ART. Switching for toxicity: how and when to switch? Case Discussion ART. Switching for toxicity:...
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ART. Switching for toxicity: how and when to switch? Case Discussion ART. Switching for toxicity: how and when to switch? Case Discussion Luis Soto-Ramírez,
ART. Switching for toxicity: how and when to switch? Case
Discussion ART. Switching for toxicity: how and when to switch?
Case Discussion Luis Soto-Ramrez, MD Head Molecular Virology Unit
Department of Infectious Diseases Instituto Nacional de Ciencias
Medicas y Nutricion Salvador Zubiran Mxico City, MEXICO Luis
Soto-Ramrez, MD Head Molecular Virology Unit Department of
Infectious Diseases Instituto Nacional de Ciencias Medicas y
Nutricion Salvador Zubiran Mxico City, MEXICO
Slide 2
Case JMDA. Male 31 years old, MSM referred to you to evaluate
treatment switch. Smokes 1 pack a day, for the last 10 years.
Weight 93 kg (BMI 29), sedentary. Blood Pressure: 120/85. FH:
Father died at 56 due to MI, had DM type 2. PMH: Diagnosed as HIV
in March 2005 No OI, no co-infections (hep B-C)
Slide 3
Date Started Date Stopped Drug combination Cause of Change
Drawing Date CD4 cel/mm 3 VL copies/ml
24-11-200520-05-20103TC+ZDV+EFV Side effects (dyslipidemia)
10-08-200543229,100 09-11-2007697< 50 01-02-2008754< 50
02-08-2008642< 50 27-03-2009308< 50 27-11-2009468< 40
20-05-2010ACTUALABC+3TC+SQV+RTV28-08-20101,192< 40
25-03-2011973< 40 25-08-2011968< 40 26-01-20121,094< 40
26-10-2012995< 40 28-03-20131,344< 40 Case: JMDA ARV
treatment history
Slide 4
Case JMDA. Question 1 Is this a perfect ART response? 1.Yes
2.No 3.It depends I need more information
Case JMDA. Question 2 What would you do? 1. Treat with fibrate
2. Diet, exercise and quit smoking 3. Both
Slide 8
Case JDMA. Follow up. The patient decrease smoking to half a
pack/day, but stopped the fibrate due to severe muscle cramps. Six
months thereafter, had lost 4 kg, use Omega 3; his viral load is
still undetectable and his lipids are: Triglycerides: 9.50 mmol/l
(842 mg/dl). Total Cholesterol: 3.90 mmol/l ( 151 mg/dl). HDL: 0.80
mmol/l (31-mg/dl).
Slide 9
Framingham Risk.
Slide 10
Case JMDA. Question 3 He is not willing to start a fibrate
again. Should we consider the TG important? 1. Yes 2. No 3.
Depends
Slide 11
Slide 12
Factors associated with mortality in HIV infected patients with
metabolic syndrome
Slide 13
Case JMDA. Question 4 Would you switch treatment to decrease TG
and CV risk? 1. Yes 2. No
Slide 14
Respond to lipid-lowering agents in HIV infected individuals
Retrospective, age-matched study of HIV+ and HIV- veterans with
dyslipidemia BL TC or TGs > 200 mg/dL On lipid-lowering therapy
> 2 months HIV+ subjects on HAART HIV+ subjects less frequently
met NCEP goals after 6 months of treatment for dyslipidemia HIV+
subjects may not be receiving optimal care for dyslipidemia 85% of
HIV- received simvastatin vs 23% of HIV+ Difference in usage likely
due to interactions b/w simvastatin and PIs Hollowell S, et al.
ICAAC 2005. Abstract H-338. P =.033 P =.014 Patients Achieving NCEP
Goal at 6 Months (%) TGLDLHDL 0 20 40 60 TC 80 100 HIV-HIV+ 28 60
25 64 43 58 11
Slide 15
Switch Pis to NNRTIs vs lipid lowering agents Colesterol total
a los 12 meses
Slide 16
Case JMDA. Question 5 Would you switch? 1. Backbone 2. Third
agent 3. Both
Slide 17
Case JMDA. Question 6 Would you do with the backbone? 1.
