HIV Transmission in Hospital Settings

Objectives

• Epidemiology of occupational HIV transmission

• Rationale for postexposure prophylaxis (PEP)

• NYSDOH / CDC recommendations

• Reality of PEP

U.S. Health-Care Workers with DocumentedOccupationally Acquired HIV Infection, by

Occupation through December 1998Occupation

Clinical laboratory technician 16

Nurse 22

Physician 6

Non-clinical laboratory technician 3

Surgical technician 2

Autopsy technician 1

Health aide / attendant 1

Housekeeper / maintenance worker 1

Respiratory therapist 1

Dialysis technician 1

Total 54

Healthcare Workers with Documented and Possible Occupationally Acquired HIV

Worldwide*

US54 134 188

France 11 27 38

UK 4 9 13

Mexico 0 9 9

Italy 5 0 5

Australia 4 0 4

Spain 5 0 5

South Africa3 1 4

Germany 3 3 6

Others 7 7 14

Total 96 190 286

* USA through 12/98 Other countries through 12/97

Types of Exposures Resulting in Occupational HIV Transmission

46

1

25

percutan

unk

both

mucocutan

N=54

US HCW reported through 12/98

Source Fluids for Exposures Resulting in Occupational HIV Transmission

49

11 3

blood

vis bld fluid

unspec

conc virus

N=54

US HCW reported through 12/98

Risk Factors For HIV Transmission

CDC Case Control Study

Risk Factor Odds Ratio

Deep Injury 15

Visible blood 6

In vessel 4

Terminal illness 6

ZDV use 0.2

Cardo et al., NEJM;1997;337:1485-90

Average Risk of HIV Infection to HCWs by Exposure Route

• Percutaneous 0.3%

• Mucous membrane 0.1%

• Non-intact skin <0.1%

Rationale for PEP

• Window of opportunity…

• Animal studies

• Human studies

Outcomes of HIV Exposures

• No infection

• Aborted infection

• Acute infection

no immune memory

cellular immune response

seroconversion

CTL Reactivity to HIV Envelope Peptides in HCWs with Percutaneous Exposure to HIV

Source patient HCW CTL

HIV+ Exposed 7/20 (35%)

HIV– Exposed 0/20 (0%)

Blood bank donors 0/7 (0%)

Adapted from Pinto et al, J Clin Invest 1995;96:867-76

Animal Studies of PEP: Prevention of SIV in macaques with

PMPA• 24 macaques

- 4 / study arm• IV inoculation of SIV

– 10 X 50% animal infectious dose

• Initiation at 24, 48, 72h post exp

• Duration 3,10, 28 days

Tsai et al, J Virol, 1998;72:4265

Animal Studies of PEP: Prevention of SIV in macaques with

PMPA

Initiation / duration % Protected

24h / 28d 100%

48h / 28d 50%

72h / 28d 50%

24h / 10d 75%

24h / 3d 0

Tsai et al, J Virol, 1998;72:4265

PEP in Humans

• 076 study– randomized– ZDV last trimester, intrapartum and

post-partum vs no rx– controls 25% rate of transmission

ZDV 7% rate of transmission

• Shorter courses…encouraging

CTL Reactivity to HIV Envelope Peptides in HCWs with Percutaneous Exposure to HIV

Source patient HCW CTL

HIV+ Exposed 7/20 (35%)

HIV– Exposed 0/20 (0%)

Blood bank donors 0/7 (0%)

Adapted from Pinto et al, J Clin Invest 1995;96:867-76

ZDV Reduces CTL Response

20 HCW (HIV+ SP)

7 Rx ZDV 13 No ZDV

(1 CTL +) (6 CTL +)

D’Amico, Infect Control Hosp Epidemiol 1999;20:428

PEP in Humans / HCW

• CDC Case Control Study

– 33 cases / 679 controls

– Identify risk factors

– Logistic regression model

Logistic Regression Analysis of Risk Factors For HIV

Transmission

Risk Factor Odds Ratio

Deep Injury 15

Visible blood 6

In vessel 4

Terminal illness 6

ZDV use 0.2

CDC Case Control Study

cases(%) controls(%)

