hiv opportunistic infections and hiv treatment sabrina assoumou, md section of infectious diseases
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HIV opportunistic HIV opportunistic infections and HIV infections and HIV treatmenttreatment
Sabrina Assoumou, MDSabrina Assoumou, MD
Section of Infectious DiseasesSection of Infectious Diseases
OutlineOutline
Case 1Case 1 HIV opportunistic infectionsHIV opportunistic infections HIV treatment principlesHIV treatment principles HIV treatment optionsHIV treatment options Case 2Case 2
Case 1 Case 1
40 y/o F admitted with40 y/o F admitted with– Fever, HA, and sweats for 3 weeksFever, HA, and sweats for 3 weeks– Diplopia and increased somnolence for Diplopia and increased somnolence for
1d1d Diagnosed with HIV two months ago ( Diagnosed with HIV two months ago (
CD4 166, vl 66,923). ARVs were CD4 166, vl 66,923). ARVs were started immediately.started immediately.
Current regimen: tenofovir, Current regimen: tenofovir, emtricitabine and efavirenzemtricitabine and efavirenz
Case 1 (con’t)Case 1 (con’t)
PE: 100.8 FPE: 100.8 F– Awake but drowsy and oriented to Awake but drowsy and oriented to
person, but not timeperson, but not time– L eye cannot move laterally with L eye cannot move laterally with
leftward gazeleftward gaze CT scan: mildly increased ventricle CT scan: mildly increased ventricle
sizesize LP: Cell count 122, gluc 62, Protein LP: Cell count 122, gluc 62, Protein
433433
Case 1 (con’t)Case 1 (con’t)
Infection with which of the Infection with which of the following is the most likely following is the most likely cause of this patient’s clinical cause of this patient’s clinical presentation?presentation?
a)a)Cryptococcus neoformansCryptococcus neoformans
b)b)CMVCMV
c)c)Histoplasma capsulatumHistoplasma capsulatum
d)d)Toxoplasma gondiiToxoplasma gondii
Primary OI prophylaxisPrimary OI prophylaxis
CD4 <200: PCPCD4 <200: PCP
CD4 <100: Toxoplasmosis if CD4 <100: Toxoplasmosis if positive positive serology serology
CD4 <50: MAICD4 <50: MAI
Goals of therapyGoals of therapy
Improve quality of lifeImprove quality of life Reduce HIV-related morbidity and Reduce HIV-related morbidity and
mortality mortality Restore and/or preserve Restore and/or preserve
immunologic functionimmunologic function Maximally and durably suppress Maximally and durably suppress
HIV viral loadHIV viral load Prevent HIV transmissionPrevent HIV transmission
HIV therapyHIV therapy
Who?Who? What?What? When?When?
Check genotype prior to initiationCheck genotype prior to initiation
Initial ART Regimens: Initial ART Regimens: DHHS CategoriesDHHS Categories PreferredPreferred
– Randomized controlled trials show optimal Randomized controlled trials show optimal efficacy and durabilityefficacy and durability
– Favorable tolerability and toxicity profilesFavorable tolerability and toxicity profiles AlternativeAlternative
– Effective but have potential disadvantagesEffective but have potential disadvantages– May be the preferred regimen in individual May be the preferred regimen in individual
patients patients AcceptableAcceptable
– Less virologic efficacy, lack of efficacy Less virologic efficacy, lack of efficacy data, or greater toxicitiesdata, or greater toxicities
Preferred regimenPreferred regimen
3 main categories:3 main categories:
– 1 NNRTI + 2 NRTIs1 NNRTI + 2 NRTIs– 1 PI + 2 NRTIs1 PI + 2 NRTIs– 1 II + 2 NRTIs1 II + 2 NRTIs
