TO EVALUATE EARLY ANTIVIRAL RESPONSE AND SAFETY OF A DUAL BOOSTED PROTEASE INHIBITORS REGIMEN INCLUDING LOPINAVIR/r (LPV) PLUS AMPRENAVIR (AMP) OR FORTOVASE (FTV) IN HEAVILY PRETREATED HIV INFECTED PATIENTS.Zala, C.; Patterson, P.; Coll, P.; Bouzas, M. B.; Kaufman, S.; Gun, A.; Pérez, H.; Cahn, P. Fundación Huésped, Buenos Aires, Argentina.

RESULTS: From July 00 to Jan 01, forty two (42) consecutive patients (8 women) received a prescription for LPV+AMP (19) and LPV+FTV (23). Twenty seven (64%) had prior AIDS defining illness. Median plasma HIV RNA at BSL was 358.125 cps/mL (5,55 log10) with no significant differences between the AMP and the FTV pts. Median BSL CD4 T cell count was 93/mm3 (2-383). Prior number (mean) of prescribed PIs was 3 per patient. By June 01, one FTV patient died due to lymphoma. Seven patients (3 AMP and 4 FTV) discontinued therapy due to GI intolerance and/or poor adherence. Twenty five (25) patients have completed 48 weeks follow up. Median plasma HIV RNA decline from baseline was 3,0 log 10. Twenty (20) out of 25 patients (80%) had HIV RNA reductions from BSL greater than 1 log10 (7/10 (70%) AMP, 13/15 (86,7%) FTV). Proportion of patients with pVL <500 cps/mL (ITT, nc=failure) at 48 weeks follow up was 31% (4/19 (21%) AMP, 9/23 (39,1%) FTV). Four patients experienced Grade III/IV increase in cholesterol and/or triglycerides levels. No treatment limiting toxicity was reported.CONCLUSIONES: Within this cohort, a double boosted PI regimen including Lopinavir/r in addiction to either Amprenavir or Fortovase allowed to rescue one third of patients experiencing multiple treatment failure with no significant toxicity.

OBJECTIVES: To evaluate efficacy and safety of a dual boosted PI regimen including Lopinavir/r (LPV) plus Amprenavir (AMP) or Fortovase (FTV) in heavily pretreated HIV infected patients.

METHODS: Prospective, open label, observational cohort study of patients referred to a single HIV clinic for prescription of a salvage regimen. Eligible patients for analysis are those who failed 3 drug classes and consented to receive LPV (3 capsules BID or 4 BID if a concomitant NNRTI was prescribed) plus either AMP or FTV dosaged at 750 and 1000 mg BID respectively. Second PI (AMP or FTV) was prescribed according to patients and physician preferences. Backbone nucleosides and/or NNRTIs were prescribed according to patient drug history. Plasma HIV RNA, CD4 cell count and safety lab were measured at regular intervals. Tolerability and compliance were evaluated on monthly basis.

PATIENTS CHARACTERISTIC

S

AMP FTV TOTAL

n 19 23 42

Age (median yrs) 38,7 36,4 37,4

Male 13/19 (68%) 21/23 (91%) 34/42 (81%)

Prior AIDS 14/19 (74%) 13/23 (57%) 27/42 (64%)

NADIR CD4 cell count (median)

27/mm3 40/mm3 39,5/mm3

BSL CD4 Cell count

(median)

90/mm3 96/mm3 93/mm3

BSL pVL (median) 307.000 (5,49)

402.000 (5,60)

358.125 (5,55)

Corresponding author: Carlos Zala, MD. czala@huesped.org.ar

AMP FTV TOTAL

Prior exposure to PI’s (mean)

3,3(1 – 5)

3,0 (1 - 4)

3,2(1 - 5)

Prior exposure to NRTI’s (mean)

5,0(4 – 6)

4,5(3 – 6)

4,7(4 – 6)

Prior exposure to NNRTI’s (mean)

1,3(0 – 3)

1,0(0 – 2)

1,1(0 – 2)

Prior exposure to hydroxiurea

(mean)

9/19 (47%) 6/23 (26%) 15/42 (36%)

Pts. off therapy at BSL

9/19 (47%) 15/23 (65%) 24/42 (57%)

THERAPY DISCONTINUATIONS

AMPn=19

FTVn=23

TOTALn=42

DEATH* ADVERSE EVENT GI INTOLERANCE

POOR COMPLIANCE VIROLOGICAL FAILURE

10305

21221

31526

THERAPY D/C 9 8 17

Backbone NRTI’s AMP FTV TOTAL

ABACAVIRSTAVUDINELAMIVUDINEDIDANOSINEZIDOVUDINE

108240

147200

2415440

Backbone NNRTI’s

EFAVIRENZNEVIRAPINE

50

71

121

PATIENTS DISPOSITION

AMP FTV TOTAL

SCR 19 23 42

BSL 18 22 40

W 4-8 16 20 36

W 12 15 17 32

W 24 13 16 29

W 36 12 16 28

W 48* 10 15 25

1300

0

5

10

15

20

25

30

35

40

TOTAL FTV AMP TOTAL FTV AMP TOTAL FTV AMP

GRADE I / I I NORMALFASTING TRIGLYCERIDES

Normal Range: 0,7 - 1,7 mmol/L

0

5

10

15

20

25

30

35

40

TOTAL FTV AMP TOTAL FTV AMP TOTAL FTV AMP

GRADE I / I I NORMALFASTING CHOLESTEROL Normal Range: 3,9 – 5,2 mmol/L

0

2

4

6

8

10

12

14

16

18

20

<0,5 log >3 log >2 log >1 log >0,5 log

AMP FTV

HIV RNA CHANGE AT WEEK 48 (ITT)

28,6

21

34,8

40,5

36,8

43,5

38,1

31,6

43,5

33,3

21

43,5

31

21

39,1

0

5

10

15

20

25

30

35

40

45

WEEK 4 WEEK 12 WEEK 24 WEEK 36 WEEK 48

TOTAL AMP FTV

PROPORTION OF PATIENTS WITH HIV RNA <500 cps/mL (ITT)

*2 deaths before BSL

*17 patients d/c therapy

n 12 - 4 - 8 17 - 7 - 10 16 - 6 - 10 14 – 4 - 10 13 – 4 - 9 n 5 13 16 19 20

n 40 - 18 – 22BSL

35 - 16 – 19WEEK 4-8

32 - 15 – 17WEEK 12

29 – 13 – 16WEEK 24

28 – 12 – 16WEEK 36

25 – 10 – 15WEEK 48

n 40 - 18 – 22BSL

35 - 16 – 19WEEK 4-8

32 - 15 – 17WEEK 12

29 – 13 – 16WEEK 24

28 – 12 – 16

WEEK 36

25 – 10 – 15WEEK 48