Studies Flashcards
What did the ATLAS study look at?
Suppressed switch to injectable RPV/CAB vs continuing oral therapy
End point - VL <50 at 48 weeks
What was the outcome of ATLAS study
Monthly CAB/RPV injectables non inferior to oral therapy
What did ATLAS 2M look at?
2 monthly vs 1 monthly injectable CAB/RPV
Outcome of ATLAS 2M
2 monthly injections non inferior to monthly.
However 1.5% on 2 monthly had CVF (<1 on monthly) hence strict criteria for having injectables ‘caution if patient has at least 2 of bmi > 30, subtype a1/a6, incomplete resistance testing and tx history’
Outcome of DUALIS study
Switching to dolutegravir plus boosted darunavir non inferior to continuing 3Dr with boosted darunavir in suppressed patients already on bDRV
ACTG 5257
Raltegravir superior to darunavir/ritonavir which is superior to atazanavir ritonavir
DAWNING study
In treatment failure with with NNRTI resistance - DTG is superior to lop/r
NADIA
If treatment failure with NNRTI resistance DTG non inferior to darunavir/r
What study compared AZT/3TC with TDF/3TC risk of virological failure?
NADIA
TDF/3TC associated with reduced risk of VF at 96wks
Risk of emergence of DTG resistance also less in TDF group
RAKAI study
If undetectable cannot pass virus on
DAD study
Ongoing use of abacavir increase risk of stroke and heart attack particularly in those already at high risk (>10%)
ADNES study
3TC/drv/r vs 3TC/drv/r/tdf
2 drug arm non inferior
No significant adverse events
Significantly greater total cholesterol in 2Dr so TDF may have favourable impact on lipids
GEMINI 1 and 2
Dtg/3TC - individual components vs dtg/tdf/ftc
1 and 2 in different studies
Naive adults
Now at week 144
VL 1000-500000, no mutations, no HBV or HCV
At 48 weeks non inferiority of 2drug arm
One significant failure between 96 and 144 weeks - found to have m184v and II resistance mutations
TANGO
Stable switch from 3DR to DTG/3TC as dovato
All had to be on TAF based regimen prior to switch
Dovato noninferior at 48weeks
Therefore is recommended as a stable switch option
TANGO - m184v?
Proviral m184v looked at - these patients still suppressed
SALSA
Stable switch from diverse baseline regimens to DTG/3TC
Dovato non inferior at week 48
Gs1489
Biktarvy vs TMQ
Non inferiority
Naives
Gs1490
Naives
Biktarvy vs descovy DTG
non inferiority at 96 weeks
DRIVE-AHEAD
Naives delstrigo vs atripla
No resistance, VL >1000
Non inferiority
Neuropsychiatric SEs less in delstrigo than atripla arm
DRIVE-FORWARD
2NRTI + doravirine vs 2NRTI+drv/r
Non inferiority
SWORD
Switch vs continuing on 1st or 2nd combination
Showed non inferiority
One k101k/e at 36 weeks - virological withdrawl- had been non adherent. Resuppreased on juluca. No II resistance.
LATTE studies 1 and 2
Phase 2 studies of injectables
DRIVE-SWITCH
Delstrigo switch study
Non inferior
FLAIR
‘Recently naive’
All had 20 weeks TMQ
After this continues TMQ or went onto cab/RPV
CAB/RPV Non inferior to TMQ
BRIGHTE
Fostemsavir study
Phase 3 study
CALIBRATE
lenacapavir
4 treatment groups
2 arms 2DR and 2 3DR
Equivalent viral suppression groups
Some failure with resistance in Lenacapavir 6 monthly arms - ?missing oral doses
CAPELLA
Highly treatment experienced individuals
Adding LEN to optimised background regimen - this lead to reasonable viral suppression
Again some failure in 6/12 s/c LEN with resistance ?not adhering to oral whence
START study
Immediate ART vs deferred therapy until CD4 <350
53% risk reduction at interim review
Trial stopped early
Guidelines changed for treatment to be started irrespective of CD4 count
Which trial demonstrated increased neonatal death and prematurity with combo of TDF/FTC LOP/r?
PROMISE
Partner 1
MSM and heterosexual couples - no transmissions when positive partner suppressed
Partner 2
Further data on MSM - 76000 episodes condomless sex zero transmissions
Opposites attract
MSM serodifferent - zero transmissions
Actg 5164 - when to start therapy in context of aids defining infection or bacterial infection and cd4 <200
Fewer aids progressions/deaths and improved cost effectiveness with ART initiated within 14 days compared to after tx of compared to waiting until infection treated
No increased IRIS but most had pcp
COAT study
Cryptococcal meningitis - higher risk of death with early art initiation in those with decreased level of consciousness or acellular spinal fluid
Therefore defer ART 2 weeks
START
For those with CD4 > 500 art was associated with significant reduction in relative risk of disease progression but absolute risk relatively small (4.1% deferred arm 1.8% immediate treatment arm)
ADVANCE study
Week 48 DTG non inferior to EFV but DTG arm less discontinuation due to adverse events
Spring2
Dtg vs RAL
48 weeks no significant difference
96 weeks favoured success with DTG
Less virological failure on DTG
Less failure with resistance on DTG
FLAMINGO
DTG vs DRV/r
DTG superior - fever discontinuations but no difference in rates of virological failure or resistance
Actg 5257 RAL VS DRV/r
DRV/r higher proportion of failure but those on RAL more likely to develop resistance