Initial Treatment: Initial Treatment: PreferredPreferredNNRTI basedNNRTI based Efavirenz/Tenofovir/Efavirenz/Tenofovir/
EmtricitabineEmtricitabine
PI basedPI based Atazanavir/ritonavir + Atazanavir/ritonavir + Tenofovir/EmtricitabineTenofovir/Emtricitabine
Darunavir/ritonavir + Darunavir/ritonavir + Tenofovir/EmtricitabineTenofovir/Emtricitabine
II basedII based Raltegravir + Raltegravir + Tenofovir/EmtricitabineTenofovir/Emtricitabine
ARV Components in Initial ARV Components in Initial Therapy: NNRTIsTherapy: NNRTIs
ADVANTAGESADVANTAGES Long half-livesLong half-lives Less metabolic toxicity Less metabolic toxicity
(dyslipidemia, insulin (dyslipidemia, insulin resistance) than with resistance) than with some PIssome PIs
PIs and II preserved PIs and II preserved for future usefor future use
DISADVANTAGESDISADVANTAGES Low genetic barrier to Low genetic barrier to
resistance – single resistance – single mutationmutation
Cross-resistance among Cross-resistance among most NNRTIsmost NNRTIs
Rash; hepatotoxicityRash; hepatotoxicity Potential drug Potential drug
interactions (CYP450)interactions (CYP450) Transmitted resistance Transmitted resistance
to NNRTIs more to NNRTIs more common than resistance common than resistance to Pisto Pis
ARV Components in Initial ARV Components in Initial Therapy: PIsTherapy: PIs
ADVANTAGESADVANTAGES Higher genetic Higher genetic
barrier to resistancebarrier to resistance PI resistance PI resistance
uncommon with uncommon with failure (boosted PI)failure (boosted PI)
NNRTIs and II NNRTIs and II preserved for future preserved for future useuse
DISADVANTAGESDISADVANTAGES Metabolic Metabolic
complications complications (fat maldistribution, (fat maldistribution, dyslipidemia, insulin dyslipidemia, insulin resistance)resistance)
GI intoleranceGI intolerance Potential for drugPotential for drug
interactions (CYP450), interactions (CYP450), especially with RTVespecially with RTV
ARV Components in Initial ARV Components in Initial Therapy: RaltegravirTherapy: Raltegravir
ADVANTAGESADVANTAGES Virologic response Virologic response
noninferior to EFVnoninferior to EFV Fewer adverse events Fewer adverse events
than with EFVthan with EFV Fewer drug-drug Fewer drug-drug
interactions than with interactions than with PIs or NNRTIsPIs or NNRTIs
NNRTIs and PIs NNRTIs and PIs preserved for future preserved for future useuse
DISADVANTAGESDISADVANTAGES Twice-daily dosingTwice-daily dosing Lower genetic barrier Lower genetic barrier
to resistance than PIsto resistance than PIs
ARV-Associated ARV-Associated Adverse Effects: Adverse Effects: RashRash Most common with NNRTIs, especially Most common with NNRTIs, especially
NevirapineNevirapine– Most cases mild to moderate, occurring in first 6 Most cases mild to moderate, occurring in first 6
weeks of therapy; occasionally serious (eg, Stevens-weeks of therapy; occasionally serious (eg, Stevens-Johnson syndrome)Johnson syndrome)
PIs: especially Darunavir PIs: especially Darunavir
NRTIs: especially abacavir (hypersensitivity NRTIs: especially abacavir (hypersensitivity syndrome)syndrome)
CCR5 antagonist: MaravirocCCR5 antagonist: Maraviroc
ARV-Associated ARV-Associated Adverse Effects: Adverse Effects: NephrotoxicityNephrotoxicity Renal insufficiency associated with Renal insufficiency associated with
Tenofovir, IndinavirTenofovir, Indinavir TDF:TDF:
– Cr, proteinuria, glycosuria, hypophosphatemia, Cr, proteinuria, glycosuria, hypophosphatemia, hypokalemiahypokalemia
