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HIV treatment is::

Primary care with “benefits”
the scoop : :
• Guidelines Rule

• treat anyone who is willing

• compliance is KING

• beware of the drugs
DHHS Guidelines for the Use of
Antiretroviral Agents in HIV-1-Infected
        Adults and Adolescents

         www.aidsinfo.nih.gov
who to treat : :

• CD4 < 200, 350, 500, what next?

• treatment is prevention
  – serodiscordant couples
  – pregnancy



• think of the viral load of the community
who to treat::
Clinical Category          CD4 Count                  Recommendation

AIDS defining illness or   Any value                  TREAT
severe symptoms*
Pregnancy, HIVAN,          Any value                  TREAT
tx HBV co-infection
Asymptomatic               <350/mm3                   TREAT

Asymptomatic               350-500/mm3                55% strongly
                                                      45% moderately
Asymptomatic               >500/mm3                   50% favored
                                                      50% optional


                               *http://www.aegis.com/topics/definition.html
HPTN 052
who not to treat::
• anyone who is not going to take their medicine
        AKA: Non-compliance

  It is really more like Why Not to treat

  – when you know the details of a situation, the
    situation is unchanged. when you don’t know the
    details of a situation, it still is unchanged.
   Zen proverb
how to treat::
• is this person sick?
• No
how to treat::
• is this person sick?
  – CD4 < 200
  – CD4 < 50
  – Symptoms i.e. opportunistic infection
CD4 < 200
•   At risk for PCP
•   GI symptoms?
•   Candidiasis?
•   Rash?
•   Needs meds as soon as ready
CD4 < 50
•   This group of patients is TROUBLE
•   Must look for OI’s, frequently more than 1
•   IRIS is common
•   TB is bad in this group, skin test not reliable
•   1/3 mortality in first year after diagnosis
what to use::
therapy naïve regimens::
• NNRTI based-regimen
  – efavirenz/tenofovir/emtricitabine
• PI based-regimens
  – atazanavir/ritonavir/tenofovir/emtricitabine
  – darunavir/ritonavir/tenofovir/emtricitabine
• Integrase Inhibitor based-regimen
  – raltegravir/tenofovir/emtricitabine
• Pregnancy
  – lopinavir/ritonavir/zidovudine/lamivudine
how it works::

1. Fusion

2. Reverse transcription

3. Integration

4. Transcription

5. Assembly of virus particles

6. Budding of virus particles
efavirenz
• Category D, neural tube defects
   – Recommend 2 birth control methods, negative HCG
     prior to initiation
• Caution with use in prior psychiatric disease
• False + cannabinoid & benzos on screening
• AEs: Drowsiness, dizziness, insomnia, abnormal
  dreaming, agitation
• Take at bedtime on an empty stomach to ↓CNS SE
   • If need to eat, avoid taking with fatty food
• Rash is possible, as long as no other symptoms keep
  taking meds but need medical eval ASAP
efavirenz rash
efavirenz rash
tenofovir/emtricitabine ::
• Generally well tolerated: gas, headaches
• Fanconi’s syndrome and renal insufficiency
   • Check urinalysis every 6 months; PO4 suggested
• Hyperpigmentation possible
• Osteopenia
• Active against HBV
   • Know pt’s status and counsel accordingly
• Once daily with or without food
• Both agents need renal adjustment when <50ml/min
Fanconi’s Syndrome::
• The Fanconi syndrome refers to a generalized
  impairment in proximal tubular function
  leading to urinary wasting of compounds
  normally reabsorbed in the proximal tubule.
  The consequences are hypophosphatemia
  (which can lead to osteomalacia), renal
  glucosuria, hypouricemia, aminoaciduria, and
  proximal renal tubular acidosis due to
  bicarbonate loss in the urine (Up To Date).
Preferred Protease Inhibitors
atazanavir/ritonavir
• Interacts with PPIs, antacids, & H2A
   • All available OTC
• Increased unconjugated bili
   • Scleral icterus or jaundice
• Take with food
• Less impact on lipids
• Prolonged PR interval, asymptomatic 1st degree
  AV block
• 3 total: 1 atazanavir, 1 ritonavir, 1
  tenofovir/emtricitabine
darunavir/ritonavir
•   CAUTION with sulfa allergy (not contraindicated)
•   Take with food
•   Rash 10%
•   Abdominal pain
•   Headache
•   Hepatotoxicity
•   Diarrhea (usually less than Kaletra)
•   4 tablets total: 1 ritonavir, 2 darunavir, 1
    tenofovir/emtricitabine
preferred integrase inhibitor::
raltegravir::
• Taken BID
• Minimal drug interactions
   • PPI increases raltegravir
• AEs: diarrhea, nausea, headache, and pyrexia
• Increased ALT, AST, CPK possible
   • Myopathy and rhabdomyolysis reported
• 3 tablets total: 1 raltegravir BID, 1
  tenofovir/emtricitabine
compliance ::
• The tendency to yield to others especially in a
  weak or subservient way
• The strain of an elastic body expressed as a
  function of the force applied to it
• How many doses have you missed in the last
  month?
• How many have you taken late?
compliance ::
• How many doses have you missed in the last
  month?
• How many have you taken late?

