From the Conference: Hot Topics in HIV

As presented by Sharon Walmsley:

1. "When to start"
   At diagnosis? Treatment as prevention
   
   • Sullivan P et al., 16th CROI Montreal, Feb 2009: 3,000 discordant couples no ARV vs. partner on treatment -- dramatically reduced risk of linked infections 3.4/100 vs. 0.7/100 person years
   CD4 500? 350? 200?
   Viral load - higher?
   Co-morbid illness
   Initiate at dx vs. CD4:
   • Fitzgerald D, et. al, 5th IAS: Cape Town, South Africa July 19-22, Abst. WESY201 stopped due to excess death in delayed arm
   • Kitahata M, et al: Cohort study: individuals who deferred HAART to below CD4 500 were at increased risk of progression.
   • Sterne J et al., 16th CROI Montreal Feb 2009: Cohort study: advantage to starting earlier in terms of risk of AIDS or death regardless of CD4 count
2. "Inflammation is BAD"
   DAD Study:
   
   • Friis-Moller N et al, CROI 2006: Are ARVs associated with increased cardiovascular events? PIs associated with increased risk of CVD above risk of dyslipidemia.
     
     • Baseline MI risk 1.6%, 1.9x more ABC, 1.6 more PI, 3x more smoking
       
     • Associated editorial by Friis-Moller here
       
   • Sabin C et al., CROI 2008; Lundgren JD et al, CROI 2009: Increased risk with ABC, ddI, lopinavir
   • Lang S et al, 16th CROI: ABC exposure within 6 months was associated with slight increase in MI risk, also lopinavir and indinavir
   • GSK and VA study to not find similar ABC risk
     
   SMART Study:
   
   • Do planned structured treatment interruptions benefit patients? No -- there was increased risk of CV death and death from OI
3. Antiretroviral monotherapy - Has it come of age?
   AZT inferior to AZT+3TC inferior to AZT+3TC+PI/NNRTI
   But what about newer single agent:
   
   • LPV/r monotherapy (example publication of this data here):
     
     • Either as initial therapy, with NRTI backbone then stop, with any regimen that supresses then change to monotherapy
   • MONOI Study (Katlama, IAS 2009 Abstract) - Darunavir/ritonavir as monotherapy:
     
     • Suppress then monotherapy vs. continue -- 94% virologic success with DRV/r monotherapy at 48 weeks vs. 99% with DRV/r +NRTIs. Failed to meet pre-specified inferiority
   • MONET Study (J. Arribas et al, IAS, Cape Town July 2009)
     
     • Non-inferiory of monotherapy to with NTRIs -- 84.3% vs. 85.3% @ 48 weeks
4. "Mother to child transmission - has it been eliminated?"
   Risk is currently less than 1% with antenatal testing, antenatal ARV to VL below 50, selective elective C-section, neonatal ART and avoidance of breast feeding
   
   • Does C-section add anything to HAART? Yes, if not on ART or VL not less than 50
   • Treat mother or newborn? Shapiro R, et. al 5th IAS Cape Town/Chasela C. et al, 5th IAS
     
     • If you treat the mothers, get them undetectable, than even with breast feeding transmission can be less than 1% -- of potential great benefit in the developing world
5. "New Drugs"
   
   • Goal is VL less than 50 regardless of naive or experienced with regimens of 2-3 active drugs from different classes
   • Will initial regimens change?
     
   • Entry inhibitors (CCR5 blocker - requires tropism assay) - miraviroc
   • Integrase inhibitor - raltegravir, elvitegravir
   • Maturation inhibitor - bevirimat
   • New agents, old classes: etravirine, rilpilvarine (NNRTI), tipranavir, darunavir (PI)