1. Standard Precautions and Post Exposure Prophylaxis
HIV Care and ART: A Course for Healthcare Professionals

2. Learning Objectives
Describe the basic principles and procedures of standard precautions
Identify the risks of HIV, HCV, and HBV seroconversion following accidental occupational exposures
List the management steps of occupational exposure
Describe the principles of HIV post-exposure prophylaxis

3. Case study
Abebech is a 32 year-old nurse. She came to the ART clinic after she sustained a needle stick while providing an injection to a hospitalized patient. She thinks that the patient is HIV positive and she is requesting HIV post-exposure prophylaxis
What measures are important for preventing this problem in the future?
What further information is needed to manage this patient?
This is not an uncommon situation. As described later in this section, occupational exposures can be reduced by use of universal precautions. The evaluation of this patient includes assessment of both the exposure type and the source patient.

4. Occupational Exposure Risk

5. Estimated Pathogen-Specific Seroconversion Rate Per Exposure for Occupational Needle stick Injury
This slide illustrates the risk of transmission of HIV, which is much less than that of Hepatitis B or Hepatitis C.
Source: AETC at (table adapted from Centers for Disease Control & Prevention. MMWR 2001;50(RR-11):1-52.) .
AETC

6. Type of Exposure Involved in Transmission of HIV to Health Care Workers
Most occupational exposures are due to contaminated sharp injuries. Mucous membranes exposure to infected body fluid also poses an important risk.
Source: AETC at (table adapted from Centers for Disease Control & Prevention. MMWR 2001;50(RR-11):1-52.)
AETC

7. Source of HIV Involved in HIV Transmission to Health Care Worker
Source: AETC at (table adapted from Centers for Disease Control & Prevention. MMWR 2001;50(RR-11):1-52.)
AETC

8. Risk Factors for HIV Transmission with Occupational Exposure to HIV-Infected Blood
Odds Ratio
Confidence Interval
Deep Injury 15
6.0-41
Visibly Bloody Device
6.2
2.2-21
Device Used in Artery or Vein
4.3
1.7-12
Terminally Ill Source Patient
5.6
2.0-16
Use of Zidovudine for PEP
0.19
P<0.01 for all associations
Retrospective study of 33 HCW who seroconverted compared to 665 controls (N Engl J Med 1997;337: ).
Source person – the stage of illness/level of viremia reflects the size of the HIV inoculum transmitted to the exposed patient.
Patients with deep injury exposure were 15 times more likely to acquire HIV than those without deep injury.
Use of AZT associated with reduced risk of seroconversion:
OR = 0.19 (CI ); 79% relative risk reduction in transmission
However, recent data shows 21 cases of HIV transmission to exposed HCW despite AZT prophylaxis (NEJM 2003;348:826) in multivariate analysis, several important risk factors were identified.
Source: AETC at

9. Other Possible Risk Factors
Hollow bore vs solid bore
No documented cases to date of seroconversion from suture needles
Glove use
50% decrease in volume of blood transmitted
Mucous membrane exposure
Type of exposure – or route of exposure is important. Hollow bore needles are more likely than solid needles to cause seroconversion because they can contain and transmit a larger volume of blood. Similarly, large diameter needles are associated with trend towards increased risk (though not significant; p = 0.08).
Glove material reduced the transferred blood volume by 46%-86% in one study (“Efficacy of gloves in reducing blood volumes transferred during simulated needle stick injury.” Mast ST, Woolwine JD, Gerberding JL. Department of Medicine and Infectious Diseases, University of California, San Francisco).
HIV may be transmitted by mucous membrane exposure, though this is much less common. Simple cutaneous exposure is unlikely to transmit HIV; in fact not a single case of transmission has been ascribed to this route.

10. HIV in the Environment How long does HIV live outside the body?
HIV does not survive well in the environment
When HIV-infected blood or body fluids dry, the theoretical risk of environmental transmission is essentially zero
No reports of environmental transmission
Source: CDC, Division of AIDS prevention.

11. Standard Precautions

12. Standard Precautions Definition
Standards developed to prevent exposure and transmission of disease in occupational setting
Provide guidance for the safe handling of infectious material
Formerly referred to as Universal Precautions. “Universal” means everyone, everywhere, always
Most patient care does not involve any risk of HIV transmission, and most HIV-infected health care workers are infected through sexual contact. Occupational exposure is unusual and can be minimized by adopting appropriate accident prevention procedures.
Universal Precautions were developed by CDC in 1985 to help address the concern of risk faced by healthcare workers when providing care to patients with HIV and other blood borne pathogens like Hepatitis B and C. These precautions are designed to guide safe handling of infectious material including blood and body fluids. The name has recently been changed to Standard Precautions, to show that they are the standard for health care practice.