• WHY?
• How can we improve this?
compliance ::
• 95% compliance is MINIMUM required to
  receive maximal drug benefit
• 19/20 days or once per month for a once daily
  drug
• compare self-report to pill counts
• works great with diabetes too
beware of the drugs::
bone disease::
•   Osteoppenia
•   Avascular Necrosis
•   Vitamin D metabolism impacted
•   Osteoporosis down the road?
AVN on the left
energy metabolism complications::
•   Lactic acidosis
•   Lipoatrophy
•   Fat redistribution
•   Hyperlipidemia
•   Glucose intolerance
•   Hypertriglyceridemia
Lipoatrophy
renal complications::
• Fanconi’s syndrome
• Stone disease
Fanconi’s Syndrome::
• The Fanconi syndrome refers to a generalized
  impairment in proximal tubular function
  leading to urinary wasting of compounds
  normally reabsorbed in the proximal tubule.
  The consequences are hypophosphatemia
  (which can lead to osteomalacia), renal
  glucosuria, hypouricemia, aminoaciduria, and
  proximal renal tubular acidosis due to
  bicarbonate loss in the urine (Up To Date).
Fanconi’s labs::
• Creat 1.0 ->1.4->1.2
• PO4 3.0 ->2.1->2.9

• Urine glucose 150-> neg
• Urine protein 100 mg/dl-> neg
resources::
•   consult with US – AFCAHN, phone, email
•   Guidelines
•   Warmline is AWESOME
•   Community providers

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Primary Care Perspective on HIV Treatment Bloomquist

