Post-Exposure Prophylaxis Guidelines

In 1994, a large international study showed that administration of ZIDOVUDINE to an HIV-infected mother during pregnancy and labor, and subsequently to the baby after delivery reduced the risk for the baby becoming infected with HIV from about 25% to 9%. A second case-control study of healthcare workers, who had suffered needlestick exposure to HIV-infected blood, showed that ZIDOVUDINE post-exposure prophylaxis was associated with a decrease in the rate of seroconversion by 79%. These two studies demonstrate a potential benefit of using antiretroviral therapy at the time of, or shortly after, exposure to HIV. The recent availability of a wide selection of new antiviral combinations, which are far more powerful than ZIDOVUDINE alone, has triggered a more aggressive approach towards considering prophylaxis of individuals recently exposed to HIV, regardless of whether the exposure was occupational or non-occupational.

Categories

Needlestick Injury | Acute Sexual Exposure | Pregnancy

Needlestick Exposure --- Introduction

The average risk for HIV infection from significant percutaneous exposures to HIV-infected blood is 0.3%. One case control study has suggested that this risk can be reduced by the use of post-exposure prophylaxis with antiretroviral therapy. An abbreviated algorithm for the proper assessment of a risk and the interventions currently available are provided below.

Acute Sexual Exposure --- Introduction

The widespread use and success of antiretroviral therapy in reducing the risk of HIV transmission after a needlestick injury or during childbirth has raised a question regarding the prophylactic use of an antiretroviral by an uninfected person shortly after sexual exposure or needleshare exposure. In situations such as a ruptured condom, unprotected sexual intercourse (either consensual or non-consensual), or needle-sharing with an HIV-infected person, the risk of HIV transmission may be high. Consideration of antiretroviral prophylaxis should be considered as below.

Protocol: Needlestick & Acute Sexual Exposure

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RAPID INTERVENTION SOON AFTER EXPOSURE IS MORE LIKELY TO BE SUCCESSFUL!

1. Is the source known to be HIV-infected.

· If YES, proceed to 2.

· If source’s HIV status is unknown and he/she agrees to HIV testing, conduct a rapid point-of-care HIV test which is available through Calgary Lab Services. This testing is accessible by physician request at any hospital Emergency Department in the Calgary Health Region, as well as at the 8th & 8th Medical Clinic.

· If NO, and there is no compelling history suggestive the source is likely in window period for seroconversion, reassure recipient.

· If source is unknown or refuses testing: Does source have clinical signs of HIV/AIDS (e.g. oral candida, hairy leukoplakia, unexplained lymphadenopathy, etc) or a significant risk factor for HIV? If YES, proceed to 2

2. How significant is the exposure? When did it occur?

This assesses magnitude, type, and duration of exposure, all important when considering management.

· Magnitude depends on fluid type (e.g. blood versus saliva), volume, viral titer (e.g. stage of HIV infection), and the mode of exposure (hypodermic needle versus cutting needle). Needlestick injury from an HIV-infected person poses an increased risk if there is a deep injury, visible blood on the device, recent needle penetration of a vein or artery, or if the source person has advanced disease.

· Mucocutaneous injury/skin exposures pose less risk than a percutaneous injury, but factors such as the volume of blood, viral titer, duration of exposure and tissue integrity should be considered.

· When did the exposure occur? Animal studies suggested intervention with ZIDOVUDINE monotherapy was most successful if commenced within a few hours of the exposure. The potency of newer combinations of antiretroviral drugs may have extended this window period of opportunity for successful, but late prophylaxis (greater than 3 days after an exposure) is less likely to be successful as infection will have become established by then if it is less likely to occur.

3. Decision

In the CDC guidelines prophylaxis is recommended for incidents with highest or increased risk of transmission following percutaneous exposure to blood. Prophylaxis is not offered for percutaneous skin exposure to non-bloody body fluids. In other situations of intermediate risk, prophylaxis is offered and the decision rests with the individual to make a decision whether to initiate prophylaxis based on the best information available and their personal acceptance of risk.

4. Drug Selection

ZIDOVUDINE has been shown in a case control study to provide benefit after exposure to HIV. However, due to the increasing prevalence of strains of ZIDOVUDINE-resistant virus, combinations of two or more drugs should be offered for prophylaxis rather than monotherapy. The nucleoside reverse transcriptase inhibitors ZIDOVUDINE (AZT) + LAMIVUDINE (3TC) in combination appear to offer the greatest potency and provide the backbone of the regimen recommended in the current CDC guidelines. If a significant 3TC-resistant virus is suspected, after the widespread use of the drug for treatment, this recommendation may change. In the case of a significant exposure to a known HIV-positive source (where resistant virus may have been transmitted), a third agent is often added, from the protease inhibitor class.

In the Calgary Health Region, the currently used Post-Exposure Prophylaxis consists of the following:

Basic Regimen: Combivir® one tablet twice daily (each tablet contains AZT 300 mg + 3TC 150 mg) for 4 weeks.
Expanded Regimen (for significant exposures to a known HIV positive source): Combivir® one tablet twice daily + NELFINAVIR (Viracept®) FIVE tablets (total of 1250 mg) twice daily with food for 4 weeks.

