Prevention and CareDr S Charalambous

www.kaizernetwork.orgwww.aids2006.orgWHO guidelines

Toronto : new information

• Kericho, Kenya : tea plantation workers - 2800 volunteers*– Circumcised 0.79/100py– Uncircumcised 2.84/100py – HRR 0.31 (95%CI 0.15 – 0.64)– (Models : Demographic factors – less significant,

Behavioural factors – still significant)• Modelling study of HIV prevalence in Soweto* in 20

years (61% protective effect)– 318 000 HIV infxns – HIV prev 16% - 23%– Current rates of circ : 17%– 10% per year –32000 fewer infections: 17% to 14% HIV prevalence– 20% per year –53000 fewer infections: 17% to 13% HIV prevalence– 30% risk behaviour – 18 000 fewer infections: 17% to 15% HIV prev

*TUAC0201 **TUAC0203

Toronto : new information Cost-effectiveness of male circumcision, J Khan*

– Orange Farm study data: Total cost: $ 56– Assumptions:

• No effect on women• 25% increased risk compensation• Life time cost of treatment $ 8000

– Cost of HIV infection averted $181 ($91 – 668 HIV Prev) Savings: $2,4 million

– Cost of circumcision must inc 45x for no cost difference

Kenya : assessment of behavioural disinhibition** following male circumcision– 648 men : 324 circumcised vs 324 uncircumcised– Baseline : Risky acts 33.6% circum vs 25.6% uncirc 0.025– No increase in sex acts or unprotected sex acts

*TUAC0203 **TUAC0205

STATE-OF-THE-ART

• Treatment naïve patients: New IAS guidelines

• Treatment experienced patients: achieving undetectable viral load

• Role of HAART in HIV prevention

Antiretroviral regimens recommended for first-line therapy (new IAS-USA guidelines)

*In selected patients #No longer recommended for initial therapy except when use of NNRTIs or PIs is precluded

Adapted from Hammer et al. JAMA 2006; 296:827-43

Recommended components

NRTI NNRTI PI

TDF + FTC ZDV + 3TC

ABC + FTC

EFV(or NVP*)

LPV/r SQV/r

ATV/r FPV/r

Alternate components

TDF + 3TC ABC + 3TC

ZDV + FTC

Special circumstances only (3-NRTI regimen)

ZDV+3TC+ABC#*In selected patients #No longer recommended for initial therapy except when use of NNRTIs or PIs is precluded

Adapted from Hammer et al. JAMA 2006; 296:827-43

Staccato: Highest response of 24-week analyses (HIV RNA < 50 copies/mL; ITT)

1. Murphy et al. AIDS 2003; 17:2603–14 2. Gathe et al. AIDS 2004; 18:1529–37 3. Podzamczer et al. 9th EACS 2003. Abstract F1/3 4. Walmsley et al. N Engl J M,ed 2002; 346:2039–46 5. van Leth et al. Lancet. 2004; 363:1253–63 6. Saag et al. JAMA 2004; 292:180–97. Staszewski et al. 10th CROI 2003. Poster 564b 8. Eron J, et al. Lancet 2006; 368: 476–829. Ananworanich et al. Antivir Ther 10: 761-7

Subjects with HIV RNA < 50 copies/mL (%)

Gilead FTC-301

0 20 40 60 80 100

StaccatoSQV/r** + 2 NRTIs

EFV + ddI + d4T

Gilead 903EFV + TDF + 3TC

Gilead FTC-301EFV + ddI + FTC

89%

Abbott 418 57%

74%78%

81%

GSK - SOLO 55%

Abbott M98-863* 65%

BMS-008*†

LPV/r (od) + FTC + TDF

FPV/r + ABC + 3TC

LPV/r + d4T + 3TC

NVP (bid) + d4T + 3TC 65%

ATV + d4T + 3TC 38%

2NN*

KLEAN*LPV/r + ABC + 3TC 72%KLEAN*FPV/r + ABC + 3TC 68%

† ATV 400 mg results used; *HIV RNA at 24 weeks estimated from graph; **Investigational Invirase/r 1600/100 mg qd dosage. The approved dosing regimen is Invirase/r 1000/100 mg bid

Tenofovir

• 903 Trial: 96 week results: safety and tolerability of tenofovir,

• Uganda: reduction in side effects due to tenofovir

• Subtype C isolates may develop the K65R mutation more rapidly than Subtype B isolates

• Uganda & Zimbabwe: 1.3% patients developed severe GFR reduction, found to have similar rates of glomerular filtration reduction as other regimens

Treatment-experienced patients

• Undetectable viremia is now a realistic goal of therapy for treatment-experienced patients

• Before adding a new agent, ARVs should be selected to provide the maximum activity – Baseline characteristics are important prognostic

factors predictive of a treatment response– Resistance testing may overestimate the number

of active drugs– Drugs from a new mechanistic class (e.g. ENF)

should retain their full activity in treatment-experienced patients

30%

60%

< 400 copies/mLWeek 24

Pat

ien

ts (

%)

TORO 1 & 2

LPV/rLPV/r + ENF

46%

64%

< 50 copies/mLWeek 24

Pat

ien

ts (

%)

POWER 1 & 2

DRV/rDRV/r + ENF

30%

54%

Pat

ien

ts (

%)

RESIST 1 & 2

TPV/rTPV/r + ENF

< 400 copies/mLWeek 24

Haubrich et al. IDSA 2005; Abstract 785; Hill and Moyle. BHIVA 2006; Abstract P1.

Summary of TORO, RESIST and POWER trials

HAART and HIV Prevention

• PMTCT works by reducing viral load to reduce transmission

• Uganda, Quinn et al – reduction of transmission in serodiscordant couples – no transmission if VL<1500

• Taiwan, reduction in HIV transmission 53% after introduction of HAART

• Call for cost-effectiveness of use of HAART as prevention : immediate treatment of 100% HIV population– Cost $7 billion/year – total cost $42 billion– HIV infected people 38 million to <1 million

• “History will judge us not by our scientific advances, but what we do with our scientific advances” A Fauci