Transcript CFAR research in progress talk

HIV opportunistic
infections and HIV
treatment
Sabrina Assoumou, MD
Section of Infectious Diseases
Outline
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Case 1
HIV opportunistic infections
HIV treatment principles
HIV treatment options
Case 2
Case 1
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40 y/o F admitted with
– Fever, HA, and sweats for 3 weeks
– Diplopia and increased somnolence for 1d
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Diagnosed with HIV two months ago (
CD4 166, vl 66,923). ARVs were
started immediately.
Current regimen: tenofovir,
emtricitabine and efavirenz
Case 1 (con’t)
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PE: 100.8 F
– Awake but drowsy and oriented to
person, but not time
– L eye cannot move laterally with leftward
gaze
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CT scan: mildly increased ventricle size
LP: Cell count 122, gluc 62, Protein
433
Case 1 (con’t)
Infection with which of the
following is the most likely cause of
this patient’s clinical presentation?
a)Cryptococcus neoformans
b)CMV
c)Histoplasma capsulatum
d)Toxoplasma gondii
HIV Opportunistic
Infections
Primary OI prophylaxis
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CD4 <200
CD4 <100
CD4 <50
Primary OI prophylaxis
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CD4 <200: PCP
CD4 <100: Toxoplasmosis if positive
serology
CD4 <50: MAI
Severe PCP
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Toxoplasmosis
PML
MAI-filled macrophages in
spleen
Thrush
Herpes Zoster (Shingles)
Cytomegalovirus Retinitis
HIV therapy
Goals of therapy
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Improve quality of life
Reduce HIV-related morbidity and
mortality
Restore and/or preserve immunologic
function
Maximally and durably suppress HIV
viral load
Prevent HIV transmission
HIV therapy
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Who?
What?
When?
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Check genotype prior to initiation
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Initial ART Regimens:
DHHS Categories
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Preferred
– Randomized controlled trials show optimal
efficacy and durability
– Favorable tolerability and toxicity profiles
Alternative
– Effective but have potential disadvantages
– May be the preferred regimen in individual
patients
Acceptable
– Less virologic efficacy, lack of efficacy data, or
greater toxicities
Preferred regimen
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3 main categories:
– 1 NNRTI + 2 NRTIs
– 1 PI + 2 NRTIs
– 1 II + 2 NRTIs
Initial Treatment: Preferred
NNRTI based
Efavirenz/Tenofovir/Emtricitabine
PI based
Atazanavir/ritonavir
+
Tenofovir/Emtricitabine
Darunavir/ritonavir
+
Tenofovir/Emtricitabine
II based
Raltegravir
+
Tenofovir/Emtricitabine
ARV Components in Initial
Therapy: NNRTIs
ADVANTAGES
DISADVANTAGES
 Long half-lives
 Low genetic barrier to
resistance – single
 Less metabolic toxicity
mutation
(dyslipidemia, insulin
resistance) than with
 Cross-resistance among
some PIs
most NNRTIs
 PIs and II preserved for  Rash; hepatotoxicity
future use
 Potential drug interactions
(CYP450)
 Transmitted resistance to
NNRTIs more common
than resistance to Pis
ARV Components in Initial
Therapy: PIs
DISADVANTAGES
ADVANTAGES
 Metabolic complications
 Higher genetic barrier
(fat maldistribution,
to resistance
dyslipidemia, insulin
 PI resistance
resistance)
uncommon with failure
 GI intolerance
(boosted PI)
 Potential for drug
 NNRTIs and II
interactions (CYP450),
preserved for future
especially with RTV
use
ARV Components in Initial
Therapy: Raltegravir
ADVANTAGES
DISADVANTAGES
 Virologic response
 Twice-daily dosing
noninferior to EFV
 Lower genetic barrier to
 Fewer adverse events
resistance than PIs
than with EFV
 Fewer drug-drug
interactions than with PIs
or NNRTIs
 NNRTIs and PIs
preserved for future use
ARV-Associated Adverse
Effects: Rash
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Most common with NNRTIs, especially Nevirapine
– Most cases mild to moderate, occurring in first 6 weeks of
therapy; occasionally serious (eg, Stevens-Johnson
syndrome)
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PIs: especially Darunavir
NRTIs: especially abacavir (hypersensitivity
syndrome)
CCR5 antagonist: Maraviroc
ARV-Associated Adverse
Effects: Nephrotoxicity
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Renal insufficiency associated with
Tenofovir, Indinavir
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TDF:
– Cr, proteinuria, glycosuria, hypophosphatemia,
hypokalemia
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Indinavir: Cr, pyuria, hydronephrosis or renal atrophy
Nephrolithiasis: Indinavir, Atazanavir
ARV-Associated Adverse
Effects: Hepatotoxicity
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Severity variable: usually asymptomatic,
may resolve without treatment interruption
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May occur with any NNRTI or PI, most
NRTIs
– Nevirapine:
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risk of severe hepatitis in first 18 weeks of use
(monitor LFTs closely)
increased risk in chronic hepatitis B and C
women, and high CD4 count at initiation (>250
cells/µL in women, >400 cells/µL in men)
ARV-Associated Adverse
Effects: Insulin
Resistance, Diabetes
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Insulin resistance, hyperglycemia, and
diabetes associated with AZT, some PIs
(LPV/r), especially with chronic use
Mechanism not well understood
– Insulin resistance, relative insulin
deficiency
Screen regularly: fasting glucose
ARV-Associated Adverse
Effects: Hyperlipidemia
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 Total cholesterol, LDL, and triglycerides
– Associated with all RTV-boosted PIs, efavirenz, AZT,
abacavir
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 HDL seen with efavirenz, ritonavir-boosted PIs
Concern for cardiovascular events, pancreatitis
Monitor regularly
Treatment: consider ARV switch; lipid-lowering
agents (caution with PI + certain statins)
Case 2
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25 yo F who is 12 weeks pregnant
– Found to be HIV-infected during routine
pregnancy evaluation
– She is asymptomatic
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PE: normal. No oral thrush, LAD
CD4 865, vl 510
Hepatitis B negative, Genotype: no
resistance
Case 2 ( con’t)
Which of the following is the most
appropriate management?
a) Begin ARVs at the onset of labor
b) Begin tenofovir, emtricitabine, and
efavirenz, now
c) Begin AZT, lamivudine, lopinavirritonavir
d) Repeat CD4 and treat if the CD4 is
<500
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Conclusions
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Remember CD4 cut offs for primary OI
prophylaxis ( 200, 100, 50)
ALL HIV-infected patients should be
on ARVs
Basic regimen 2NNRTI + PI or NNRTI
or II