13. Components of Standard Precautions
Hand washing – Key step in limiting nosocomial spread of disease
Use protective barriers when indicated
Gloves: mucus membranes, body fluids, broken skin
Goggles: procedures
Gowns/masks: procedures
Protective barriers and hand washing are important components of SP.
The single most important personal action that the healthcare worker can take to limit nosocomial spread of disease is hand washing with soap and water before and after all procedures.

14. Components of Standard Precautions (2)
Sharps and waste - handle with gloves and dispose in designated containers
Needles
Scalpels
Suture material
Bandages
Dressings
Anything contaminated with any body fluid
Proper handling of sharps and waste is probably the most important factor in limiting occupational exposure to blood borne pathogens like HIV.

15. Rules to Follow While Disposing Sharps
Do not recap needles!
Put containers within arms reach
Use adequate light source when treating patients
Wear heavy-duty gloves when transporting sharps
Incinerate used needles to a sufficient temperature to melt
Keep sharps out of reach of children

16. Components of Standard Precautions (3)
Re-usable instruments - must be thoroughly disinfected
Speculums
Surgical tools
Thermometers
Immunizations
Hepatitis A and B
Immunizations against hepatitis A and B are recommended for all health care workers as a component of standard precautions.

17. Recommended Antiseptic Solutions
Ethyl alcohol, 70%
Chlorhexidine, 2-4% (e.g. Hibtane, Hibiscrub)
Chlorhexidine gluconate and cetrimide, at least 2% (e.g. Savlon*)
Iodine tincture, 3%
Iodophores, % (e.g. Betadine)
Chlorozylenol in alcohol, %, (e.g. Dettol*)
*Use undiluted
Antiseptic solutions are chemicals that are applied to skin or other living tissues to inhibit or kill transient or resident microorganisms.
Don’t dilute Savlon or Dettol.
Don’t use Hexachlorophene, Benzalkonium chloride and mercury containing compounds as antiseptics.

18. Recommended Disinfectants
Chlorine, 0.5% (Barkina)
Sedex and Ghion brands contain 5% Chlorine, dilute for use
Glutaraldehyde, 2-4% (e.g. Cidex)
Formaldehyde, 8%
Hydrogen peroxide, 6%
Soak the instrument for 20 minutes after decontamination and cleaning
Disinfectants are chemicals that are applied on non-living and non critical surfaces such as walls, floors, and furniture.

19. Management of Occupational Exposure

20. Wound Care
Gently wash wounds with soap and water (don’t scrub vigorously)
Allow wounds to bleed freely
Irrigate exposed mucosal surfaces with sterile saline

21. Post Exposure Prophylaxis
Definition:
Use of therapeutic agent to prevent establishment of infection following exposure either occupationally or non-occupationally to pathogen
Roles in Occupational Exposure:
HIV prevention
HBV prevention

22. HIV PEP for Occupational Exposure
Overview
Limited data (animal)
Better to err on side of treatment
Exposed patient must be tested for HIV prior to PEP
Start immediately after exposure
Duration 28 days
As in all things, it is important to balance the benefit against the risk of therapy.
Don’t forget to test the exposed patient for HIV before committing to a course of PEP; however, sometimes the first dose of PEP might be given prior to this test because of logistical difficulties in obtaining a rapid test. PEP should be started as soon as possible, at least within 72 hours.

23. Decision-making Tools for PEP
Source code (SC)
Risk assessment of the source patient
SC 1, SC 2, SC Unknown
Exposure code (EC)
Risk assessment of exposure type
EC 1, EC 2, EC 3
The SC and EC are used to estimate the risk of transmission from the occupational exposure and help determine the type of PEP regimen

24. Step 1: Does This Patient Need HIV PEP?
Source patient
Unknown / Unwilling to get tested*
HIV -
HIV +
High back-ground risk
Low back-ground risk
The initial step - not shown here - is to determine the status of the exposed person. If this person is seronegative (and the exposure was not simply cutaneous) then:
Determine the status of the source patient
If the source patient’s status is unknown or the patient is unwilling to get tested, assess the background risk of the patient. In general, hospitalized patients in Ethiopia are high risk (>3% background prevalence)
If the source patient is positive or comes from a high risk background, PEP is indicated
No PEP
PEP
No PEP
*CDC recom: usually PEP unnecessary; consider use if source patient is high risk