Note: Other regimens may be appropriate if a detailed history of the antiretroviral use of the source patient is known of the antiretroviral resistance profile of the source patient’s virus is known.

Patient Medication Information Sheets: links to AZT – 3TC - NELFINAVIR

5. Duration of Prophylaxis

Prophylaxis should be started immediately and continued for a four-week course. This period is a balance between efficacy and toxicity, and also accommodates to some degree individuals who start prophylaxis later.

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6. Drug Toxicity

All data on tolerance to Post-Exposure Prophylaxis (PEP) is based on literature involving healthcare professionals accidentally exposed to blood or body fluids. Up to 88% of subjects on two-drug prophylaxis, and 97% of subjects on triple-drug prophylaxis experienced some adverse effect. The drugs used in PEP may be associated with hematologic and/or biochemical abnormalities. Many antiretrovirals are associated with GI side effects, such as nausea, vomiting, and diarrhea. If unaddressed, these may lead to decreased adherence to the prophylactic regime, placing the patient at risk for treatment failure. In general, these symptoms are easily managed with antiemetics and antidiarrheal medications, and appropriate counselling and encouragement.

The medium- to long-term adverse effects of PIs seen in HIV-positive individuals, such as lipodystrophy and diabetes mellitus, appear not to be a serious problem with short-term use. However, it is important for clinicians prescribing PEP to be aware of these conditions and also of interactions of antiretrovirals with other medications. Baselines of hematology, renal, and liver function should be performed before starting therapy.

7. Access to Medication, Cost of Prophylaxis

In Calgary, HIV prophylaxis starter kits with a 72-hour supply of drug are available in all hospital Emergency Rooms, and at the 8th &8th 24-hour walk-in medical clinic. All antiretroviral drugs are stored in the Pharmacy at Foothills Medical Centre. Starter kits are available at no cost to the patient. For persons who have an occupation-related exposure, the cost of the full course of prophylaxis is usually covered by the Workers Compensation Board or by the employer. In cases of non-occupational voluntary exposures (ie needle sharing), costs of prophylaxis are not generally covered. The costs associated with non-voluntary or violent exposures (ie. assault) will typically be absorbed by the Health Region.

8. Follow-up

All individuals reviewed for postexposure prophylaxis should have baseline and follow-up HIV serology undertaken. Screening, prophylaxis, or therapy for other blood-borne pathogens (eg. HBV, HCV, HTLV-1) should also be considered. Advice regarding safer sex activity and possible symptoms of seroconversion and of adverse effects of antiviral agents (if used) should also be provided.

Pregnancy --- Introduction

ZIDOVUDINE (AZT) when administered as prophylaxis to HIV-infected mothers and their infants may have contributed to a 67% reduction in perinatal transmission. This has led to the current recommendation that all untreated HIV-infected pregnant women should be offered an antiviral regimen in the form of Highly Active Anti-Retroviral Treatment (HAART) after the first trimester. It has also led to enhanced HIV screening programs in pregnant women. Currently an HIV screen is usually performed as part of standard prenatal care at three months of pregnancy in women living in Alberta unless they refuse testing. Encouraging epidemiological data on reduced perinatal transmission has supported the effectiveness of this local program in clinical practice.

Protocol: Reducing Perinatal HIV Transmission

1. For pregnant women who were not receiving antiviral therapy at time of conception:

· Start HAART between weeks 14 – 34 of pregnancy, usually ZIDOVUDINE (AZT) combined with other antiretroviral agents believed to be safe during pregnancy. Continue until labor commences.

· When labor starts, switch to AZT intravenous infusion, with a 2 mg/kg loading dose followed by 1 mg/kg/h continuous infusion until the cord is clamped.

· Start infant on AZT within 8 – 12 hours after delivery. If infant is full-term, dose is 2 mg/kg/dose every six hours, continued for six weeks. The dosage needs to be adjusted for increases in body weight, and may also need to be adjusted according to gestational age and tolerance. A physician at the Pediatric Infectious Diseases Clinic should see the infant at six weeks for assessment.

2. For pregnant women presenting in labor who test HIV-positive and who were not receiving antiviral therapy previously:

· Commence AZT intravenous infusion, with a 2 mg/kg loading dose followed by 1 mg/kg/h continuous infusion until the cord is clamped.

An additional (or alternative) medication to AZT….

NEVIRAPINE (Viramune^®) 200 mg administered once orally to the mother in the immediate pre-partum period, plus a dose of 2 mg/kg administered orally to the infant once at day three has also been shown to reduce perinatal HIV transmission from mothers who had not receiving antiretroviral therapy before delivery. Nevirapine may be administered with zidovudine.

Patient Medication Information Sheets: link to NEVIRAPINE

Note: Strict adherence to the above protocols is necessary to minimize the risk of prophylaxis failure.

Other Considerations

· In most situations, women already receiving treatment for their HIV, who become pregnant, elect to remain on those antiretrovirals. No good data is currently available on safety of most antiretrovirals.

· Similar, to needlestick injuries, the increasing prevalence of transmitting drug-resistant virus is of concern; combination therapy may be advised in some circumstances during labor and childbirth to obtain similar or hopefully even superior efficacy to that achieved with AZT monotherapy.

· AZT for Newborns

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