History

1
Strategies for Initial Therapy What to Start?
Case-based Presentation
M. Keith Rawlings, MD Medical DirectorAIDS Arms,
Inc
The International AIDS SocietyUSA
2
Antiretroviral Naive Patient with Cardiovascular
RiskCase 1
From MK Rawlings, MD, at 11th RW Program Clinical
Update, IASUSA.
3
History

• 49-year-old Black male recently diagnosed with
  HIV-1 infection, which he suspects he may have
  acquired approximately 7 years ago through
  male-to-male sexual contact with a former
  co-worker.

4
History

• Pt is married with no children works as a nurse.
• His wife has recently been tested for HIV but the
  results are pending.
• Smokes 15 cigarettes/day x 25 years.
• Does not drink alcohol.
• H/O hypertension.
• FHx brother had CABG at age 45 years.

5
Initial Labs

• CD4 250 cells/mm3
• HIV-1 RNA level 135,000 copies/mL
• Hepatitis A and C negative
• Antibodies show previous successful vaccination
  for HBV

6
QUESTION

• How would you proceed with ARV management?
• Start pt on fixed dose NRTI EFV
• Start pt on fixed dose NRTI ritonavir-boosted
  PI
• Defer antiretroviral therapy
• Perform a cardiovascular risk assessment before
  making further treatment decisions
• Do something else

7
QUESTION

• How would you proceed with ARV management?
• Start pt on fixed dose NRTI EFV
• Start pt on fixed dose NRTI ritonavir-boosted
  PI
• Defer antiretroviral therapy
• Perform a cardiovascular risk assessment before
  making further treatment decisions
• Do something else

8
Cardiovascular Disease (CVD) Risk

• Fasting glucose
• 140 mg/dL
• Fasting lipids
• TC 243 mg/dL
• HDL 31 mg/dL
• TGs 177 mg/dL
• LDL 135 mg/dL

• Physical exam
• height 57"
• weight 172.5 lbs
• BMI 27 kg/m2
• Blood pressure
• 166/95 mm Hg

9
Cardiovascular Disease (CVD) Risk

• Based on lab and physical exam findings the
  patients has a 10-year risk of developing a
  myocardial infarction or coronary death using
  the Framingham Risk Assessment Tool of 30

10
QUESTION

• Based on the current data, what is your next step
  in management?
• Start PI-sparing or ATV-based regimen avoid d4T
• Refer to dietitian regarding diet and exercise
  counsel patient to stop smoking and start
  PI-sparing or ATV-based regimen avoid d4T
• Refer to dietitian regarding diet and exercise
  counsel patient to stop smoking and start d4T
  3TC LPV/r
• Do something else

11
QUESTION

• Based on the current data, what is your next step
  in management?
• Start PI-sparing or ATV-based regimen avoid d4T
• Refer to dietitian regarding diet and exercise
  counsel patient to stop smoking and start
  PI-sparing or ATV-based regimen avoid d4T
• Refer to dietitian regarding diet and exercise
  counsel patient to stop smoking and start d4T
  3TC LPV/r
• Do something else

12
MANAGEMENT

• Patient manages to lose about 18 lbs of body
  weight over the next 6 months with the help of
  the dietitian
• Swims 30 minutes/day, 3 days a week
• However continues to smoke
• ART fixed dose TDF/FTC ritonavir-boosted ATV is
  initiated

13
Six months F/U

• BP ? to 130/90 mmHg
• fasting glucose 102 mg/dL
• HgbA1c 6.4
• fasting lipids
• TC 208 mg/dL
• HDL 34.8 mg/dL
• TG 142 mg/dL
• LDL 100.5 mg/dL

• HIV-1 VL lt 50 copies/mL
• CD4 - 340 cells/mm3
• Framingham Risk score dropped to 17
• However, patient is now jaundiced

14
QUESTION

• How would you address the patients complaint of
  jaundice?
• Identify type of bilirubin, perform additional
  LFT (including transaminase levels), and act
  accordingly
• Immediately discontinue ATV/r and replace with
  NVP or EFV
• Immediately discontinue ATV/r and replace with
  LPV/r

15
QUESTION

• How would you address the patients complaint of
  jaundice?
• Identify type of bilirubin, perform additional
  LFT (including transaminase levels), and act
  accordingly
• Immediately discontinue ATV/r and replace with
  NVP or EFV
• Immediately discontinue ATV/r and replace with
  LPV/r

16
DIAGNOSTIC WORK-UP

• Labs
• Conjugated hyperbilirubinemia
• Transaminase elevation without prothrombin time
  prolongation.
• Serologic HAV IgM antibodies
• suggesting acute hepatitis A infection.

