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Complications of HAART

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Five weeks ago Mr B has started HAART with a combination of d4T, 3TC plus NVP. ... both his fingers and toes and he dislikes wearing shoes. ... – PowerPoint PPT presentation

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Title: Complications of HAART


1
Complications of HAART
  • Elly Katabira
  • Makarere University
  • Uganda
  • Peter Schellekens
  • PharmAccess

2
Case Mr. F
3
Case Mr. F
  • 34 years old
  • HIV since 2000
  • Started with HAART in 2001
  • Returns home after a long stay abroad

4
Case Mr. F
  • Question summarize what you need to know

5
Case Mr. F
  • Main points
  • Current medical condition
  • Clinical immunological status

6
Case Mr. F
  • Regimen has remained the same because of good
    results
  • Regimen d4T, 3TC, LPV/r

7
Case Mr. F
  • Feeling well, but he doesnt like his family
    asking him if he feels ill because his face is so
    thin
  • Examining him you notice that he indeed has
    sunken cheeks and also skinny limbs.

8
Lipodystrophy syndrome associated with HAART
  • Changes in fat distribution
  • Subcutaneous fat wasting
  • Fat accumulation
  • Intra-abdominal fat
  • Localised
  • Breast enlargement
  • Buffalo hump
  • Lipomata
  • Metabolic complications
  • Dyslipidemia
  • Insulin resistance
  • Diabetes mellitus (rare)

9
Case Mr. F - follow up
  • Assuming that the HAART regimen is causing these
    complications
  • Which drug is most likely to cause these
    symptoms?
  • Do you know how often and when this side effect
    may occur?
  • Is the mechanism of this side effect known?
  • What would you advise your patient?
  • Is switching indicated ? If yes, which
    alternative drug/regimen would you consider?

10
HAART-related metabolic complications
Lipid(cholesterol/triglyceride) abnormalities
Abnormal blood sugar (glucose) metabolism
Body fat redistribution
Mitochondrial toxicity
Haematological toxicity
  • One syndrome or several?
  • One aetiology or multifactorial?

11
Case Mrs U.M.
12
Case Mrs U.M.
  • 22 years old
  • Known HIV positive since 2004
  • Question
  • Summarize what you need to know before a decision
    on HAART can be made ?

13
Case Mrs U.M.
  • Main points
  • Current medical condition
  • Clinical and immunologic status
  • Prior use of HAART?
  • If HAART is indicated, assess readiness for HAART
    (barriers to adherence)

14
Case Mrs U.M.
  • Which regimen is the first line in your clinic?
  • Why has this regimen been chosen?
  • Are you satisfied with this regimen or would you
    prefer another? Please explain your answer
  • Which alternative first line regimens are
    available in your clinic?

15
Case Mrs UM-follow-up 1
  • Mrs UM is started on HAART
  • ZDV, 3TC and NVP
  • She responds well, her clinical condition
    improves
  • Her CD4 increases from 95/mm3 to 120/mm3 in a
    year
  • Question
  • Are you content with this rise in CD4?
  • Please explain your answer

16
HAART CD4 increase(Example from literature)
17
Case Mrs U.M.
  • Median CD4 increase predicted in literature
  • 100-200 cells/ml in first year
  • 100 cells/ml in next years
  • Some patients show slow CD4 recovery, whereas
    their clinical condition improves
  • What will be your strategy in this patient?

18
Possible strategy in this patient
  • Continue HAART and OI prophylaxis
  • Many patients remain in good clinical condition
  • As long as HAART plus cotrimoxazole prophylaxis
    is taken well can remain free of opportunistic
    diseases for years

19
Mrs UM-follow-up 2
  • After 2 years of HAART Mrs U.M. comes for a
    follow-up visit and tells you that she doesnt
    feel very well
  • She has lost a few kilos in the previous months,
    and suffered from periods of oral thrush
  • Questions
  • What will you do and why?
  • Are there reasons to suspect failure of the HAART
    treatment?

20
Definitions of therapy failure
  • Treatment failure can be defined as
  • Clinical failure and/or
  • Immunologic failure and/or
  • Virologic failure

21
Clinical criteria of HAART failure
  • Occurrence of new OI or malignancy signifies
    clinical disease progression after at least 6
    months of HAART
  • Must be differentiated from IRIS
  • Recurrence of previous OI (caution since
    reinfection may occur)
  • Onset of WHO 3 or 4 conditions

22
Immunologic criteria of failure
  • Return of CD4 T-cell level to pre-therapy
    baseline (exclude transient CD4 T-cell decrease
    caused by concomitant infection)
  • gt 50 fall from therapy CD4 peak level while on
    HAART (again, exclude transient CD4 T-cell
    decrease caused by concomitant infection)

23
Virologic criteria of failure
  • Failure to achieve undetectable viral load within
    6 months of HAART
  • Or
  • Any sustained return of the viral load after
    having been undetectable
  • The level of undetectability depends on the
    measurement technique used in the laboratory

24
Causes of treatment failure
  • Poor adherence
  • Viral resistance to one or more antiretroviral
    drugs
  • Use of less potent regimen
  • Impaired drug absorption
  • Altered drug pharmacokinetics (e.g interaction
    with other drugs)

25
Case Mrs UM
  • Suppose
  • CD4 is now 150/mm3. What will you do?
  • And
  • If CD4 has decreased to 110/mm3, will that
    influence your decision?