25. Step 2: Determine HIV Status Code of Source (HIV SC)
HIV Negative
HIV Positive
Asymptomatic/high CD4 = HIV SC 1
Advanced disease, primary infection or low CD4 =HIV SC 2
HIV Status Unknown or Source Unknown
= HIV SC Unknown
No PEP
If the patient needs PEP, then the next step (Step 2) is to determine the HIV status of the source patient or (SC). If the HIV positive patient is asymptomatic and their CD4 count is preserved, the source code (SC) = 1. In the case of advanced disease, primary infection, or a low CD4 count/high viral load, the SC = 2. In some cases you may not know the HIV status or the source and in this case the HIV SC is unknown.
This code will help determine the most appropriate PEP regimen, as shown later.

26. Step 3: Type of Exposure: Determine the Exposure Code
Exposure on
Mucous membrane or broken skin
Exposure on Intact Skin
Percutaneous
Exposure
Determine Volume
No PEP
Determine Severity
Few drops, short
duration,
SMALL = EC 1
Several drops/long
duration/major
blood splash
LARGE = EC 2
Solid, superficial
Scratch
LESS SEVERE = EC 2
Hollow needle, deep
Puncture
MORE SEVERE = EC 3
This step examines the type of exposure and is combined with the SC to determine the best PEP regimen.
In the case of mucous membrane or broken skin, the volume and exposure time of fluid will determine the EC (exposure code). Few drops, short amount of time = EC1; anything else = EC2.
Percutaneous exposure is either EC2 (solid bore needle or superficial scratch) or EC3 (hollow bore needle or deep puncture).

27. Step 4: Determine PEP Regimen
HIV SC EC
PEP Recommendation 1
PEP may not be warranted 2
Consider basic regimen
Recommend basic regimen
Expanded regimen recommended
1 or 2 3
Unknown
If EC is 2 or 3 and a risk exists, consider PEP basic regimen
The combination of EC and SC guides the recommendation for 2 or 3 drug PEP regimens.
The important thing to consider is the fact that you have only one chance to give PEP. It is better to err on the side of treatment with 3 versus 2 drugs if there is doubt. However, it is equally important protect scarce resources when PEP is not warranted.

28. Step 4: Determine PEP Regimen (2)
Exposure Type
Source Infection Status
HIV+ Class 1
HIV+ Class 2
Less Severe
Basic (2 Drugs)
Expanded (3 Drugs)
More Severe
Less Severe: Solid needle, superficial injury
More Severe: Large-bore hollow needle, deep puncture, visible blood on device, or needle used in patient's artery or vein
HIV Class 1: Asymptomatic or HIV RNA less than 1500 copies/ml
HIV Class 2: Symptomatic HIV infection, AIDS, acute seroconversion, or known high HIV RNA
This slide shows the same information provided on the previous slide. It is better to err on the side of an expanded drug regimen.
Source: AETC at

29. HIV Post Exposure Prophylaxis
2 drug regimen
Zidovudine plus lamivudine (combivir)
Stavudine plus Lamivudine
Tenofovir plus lamivudine
3 drug regimen
LPV/r or Indinavir or Nelfinavir plus NRTI backbone
Efavirez plus NRTI backbone
Consider resistance potential of source patient
Don’t use NVP (hepatotoxic)
Don’t use NVP because of high risk of liver toxicity in patients with preserved immune function. When available, the resistance profile of the source person is helpful in selecting the ARV regimen.

30. HIV PEP - When to Start As soon as possible!
U.S. Public Health Service Guidelines recommends prompt initiation of PEP (within hours of exposure), but does not rule out consideration of PEP even if more than 36 hours have elapsed since the exposure
Animal data show no benefit when treatment is delayed hours
Most experts use 72 hour window limit
Although there is no human data regarding optimal timing of PEP, animal studies suggest that the optimal time to begin PEP is immediately after the exposure.
The benefits of PEP decrease after 24 to 36 hours. This highlights the importance of having a PEP program in all high risk areas to ensure prompt assessment and management of the exposed person.

