiliary disorders	0/51	1/52
hyperuricemiaRenal and urinary disorders	0/51	1/52

Baseline characteristics

Age, Continuous
Age, Continuous(years)	Atazanavir/Ritonavir Monotherapy	Atazanavir/Ritonavir Triple Therapy	Total
Median	41.4 (35.4 to 47.7)	41.7 (36.6 to 49.8)	41.5 (35.6 to 48)

Sex: Female, Male
Sex: Female, Male(Participants)	Atazanavir/Ritonavir Monotherapy	Atazanavir/Ritonavir Triple Therapy	Total
Female	9	7	16
Male	42	45	87

Region of Enrollment
Region of Enrollment(participants)	Atazanavir/Ritonavir Monotherapy	Atazanavir/Ritonavir Triple Therapy	Total
Italy	51	52	103

nadir CD4+
nadir CD4+(cells/mm3)	Atazanavir/Ritonavir Monotherapy	Atazanavir/Ritonavir Triple Therapy	Total
Median	274 (221 to 355)	278 (183 to 364)	276 (211 to 361)

Years of antiretroviral treatment
Years of antiretroviral treatment(years)	Atazanavir/Ritonavir Monotherapy	Atazanavir/Ritonavir Triple Therapy	Total
Median	25 (16 to 47)	25 (18 to 54)	25 (17 to 53)

HIV-1 RNA <50 copies/ml
HIV-1 RNA <50 copies/ml(months)	Atazanavir/Ritonavir Monotherapy	Atazanavir/Ritonavir Triple Therapy	Total
Median	20 (10 to 49)	18 (12 to 49)	19 (11 to 49)

HIV-RNA at ARV start
HIV-RNA at ARV start(copies/mL)	Atazanavir/Ritonavir Monotherapy	Atazanavir/Ritonavir Triple Therapy	Total
Median	79399 (31046 to 183613)	42630 (9696 to 123700)	59062 (10834 to 165850)

CD4+
CD4+(cells/mm3)	Atazanavir/Ritonavir Monotherapy	Atazanavir/Ritonavir Triple Therapy	Total
Median	599 (457 to 774)	570 (417 to 735)	575 (432 to 744)

1 further baseline measures are reported on the registry.

Study locations

1 site

Infectious Diseases Department Fondazione Centro San Raffaele
Milan, Lombardia 20127, Italy