26
Mrs UM Follow-up 3
  • Then Mrs UM tells you that she has taken her
    medication irregularly during the past 5 months
    or so
  • She thought that she didnt need the pills
    anymore, because a traditional healer told her
    she was cured
  • Now she notices that her condition is worsening
    and she is motivated to restart if you think that
    this is needed

27
Case Mrs UM
  • What will you advise?
  • If you decide to restart HAART would you choose
    her old regimen or would you advise differently?
  • Explain your answer
  • Which alternative regimens would be a good choice
    taking into account the resistance patterns that
    may have occurred?

28
Case Mrs UM
  • Feedback
  • Discuss second-line options

29
Toxicity cases
30
Case 1. Mrs. A
  • Mrs A, 25 years old visits your office
  • She began HAART with ZDV, 3TC and NVP 4 weeks
    ago.
  • She feels nauseous after taking her pills and has
    vomited several times in the past weeks

31
Case 1. Mrs. A
  • Mrs A, 25 years old visits your office
  • She began HAART with ZDV, 3TC and NVP 4 weeks
    ago.
  • She feels nauseous after taking her pills and has
    vomited several times in the past weeks
  • Which drug is most likely to cause these symptoms
    ?
  • Do you know how often and when this side effect
    may occur ?
  • Is the mechanism of this side effect known ?
  • What would you advise your patient ?
  • Is switching indicated ? If yes, which
    alternative drug would you consider ?

32
Case 2. Mr B
  • Five weeks ago Mr B has started HAART with a
    combination of d4T, 3TC plus NVP. The advice was
    given to start with one pill of NVP for the first
    two weeks, increasing after 2 weeks to twice
    daily.
  • Mr B has now come into your clinic showing a fine
    rash all over his body. Mr B wants to know if he
    should stop or continue with the therapy, given
    the rash all over his body.

33
Case 2. Mr B
  • Five weeks ago Mr B has started HAART with a
    combination of d4T, 3TC plus NVP. The advice was
    given to start with one pill of NVP for the first
    two weeks, increasing after 2 weeks to twice
    daily.
  • Mr B has now come into your clinic showing a fine
    rash all over his body. Mr B wants to know if he
    should stop or continue with the therapy, given
    the rash all over his body.
  • Why was Mr B advised to start with one pill of
    NVP instead of the full dose ? Explain the
    background of this advice
  • Which drug is most likely to cause these symptoms
    ?
  • Do you know how often and when this side effect
    may occur ?
  • Is the mechanism of this side effect known ?
  • What would you advise your patient ?
  • Is switching indicated ? If yes, which
    alternative drug would you consider ?

34
Case 3. Mr C
  • Mr. C has been on HAART for three months. He
    feels depressed and is considering stopping the
    medication. He believes the discomfort he feels
    at the moment has become unbearable.

35
Case 3. Mr C
  • Mr. C has been on HAART for three months. He
    feels depressed and is considering stopping the
    medication. He believes the discomfort he feels
    at the moment has become unbearable.
  • Which drug is most likely to cause these symptoms
    ?
  • Do you know how often and when this side effect
    may occur ?
  • Is the mechanism of this side effect known ?
  • What would you advise your patient ?
  • Is switching indicated ? If yes, which
    alternative drug would you consider

36
Case 4. Mr D
  • Mr. D is on a regimen with d4T, 3TC and EFV for 6
    months now.
  • For the last few weeks he has sometimes felt a
    tickling in both his fingers and toes and he
    dislikes wearing shoes.
  • He asks you why he has these symptoms and what he
    can do about them.

37
Case 4. Mr D
  • Mr. D is on a regimen with d4T, 3TC and EFV for 6
    months now.
  • For the last few weeks he has sometimes felt a
    tickling in both his fingers and toes and he
    dislikes wearing shoes.
  • He asks you why he has these symptoms and what he
    can do about them.
  • Which drug is most likely to cause these symptoms
    ?
  • How often does this side effect occur ?
  • Is the mechanism of this side effect known ?
  • What would you advise your patient ?
  • Is switching indicated ? If yes, which
    alternative drug/regimen would you consider ?

38
Case 5. Mrs E
  • Because of failure, Mrs. E switches to a HAART
    regimen consisting of ABC, ddI and
    Lopinavir/ritonavir .
  • After 3 weeks she calls you. Everything was going
    fine, but now she feels weak, has a sore throat
    and some diarrhoea. Moreover, a fine rash has
    occurred all over her body. She asks you if
    these symptoms are related to her current
    medication.

39
Case 5. Mrs E
  • Because of failure, Mrs. E switches to a HAART
    regimen consisting of ABC, ddI and
    Lopinavir/ritonavir .
  • After 3 weeks she calls you. Everything was going
    fine, but now she feels weak, has a sore throat
    and some diarrhoea. Moreover, a fine rash has
    occurred all over her body. She asks you if
    these symptoms are related to her current
    medication.
  • Which drug is most likely to cause these symptoms
    ?
  • How often does this side effect occur ?
  • Is the mechanism of this side effect known ?
  • What would you advise your patient ?
  • Is switching indicated ? If yes, which
    alternative drug/regimen would you consider ?
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