Continue ABC/3TC 2. Change to TDF/FTC 3. Other
Slide 18
LIPID CHANGES WITH ARV TREATMENT Adapted from: 1. Martin A and
Emery S. Exp Rev Clin Pharmacol 2009;2:381389; 2. Fautkenheuer G,
et al. J Antimicrob Chemother 2012;67:685690; 3. Cohen C, et al.
Lancet 2011;378:229237; 4. Mills AM, et al. AIDS 2009;23:16791688
*Effects shown are for ritonavir-boosted drugs Atazanavir not
licensed for unboosted use in the UK or EU ARV classDrug Effect
Total cholesterolTriglyceridesHDL-CLDL-C NNRTIs Nevirapine
Efavirenz Etravirine 2 No change Rilpivirine 3 No change NRTIs
Stavudine Zidovudine No change Lamivudine No change AbacavirNo
change Abacavir/lamivudine No change Abacavir/lamivudine/zidovudine
No change DidanosineNo change Emtricitabine No change TenofovirNo
change IIs RaltegravirNo change PIs Indinavir* No change Nelfinavir
No change Saquinavir* Lopinavir/ritonavir No change Fosamprenavir*
No change Atazanavir* No change Darunavir/ritonavir 4 No change
Ritonavir (full dose) No change Fusion/ent ry inhibitors
EnfurvitideNo change MaravirocNo change
Slide 19
Slide courtesy of Stefan Mauss, MD Lipid Effects of PIs This
table represents the authors judgment about the relative lipid
effects of the agents listed, based on accumulated data from
studies to date. Different studies have reported varying lipid
effects, probably influenced by stage of HIV infection, geographic
representation, and other cross-study differences. As a result,
some individual studies may seem inconsistent with the ratings in
the table; nevertheless, this table represents the authors best
attempt to reconcile all the available data.
DrugTG/VLDL-CLDL-CHDL-C RTV LPV/RTV // TPV/RTV SQV/RTV FPV/RTV
IDV/RTV DRV/RTV //?? ATV/RTV // NFV ?? ATV /?/? IDV
Slide 20
Case JMDA. Question 7 Would you do switch the third agent to?
1. Nevirapine 2. PI/r 3. Raltegravir 4. Maraviroc
Slide 21
SPIRAL Study: Change (mean) in Fasting Lipids though Week 48.
Martinez E. et al. AIDS 2010; 24: 1697-1707
Slide 22
Case JDMA. Follow up. The patient was switched to
TVD/Raltegravir. According to SPIRAL the changes in lipids would
be: Before switchAfter switch Triglycerides9.50 mmol/l (
842,g/dl)7.50mmol/L (657 mg/dl) Total Cholesterol3.90 mmol/L (151
mg/dl)3.48 mmol/L (135mg/dl) HDL0.80mmol/L (31 mg/dl)0.77 mmol/L
(30 mg/dl) Framingham 10 year general CVD prediction 3.7%2%
Slide 23
Switch strategies for virologically suppressed patients
(confirmed plasma viral load < 50 c/mL) Indications: 1. Switch
for toxicity 2. Switch for prevention of long-term toxicity 3.
Switch for simplification Principles: 1. A boosted PI may be
switched for simplification, prevention or improvement of metabolic
abnormalities or adherence facilitation to unboosted atazanavir, an
NNRTI or raltegravir only if full activity of the 2 NRTIs remaining
is guaranteed. 2. Simplification of a complex multidrug regimen in
antiretroviral-experienced patients with 1) substitution of drugs
difficult to administer (enfuvirtide) and/or with poor activity
(NRTI in case of multiple NRTI resistance) and/or poor tolerability
and 2) addition of new well-tolerable, simpler and active agent(s).
3. Bid to qd NRTI switch for simplification, prevention of
long-term toxicity. 4. Intra-class switch if drug-specific related
adverse event. 5. Review the complete ARV history and available
resistance test results. 6. Avoid switching to a drug with a low
genetic barrier in the presence of a backbone compromised by the
possibility of archived class resistance.
Slide 24
Conclusions The importance of TG elevations in HIV+ individuals
should be determined Switches can be good specially in the long
run, but are not the complete solution for dislypidemia Specific
switch guidelines should be created For dyslipidemia and CV risk
For other metabolic complications For kidney damage For bone
disease
