Post Exposure Prophylaxis

 

 

Post Exposure Prophylaxis

Risk Assess for Needlesticks

 

A 48-year-old injection drug user was referred to the emergencydepartment because of coma. A nurse sustained a deep needlestickinjury while drawing blood from the patient. On urgent HIV serologictesting, the patient was found to be at the limit of positivityfor HIV-1 and HIV-2 antibodies (AxSYM HIV 1/2 gO EIA; AbbottDiagnostics), with a signal-cutoff ratio of 1.1, and was positivefor the p24 antigen (Elecsys HIV Ag Immunoassay; Roche Diagnostics).On further analysis, the results of a confirmatory antibodyimmunoblot assay (Inno-LIA HIV I/II Score, Innogenetics) werecompletely negative but strongly reactive for the p24 antigen(signal-cutoff ratio, 1188). The results of a rapid HIV test (Determine HIV-1/2; Abbott Diagnostics) performed retrospectivelyon the first plasma sample from the source patient were negative. Postexposure prophylactic therapy with lamivudine, zidovudine,and nelfinavir was begun within 90 minutes after the accident.On receipt of an HIV RNA (Cobas AmpliPrep/Cobas TaqMan HIV-1;Roche Diagnostics) showing an extremely high viral load (5.38 x 107 HIV RNA copies/mL), and because of the high-risk nature of theexposure, the PEP regimen was modified the next day: nelfinavir was replaced by lopinavir-ritonavir, and enfuvirtide was addedto the regimen for the first week. The use of the other 3 drugswas continued for 4 weeks. The results of follow-up HIV serologictesting at 3 and 6 months remained negative.

 

 

The interval between the onset of viremia and the detection of HIV antibody, with the use of current enzyme immunoassays for HIV, is a few days at most. Hence, if the result of a reliable HIV test in the source patient is negative, the risk of transmission is assumed to be zero, unless the patient has risk factors for infection and the clinical findings are compatible with acute HIV infection (e.g., fever, pharyngitis, rash, lymphadenopathy, and malaise).

The use of a rapid HIV test can reduce the time needed to rule out HIV infection to a few hours or less. One test that is currently available, the Single Use Diagnostic System HIV-1 Test (Abbott-Murex Diagnostics), is highly sensitive, and a negative result is reliable evidence that infection is not present.

Pooled data from several prospective studies of health care personnel suggest that the average risk of HIV transmission is approximately 0.3 percent after a percutaneous exposure to HIV-infected blood and approximately 0.09 percent after a mucous-membrane exposure.

In the CDC’s retrospective case–control study of health care personnel, postexposure treatment with zidovudine was associated with an 81 percent reduction in the risk of HIV infection. However, there are no data from randomized, controlled trials to assess the efficacy and effectiveness of postexposure prophylaxis among health care personnel. Although these data are encouraging, it is clear that, whatever benefit is afforded by postexposure treatment, the protection is not absolute. 21 cases of HIV infection have been reported in health care personnel in the United States and elsewhere, despite postexposure antiretroviral treatment, which included two or more antiretroviral drugs in some cases. A variety of factors may have contributed to the treatment failure, including an intrinsic lack of efficacy of prophylactic antiretroviral treatment and resistance to antiretroviral drugs.

Nearly 50% of health care personnel report adverse events while taking antiretroviral drugs prophylactically, and about 1/3 stop taking the drugs as a result. Most of these symptoms are not serious and can be managed. Current treatment recommendations for postexposure prophylaxis against HIV following occupational exposure may be found in the EMedHome.com Database.

 

MMWR

Basic and Expanded HIV Postexposure

Prophylaxis Regimens

BASIC REGIMEN

•

Zidovudine (RETROVIR™; ZDV; AZT) + Lamivudine (EPIVIR™; 3TC);

available as COMBIVIR™

— ZDV: 600 mg per day, in two or three divided doses, and

— 3TC: 150 mg twice daily.

Advantages

— ZDV is associated with decreased risk of HIV transmission in the CDC casecontrol

study of occupational HIV infection.

