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

HIV Opportunistic HIV Opportunistic InfectionsInfections

Primary OI prophylaxisPrimary OI prophylaxis

CD4 <200CD4 <200 CD4 <100CD4 <100 CD4 <50CD4 <50

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

Severe PCPSevere PCP

ToxoplasmosisToxoplasmosis

PMLPML

MAI-filled macrophages in MAI-filled macrophages in spleenspleen

ThrushThrush

Herpes Zoster (Shingles)Herpes Zoster (Shingles)

Cytomegalovirus RetinitisCytomegalovirus Retinitis

HIV therapyHIV therapy

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