Indinavir: Cr, pyuria, hydronephrosis or renal Indinavir: Cr, pyuria, hydronephrosis or renal atrophyatrophy
Nephrolithiasis: Indinavir, AtazanavirNephrolithiasis: Indinavir, Atazanavir
ARV-Associated ARV-Associated Adverse Effects: Adverse Effects: HepatotoxicityHepatotoxicity Severity variable: usually Severity variable: usually
asymptomatic, may resolve without asymptomatic, may resolve without treatment interruptiontreatment interruption
May occur with any NNRTI or PI, most May occur with any NNRTI or PI, most NRTIsNRTIs– Nevirapine: Nevirapine:
risk of severe hepatitis in first 18 weeks of use risk of severe hepatitis in first 18 weeks of use (monitor LFTs closely)(monitor LFTs closely)
increased risk in chronic hepatitis B and Cincreased risk in chronic hepatitis B and C women, and high CD4 count at initiation (>250 women, and high CD4 count at initiation (>250
cells/µL in women, >400 cells/µL in men)cells/µL in women, >400 cells/µL in men)
ARV-Associated ARV-Associated Adverse Effects: Adverse Effects: Insulin Resistance, Insulin Resistance, DiabetesDiabetes Insulin resistance, hyperglycemia, and Insulin resistance, hyperglycemia, and
diabetes associated with AZT, some PIs diabetes associated with AZT, some PIs (LPV/r), especially with chronic use(LPV/r), especially with chronic use
Mechanism not well understoodMechanism not well understood– Insulin resistance, relative insulinInsulin resistance, relative insulin
deficiencydeficiency
Screen regularly: fasting glucoseScreen regularly: fasting glucose
ARV-Associated ARV-Associated Adverse Effects: Adverse Effects: HyperlipidemiaHyperlipidemia Total cholesterol, LDL, and triglyceridesTotal cholesterol, LDL, and triglycerides
– Associated with all RTV-boosted PIs, efavirenz, AZT, Associated with all RTV-boosted PIs, efavirenz, AZT, abacavirabacavir
HDL seen with efavirenz, ritonavir-boosted HDL seen with efavirenz, ritonavir-boosted PIsPIs
Concern for cardiovascular events, pancreatitisConcern for cardiovascular events, pancreatitis Monitor regularlyMonitor regularly Treatment: consider ARV switch; lipid-lowering Treatment: consider ARV switch; lipid-lowering
agents (caution with PI + certain statins)agents (caution with PI + certain statins)
Case 2Case 2
25 yo F who is 12 weeks pregnant25 yo F who is 12 weeks pregnant– Found to be HIV-infected during Found to be HIV-infected during
routine pregnancy evaluationroutine pregnancy evaluation– She is asymptomaticShe is asymptomatic
PE: normal. No oral thrush, LADPE: normal. No oral thrush, LAD CD4 865, vl 510CD4 865, vl 510 Hepatitis B negative, Genotype: no Hepatitis B negative, Genotype: no
resistanceresistance
Case 2 ( con’t)Case 2 ( con’t)
Which of the following is the most Which of the following is the most appropriate management?appropriate management?
a)a) Begin ARVs at the onset of laborBegin ARVs at the onset of labor
b)b) Begin tenofovir, emtricitabine, and Begin tenofovir, emtricitabine, and efavirenz, nowefavirenz, now
c)c) Begin AZT, lamivudine, lopinavir-Begin AZT, lamivudine, lopinavir-ritonavirritonavir
d)d) Repeat CD4 and treat if the CD4 is Repeat CD4 and treat if the CD4 is <500<500
ConclusionsConclusions
Remember CD4 cut offs for primary Remember CD4 cut offs for primary OI prophylaxis ( 200, 100, 50)OI prophylaxis ( 200, 100, 50)
ALL HIV-infected patients should be ALL HIV-infected patients should be
on ARVson ARVs
Basic regimen 2NNRTI + PI or NNRTI Basic regimen 2NNRTI + PI or NNRTI or IIor II