Workshop 4: “Il late-presenter”Moderatori: G. Ippolito, M. MoroniDiscussant: R. Iardino

Risposta virologico-clinica e scelta della terapiaC. Mussini

760 pazienti/ 125 morti (16%)

Kaplan Meier plot showing the cumulative proportion of patients with clinical progression, according to the type of

AIDS diagnosis that was present at the time of HIV diagnosis

Prognosis of late presenters

Adapted from Sterne et al. CROI 2009, Abstract 525 and presentation

• Based on 24,444 patients from 15 cohort studies

• 808 deaths and 2366 events in 81,071 person-years of follow-up

0 – 50

51 – 150

151 – 250

0.15

0.10

0.05

0.00

0 1 2 3 4 5 6

Prob

abili

ty o

f dea

th

Years since start of HAART

251 – 350

351 – 450

451 – 550

Years since start of cART

0.40

0.30

0.20

0.10

0.00

0 1 2 3 4 5 6Pr

obab

ility

of A

IDS

or d

eath

EFV vs LPV/RTV in Tx-Naive Pts With CD4+ < 200 in Mexico

HIV-1 RNA < 50 copies/mL at Week 48

Madero JS, et al. IAC 2008. Abstract TUAB0104.

0

20

40

60

80

100

0 16 32 48Week

8 24 40

Efavirenz (n = 95)

LPV/RTV (n = 94)

Number of Pts With HIV-1 RNA < 50 copies/mLEFV 29 70 68 67LPV 8 53 56 50

70.5%

53.2%

0

20

40

60

80

100

HIV

-1 R

NA

< 5

0 co

pie

s/m

L (

%)

79%

49%

64%57%

P = 0.012 P = 0.15

EFV

LPV/RTV

n = 42 45 53 49

≤ 50 cell/mm3 > 50 cell/mm3

EFV met criteria for superiority to LPV/RTV: Δ 17% (CI 95%: 3.5% to 31.0%; P = .017)

HIV

-1 R

NA

< 5

0 co

pie

s/m

L (

%)

By BL CD4+ Cell Count

STARTMRK: Virologic and Immunologic Efficacy at Week 48

Significantly shorter time to virologic response with RAL vs EFV (P < .001)

Significantly greater CD4+ cell count increase with RAL vs EFV

+189 vs +163 cells/mm3; Δ: 26 cells/mm3 (95% CI: 4-47)

Lennox J, et al. ICAAC/IDSA 2008. Abstract 896a. Adapted with permission of Merck & Co., Inc., Whitehouse Station, New Jersey, USA. Copyright © 2008 Merck & Co., Inc., Whitehouse Station, NJ, USA. All rights reserved.

0

20

40

60

80

100

0 16 32 48Weeks

Pat

ien

ts W

ith

HIV

-1

RN

A <

50

cop

ies/

mL

(%

)

2 4 8 12 24 40

86%

82%

RAL n = 281 279 281 279 281 279 278 280 280EFV n = 282 282 282 282 281 282 280 281 281

Δ: 4% (95% CI: -2 to 10)P < .001 for noninferiority

RAL

EFV

ITT, NC = F

Incidence of PcP if CD4 ≤ 200

VL Prophylaxis

Person-years of

follow-up events Incidence/1000y

(95% CI)

<400 no 1944 7 3.6 (1.4-7.3)

<400 yes 4444 12 2.7 (1.4-4.7)

400-9999 no 657 9 13.7 (6.3-26.1)

400-9999 yes 976 8 8.2 (3.5-16.2)

>10000 no 2046 106 51.8 (41.9-61.6)

>10000 yes 1789 39 21.8 (15-28.6)

Incidence of secondary PcPIn

cid

enc

e s

eco

nd

ary

PC

P p

er 1

000

PY

FU

(95%

CI)

0.1

1

10

100

1000

Proph

Events

No

1

No

1

No

4

Yes

5

Yes

1

Yes

2

No

5

No

0*

No

0*

Yes

2

Yes

0*

Yes

0*

CD4 < 200 CD4 > 200

<400 400-9999 >10000 <400 400-9999 >10000

*No events; incidence and lower bound of 95% CI=0.0

Pro

po

rzio

ne

co

n

Dis

turb

i N

P

Prevalenza di HAND in epoca post-HAARTPrevalenza di HAND in epoca post-HAART(Studio CHARTER)(Studio CHARTER)

15.1%

25.4%17.7%

4.8%

18.3%28.3%

26.5%

0.5%

1.9%1.8%

0%

10%

20%

30%

40%

50%

60%

HIV- CDC A CDC B CDC C

ANI MND HAD

(n=212) (n=437) (n=213) (n=113)

Letendre et al., 2007

Updated CSF Penetration Effectiveness Scores Overall CPE score = sum of following scores for the

individual agents

Classification Score Agents

Good penetrators 4 IDV/RTV, NVP, ZDV

Decent penetrators 3 ABC, DLV, DRV/RTV, EFV, FPV/RTV, FTC, IDV, LPV/RTV, MVC,

RAL

Limited penetrators 2 3TC, ATV ± RTV, d4T, ddI, ETR, FPV

Poor penetrators 1 ddC, ENF, NFV, RTV, SQV ± RTV, TDF, TPV

Letendre S, et al. CROI 2010. Abstract 172.

MONOI: 48 Wk Outcomes With DRV/RTV Monotherapy vs Triple Therapy DRV/RTV monotherapy met criteria for

noninferior virologic efficacy vs DRV/RTV + 2 NRTIs at Wk 48 in PP analysis, but not in ITT-E analysis

– PP population = all pts from ITT population except pts who d/c tx without virologic failure or SAE (n = 10) or pts withdrawn without virologic failure or SAE (n = 6)

Virologic failure in 3 pts (2.7%) on monotherapy vs 0 on standard therapy

– Low DRV drug levels noted in 1 pt

– No DRV RAMs in any pt with virologic failure

– All 3 pts regained HIV-1 RNA < 50 c/mL on reintroduction of 2 NRTIs

Virologic Response at Wk 48, %*

DRV/RTV

DRV/RTV+ 2 NRTIs

Δ Lower Limit of 90% CI

PP analysis (n = 204)

94.1 99.0 -4.9 -9.0

ITT-E analysis (n = 225)

87.5 92.0 -4.5 -11.0

Viremia detected in CSF in 2 of 3 pts with serious CNS disorders on monotherapy arm

– Each pt had HIV-1 RNA < 200 c/mL in CSF following reintroduction of NRTIs

Katlama C, et al. IAS 2009. Abstract WELBB102.

Virologic failure defined as consecutive HIV-1 RNA > 400 c/mL or treatment modification or discontinuation

CONCLUSIONI

La sopravvivenza del paziente libero da malattia deve essere l’obiettivo della TARV.

Il successo virologico costituisce un fattore essenziale per la prognosi a lungo termine.

La prescrizione di un regime terapeutico deve tener conto anche della penetrazione nei diversi comparti.