Transcript HIV Drug Resistance in Well

HIV Drug Resistance in
Well-Resourced Settings
Vincent Marconi, MD
Transmitted Drug Resistance
Acquired Drug Resistance
Europe
North America
Japan
Australia
23K pts from 75 studies in 20 countries
14
12
Percentage
10
Overall
8
NRTI
6
NNRTI
4
PI
2
0
1985-2003
Frentz 2012
2004-2009
25 cohorts with >10K pts (after 1998) 9.5% TDR
Wittkop 2011
*Trend for more NNRTI
VF if TDR even when
fully-active
• Minority Resistance
• PI durability
• More NRTI
mutations
Study
Location
Patients
Period
Overall
NRTI
NNRTI
PI
Jain (Options)
2010
CA
372
acute/early
02-09
16
11
8
4-6
Wheeler 2010
10 states
2K newly
diagnosed
2006
14.6
5.6
7.8
4.5
Poon (CFAR)
2011
WA, MA,
CA
14K mostly
chronic
03-08
14.2%
8.2%
8.3%
4.2%
Markovitz
(CDC) 2011
WA, CO
506
recent/chronic
03-07
17
11
6
3
Frentz 2012*
US + CAN
8K
93-08
12.9
7.4
5.7
3.2
*In contrast to Europe, TDR may have increased in
North America from 11.6% in the early era to 14.3%
in the late era, due to an increase in NNRTI TDR (4.18.3%), while NRTI TDR decreased (8.0-6.4%)
Jain 2010
Essentially unchanged despite improved ART
Transmission early in infection
Poon 2011
TDR led to low CD4 and opposing effects to pVL
Specific mutations (67, 184) impacted VL & CD4
•
•
•
•
New HIV pts TDR doubled 5.9% to 11.9% (2003-2010)
NRTI TDR most prevalent early (4% in 2003)
PI TDR most prevalent late (4.9% in 2010)
Less NNRTI resistance than Europe/NA (0.8%)
Hattori 2010, 2012 (CROI)
Sydney (1992-2001) 185 recent pts N/NRTI TDR peaked
in 1990s and plateau of 10–15% 1999–2001
Victoria (1996-2007) 466 recent pts TDR 16%,
predominantly associated with NRTI and NNRTI; PI
uncommon
RT
PR
Ammaranond 2003
Russell 2009
2⁰
1⁰
Factors contributing to trends are complex
Specific changes over the past 20 years
More tolerable & simpler first-line cART (FDC/STR)
Improved strategies for adherence
Better use of VL monitoring and resistance testing
More effective second-line and salvage agents
(fewer single ARV additions, better ART mgt)
Suboptimal ART (mono-/dual-Tx)  cART, PI/r, TDF
Maybe less transmitted drug resistance?
Less Virologic Failure and Drug Resistance
Study
Location
Patients
Period
Findings
van de
Vijver
2010
15 Euro
sites
2K VF
00-04
80.7% > 1 DRM (NRTI 75.5%, NNRTI
48.5%, PI 35.8); predicted resistance
to most PI/r was 25%
Prosperi
(SEHERE)
2011
7 Euro
sites
12K VF +
3K naïve
controls
99-08
80.1% > 1 DRM (NRTI 67.2%, NNRTI
53.7%, PI 32.4%); with 17.2% tripleclass; decline in overall resistance to
NRTI and PI but not to NNRTI
Gill 2010
BC
5K VF
96-08
DRM 12-fold decrease from 1996 to
2008 (1.73 to 0.13 cases/pt mos tx);
VS increased from 64.7% (2000) to
87.7% (2008)
Buchacz
2012
US –
HOPS
906 > 4
99-08
mos ART
VL >1000
DRM from 88% to 79% (esp PI/r),
decrease in viremic pts
Prosperi 2011
Buchasz 2011
Lima 2008
Hull 2009
Lima 2010
ITT
Genotypes
Gupta 2008
Hogg 2006
Cozzi-Lepri
EUROSIDA 2008
Deeks 2010
Transmitted Drug Resistance
10-17% ARV-naïve patients in Europe, North
America, Japan and Australia have DR > ARV
NNRTI stable or increased over time
Acquired Drug Resistance
VS has increased over time, thus minimizing the
emergence of acquired DR and its subsequent
transmission
DR frequency following VF: NRTI > NNRTI > PI
Mortality association