Prophylaxis for Blood Prophylaxis for Blood (Occupational) and Sexual (Occupational) and Sexual

HIV ExposuresHIV Exposures

Allen McCutchan, M.D., M.Sc.Allen McCutchan, M.D., M.Sc.

Revised from material supplied by Revised from material supplied by

Jennifer Blanchard, M.D.Jennifer Blanchard, M.D.

Exposure Risk - What’s an exposure?Exposure Risk - What’s an exposure?

Violation of skin barrier by HIV containing fluids Violation of skin barrier by HIV containing fluids fromfrom– Penetrating injuries (needle sticks)Penetrating injuries (needle sticks)– Mucous Membrane contactMucous Membrane contact– Contact with – chapped, abraded, or inflamed skin or Contact with – chapped, abraded, or inflamed skin or

with an open woundwith an open wound

Rarely, if everRarely, if ever, from sharing personal grooming , from sharing personal grooming tools like toothbrushes or razors tools like toothbrushes or razors

NotNot from contact with intact skin because HIV from contact with intact skin because HIV does not penetrate healthy skindoes not penetrate healthy skin

Exposure Risk - Exposed to what?Exposure Risk - Exposed to what?

What fluids ?What fluids ?– BloodBlood– Body fluidsBody fluids

Semen (fluids from several glands) Semen (fluids from several glands)

Vaginal secretions (vaginal fluid, cervical mucus, Vaginal secretions (vaginal fluid, cervical mucus, and menstrual blood) and menstrual blood)

Rarely Others( not Saliva, tears, sweat, or Rarely Others( not Saliva, tears, sweat, or nonbloody feces or urine) unless bloodynonbloody feces or urine) unless bloody

What viruses– HIV and Hepatitis B and CWhat viruses– HIV and Hepatitis B and C

Risk Factors for Transmission: Risk Factors for Transmission: Exposure to more HIV (or Hep B or C) Exposure to more HIV (or Hep B or C)

Exposure to larger quantity of blood Exposure to larger quantity of blood Needle placed directly in artery or veinNeedle placed directly in artery or vein Deep injuryDeep injury Hollow-bore needle Hollow-bore needle Device visibly contaminated with patients Device visibly contaminated with patients

bloodblood

Patients with higher viral load Patients with higher viral load Acutely infected (primary HIV infection)Acutely infected (primary HIV infection) Terminally illTerminally ill

Exposure Risk:Exposure Risk:Patient FactorsPatient Factors

Known HIV+ Known HIV+ – Viral load Viral load – On therapyOn therapy

Unknown HIV statusUnknown HIV status– History of risk factorsHistory of risk factors– Symptoms c/w primary HIVSymptoms c/w primary HIV– History of HIV testingHistory of HIV testing

Unknown patient (ie. sharps box stick)Unknown patient (ie. sharps box stick)– Prevalence where exposure occurredPrevalence where exposure occurred– How long sharp exposedHow long sharp exposed

Exposure RiskExposure RiskNot all needlesticks are the Not all needlesticks are the

samesame

Average risk for needlestick is 0.3% (1 HIV Average risk for needlestick is 0.3% (1 HIV infection / 300 needle sticks)infection / 300 needle sticks)

Average risk for mucous membrane Average risk for mucous membrane exposure is 0.09% (1 HIV infection / 9000)exposure is 0.09% (1 HIV infection / 9000)

As of 6/00, CDC had received 56 reports As of 6/00, CDC had received 56 reports of HCW’s with seroconversion (this is of HCW’s with seroconversion (this is likely a serious underestimate)likely a serious underestimate)

Exposure RiskExposure RiskNot all needlesticks are the sameNot all needlesticks are the same

Risk factor

Adjusted odds ratio*

Deep injury

16.1

Visible blood on device

5.2

Procedure involving needle in artery or vein

5.1

Terminal illness in source patient

6.4

Postexposure use of ZDV 0.2

*All were significant at p<0.01

PEP or no PEPPEP or no PEP

Most exposures do not result in Most exposures do not result in transmission of HIVtransmission of HIV

Consider Consider – risk of exposure and risk of exposure and – Infectivity of the source patientInfectivity of the source patient