17
CLINICAL MANAGEMENT

• ATV/r was D/Ced and EFV started
• to avoid confusion with the clinical assessment
  of jaundice despite the presence of acute HAV
  infection
• Jaundice resolved after 6 wks
• bilirubin and transaminases levels return to
  normal
• 3 months HIV-1 RNA lt 50 copies/mL
• ? CD4 cell counts 380 cells/mm3
• Fasting lipids essentially unchanged
• TG 168 mg/dL
• HDL 42.5 mg/dL

18
Initial ARV in Patient with Renal Impairment and
Hepatitis B Co-infectionCase 2
From MK Rawlings, MD, at 11th RW Program Clinical
Update, IASUSA.
19
HISTORY

• 45-year-old Hispanic female recently diagnosed
  with HIV-1 infection. Patient first tested 1 year
  ago after her divorce.
• Was tested by primary care provider 6 months ago
  as part of a w/u for newly developed scleral
  icteris.

Rawlings Case 2
20
HISTORY

• Recently divorced, works as a bookkeeper
• Is the primary care giver for two teenage
  children and her mother who has Alzheimer
• PMHx remarkable for HTN controlled on ACE
  inhibitor
• Reports 2 episodes of unprotected sex with new
  partners since divorce
• Never been on ARV

Rawlings Case 2
21
INITIAL LABS

• CD4 108 cells/mm3
• PCR 120,000 copies/mL
• Geno 103N, 184v
• Creat 1.5
• MDRD 48
• Cr Clearance 42.7
• U/A 1 protein

• HepBsAg
• HepBcAb
• HBV PCR 2.2 mil
• HAV HCV neg
• AST gt5x nl
• ALT gt5x nl
• Fasting lipids normal
• HLA-B5701 positive

Rawlings Case 2
22
PHYSICAL EXAM

• Hgt 54 Wgt 127 lbs
• BMI 21.8
• BP 124/78 on ACE inhibitor
• Renal biopsy reveals no evidence of HIV
  Associated Nephropathy (HIVAN)

Rawlings Case 2
23
QUESTION

• Based on these findings, which DHHS guidelines
  recommended ARV option would be your choice?
• Fixed-dose TDF/FTC LPV/r
• Fixed-dose TDF/FTC ATZ/r
• Fixed dose TDF/FTC /EVF
• Fixed-dose 3TC/ABC LPV/r
• Fixed-dose 3TC/ABC ATZ/r
• None of the above

Rawlings Case 2
24
QUESTION

• Based on these findings, which DHHS guidelines
  recommended ARV option would be your choice?
• Fixed-dose TDF/FTC LPV/r
• Fixed-dose TDF/FTC ATZ/r
• Fixed dose TDF/FTC /EVF
• Fixed-dose 3TC/ABC LPV/r
• Fixed-dose 3TC/ABC ATZ/r
• None of the above

Rawlings Case 2
25
DISCUSSION

• Transmitted viral resistance
• Renal insufficiency
• HLA positive
• Hepatitis B co-infection

Rawlings Case 2
26
CLINICIAL MANAGEMENT

• Pt was started on LPV/r TDF/FTC (q 48 hrs)
• After 3 months
• CD4 198 cells/mm3
• PCR 850 copies/mL
• Creat 1.2
• MDRD 63
• Cr Clearance 78.7
• U/A 1 protein
• Pt complains of frequent diarrhea
• BP 134/80 on ACE inhibitor

Rawlings Case 2
27
QUESTION

• Given level of viral load how would you adjust
  antiretroviral therapy?
• No change
• D/C TDF/FTC, continue LPV/r
• Continue TDF/FTC, D/C LPV/r
• Change entire regimen

Rawlings Case 2
28
CLINICIAL MANAGEMENT

• Pt was maintained on current ARV with repeat labs
  3 months later.
• CD4 213 cells/mm3
• PCR 750 copies/mL
• Creatinine 1.3
• MDRD 53
• Cr Clearance 68.3
• U/A neg protein
• HBV PCR 134,000
• Reports that frequent diarrhea is interfering
  with work and elder care.

Rawlings Case 2
29
QUESTION

• Given level of viral load and AE of diarrhea how
  would you adjust antiretroviral therapy?
• No change
• D/C TDF/FTC, continue LPV/r
• Continue TDF/FTC, D/C LPV/r
• Change entire regimen

Rawlings Case 2
30
CLINICIAL MANAGEMENT

• Pt switched from TDF/FTC LPV/r
• New regimen DRV/r Etravirine TDF/FTC
• 3 months later
• CD4 291 cells/mm3
• PCR lt48 copies/mL
• Creat 1.1
• MDRD gt60
• U/A neg protein

Rawlings Case 2