Optimizing and simplifying the toolkit (drugs, dosing, and diagnostics)

and delivery of ART

Dr Eric Goemaere

Regional TB/HIV Advisor

MSF South Africa

Bending the curves

Reducing clinical workload Bending the epidemic curve Distributing tasks

Increasing patient autonomy & adherence Long term community based chronic care

Reducing pill burden and toxicitiesARV dosage optimization New formulationsNew ARVs

Doctors

Increased coverage

Lower Cd4 threshold

PHC decentralised care, nurse based CHW supported

Patient self management

Reduced clinical time /patient

Patient friendly regimen: easy to use

low toxicity, forgiving

Patient-centered efficiency

Bending the epidemic curve Moving from emergency to a chronic phase

46 42

7285

100 109131

0

50

100

150

200

250

2001 2002 2003 2004 2005 2006 2007

Med

ian

bas

elin

e C

D4

in y

ear

Adults starting ART in year 288 389 1063 1647 2094 1863Number of patients starting with stage IV disease 158 200 446 612 652 539

Proportion in Stage IV 55% 51% 42% 37% 31% 29%Median CD4 count for all adults 42.5 (13-96) 73 (22-126) 85 (37-141) 100 (44-158) 109 (52-169) 131 (64-191)

Median CD4 count of patients in stage IV 32.5 (9-91) 40 (13-90) 53 (20-114) 72 (27-138) 80 (31-150.5) 98 (46-172)

0%

10%

20%

30%

40%

50%

60%

2001 / 2 2003 2004 2005 2006 2007

Stage I & II Stage III Stage IV

Khayelitsha 2001-2007

Transition needs to happen as soon as possible -> early aggressive approach ( emergency phase)

Distributing tasks

Consultation

Clinical screening

Psycho social support

Drug re-fill

Clinical screening

Psycho social support

Drug re-fill

What will Khayelitsha look like in 10 years ?

Pop. 500,000 (250,000 adults) ANC prevalence 30% =est. 60 -70,000 HIV+ Incidence =est. 4000 new infections/year

2009 2019

KhayelitshaFacility-linked, PLWHA-led

'Adherence Clubs'

Clinic Community based Clubs

Monthly doctor/nurse appointment

20-30 allocated to one club Counselor and PWHLA “facilitator”Peer support

Individual consultation Group screening

Time: 1 day in the clinic 2 hours

Monthly refills 2-3 months refills

General education, health talks Specific education & discussion

12 visits a year 6 visits, with flexibility (family member can pick up meds)

Thyolo, MalawiDecentralization to health posts

Outreach from existing health centers if > 10 km Minimum package of HIV services ARV refills dispensed by lay health workers (HSAs)

for stable patients on HAART Staffing: one community nurse and 2-3 HSAs

Tete, MozambiqueCommunity-HAART Groups

PLWHA driven Support group w/ ART provision Rep. Elecetd to collect ARV's Maximum 6 patients

Between June 08 and Dec 09199 CHG formed 1253

patients95.4 % RIC 1.7 % died 0.2 % LTFU 1.9 % TFO 0.8 % returned to HC

Dose optimization

Objectives: Reduce patient toxicity Reduce pill burden Reduce costs

d4T: from 40 mg to 30 mg BID dose for all patients AZT was initially marketed as 250mg bid in Europe until late 1990s. Dose

still available for sale in Europe For several HIV drugs, Phase 2 data showed no difference in efficacy

between doses, but higher doses were selected for Phase 3 and registration (EFV, LPV/r, RAL, 3TC)

In drug development, dosage selection is made early and not reassessed later

Source: Charlotte Schultz , GFJooste ID referral unit, cape Town

                                             

Reducing D4T dosage Impact on regimen safety

Potential Dose Optimization Investigations

_________________________________________________________Drug Current dose Target Optimised dose_________________________________________________________ZDV 300mg BID 200 mg BID3TC 300 mg OD 150 mg OD **EFV 600 mg OD 400 mg OD **LPV/r 400/100 mg BID 200/100 or 200/150 BID **ATV/r 300/100 mg OD 300/50 or 200/50 mg ODDRV/r 600/100 BID 400/50 mg OD (PI naives)RTV 100mg (booster) 50mg (booster)RAL 400mg BID 100-200 mg BID_________________________________________________________

** Encore trials : funded and support from Bill and Melinda Gates Foundation, University of New South Wales and Clinton Health Action Initiative

Source: Andrew Hill

Long term therapeutic strategy

Specific treatment paradigm for high prevalence LRC contexts ?

Future perspectives Moving away from a sequential paradigm to Induction/maintenance

paradigm ?

Drug required profile Potent regimen for induction ( Raltegravir/Darunavir/r) Systematic switch to maintenance with no monitoring Long half life, forgiving regimen( PI based ) for maintenance Safe, minimal side effects , NRTI sparing

New drugs,new formulations?

Promising drugs

Rilpivirine (Tibotec) – NNRTI, (Phase III) low dose 25mg, long half life 38 hours,

Elvucitabine (Achillion) – NRTI, (Phase II) low dose 10mg, long half life 49hrs, safety efficacy data?

CMX 157 (Chimerix) – (Phase I), prodrug of TDF,more potent than TDF++, low dose, safety efficacy data?

S/GSK 1349572 (ViiV) (Phase IIb) – Integrase Inhibitor, low dose 50mg, no booster required, long half life 30

hours, safety efficacy data?

HIV POC tests