  • 1. HIV treatment is:: Primary care with “benefits”
  • 2. the scoop : : • Guidelines Rule • treat anyone who is willing • compliance is KING • beware of the drugs
  • 3. DHHS Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents www.aidsinfo.nih.gov
  • 4.
  • 5. who to treat : : • CD4 < 200, 350, 500, what next? • treatment is prevention – serodiscordant couples – pregnancy • think of the viral load of the community
  • 6. who to treat:: Clinical Category CD4 Count Recommendation AIDS defining illness or Any value TREAT severe symptoms* Pregnancy, HIVAN, Any value TREAT tx HBV co-infection Asymptomatic <350/mm3 TREAT Asymptomatic 350-500/mm3 55% strongly 45% moderately Asymptomatic >500/mm3 50% favored 50% optional *http://www.aegis.com/topics/definition.html
  • 8. who not to treat:: • anyone who is not going to take their medicine AKA: Non-compliance It is really more like Why Not to treat – when you know the details of a situation, the situation is unchanged. when you don’t know the details of a situation, it still is unchanged. Zen proverb
  • 9. how to treat:: • is this person sick? • No
  • 10. how to treat:: • is this person sick? – CD4 < 200 – CD4 < 50 – Symptoms i.e. opportunistic infection
  • 11. CD4 < 200 • At risk for PCP • GI symptoms? • Candidiasis? • Rash? • Needs meds as soon as ready
  • 12. CD4 < 50 • This group of patients is TROUBLE • Must look for OI’s, frequently more than 1 • IRIS is common • TB is bad in this group, skin test not reliable • 1/3 mortality in first year after diagnosis
  • 14. therapy naïve regimens:: • NNRTI based-regimen – efavirenz/tenofovir/emtricitabine • PI based-regimens – atazanavir/ritonavir/tenofovir/emtricitabine – darunavir/ritonavir/tenofovir/emtricitabine • Integrase Inhibitor based-regimen – raltegravir/tenofovir/emtricitabine • Pregnancy – lopinavir/ritonavir/zidovudine/lamivudine
  • 15. how it works:: 1. Fusion 2. Reverse transcription 3. Integration 4. Transcription 5. Assembly of virus particles 6. Budding of virus particles
  • 16. efavirenz • Category D, neural tube defects – Recommend 2 birth control methods, negative HCG prior to initiation • Caution with use in prior psychiatric disease • False + cannabinoid & benzos on screening • AEs: Drowsiness, dizziness, insomnia, abnormal dreaming, agitation • Take at bedtime on an empty stomach to ↓CNS SE • If need to eat, avoid taking with fatty food • Rash is possible, as long as no other symptoms keep taking meds but need medical eval ASAP
  • 19. tenofovir/emtricitabine :: • Generally well tolerated: gas, headaches • Fanconi’s syndrome and renal insufficiency • Check urinalysis every 6 months; PO4 suggested • Hyperpigmentation possible • Osteopenia • Active against HBV • Know pt’s status and counsel accordingly • Once daily with or without food • Both agents need renal adjustment when <50ml/min
  • 20. Fanconi’s Syndrome:: • The Fanconi syndrome refers to a generalized impairment in proximal tubular function leading to urinary wasting of compounds normally reabsorbed in the proximal tubule. The consequences are hypophosphatemia (which can lead to osteomalacia), renal glucosuria, hypouricemia, aminoaciduria, and proximal renal tubular acidosis due to bicarbonate loss in the urine (Up To Date).
  • 22. atazanavir/ritonavir • Interacts with PPIs, antacids, & H2A • All available OTC • Increased unconjugated bili • Scleral icterus or jaundice • Take with food • Less impact on lipids • Prolonged PR interval, asymptomatic 1st degree AV block • 3 total: 1 atazanavir, 1 ritonavir, 1 tenofovir/emtricitabine
  • 23. darunavir/ritonavir • CAUTION with sulfa allergy (not contraindicated) • Take with food • Rash 10% • Abdominal pain • Headache • Hepatotoxicity • Diarrhea (usually less than Kaletra) • 4 tablets total: 1 ritonavir, 2 darunavir, 1 tenofovir/emtricitabine
  • 25. raltegravir:: • Taken BID • Minimal drug interactions • PPI increases raltegravir • AEs: diarrhea, nausea, headache, and pyrexia • Increased ALT, AST, CPK possible • Myopathy and rhabdomyolysis reported • 3 tablets total: 1 raltegravir BID, 1 tenofovir/emtricitabine
  • 26. compliance :: • The tendency to yield to others especially in a weak or subservient way • The strain of an elastic body expressed as a function of the force applied to it • How many doses have you missed in the last month? • How many have you taken late?
  • 27. compliance :: • How many doses have you missed in the last month? • How many have you taken late? • WHY? • How can we improve this?
  • 28. compliance :: • 95% compliance is MINIMUM required to receive maximal drug benefit • 19/20 days or once per month for a once daily drug • compare self-report to pill counts • works great with diabetes too
  • 29. beware of the drugs::
  • 30. bone disease:: • Osteoppenia • Avascular Necrosis • Vitamin D metabolism impacted • Osteoporosis down the road?
  • 31. AVN on the left
  • 32. energy metabolism complications:: • Lactic acidosis • Lipoatrophy • Fat redistribution • Hyperlipidemia • Glucose intolerance • Hypertriglyceridemia
  • 34. renal complications:: • Fanconi’s syndrome • Stone disease
  • 35. Fanconi’s Syndrome:: • The Fanconi syndrome refers to a generalized impairment in proximal tubular function leading to urinary wasting of compounds normally reabsorbed in the proximal tubule. The consequences are hypophosphatemia (which can lead to osteomalacia), renal glucosuria, hypouricemia, aminoaciduria, and proximal renal tubular acidosis due to bicarbonate loss in the urine (Up To Date).
  • 36. Fanconi’s labs:: • Creat 1.0 ->1.4->1.2 • PO4 3.0 ->2.1->2.9 • Urine glucose 150-> neg • Urine protein 100 mg/dl-> neg
  • 37. resources:: • consult with US – AFCAHN, phone, email • Guidelines • Warmline is AWESOME • Community providers

Editor's Notes

  1. HIV transmission between sero-discordant partners. Dash line is with + partner delaying treatment, solid line is with partner treated early. Clinical events were TB, candidiasis, pneumocysitits. The composite group was #C plus transmission to seronegative partner