31. The Early Stages of HIV Infection
Cell free HIV
CD40—CD40
T-cell
Immature Dendritic cell
PEP
Skin or mucosa
Via lymphatics or circulation
Burst of HIV replication
The rational for starting PEP as soon as possible is based on the pathophysiology depicted here.
From time of crossing the skin or mucous membrane it takes only about 48 hours to establish HIV infection.
The free HIV viron is first taken up the immature dendritic cell and travels to the T-cell where in a single replication it transfers HIV to the T-cell. It is during this time that it is possible to interrupt early replication (less than 48 hours).
24 hours
48 hours
HIV co-receptors, CD4 + chemokine receptor CC5
Mature Dendritic cell in regional LN undergoes a single replication, which transfers HIV to T- cell
Selective of macrophage-tropic HIV

32. HIV PEP - When to Stop Timing is unclear
Animal studies suggest better efficacy with 28 days of PEP when compared with shorter duration of therapy

33. Current PEP Policy in Ethiopia
Emphasis is on standard precautions
Individual ART programs may access and distribute PEP free of charge
The least expensive and most effective way to deal with a disease is via prevention. The implementation of Standard Precautions with appropriate training and monitoring will be step one. The second step will be a national policy enabling free PEP for occupational exposures.

34. Case Study 1
27 year-old female nurse presents to OPD for evaluation of needle stick injury 2 days ago from a diabetic lancet
Source patient (SP): 35 year-old male, HIV+
Discussion:
What do we need to know about the source patient and exposure in order to manage this nurse?
Would you offer her PEP? If so, which agents?

35. Additional Information
The SP has been taking AZT/3TC/NVP (1st regimen) for one year.
He was WHO stage II prior to starting ART, and is currently in good health
The SP’s most recent CD4 count was 200; his initial CD4 before starting ART was 180
Viral load 2 months ago was 60,000
How does this information influence the choice of PEP regimen?
The patient’s detectable viral load and non-significant increase in CD4 count after one year of therapy suggests treatment failure. This may be due to suboptimal drug levels (non-adherence, malabsorption, unfavorable pharmacokinetics), drug resistance, or combination of all of these.
Therefore, choosing a 3 drug regimen that differs from that of the source patient would be appropriate

36. Case Study 1 - Questions What is her risk for contracting HIV?
What factors influence this risk?
Is it too late to start PEP?
Which regimen(s) should be considered?
What follow-up should be arranged?

37. Case Study 1: PEP Options
Source patient’s high-level viremia despite HAART suggests that he is either not taking his medications, or that he has developed resistance to his regimen
Resistance assay is not performed in Ethiopia – therefore must reason around patterns of anticipated resistance to SP’s regimen
If resistance has developed, would suspect resistance to lamivudine and zidovudine
May have NNRTI cross resistance as well
Although resistance testing genotype, phenotype, and virtual phenotype are helpful in determining ARV selection, it is only recently that we have had this luxury.
Even with the availability of ARV testing, it is essential to take an ARV drug history. In that history it would be important to find out which drugs, when they were taken (dates started – date finished), and why they were stopped.
By using this information and what you know about ARVs, it may be possible to predict resistance to ARV and cross resistance.

38. Case Study 1: PEP Options
High viral load of source patient would warrant use of a three drug PEP regimen
One reasonable PEP regimen: didanosine + tenofovir + lopinavir/ritonavir
In high risk exposure it may be prudent to use a three drug PEP regimen. Inclusion of a PI in the high risk PEP may be expensive, but it is not unreasonable.

39. Case Study 2
24 year-old dental technician splashed in the eye during dental procedure 3 hours ago
Source patient: 33 year-old male, co-infected with HIV and HCV
What else do you need to know?
In this case there are two considerations: Hepatitis C and HIV. Classify the level of risk for the exposure as well as information about the source patient. Additionally, be sure to ask about the stage of disease, viral load, CD4, ARV, OI as related to HIV.
In this case there is also co-infection with Hepatitis C which also presents a risk factor for the healthcare worker. Although treatment is unusual even in developed countries it would be appropriate to ask about the serotype of Hepatitis C, treatment, and stage of Hepatitis C disease as well as a confirmation of the disease. While the risk for transmission of HIV (via sharps injury) is 0.3% the risk for Hepatitis C is 1.8%. If available quantitative HCV RNA tests should be done in those who are Hepatitis C positive. There is NO prophylaxis with IG or with antiviral.

40. Which Fluids are Potentially Infectious for HIV?
Blood?
Saliva?
Sweat?
Feces?
Spinal fluid?
Pleural fluid?
Pus?
Urine?

41. Which Fluids are Potentially Infectious for HIV? (2)
Blood
Saliva
Sweat
Feces
Spinal fluid
Pleural fluid
Pus
Urine
The body fluids highlighted here may transmit the HIV virus.
The highest concentration of virus resides in blood, but spinal fluid, pleural fluid, genital secretions (semen and vaginal secretions) and pus also harbor the HIV virus.
Normal feces and urine does not contain the virus, unless the stool or urine is grossly bloody.
Likewise, saliva and sweat does not transmit the virus unless mixed with blood.