Consider health of HCWConsider health of HCW

If Source’s Serostatus is If Source’s Serostatus is UnknownUnknown

PEP until lab results obtained and then PEP until lab results obtained and then modify or discontinuemodify or discontinue

Get consent for testing from source Get consent for testing from source patientpatient

Test source patient and assess risk Test source patient and assess risk factors for window period (HIV without factors for window period (HIV without HIV antibody)HIV antibody)

Legal Issues in Testing Legal Issues in Testing Unknown PatientsUnknown Patients

Source patient’s consent is not required to tell Source patient’s consent is not required to tell HCW of known HIV statusHCW of known HIV status

Source pts MD must make “good faith” effort Source pts MD must make “good faith” effort to obtain consent to test for HIVto obtain consent to test for HIV

Testing may proceed without pts consent and Testing may proceed without pts consent and results given to exposed HCWresults given to exposed HCW

Patient must be informed of this and may Patient must be informed of this and may elect not to receive results. elect not to receive results.

HCW must maintain confidentialityHCW must maintain confidentiality

Primary PreventionPrimary Prevention

Don’t get stuckDon’t get stuck

– Never recapNever recap

– Sedate the patient if necessary and Sedate the patient if necessary and possiblepossible

– Wear glovesWear gloves

Don’t get splashedDon’t get splashed

– Wear glasses or gogglesWear glasses or goggles

The Rationale for Postexposure The Rationale for Postexposure Prophylaxis Prophylaxis

Systemic infection does not occur Systemic infection does not occur immediately, leaving theoretical “window of immediately, leaving theoretical “window of opportunity” to modify viral replicationopportunity” to modify viral replication

Animal data on PEPAnimal data on PEP– ARV may block dissemination from dendritic cells ARV may block dissemination from dendritic cells

to susceptible T cellsto susceptible T cells– ARV may prevent intravenous infection of T cellsARV may prevent intravenous infection of T cells

Human data on PEP is limited but supportiveHuman data on PEP is limited but supportive

Primary HIV infection – Primary HIV infection – Rhesus Monkeys & SIVRhesus Monkeys & SIV

Rhesus monkeys exposed intravaginally with Rhesus monkeys exposed intravaginally with SIVSIVAt 24 hours, SIV detected in vaginal dendritic At 24 hours, SIV detected in vaginal dendritic cellscellsThese cells fuse with CD4 lymphocytes and then These cells fuse with CD4 lymphocytes and then migrate to regional lymph nodes migrate to regional lymph nodes By 48 hours, SIV detected in inguinal LNsBy 48 hours, SIV detected in inguinal LNsLymphatic spread of virus and infected cells to Lymphatic spread of virus and infected cells to the spleen and other lymphoid tissuesthe spleen and other lymphoid tissuesBy 5 days, SIV detected in the blood By 5 days, SIV detected in the blood

Primary HIV InfectionPrimary HIV InfectionHuman DataHuman Data

Viral dynamics in acute HIV infection in Viral dynamics in acute HIV infection in humans were similar to the SIV modelhumans were similar to the SIV model

Time from mucosal infection to initial Time from mucosal infection to initial viremia varies from 4-11 daysviremia varies from 4-11 days

After infection, there is a rapid rise in After infection, there is a rapid rise in plasma viremia, with widespread plasma viremia, with widespread dissemination of the virus ass’d with dissemination of the virus ass’d with seeding of lymphoid organsseeding of lymphoid organs

Primary HIV InfectionPrimary HIV InfectionHuman DataHuman Data

Viral doubling time in acute HIV ~ 12 Viral doubling time in acute HIV ~ 12 hourshoursPeak HIV RNA levels were detected 12-29 Peak HIV RNA levels were detected 12-29 days post exposure (mean 21 days)days post exposure (mean 21 days)Rise in viral load exceeds 1 million RNA Rise in viral load exceeds 1 million RNA molecules/mLmolecules/mLDrop in viral load ass’d with appearance of Drop in viral load ass’d with appearance of cytotoxic T lymphocytescytotoxic T lymphocytesViral set point is then establishedViral set point is then established

Animal PEPAnimal PEPMice and AZT Mice and AZT

SCID mice inoculated IV with HIVSCID mice inoculated IV with HIV

AZT PEP initiated 0.5, 1,2,4,8,24,36, & 48h AZT PEP initiated 0.5, 1,2,4,8,24,36, & 48h laterlater

All mice treated at 0.5, 1, & 2 h were All mice treated at 0.5, 1, & 2 h were protectedprotected

80% treated at 8h protected80% treated at 8h protected

40% treated at 24 h protected40% treated at 24 h protected

No protection of treatment started at 48h.No protection of treatment started at 48h.