First dose < 4 hrs 67 89

Completed 4 wks 44 66

1000 mg ZDV 75 78

Receiving ZDV 71 70

Limitations of CDC Study

• Study design

• Bias

• Small numbers of cases

• Non-standard ZDV use

Designing a PEP Program

• Indications

• Timing

• Drugs

• Testing

Indication for PEP NYSDOH CDC

• A mucous membrane, non-intact skin or percutaneous exposure to blood or visibly bloody fluid

• Source is potentially HIV infected

• A mucous membrane, non-intact skin or percutaneous exposure to blood or visibly bloody fluid

• Source is potentially HIV infected

Prophylaxis RecommendationsNYSDOH CDC

• Independent of source patient and the severity of the exposureTreat mucocutaneous and percutaneous the same

• 2 NRTI + PI

(or NNRTI)

• Dependent upon specific character-istics of the source patient and the exposureSevere (large bore, in source pt vessel, deep puncture)

Large volume (several drops or long duration)

High titer exposure (advanced AIDS, low CD4, high viral load)

• 2 NRTI PI

Antiretroviral RegimensNYSDOH CDC

Universal Regimen

ZDV

3TC

IDV or Nelf or

efavirenz (nevirapine)

Basic Regimen

ZDV

3TC

Expanded Regimen

Basic

IDV or Nelf

Recommended PEP Regimen2

ZDV 300 mg po bid +Epivir 150 mg po bid +PI1 or efavirenz

1 Indinavir 800 mg po tid or nelfinavir 750 mg po tid are suggested. Efavirenz 600 mg po daily as single dose.

2 4 weeks total duration suggested.

Initiation of PEPNYSDOH CDC

• Up to 36 hours post-exposure

(within 1 hour) • Referral to “HIV

specialist” within 72 hours

• 1-2 hours up to 1-2 weeks post-exposure

HIV Testing

• Methods– ELISA– PCR (viral load)

• Concerns– accuracy– time to positive

• Effect of PEP

HIV Testing

• ELISA method

• Baseline

4-6 weeks

12 weeks

6 months

1 year (?)

CDC GuidelinesPro Con

• Less expensive• Less toxic

greater compliance?

• Complex• Imprecise definitions• Basic regimen is

inadequate if sero-conversion occurs

NYSDOH Pro Con

• Scientifically rational• Simplified decision

points

• Expensive• Toxic• Compliance issues• Prolong uncertainty

Controversies in PEP

• CDC and NYS disagree ?– Legal ramifications

• DOH regulated facility

DOH guidelines

ZDV PEP Treatment Failures in HCWs

World-wide Cases• 18 failures in health

care providers • 5 failures in other

settings• no delay in time to

seroconversion• no adverse effects on

natural history

Potential Explanations• delay in treatment• dose too low / low drug

levels• resistant virus• high inoculum exposure• treatment duration too

short• zidovudine is not

efficacious

ZDV PEP Failures in HCWs: United States

Hrs to ZDV Rx Acute Time SP on

Exposure Rx Dose Days RVI ? to SC ZDV?

Bx needle .5 1000* 45 23d 23d yes

hollow needle .75 800 10 14d 90d yes

glass 1.5 600 10 21d 73d yes

hollow needle 2 1000 17 38d 121d no

IV cannula 3-7 1000 8 36d 94d yes

mucocutaneous 192 1200 21 75d 134d ?

hollow needle .67 ? 42 70d 83d yes

hollow needle 1 1000 5 16d 20d Yes

Failure of Four-Drug HIV PEP

• Needle used in art/vein

• Source patient – HIV+ and HCV+

– Hx of Rx w/ d4T/3TC

– Current Rx ZDV/3TC

– low CD4/ low viral load

– Virus - ZDV resistant

• PEP regimen– ZDV/3TC/ddI/Ind - 6

weeks – HIV- pre/post PEP

• Post PEP Course– viral syndrome 4 wk later– HIV +, viral load >750K– anti-HCV+/ HCV RNA -– HCW virus sensitive

Perdue B. et al, Retrovirus Conference, Poster 210

Implications of PEP Failures

• PEP does not eliminate transmission risk

• Not just “resistance”

Reality of PEP

• Uncertain science

• Rapid evaluation / implementation

• Adverse effects compliance

Conclusion

• Epidemiology of occupational HIV transmission

• Rationale for postexpsoure prophylaxis (PEP)

• NYSDOH recommendations for PEP

• Reality of PEP

For more HIV-related resources, please visit www.hivguidelines.org