Challenging Cases from the Clinic

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Challenging Cases from the Clinic
Eric S. Daar, MDProfessor of MedicineDavid
Geffen School of Medicine at University of
California Los Angeles
International AIDS SocietyUSA
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Current challenges facing treatment-experienced
patients

• Adherence
• Drug resistant virus
• On therapy
• Off therapy
• Persistent low-level viremia
• Poor immune reconstitution
• Drug toxicity
• Comorbid conditions
• Coinfection
• Metabolic, renal, hepatic dysfunction

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Patient NL

• 43-year-old man presents to ED with four weeks
  fever, increasing DOE, cough and weight loss
• Known to be HIV-infected since 2000 with
  intermittent ARV therapy in Texas prior to
  stopping all meds and moving to Los Angeles
  approximately 12 months ago
• Lowest CD4 in past was 25 cells/uL
• Patient states last CD4 was 290 cells/uL but not
  aware of previous viral loads
• ARVs changed several times in the past he is
  aware of having received at least ZDV, 3TC, d4T,
  TDF, EFV, NFV, LPV/r and most recently DRV/r

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Patient NL

• Physical exam
• T-103.2o F, BP 110/60, HR 110 regular, RR 25, RA
  pulse ox 88 (RA ABG 7.45/30/55)
• Dyspneic, thin, oral thrush, onychomycosis
• Labs
• HCT 32, normal liver enzymes, creatinine 0.9
  mg/dL, LDH 722 Units/L
• CD4 12 cells/uL
• Started on TMP/SMX and prednisone

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Immediate vs. Deferred ARVs during Acute OI
ACTG 5164
HR 0.53 Immediate versus Deferred 95 CI
0.30, 0.92, p0.023
Zolopa AR, et al. PLoS ONE 20094e5575.
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Patient NL Clinical course

• It is decided that ARV therapy would not be
  started during the acute illness
• Patient responds to therapy and BAL confirms
  diagnosis of PCP
• Patient is discharged and follows up in clinic
  post discharge and then again one week later with
  marked improvement in status and states ready to
  start ARVs
• CD4- 10 cells/uL
• HIV RNA 1.2 million c/mL
• No information regarding previous treatment has
  become available

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Disappearance of Resistance after Treatment
Interruption
Deeks SG, et al. N Engl J Med 2001344 477-80.
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BENCHMRK-1 and -2 VL lt50 c/mL at Week 24 by
Specific Agents in OBR
of pts with HIV RNA lt50 c/mL at Week 24 by
selected ARTs in OBT
Mean ? from BL
Enfuvirtide
N
Darunavir
80
44


74
23
45
82

-
50
24
78
68
-

48
48
191
62
-
-
91
22
First use in OBT - Not used in OBT
0
20
40
60
80
100
Virological failures carried forward ARTs
antiretroviral therapies
Cooper DA, et al. NEJM 2008 359355-365.
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Patient NN

• 45-year-old AA man diagnosed with HIV and Candida
  esophagitis
• CD4 count- 20 cells/uL
• HIV RNA- 476,000 c/mL
• History of HTN
• No drug or alcohol use
• Labs normal except CrCl- 61 mL/min, 1
  proteinuria, ALT- 80-100 U/L
• HCV-negative
• HBsAg, HBeAg-neg, HBV DNA gt1 million copies/mL
• Baseline HIV drug resistance GT- wild type

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IAS-USA Guidelines When to Initiate Therapy in
Treatment-Naïve Patients
Hammer SM, et al. JAMA 2008 300 555-570
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DHHS Guidelines When to Initiate Therapy in
Treatment-Naïve Patients (Nov 3, 2008)
DHHS Guidelines for the Use of ARV Agents in
HIV-1-Infected Adults and Adolescents November
3, 2008. http//www.aidsinfo.nih.gov/ContentFiles/
AdultandAdolescentGL.pdf. Accessed November 3,
2008
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Treatment Criteria for ChronicHepatitis B
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Patient NN

• Factors associated with poor immune
  reconstitution
• Starting with lower CD4 cells
• Older age
• HIV-2 coinfection
• HTLV coinfection
• Other coinfections
• Suboptimal virologic response
• Select antiretrovirals (e.g. ZDV, EFV?)

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SILCAAT Primary EndpointOpportunistic Disease
or Death
Avg. Difference in CD4 counts over study period
59 cells/mm3 (Plt0.001)
Levy Y, et al. 16th CROI Montreal, Canada
February 8-11, 2009. Abst. 90bLB.
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HBV Antiviral Therapy Cross Resistance
N236T
L180M
M204V
M250V
A184G
V173L
A181V
S202I
M204I
LAM
ETV
LdT
FTC
ADV
TDF
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Patient RLB

• 48-year-old male diagnosed with HIV in 1984 (CD4-
  220 cells/uL)
• Antiretroviral experience through 2006
• All NRTIs, EFV and all PIs except DRV and TPV
• Mostly viremic throughout
• 2006-2007 ZDV/3TC/ABC TDF LPV/r
• CD4 250 cells/uL, RNA 5-10,000 copies/mL
• Historical GTs have shown multiple TAMs, protease
  mutations and NNRTI mutations- 98G, 108I, 181C
• 2007 resistance testing
• GT- resistant to all drugs
• PT- resistant to all except intermediate to DRV/r

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DUET-1 and -2 Predictors of ETR Response and
Resistance at Failure

• ETR mutations (n17) weighted based upon impact
  on response (weight factor)1
• 3.0- Y181I/V
• 2.5- L100I, K101P, Y181C, M230L
• 1.5- V106I, V179F, E138A, G190S
• 1.0- V90I, A98G, K101E/H,
  V179D/T, G190A

Adapted from Vingerhoets J, et al.
Vingerhoets J, et al. 17th IHDRW Sitges, Spain,
2008, Abstract 24.