Download Document

www.guscairns.com
Glasgow HIV Conference
2006
Gus Cairns
UK-CAB 24.11.06
GEMINI Study (saquinavir/r vs
lopinavir/r)



48 weeks, open-label
24-week data presented
75.5% under 50 on LPV; 69.4% on SQV





On-treatment: 85.9% LPV; 79.4% SQV
Same discon. rate both arms (22%)
One LPV-related death (Thai woman, liver failure)
2 VL failures on LPV vs 5 on SQV


Not statistically significant
NB only had 8 weeks in which to be a ‘failure’
>grade 1 raised lipids: 21% SQV; 38% LPV

Statistically significant
www.guscairns.com
UK-CAB 24.11.06
TMC125 trial






Etravirine: new NNRTI
Compared with LPV or ATV + 2 NRTIs
Designed to work with HIV resistant to NVP and EFV
but…
Patients on TMC125 rebounded at 16 weeks: trial
stopped
Why? Patients from Thailand. Brazil, South Africa
50% of Thais and 25% of S Africans had ≥ 3 NNRTI
and ≥ 3 NRTI mutations



Prob due to waiting too long before switching
Even 1 NRTI mutation led to rebound
Can probably only be used in NNRTI sequencing if
patients have no NRTI mutations
www.guscairns.com
UK-CAB 24.11.06
Is drug resistance in decline?


3 studies: resistance on treatment
Portugal: resistance data base: 3093 samples


Italy: Catholic University of Rome: one clinic: 19992005




‘MDR’ HIV (excluded T20, TPV, DRV) declined from 5.7% in
2001/2 to 2.1% in2005/6: 20% decline p.a.: significant
VL failures >1000 declined from 59.5% to 9.4% of patients
Of these patients resistance-tested, proportion with any
resistance went down from 95% to 55%
Sudden decline 2004/5: ascribed to use of boosted PIs and
taking people off thymidine analogues (AZT/d4T)
Spain: Patients with VLs over 1000 declined from
129 out of 1201 patients in 2000 (10.7%) to 41 out
of 1204 patients in 2005 (3.4%).
www.guscairns.com
UK-CAB 24.11.06
Is drug resistance in decline? NAÏVE patients, UK
www.guscairns.com
Tipranavir fails naïve trial
UK-CAB 24.11.06


Two doses of TPV (+100mg or +200mg
RTV) versus LPV/r
At week 60 viral loads under 50 = 72.4% for
lopinavir, 69.9% for tipranavir/r200 and
67.9% for tipranavir/r100.


TPV/r 100 statistically inferior
TPV/r200 produced serious (grade 3 and 4)
raised liver enzymes

17.7% vs 5.9% on TPV/r100 and 3.4% on LPV/r
www.guscairns.com
UK-CAB 24.11.06








Diabetes and d4T
D:A:D study now contains 33,389 patients
952 had diabetes when entering study
745 more got it = 6% a year incidence
d4T increased diabetes risk by 19% a year
spent on the drug
AZT and ddI by 6%
Nevirapine reduced risk by 11% a year
Surprisingly, ritonavir reduced risk by 6% due to better boosted PI regimens?
Surprising no PI association
www.guscairns.com
UK-CAB 24.11.06
Pregnancies in east London





95 pregnancies in 84 HIV+ women in
Newham
41% didn’t know had HIV: 10% diagnosed
last three months
50%! Had viral loads over 50 at delivery
(34/73 = 47%)
14% had VLs over 1000 (10/73)
Why?



PIs suppress viral load slower?
Late presentation – many asylum seekers etc
HAART (instead of AZT monotherapy) 
premature labour: caesareans didn’t go down
www.guscairns.com
UK-CAB 24.11.06
Tenofovir and kidney toxicity










11 posters and 2 oral presentations
Multiple definitions of toxicity
Is associated with tenofovir, at least in comparison
with abacavir
Fairly rare: 0.5-4.0% clinically relevant
Reversible (usually)
Two kidney failure deaths
Other risk factors: older++, other renally toxic
drugs +++, female? HCV?
Possibly less common in Africans
Not always predictable: patients don’t always have
history of kidney probs
BONE mineral loss: significant decline over longterm
www.guscairns.com
UK-CAB 24.11.06
Weight-based ribavirin for
HCV





PRESCO study
Used Pegasys® and 1000 or 122mg RBV cf.
APRICOT study 800mg
Option to extend treatment to 48 weeks
(G2-3) 72 weeks (G1-4)
Sustained viral response: 49.6% for all,
35.6% for genotype 1, 32.6% for genotype
4, 72.4% for genotype 3
Cf. APRICOT 29% for G1 and 62% for G2-3
www.guscairns.com
UK-CAB 24.11.06






Darunavir (TMC114)
resistance
Eleven characteristic mutations
Having one or even two doesn’t confer
clinical resistance
Mostly different from other PI mutations
C. Loveday study: DRV mutations in 14% of
patients failing PIs: only 1.5% with ≥ 3: only
2 patients (out of 885) with 5
Did not occur before 2000 so other PIs can
generate the
DRV failure = failure to all PIs except (in c
40-50% of cases) to tipranavir
www.guscairns.com
UK-CAB 24.11.06
General comments
Get viral loads under 50! Debate on
how soon we should strive to do this
is developing world
 Also applies to children: kids kept on
suboptimal regimens too long
 Trials should stop using VL log drops
as endpoint = ‘success’ and only
measure VL<50

www.guscairns.com