Glasgow HIV Conference 2006

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Glasgow HIV Conference 2006

• Gus Cairns

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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
• Not statistically significant
• 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
• NB only had 8 weeks in which to be a failure
• gtgrade 1 raised lipids 21 SQV 38 LPV
• Statistically significant

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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

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Is drug resistance in decline?

• 3 studies resistance on treatment
• Portugal resistance data base 3093 samples
• MDR HIV (excluded T20, TPV, DRV) declined from
  5.7 in 2001/2 to 2.1 in2005/6 20 decline
  p.a. significant
• Italy Catholic University of Rome one clinic
  1999-2005
• VL failures gt1000 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).

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Is drug resistance in decline? NAÏVE patients, UK
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Tipranavir fails naïve trial

• 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

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Diabetes and d4T

• DAD 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

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Pregnancies in east London

• 95 pregnancies in 84 HIV women in Newham
• 41 didnt 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 didnt go down

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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 dont always
  have history of kidney probs
• BONE mineral loss significant decline over
  long-term

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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

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Darunavir (TMC114) resistance

• Eleven characteristic mutations
• Having one or even two doesnt 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

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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 VLlt50