42. Case Study 2 – cont.
Saliva was visibly bloody - in fact, it was mostly blood that splashed her
She rinsed out her eye immediately
Source patient has never taken antiretrovirals, has a CD4 count of “about 500” and a viral load of 20,000 last time it was checked.
The exposed patient is 8 weeks pregnant

43. Case Study 2 – Questions Discuss: What are your PEP recommendations?
How does her pregnancy affect your decision making?

44. PEP in Pregnancy Most antiretrovirals class B or C in pregnancy
Antiretroviral Pregnancy Registry has not detected increased teratogenic risk for ARVs in general, nor specifically for AZT and 3TC, in the first trimester1
Avoid efavirenz (anencephaly in monkeys), amprenavir (ossification defects in rabbits), and, in late term, indinavir (hyperbilirubinemia)
Avoid combination d4T and ddI
Theoretically higher risk of vertical transmission with primary HIV infection.
There are no safe drugs in pregnancy, but using our risk benefit equation these are some medications (including retrovirals) that are safer than others.

45. Case Study 2 - cont. The patient starts AZT/3TC/Nelfinavir
3 days later she calls complaining of headache, congestion, an itchy rash, and URI symptoms
What further information is needed for managing this patient?

46. Case 2 – cont. Exam: VS: T 99.0 R 14 P 78 BP 134/76
Gen - alert, tired-appearing, no acute distress
HEENT - hyperemic nasal mucosa with frontal sinus tenderness; pharynx is also red
Neck - 3 cm. left ant cervical lymph node
Lungs, cardiac, abdomen: normal
Neuro: normal
Skin: urticarial rash on trunk and legs; no ulcerations

47. Case 2 – Questions What is the most likely diagnosis?
How would you manage this patient?

48. Primary HIV Infection
Flu-like or mono-like illness often accompanied by a rash1
Onset typically 2-6 weeks following exposure, but high variability
Symptoms generally resolve spontaneously in 1-3 wks (corresponding with VL reduction)
Treatment of PHI with antiretroviral therapy may have significant long-term benefit3
Acute seroconversion to HIV positive is a diagnosis that is easy miss or misdiagnose.
These patients are symptomatic, but are seldom diagnosed with acute HIV disease. Observe carefully for patients with a flu-like illness with a rash.
These symptoms can be confused with “any viral syndrome” and disappear in a few days to a week or so.
If the diagnosis can be made via PCR antiretrovirals may be of benefit in preventing vertical transmission as well as in lowering the “viral set point” and improving the course of HIV disease over the long term.

49. PHI: Diagnostic Testing
1 mil
100,000
10,000
1,000
100 10 + _
HIV RNA
HIV-1 Antibodies
Exposure 14 21 28
Symptoms
Days Ab 7
Typical Sequence of Events in Primary HIV
Event Day
Infection 0
Entry of virus into bloodstream 3-7
Detectable HIV-1 RNA
Detectable p24 antigen
Onset of symptoms
Antibody seroconversion
Within two to eight weeks after the symptoms of primary HIV infection it should be possible to obtain a positive antibody test for HIV via EIA and Western blot or any of the rapid antibody tests in use. P24 antigen and HIV PCR would be positive BEFORE these symptoms occur.
Image courtesy of The Center for AIDS Information & Advocacy,

50. Could She Have Primary HIV Infection?
Primary HIV Infection less likely
Only three days since the exposure
Presence of nasal congestion
Rash is urticarial
However, would not be unreasonable to check an HIV viral load to rule out PHI

51. Follow-up HIV Testing
CDC recommendations: HIV Ab testing at 6 weeks, 3 months, 6 months following exposure
Extended HIV Ab testing at 12 months recommended if health care worker contracts HCV from a source patient co-infected with HIV and HCV
VL testing not recommended unless Primary HIV Infection (PHI) suspected
In Ethiopia, it may be some time before all of these laboratory tests are widely available, but it is nevertheless important to know of their existence.
MMWR June 29, 2001 / 50(RR11);1-42.

52. Key Points
Standard precautions should be implemented and practiced by all healthcare providers
The most important infection control method is hand washing
Proper handling of sharps is critical for reducing occupational exposure to blood borne pathogens
Risk of HIV seroconversion after occupational exposure varies depending on source patient and exposure circumstance
When indicated, PEP should be employed immediately (within hours)

53. Thanks