Results of the STACCATO trial

1The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), Bangkok, Thailand, 2Geneva University Hospital, Geneva, Switzerland, 3University Hospital, Bern,

Switzerland, 4Bamrasnaradura Institute, Bangkok, Thailand, 5Khon Kaen University, Khon Kaen, Thailand, 6Mahidol University, Bangkok, Thailand, 7 NCHECR, Sydney, Australia

CD4-guided scheduled treatments interruptions (STIs) compared to

continuous therapy (CT) :

Jintanat Ananworanich1, Angele Gayet-Ageron2, Michelle Le Braz2, Hans-Jakob Furrer3, Wisit Prasithsirikul4,

Ploenchan Chetchotisakd5, Sasisopin Kiertiburanakul6, Praphan Phanuphak1, David A. Cooper7, Kiat Ruxrungtham1, Bernard Hirschel2, and The Staccato Study Group

Staccato Study DesignHAART-treated Patients with CD4 > 350 and VL < 50

(n = 548)

CD4-guided arm (STI)( n = 299)

Continuous treatment arm (CT)(n = 154)

Week on Week offPrematurely Terminated (n = 44)

284 patients analyzed 146 patients analyzed

Stop at CD4 > 350Start at CD4 < 350

Continue HAART

Last 12 – 24 weeks, all patients treated with continuous HAARTin order to compare VL response

At a median FU of 21.9 months: CD4, ARV savings, AE compared

Baseline CharacteristicsCD4-guidedN = 284

Continuous N = 146

Median age in years (range) 35.2 (17-70) 35.9 (21-70)

Gender (% male) 138 (48.6) 60 (41.1)

Men who have sex with menHeterosexual transmissionOthers

46 (16.2)228 (80.3)9 (3.5)

20 (13.7)117 (80.1)8 (6.2)

CDC ACDC BCDC C

171 (60.2)90 (31.7)23 (8.1)

88 (60.3)42 (28.8)16 (10.9)

Median CD4 cells/L (IQR) 470 (398-619) 506 (397-600)

Median pre-ARV CD4 cells/L (IQR)

267 (205-339) 253 (201-334)

Median pre-ARV HIV RNA (log10 copies/mL) (IQR)

4.72 (4.28-5.25) 4.76 (4.31-5.17)

Median duration of prior ARV treatment in months (IQR)

13.7 (6.7-34.1) 15.6 (7.0 – 34.3)

Population and HAART Regimens

Regimen Patient days Percent of total

Ritonavir-boosted saquinavir

87297 80.0

Other protease inhibitor-based regimens

4547 4.2

Non-nucleoside reverse transcriptase inhibitors

15284 14.0

3 nucleoside reverse transcriptase inhibitors

1945 1.8

80% from Thailand18.5% from Switzerland1.5% from Australia

AIDS-defining Illnesses and Death

No patient had AIDS-defining illness

There were 2 deaths

– One in CT arm from stroke

– One in STI arm from colon cancer

Proportion of Patients with CD4 > 350 Proportion of Patients with CD4 > 350

60.5

96.285.9

96.9

0

20

40

60

80

100

End ofrandomization

After HAARTre-treatment

STI CT

% with CD4 > 350

STI CTMedian CD4 374 601IQR 312 – 452 472 - 696

P < 0.001

Median CD4 (IQR) During the Randomization Period

P < 0.002

Proportion of Patients with Viral Load < 50 copies/ml

after 12-24 Weeks of HAART Re-treatment

91 92

50

60

70

80

90

100

STI CT

STI

CT

% VL < 50 copies/ml

P = 0.90

Virological Failure in 9 STI and 6 CT patientsResistance mutations not different between arms (~ 2%) Poster 622B

Adverse Events

3.5

01.7

0.61.9

4.6

15.8

23.8

0

5

10

15

20

25

OC VC Neuropathy Diarrhea

STI

CT

% with AE

P = 0.04P = 0.03

P = 0.04

Only seen in STI armsAcute Retroviral Syndrome in 5.7% (Confirmed high VL in 2.5%)

Thrombocytopenia in 2.5%

4.65

1.8 1.9

00.5

1

1.52

2.53

3.54

4.55

Cholesterol TriglycerideSTI

CT

7.9

13.4

0

2

4

6

8

10

12

14

Lipodystrophy

mmol/L

% with LD

P < 0.05

P < 0.05

Lipids

Self-reported lipodystrophy

At End of Randomization

Actual Time on ARV

37.5

99

0

20

40

60

80

100

ARV Used

STI

CT

% Time on ARV

61.5% ARV Savings

Summary Compared to the CT arm, STI arm had

– No AIDS-defining illnesses– More oral/vaginal candidiasis, thrombocytopenia and

acute retroviral syndrome– Lower median CD4 count– Similar VL response to HAART retreatment– Low and similar rates of resistance– Less ARV-related diarrhea and neuropathy– Lower lipids and self-reported lipodystrophy– 62% ARV savings

Staccato Trivacan SMART

N of pts 430 326 5472

PY FU (in STI arm) 490 ? 3062

CD4 at Stop

CD4 at Start

350

350

350

250

350

250

Median age (years) 35 34 46

AIDS, death/100PY

STI

CT

0.2

0.4

17.6

6.7

3.1

1.4

Oral and vaginal candidiasis

STI

CT2.28

0.34

6.4

2.3

?

?

Time on ARV before study (mo)

15 7 72

Conclusion The incidence rates of SMART would have produced approximately 17

AIDS-defining opportunistic events or deaths in Staccato's STI group, whereas no AIDS-defining event and only one death was observed

Staccato had a higher CD4 restart criterion than Trivacan and SMART (350 vs 250)

The time on ARV before the trial in SMART was much longer than in Staccato (72 vs 15 months)

The results of the different STI studies need to be compared carefully

The Staccato Study Group

Bernard Hirschel, Kiat Ruxrungtham, Wisit Prasithsirikul, Ploenchan Chetchotisakd, Sasisopin Kiertiburanakul, Warangkana Munsakul, Phitsanu Raksakulkarn, Somboon Tansuphasawadikul, Praphan Phanuphak, David A. Cooper, Jintanat Ananworanich, Sasiwimol Ubolyam , Apicha Mahanontharit, Jongkol Sankote, Sunee Sirivichayakul, Saijai Wicharuk, Siriporn Nonenoy, Natnipa Wannachai, Thidarat Jupimai, Sukontha Saenawat , Sineenart Chautrakarn, Theshinee Chuenyam, Thantip Nuchapong, Suchittra Putthawong , Sirirat Liganonsakul, Wattana Sanchiem, Parichat Seawsirikul , Wiphawee Kiatatchasai , Vantanit Pairoj, Nawaporn Seekaow Wipawan Karakate , Wirat Klinbuayam , Yaowaluk Penglimoon , Siraporn Artharn, Sopha Khongsawad, Pongpan Boonchoo, Malee Suannum, Angele Gayet-Ageron, Michelle Lebraz, Matthias Cavassini, Claudia Satchell, Sabine Yerly, Andrew Hill, Véronique Schiffer, Laurent Kaiser, Hansjakob Furrer, Reto Nuesch, Daniel Genné, Urs Karrer, Matthias Cavassini, Pietro Vernazza, Enos Bernasconi, Lorenzo Magenta, Dominic Leduc

Acknowledgement

The Swiss Cohort Study funded this study

We are grateful to Roche for providing unrestricted research funds for this study and for providing Invirase® during and after the study

We thank Gilead for providing Viread® and Emtriva® during the study, and Abbott for providing Norvir® during the study