1. Wits Reproductive Health & HIV Research Institute (RHI)
Research gaps in treatment optimization and how Africa can solve these gaps
Francois Venter
Wits Reproductive Health & HIV Research Institute (RHI)
Nov 2015

2. So what can we improve? (my in-order-of-priority list)
Cost
Delivery systems
More convenient HIV testing
Resistance ‘’forgiveness’’
Side effects
Active pharmaceutical ingredients (API)
Size of tablets and packaging
Paeds: need more harmony with adults

3. SA Snapshot Oct 2015
6-7 million HIV positive – 18% world total, 25% of Southern Africa
3.2 million on first line ART – consume 25% of global generic ART
children – PMTCT working well
on second line, 400 on third line

4. PI(lopinavir or atazanavir)
ART regimens
TDF
XTC
EFV
AZT
XTC
PI(lopinavir or atazanavir)
XTC, other nukes
Darunavir
Raltegravir
Etravirine

5. Cost

7. PI(lopinavir or atazanavir)
Cost culprits…
TDF
XTC
EFV
AZT
XTC
PI(lopinavir or atazanavir)
XTC, other nukes
Darunavir
Raltegravir
Etravirine

8. Alternatives to TDF cost
Abacavir too expensive, AZT expensive and toxic
Low dose d4T? Not a massive saving, concerns re long term toxicity – being done in 3 countries
TAF – TDF pro-drug - potential for BIG savings (?50%), less API – but NOT being tested with dolutegravir (more on this later)
Or could we dump TDF altogether? (DTG/3TC - 75% savings!!)

9. PI(lopinavir or atazanavir)
Cost culprits…
TDF
XTC
EFV
AZT
XTC
PI(lopinavir or atazanavir)
XTC, other nukes
Darunavir
Raltegravir
Etravirine

10. Containing 2nd line cost
Stop migration from first line!
AZT: recycling TDF would be better, but we’d need more data; dump AZT altogether
PI: lower doses of darunavir (?atazanavir), or dolutegravir – large consortium looking at this

11. PI(lopinavir or atazanavir)
Cost culprits…
TDF
XTC
EFV
AZT
XTC
PI(lopinavir or atazanavir)
XTC, other nukes
Darunavir
Raltegravir
Etravirine

12. Delivery systems
Endless ‘’health systems strengthening” – can we seriously expect the current system to work?
Adherence clubs, deliveries at home, kiosks, vending machines
Probably needs local tailoring – but not a lot of scaled innovation

13. Testing, testing… First 90 possibly the hardest
Innovative operational testing strategies needed beyond:
Facility based testing
Community based testing
? Self testing ?workplaces ?key populations ?schools
Thanks WHO: Cheryl Johnson/Rachel Baggaley

14. Resistance and side effects culprits…
TDF
XTC
EFV
AZT
XTC
PI(lopinavir or atazanavir)
XTC, other nukes
Darunavir
Raltegravir
Etravirine

15. Resistance and side effects
First line:
?EFV 400mg vs 600mg (PK work being done)
Rilpivarine – cheap, good profile (but PMTCT/viral load/food issue)
Dolutegravir – almost unbreakable, very good side effect profile, TB/PMTCT needs sorting – protocol being designed in SA
PI: lower dose darunavir (protocol in SA), ??atazanavir

16. Size of tablet/packaging?
TAF/FTC/DTG (275mg) vs TDF/FTC/EFV (1.1g)
Vs DTG monotherapy?
2nd line: darunavir 400/100 - ? Single tablet with rilpivarine or DTG? (400mg DRV study in SA starting in Jan)

17. Finally: paeds
Always left behind, canaries in the mine for drug stock outs
Lots of work on DTG; but TDF a problem (?TAF will solve it)