Shih CC et al. JID 1991Shih CC et al. JID 1991

Animal PEPAnimal PEPTenofovir and MacaquesTenofovir and Macaques

IV SIV inoculation to long-tailed IV SIV inoculation to long-tailed macaquesmacaques

Tenofovir given Tenofovir given – 48 hours before48 hours before– 4 & 24 hours after4 & 24 hours after– For 28 daysFor 28 days

No treated animals infected; all controls No treated animals infected; all controls infectedinfected

Tsai CC et al. Science,1995;270: 1197-1199Tsai CC et al. Science,1995;270: 1197-1199

Animal PEPAnimal PEPTenofovir and MacaquesTenofovir and Macaques

Macaques infected IV with SIVMacaques infected IV with SIV

3,10 or 28d PEP with tenofovir initiated 3,10 or 28d PEP with tenofovir initiated at 24, 48, & 72 hours after inoculation. at 24, 48, & 72 hours after inoculation.

All controls infectedAll controls infected

All animals treated at 24h for 28d All animals treated at 24h for 28d protectedprotected

50% showed persistent viremia in other 50% showed persistent viremia in other treatment groups.treatment groups.

Tsai CC et al. J Virology 1998;72:4265-73.Tsai CC et al. J Virology 1998;72:4265-73.

Summary of Animal PEPSummary of Animal PEPProphylactic EfficacyProphylactic Efficacy

Decreased with large viral inoculaDecreased with large viral inoculaDecreased with delayDecreased with delay– Best results within 24 hoursBest results within 24 hours

Decreased with shortened durationDecreased with shortened duration– 4 weeks ass’d with highest protection4 weeks ass’d with highest protection– 3 & 10 days not protective for macaques 3 & 10 days not protective for macaques

exposed to SIVexposed to SIV

Decreased with lower dose PEPDecreased with lower dose PEPIncreased with normal host immune Increased with normal host immune systemsystem

Human PEP - EfficacyHuman PEP - Efficacy

No prospective studies No prospective studies Retrospective case-control studies, risk Retrospective case-control studies, risk of HIV infection was reduced by 80% in of HIV infection was reduced by 80% in those who took AZT as PEPthose who took AZT as PEPACTG 076 – maternal-fetal transmission ACTG 076 – maternal-fetal transmission decreased by 67%decreased by 67%Numerous studies of decreased Numerous studies of decreased perinatal transmission with ARVsperinatal transmission with ARVsCase reportsCase reports

Indications for PEP for InjuriesIndications for PEP for Injuries

PEP IndicatedPEP IndicatedHigh risk exposureHigh risk exposure

Known + patientKnown + patient

AIDS/high viral loadAIDS/high viral load

No delay to rxNo delay to rx

PEP not indicatedPEP not indicatedLow risk exposureLow risk exposure

Low risk ptLow risk pt

Found needleFound needle

Delay > 72 hoursDelay > 72 hours

Drug interactions/ Drug interactions/ coexisting medical coexisting medical problemsproblems

Human PEP for Blod Human PEP for Blod TransfusionsTransfusions

13 y/o girl transfused 1 unit of packed red 13 y/o girl transfused 1 unit of packed red cells from donor in the “window period”cells from donor in the “window period”

Infection risk estimated to be 100%Infection risk estimated to be 100%

3-drug PEP initiated at 50 h post-3-drug PEP initiated at 50 h post-transfusion, continued for 9 motransfusion, continued for 9 mo

No evidence of HIV infection 15 mo laterNo evidence of HIV infection 15 mo later– Ann Int Med 2000;133:31-4Ann Int Med 2000;133:31-4

Limitations of the DataLimitations of the Data

Very difficult to study human primary Very difficult to study human primary infectioninfection