References and documents

Publications

Delfraissy JF, Flandre P, Delaugerre C, Ghosn J, Horban A, Girard PM, Norton M, Rouzioux C, Taburet AM, Cohen-Codar I, Van PN, Chauvin JP. Lopinavir/ritonavir monotherapy or plus zidovudine and lamivudine in antiretroviral-naive HIV-infected patients. AIDS. 2008 Jan 30;22(3):385-93. doi: 10.1097/QAD.0b013e3282f3f16d. PubMed 18195565 ↗
Cameron DW, da Silva BA, Arribas JR, Myers RA, Bellos NC, Gilmore N, King MS, Bernstein BM, Brun SC, Hanna GJ. A 96-week comparison of lopinavir-ritonavir combination therapy followed by lopinavir-ritonavir monotherapy versus efavirenz combination therapy. J Infect Dis. 2008 Jul 15;198(2):234-40. doi: 10.1086/589622. PubMed 18540803 ↗
Pulido F, Arribas JR, Delgado R, Cabrero E, Gonzalez-Garcia J, Perez-Elias MJ, Arranz A, Portilla J, Pasquau J, Iribarren JA, Rubio R, Norton M; OK04 Study Group. Lopinavir-ritonavir monotherapy versus lopinavir-ritonavir and two nucleosides for maintenance therapy of HIV. AIDS. 2008 Jan 11;22(2):F1-9. doi: 10.1097/QAD.0b013e3282f4243b. PubMed 18097218 ↗
Arribas JR, Delgado R, Arranz A, Munoz R, Portilla J, Pasquau J, Perez-Elias MJ, Iribarren JA, Rubio R, Ocampo A, Sanchez-Conde M, Knobel H, Arazo P, Sanz J, Lopez-Aldeguer J, Montes ML, Pulido F; OK04 Study Group. Lopinavir-ritonavir monotherapy versus lopinavir-ritonavir and 2 nucleosides for maintenance therapy of HIV: 96-week analysis. J Acquir Immune Defic Syndr. 2009 Jun 1;51(2):147-52. doi: 10.1097/QAI.0b013e3181a56de5. PubMed 19349870 ↗
Arribas JR, Horban A, Gerstoft J, Fatkenheuer G, Nelson M, Clumeck N, Pulido F, Hill A, van Delft Y, Stark T, Moecklinghoff C. The MONET trial: darunavir/ritonavir with or without nucleoside analogues, for patients with HIV RNA below 50 copies/ml. AIDS. 2010 Jan 16;24(2):223-30. doi: 10.1097/QAD.0b013e3283348944. PubMed 20010070 ↗
Katlama C, Valantin MA, Algarte-Genin M, Duvivier C, Lambert-Niclot S, Girard PM, Molina JM, Hoen B, Pakianather S, Peytavin G, Marcelin AG, Flandre P. Efficacy of darunavir/ritonavir maintenance monotherapy in patients with HIV-1 viral suppression: a randomized open-label, noninferiority trial, MONOI-ANRS 136. AIDS. 2010 Sep 24;24(15):2365-74. doi: 10.1097/QAD.0b013e32833dec20. PubMed 20802297 ↗
Swindells S, DiRienzo AG, Wilkin T, Fletcher CV, Margolis DM, Thal GD, Godfrey C, Bastow B, Ray MG, Wang H, Coombs RW, McKinnon J, Mellors JW; AIDS Clinical Trials Group 5201 Study Team. Regimen simplification to atazanavir-ritonavir alone as maintenance antiretroviral therapy after sustained virologic suppression. JAMA. 2006 Aug 16;296(7):806-14. doi: 10.1001/jama.296.7.806. PubMed 16905786 ↗
Karlstrom O, Josephson F, Sonnerborg A. Early virologic rebound in a pilot trial of ritonavir-boosted atazanavir as maintenance monotherapy. J Acquir Immune Defic Syndr. 2007 Apr 1;44(4):417-22. doi: 10.1097/QAI.0b013e31802e2940. PubMed 17159658 ↗
Wilkin TJ, McKinnon JE, DiRienzo AG, Mollan K, Fletcher CV, Margolis DM, Bastow B, Thal G, Woodward W, Godfrey C, Wiegand A, Maldarelli F, Palmer S, Coffin JM, Mellors JW, Swindells S. Regimen simplification to atazanavir-ritonavir alone as maintenance antiretroviral therapy: final 48-week clinical and virologic outcomes. J Infect Dis. 2009 Mar 15;199(6):866-71. doi: 10.1086/597119. PubMed 19191590 ↗
Vernazza P, Daneel S, Schiffer V, Decosterd L, Fierz W, Klimkait T, Hoffmann M, Hirschel B. The role of compartment penetration in PI-monotherapy: the Atazanavir-Ritonavir Monomaintenance (ATARITMO) Trial. AIDS. 2007 Jun 19;21(10):1309-15. doi: 10.1097/QAD.0b013e32814e6b1c. PubMed 17545707 ↗

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Feb 9, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT01511809
Lead sponsor: IRCCS San Raffaele
Collaborators: Bristol-Myers Squibb
Responsible party: Castagna Antonella (Co- Investigator, Ospedale San Raffaele) — Principal investigator
First posted: Jan 19, 2012
Start date: Sep 2010
Primary completion: Jul 2013
Completion: May 2015
Results posted: Nov 24, 2014
Last update: Feb 9, 2024

Study contacts

Adriano Lazzarin, Professor

principal investigator · Ospedale San Raffaele

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Feb 2024. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies from this sponsor

IRCCS San Raffaele

Start the discussion