The following slides and audio are taken from a public HIV health and treatments update forum held in Sydney,

Australia on 25 November 2008. The slides and audio have been edited for presentation on the web.

The speaker is Dr Fraser Drummond, National Centre in HIV Epidemiology and Clinical Research.

For more presentations from this event, visit the sponsor organisations’ websites:

HIV Treatment and Health UpdateHIV Treatment and Health Update25 November 2008

Part 3

Starting treatment, treatment breaks

and treatment trends

What is a Biomarker?

...a characteristic that is objectively measured and evaluated as an indicator of

normal biological processes

pathogenic processes

pharmacological responses to a therapeutic intervention

Proposed Hypothesis by which HIV affects inflammation/coagulation

HIV

Tissue Factor

Extrinsic Clotting Pathway

Thrombogenesis

Secondary Inflammation (IL6)

Coagulation Cascade

Increased D-dimer

Vascular endothelium of smooth muscle cells

Change in D-dimer* (µg/mL) & IL-6 (log)* from Baseline to 1 Month

0

0.1

0.2

0.3

0.4

≤ 400 401-10,000 10,000-50,000 >50,000

Month 1 HIV RNA Level (copies/mL)

∆ D

-dim

er

(µg

/mL

)/ ∆

IL-6

(lo

g)

p=0.0005 for trend

* DC patients on ART at baseline with HIV RNA ≤ 400 copies/mL

p=0.0003 for trend

When to Start cART: 2008

CD4 count (cells/µL)

ARV recommendation

<350 cART recommended

>350 – <500*†‡ cART generally deferred; clinicians may treat if VL>100,000 copies/mL

>500*†‡ cART generally not recommended

symptomatic HIV disease: ARV recommended for all patients

asymptomatic HIV disease decision based on CD4+ T-cell count

DHHS, 2008; BHIVA, 2008; IAS, 2008

*BHIVA, consider ARV if HBV requiring Rx; HCV/HIV co-infection; low CD4%; established CVD or Framingham score >20% over 10 yrs; malignancy requiring chemotx; pregnancy†DHHS consider ARV if HBV requiring Rx; HIVAN; pregnancy‡“individualise” as above plus rapid decline of CD4+

Evolution of Focus of ConcernOpportunisticInfections &Malignancies

CMVPJPMAC

toxoplasmosiscryptococcosis

candidiasishistoplasmosis

Kaposi’s sarcomaothers?

Time

Evolution of Focus of ConcernOpportunisticInfections &Malignancies

CMVPJPMAC

toxoplasmosiscryptococcosis

candidiasishistoplasmosis

Kaposi’s sarcomaothers?

Complications of Therapy

CVDmetabolic

renal hepatic

neurologichaematologic

others?

Time

Evolution of Focus of ConcernOpportunisticInfections &Malignancies

CMVPJPMAC

toxoplasmosiscryptococcosis

candidiasishistoplasmosis

Kaposi’s sarcomaothers?

Complications of Therapy

CVDmetabolic

renal hepatic

neurologichaematologic

others?

SeriousNon-AIDS

Morbidities

MIstroke

renal Failurehepatic Failuremalignancies

others?

Time

Pros of Earlier Rx

Reduced viraemia

Improved QoL

Reduced risk of disease progression

Reduced infectiousness??

Cons of Earlier Rx

Adherence

Costs

Toxicity – do we have the best starting combinations yet?

Risk of resistance

Interrupting Therapy?

SMART results - not recommended

Certain situations:Acute toxicityIntercurrent illness limiting oral intakeSurgery

Planned interruptions should only be done in clinical trials

What to Start?

FEIN(t)RTI NNRTI IntI PI

AZT EFV SQV/r

NVP*

LPV/r

3TC ATV

ABV ATV/r

TFV fAPV/r

FTC DRV/r

*CD4+ restrictions apply

NRTI Backbone

Truvada – renal and bone issues, caution with NVP?

Kivexa – CVD and potency issues

Combivir – Lipoatrophy and Anaemia

Factors – need maximum potency, low side effects and ease of use, blood-brain barrier?

NRTI Backbone

Abacavir Concerns

Potency – is it strong enough?CVD risk

DAD and SMART?Channelling BiasNot naïve patientsMore data expected

Avoid if high CVD risk factorsMore data awaited – discuss with your doctor

Antiretroviral Drug Approval:1987 - 2008

0

5

10

15

20

25

30

1987 1989 1991 1993 1995 1997 1999 2001 2003 2005 2007

AZT ddIddC d4T

3TCSQV

RTVIDVNVP

NFVDLV

EFVABC

APVLPV/r

TDF

ENFATVFTCFPV TPV

DRV

ETRRAL MVC

New treatments

Integrase inhibitors work!

Raltegravir, Elvitegravir

CCR5 inhibitors – what role?

Maraviroc, Vicriviroc

New NNRTI(s)

Etravirine, Rilpivirine

Newish PIs

Darunavir, Tipranavir

Treatment Simplification

Improve QoL, adherence, avoid long term toxicities, reduce risk of viral failure

Resistance or not, within class or new class

Monitor closely after any switch

Will Treatment Be Forever?

Currently yes

Future??

Therapeutic Vaccination

Genetic ART selection

Novel monthly injections

For more presentations from this event, visit

www.napwa.org.au

or

www.acon.org.au