Extrapolating animal data to humansExtrapolating animal data to humans

Maternal-fetal transmission is not the Maternal-fetal transmission is not the same as occupational exposuressame as occupational exposures

PEP DrugsPEP Drugs2 or 3 drugs based on risk of exposure/pt2 or 3 drugs based on risk of exposure/pt– AZT/3TCAZT/3TC– AZT/3TC + Lopinavir/ritonavir + 1 dose AZT/3TC + Lopinavir/ritonavir + 1 dose

nevirapinenevirapine– Modify based on source pt/drug resistanceModify based on source pt/drug resistance

Important goal is completing 4 week Important goal is completing 4 week regimenregimen– 50% stop b/c source pt HIV-50% stop b/c source pt HIV-– 50% stop d/t side effects50% stop d/t side effects

PEP Drugs – Side EffectsPEP Drugs – Side Effects

N/V/D, hepatitisN/V/D, hepatitisNephrolithiasis Nephrolithiasis Anemia, NeutropeniaAnemia, NeutropeniaHeadache, RashHeadache, RashPancreatitisPancreatitisHyperglycemiaHyperglycemiaHyperbilirubinemiaHyperbilirubinemiaHypersensitivity reactionsHypersensitivity reactionsOther…Other…

PEP Drugs – Side effectsPEP Drugs – Side effects

Is it worth it?Is it worth it?

– 50% of HCW have side effects50% of HCW have side effects

– No long term data on carcinogenesisNo long term data on carcinogenesis

1/3 of HCW’s discontinue PEP d/t side effects1/3 of HCW’s discontinue PEP d/t side effects

Most side effects reversible or modifiableMost side effects reversible or modifiable

– Anti-emetics, anti-diarrhealsAnti-emetics, anti-diarrheals

– EpogenEpogen

Nevirapine: Serious Adverse Nevirapine: Serious Adverse EventsEvents

MMWR 1/5/01 report of 22 cases of severe MMWR 1/5/01 report of 22 cases of severe toxicity in people taking NVP for PEP from 3/97 toxicity in people taking NVP for PEP from 3/97 through 9/00through 9/00Clinical syndromes reported:Clinical syndromes reported:– 12 cases of hepatoxicity (2 fulminant hepatitis, 1 12 cases of hepatoxicity (2 fulminant hepatitis, 1

required liver transplant)required liver transplant)– 14 cases of skin reactions (1 Stevens-Johnson)14 cases of skin reactions (1 Stevens-Johnson)– 1 case of rhabdomyolysis1 case of rhabdomyolysis

Not recommended for long term use unless Not recommended for long term use unless exposure high risk, high risk of MDR virus, exposure high risk, high risk of MDR virus, HCW with no liver hx and EFV contraindicatedHCW with no liver hx and EFV contraindicated

Pregnant HCWPregnant HCWPregnancy should not preclude the use of Pregnancy should not preclude the use of postexposure prophylaxispostexposure prophylaxis

Less data on safety of PI’s in first trimesterLess data on safety of PI’s in first trimester

Sustiva contraindicated Sustiva contraindicated

Avoid IDV near term d/t hyperbilirubinemia in Avoid IDV near term d/t hyperbilirubinemia in newbornsnewborns

D4T/ddI contratindicated d/t mitochondrial D4T/ddI contratindicated d/t mitochondrial toxicity in newbornstoxicity in newborns

Drugs usually started after 14 weeks gestation Drugs usually started after 14 weeks gestation in chronically infected pts if not already on in chronically infected pts if not already on ARVsARVs

Drug Resistant VirusDrug Resistant Virus

Very little dataVery little data

Combination regimens recommended Combination regimens recommended based on data for chronically infected based on data for chronically infected individualsindividuals

Resistance testing not helpfulResistance testing not helpful

Use agents that the source has not been Use agents that the source has not been exposed toexposed to

PEP FailuresPEP Failures

21 cases reported21 cases reported16 AZT monotherapy16 AZT monotherapy2 AZT/ddI2 AZT/ddI3 with 3 with >> drugs (AZT/3TC/IDV; drugs (AZT/3TC/IDV; AZT/3TC/ddI/IDV)AZT/3TC/ddI/IDV)13/21 source pts previously treated with 13/21 source pts previously treated with ARVsARVs4/7 resistance assays showed 4/7 resistance assays showed decreased sensitivity to PEP meds useddecreased sensitivity to PEP meds used

