switch to tdf/ftc/rpv spirit study. spirit study: switch pi/r + 2 nrti to tdf/ftc/rpv tdf/ftc/rpv...

Switch to TDF/FTC/RPV

SPIRIT Study

SPIRIT study: Switch PI/r + 2 NRTI to TDF/FTC/RPV

TDF/FTC/RPV STR

24 weeks 48 weeks Primary Endpoint Secondary Endpoint

N = 317

N = 159PI/r + 2 NRTIs

TDF/FTC/RPV STR

TDF/FTC/RPV STR

Design Randomisation2 : 1

Open-label

24 weeks Primary

Endpoint

48 weeksSecondary Endpoint

Objective– Primary Endpoint : Non-inferiority in the proportion of patients with HIV-1 RNA < 50 c/mL

at W24 (FDA snapshot analysis) ; upper limit of the 95% CI for the difference = 12%– Secondary Endpoints: Proportion of HIV1 RNA < 50 copies/mL at W48 ; Change in

fasting lipid and CD4 cell count at W24 and W48 ; Safety and tolerability

SPIRIT Palella F, AIDS 2014;28:335-44

476 HIV+ adultsStable PI + RTV + 2 NRTI ≥ 6

months with HIV RNA < 50 c/mL

On 1st or 2nd regimenNo prior NNRTI use

No known resistance to study agents

W24 W48

Baseline characteristics and disposition

TDF/FTC/RPVN = 159

2 NRTI + PI/rN = 317

Female 14% 9%

Baseline CD4/mm3 (mean) 576 600

Time since first ART, years (median) 2.9 2.6

Discontinued before W24 N = 20 N = 7

Adverse event / Lack of efficacy 7 / 1 0 / 0

Discontinued between W24 and W48 N = 7 N = 9

Adverse event / Lack of efficacy 0 / 1 5 / 1

NRTI PI/r

TDF/FTC 81% ATV/r 37%

ABC/3TC 13% DRV/r 20%

ZDV/3TC 3.4% FPV/r 33%

LPV/r 33%

ART at screening



HIV RNA < 50 c/mL at W24 and W48 (ITT, snapshot)2 NRTI + PI/r (D1 to W24)TDF/FTC/RPV (D1 to W24)

93.789.9

≠ (95%CI)3.8 (- 1.6 ; 9.1) : non inferiority

0

20

40

60

80

100

100

≠ (95%CI) :3.2 (- 4.8 ; 11.3)

≠ (95%CI) :5.8 (- 1.4 ; 12.9)HIV RNA < 50 c/mL, ITT, M = excluded

RPV = 99.7% vs PI/r = 94.7% Non inferiority

95 95.589.2 92.3

0

20

40

60

80

HIV RNA, pre-ART (23 patients TDF/FTC/RPV and 14 PI/r

excluded from analysis [data not avalaible])

> 100 000 c/ml< 100 000 c/ml

152/160

83/93

48/52

128/134

%

%

92.1

0.9

5

1.3


SPIRIT

TDF/FTC/RPV (delayed switch, W24 to W48)

3/317 8/159 2/152

Virologic failure%

TDF/FTC/RPV (immediate switch, D1 to W48)

89.3

HIV RNA < 50 c/mL at W24according to pre-ART HIV RNA

2.5

8/317

Palella F, AIDS 2014;28:335-44

Among the 24 patients with the K103N mutation on historical genotype– 18 in the immediate switch arm

• All maintain HIV RNA < 50 c/mL at W24• 1 virologic failure at W48 (pre-existing mutations : K103N + V179I,

emergence : M184V, E138K and V108V/I)– 6 in the delayed switch arm

• 5 maintain HIV RNA < 50 c/mL at W48 (24 weeks after switch)• 1 without data at W48 (HIV RNA < 50 c/mL at last study visit)

Virologic failure on TDF/FTC/RPV, N = 7 (1.5%)– 3 without emergence of resistance mutations– 4 with emergence of resistance mutations

• K103N + L100I + M184I• M184I• E138E/K + M184M/V• E138K + V108V/I + M184V



Mean change from baseline at W24

-60

-50

-40

-30

-20

-10

0

10

- 25

- 1

-16

0

- 53

3

- 4- 1

- 0.27

0.08

P < 0.001 for all comparisons

2 NRTI + PI/r

Total-chol(mg/dl)

LDL-c(mg/dl)

TG(mg/dl)

HDL-c(mg/dl)

Ratio total-cHDL-c dL

TDF/FTC/RPV

• Discontinuation for adverse event (W24)– TDF/FTC/RPV, N = 6

• tubulopathy, N = 1• neuro-psychiatric events, N = 4

(depression, headache, insomnia, psychiatric event)

– 2 NRTI + PI/r, N = 0

• GFR decrease significantly more important with RPV


SPIRIT

Grade 3-4 Adverse events and laboratoratory abnormalities to W48

Palella F, AIDS 2014;28:335-44

RPVImmediate switch (at W48)

PI/r(at W24)

Adverse events

5.7 % 6.9 % 7.9%

Laboratory abnormalities

8.8 % 11.3 % 15.2%

RPVDelayed switch

(at W24)

Conclusion– Switching to the STR TDF/FTC/RPV from a PI/r regimen in

virologically suppressed, HIV-1-infected participants maintained virologic suppression with a low risk of virologic failure, while improving total cholesterol, LDL-cholesterol, and triglycerides

• Participants had been virologically suppressed on a PI/r regimen for at least 6 months prior to study entry and had no previous ART failure

• Pretreatment HIV-1 RNA levels (while still ARV-naive) did not affect maintenance of viral suppression after switch to TDF/FTC/RPV

– Historical K103 resistance mutation (probably transmitted) did not affect efficacy of switch to TDF/FTC/RPV in participants of the study



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