PRotease-Inhibitors MOnotherapy

Strategies as maintenance therapy in

persons with fully suppressed HIV

replication: results from an open-label

randomized comparative trial.

PRIMO Trial

A. Ammassari

SECONDARY OBJECTIVES

1. To compare safety and tolerability of a treatment simplification regimen by a LPV/r or DRV/RTV monotherapy versus a triple PI-based combination therapy.

2. To compare the immune response in terms of changes in the CD4 cell count from baseline over 48 weeks

3. To compare incidence of viral rebound in different treatment groups.

4. To compare the frequency of development of at least one new mutations in RT and PR gene

5. To compare changes in HIV-DNA from baseline to 24, 48, and 96 weeks

6. To compare changes in laboratory parameters at all time points from baseline to 48 weeks in different treatment Groups

7. To evaluate and compare the subject-reported adherence and quality of life (QoL) at baseline and the evolution of adherence and QoL over 48 weeks in treatment groups

8. To compare the antiretroviral drug treatment cost over 48 weeks in all treatment groups

PRIMARY OBJECTIVES

To compare the efficacy of different maintenance strategies based on PIr monotherapy (LPV/r or DRV/RTV) in HIV-1 infected persons with fully suppressive PI/r-based therapy.

•Taking 2 NRTI + PI/r at screening

•Unchanged HAART for at least 6 months

•HIV RNA <50 copies/mL for at least 12 months

•CD4 nadir >100 cell/mmc, and CD4 >200 cell/mmc at screenng

•No history of virological failure to PI/r

4, 8, 12, 24, 36, 48 weeks 48 wks

Primary Endpoint: HIV RNA< 50 at week 48 (TLOVR). Per Protocol, Switch = Failure• 2 consecutive HIV RNA > 50 copies/mL• Stopping LPV/r (Group 2) or DRV/r (Group 3)• Starting NRTIs in the monotherapy arm• Stopping NRTIs in the triple therapy arm (switches in NRTIs are permitted in arm A).

Follow-upphase 48 weeks

1:1:1 randomization375 subjects

SOC (2 NRTI+PI/r) cont.

LPV/r 800/200 mg QD Follow-upphase 48 weeks

SC 30 days BL

DRV/r 800/100 mg QD Follow-upphase 48 weeks

PRIMO Trial

Study PopulationINCLUSION CRITERIA

• At least 18 years

• Receiving unchanged HAART regimen including two NRTIs and PI/boosted for at least 24 weeks

• Plasma HIV-RNA <40 copies/mL for at least 48 weeks prior the screening (two results must be documented)

• Nadir CD4 >100 cell/mmc, and CD4>200 cell/mmc at screening

• No previous history of suspected or confirmed virological failure on PI

• Signed and dated written informed consent

SPECIFIC EXCLUSION CRITERIA

•History of any primary PI mutations as defined by the IASUSA guidelines 2008

•Positive HBsAg or HCV infection for which specific treatment is ongoing or planned

•Diagnosis of acute viral hepatitis at screening

•Previous history of intolerance to LPV/r or DRV/RTV leading to treatment disc’

•Acute opportunistic infection requiring treatment (exclusion period: 30 days)

•Mycobacteriosis under treatment

•Malignancy requiring chemotherapy or radiotherapy

Sub-studies

• Pharmacoeconomc sub-study• Pharmacokinetic sub-study• HIV-DNA sub-study• HIV resistance sub-study• Residual HIV viremia substudy• Metabolic sub-study (with DEXA)• Adherence & QoL sub-study (with MEMS)• Neurocognitive sub-study• Immunological/immunoactivation/inflammatory response

Study Population

• N°centri clinici partecipanti: 9• N°centri clinici con approvazione del Comitato Etico: 7

• N° pazienti arruolati: 106• N° pazienti randomizzati: 94

LPV/r DRV/r LPV/r DRV/r LPV/r DRV/r

TRUVADA COMBIVIR KIVEXA

Costo /mese

Costo /anno Costo /mese

Costo /anno Costo /mese

Costo /anno

438 314 398

KALETRA 376 815 -5.229 -3.523 690 -3.773 -2.030 774 -4.778 -3.035

PREZISTA400521 960 -7.009 -5.266 836 -5.516 -3.773 919 -6.521 -4.778

PREZISTA600577 1.016 -7.683 -5.939 892 -6.189 -4.446 975 -7.194 -5.451

REYATAZ300/r375 814 -5.253 -3.509 689 -3.759 -4.406 773 -4.764 -3.021

TELZIR/r 366 804 -5.142 -3.399 680 -3.649 -3.760 764 -4.654 -2.910

Risparmio paziente-anno (€) in base al regime di provenienza

RISPARMIO PAZIENTE-ANNO

LPV/RTV (n=125) DRV/RTV (n=125)

KALETRA.TRUVADA 39% - € 258050 - € 172627KALTERA.COMBIVIR 19% - € 90552 - € 48720REYATAZ300/r.TRUVADA 12% - € 78789 - € 52635TELZIR/r.TRUVADA 12% - € 77132 - € 50985PREZISTA400/r.TRUVADA 10% - € 91123 - € 62114

Totale per braccio - € 595646 - € 387086

TOTALE RISPARMIO-ANNO - € 982732

Risparmio economico per braccio di trattamento e totale nell’ambito dello studio PRIMO calcolato in base alla distribuzione dei pazienti in relazione al regime di provenienza e ai 12 mesi di follow-up