HIV Infection in HCW’sHIV Infection in HCW’s

81% experienced syndrome c/w primary 81% experienced syndrome c/w primary HIV infection at median of 25dHIV infection at median of 25d

Median time to seroconversion 46dMedian time to seroconversion 46d

Factors implicated in failureFactors implicated in failure– Viral resistanceViral resistance– Large inoculumLarge inoculum– Delayed or shortened PEPDelayed or shortened PEP

Management of Occupational Management of Occupational Exposure to HIVExposure to HIV

Wash wound with soap and water; flush mucous Wash wound with soap and water; flush mucous membranes with water, saline or sterile washmembranes with water, saline or sterile washInitiate PEP immediately (can be modified later)Initiate PEP immediately (can be modified later)– Pregnancy testPregnancy test

HIV Ab testing at baseline, 6 weeks, 12 weeks, 6 HIV Ab testing at baseline, 6 weeks, 12 weeks, 6 months & 1 year months & 1 year HIV PCR RNA ? (not recommended by CDC)HIV PCR RNA ? (not recommended by CDC)– High false + rate (2-5%)High false + rate (2-5%)– Only if symptomaticOnly if symptomatic

CBC, Chem 10,liver panel baseline and 2 weeksCBC, Chem 10,liver panel baseline and 2 weeksCounseling and education Counseling and education

Counseling: Weeks 1-12 after Counseling: Weeks 1-12 after exposureexposure

Abstain from sex or use condomsAbstain from sex or use condoms

Do not donate blood, semen, organsDo not donate blood, semen, organs

Consider stop breast-feedingConsider stop breast-feeding

Seek medical care for any acute illness Seek medical care for any acute illness that occurs during the follow up periodthat occurs during the follow up period– Acute HIV infectionAcute HIV infection– Drug reactionDrug reaction– OtherOther

Acute Retroviral SyndromeAcute Retroviral Syndrome

Symptoms start within a few to many Symptoms start within a few to many weeks after exposure, but could also weeks after exposure, but could also represent drug reactionsrepresent drug reactionsMay last few days to more than 10 May last few days to more than 10 weeks; average < 14 daysweeks; average < 14 daysSevere or prolonged symptoms Severe or prolonged symptoms correlate with more rapid disease correlate with more rapid disease progressionprogression

Signs and SymptomsSigns and Symptoms

FeverFever >80-90%>80-90%

FatigueFatigue >70-90%>70-90%

RashRash >40-80%>40-80%

HeadacheHeadache 32-70% 32-70%

LymphadenopathyLymphadenopathy 40-70% 40-70%

PharyngitisPharyngitis 50-70% 50-70%

Myalgias, arthralgiasMyalgias, arthralgias 50-70% 50-70%

Signs and Symptoms – Acute Signs and Symptoms – Acute HIV InfectionHIV Infection

N/V/DN/V/D 30-60% 30-60%

Night sweatsNight sweats 50% 50%

Aseptic meningitisAseptic meningitis 24% 24%

Oral/genital ulcersOral/genital ulcers 5-20% 5-20%

ThrombocytopeniaThrombocytopenia 45% 45%

LeukopeniaLeukopenia 40% 40%

Elevated LFTsElevated LFTs 21% 21%

Signs and Symptoms – Acute Signs and Symptoms – Acute HIV InfectionHIV Infection

ThrushThrush

Weight lossWeight loss

DepressionDepression

Retro-orbital painRetro-orbital pain

Rash – maculopapular, involves the trunkRash – maculopapular, involves the trunk

What to do if you are exposedWhat to do if you are exposed

Wash wound with soap and waterWash wound with soap and waterFlush mucous membranes with Flush mucous membranes with saline/watersaline/waterDetermine status of source patientDetermine status of source patientTest source patientTest source patientTake the meds as soon as possibleTake the meds as soon as possible– Normal working hours - Pam Scott in Normal working hours - Pam Scott in

occupational health - pager 1447occupational health - pager 1447– After hours - EDAfter hours - ED