— ZDV has been used more than the other drugs for PEP in HCP.

— Serious toxicity is rare when used for PEP.

— Side effects are predictable and manageable with antimotility and antiemetic

agents.

— Probably a safe regimen for pregnant HCP.

— Can be given as a single tablet (COMBIVIR™) twice daily.

Disadvantages

— Side effects are common and might result in low adherence.

— Source patient virus might have resistance to this regimen.

— Potential for delayed toxicity (oncogenic/teratogenic) is unknown.

ALTERNATE BASIC REGIMENS

•

Lamivudine (3TC) + Stavudine (ZERIT™; d4T)

— 3TC: 150 mg twice daily, and

— d4T: 40 mg (if body weight is <60 kg, 30 mg twice daily) twice daily.

Advantages

— well tolerated in patients with HIV infection, resulting in good adherence,

— serious toxicity appears to be rare, and

— twice daily dosing might improve adherence.

Disadvantages

— Source patient virus might be resistant to this regimen.

— Potential for delayed toxicity (oncogenic/teratogenic) is unknown.

•

Didanosine (VIDEX™, chewable/dispersable buffered tablet; VIDEX™ EC,

delayed-release capsule; ddI) + Stavudine (d4T)

— ddI: 400 mg (if body weight is <60 kg, 125 mg twice daily) daily, on an empty

stomach.

— d4T: 40 mg (if body weight is <60 kg, 30 mg twice daily) twice daily.

Advantages

— Likely to be effective against HIV strains from source patients who are taking

ZDV and 3TC.

Disadvantages

— ddl is difficult to administer and unpalatable.

— Chewable/dispersable buffered tablet formulation of ddI interferes with

absorption of some drugs (e.g., quinolone antibiotics, and indinavir).

— Serious toxicity (e.g., neuropathy, pancreatitis, or hepatitis) can occur. Fatal

and nonfatal pancreatitis has occurred in HIV-positive, treatment-naive patients.

Patients taking ddI and d4T should be carefully assessed and closely monitored

for pancreatitis, lactic acidosis, and hepatitis.

— Side effects are common; anticipate diarrhea and low adherence.

— Potential for delayed toxicity (oncogenic/teratogenic) is unknown.

EXPANDED REGIMEN

Basic regimen plus one of the following:

•

Indinavir (CRIXIVAN™; IDV)

— 800 mg every 8 hours, on an empty stomach.

Advantages

— Potent HIV inhibitor.

Disadvantages

— Serious toxicity (e.g., nephrolithiasis) can occur; must take 8 glasses of fluid per

day.

— Hyperbilirubinemia common; must avoid this drug during late pregnancy.

— Requires acid for absorption and cannot be taken simultaneously with ddI in

chewable/dispersable buffered tablet formulation (doses must be separated

by at least 1 hour).

— Concomitant use of astemizole, terfenadine, dihydroergotamine, ergotamine,

ergonovine, methylergonovine, rifampin, cisapride, St. John’s Wort, lovastatin,

simvastatin, pimozide, midazolam, or triazolam is not recommended.

— Potential for delayed toxicity (oncogenic/teratogenic) is unknown.

•

Nelfinavir (VIRACEPT™; NFV)

— 750 mg three times daily, with meals or snack, or

— 1250 mg twice daily, with meals or snack.

Advantages

— potent HIV inhibitor, and

— twice dosing per day might improve adherence .

Disadvantages

— Concomitant use of astemizole, terfenadine, dihydroergotamine, ergotamine,

ergonovine, methylergonovine, rifampin, cisapride, St. John’s Wort, lovastatin,

simvastatin, pimozide, midazolam, or triazolam is not recommended.

— Might accelerate the clearance of certain drugs, including oral contraceptives

(requiring alternative or additional contraceptive measures for women taking

these drugs).

— Potential for delayed toxicity (oncogenic/teratogenic) is unknown.

•

Efavirenz (SUSTIVA™; EFV)

— 600 mg daily, at bedtime.

Advantages

— Does not require phosphorylation before activation and might be active earlier

than other antiretroviral agents (note: this might be only a theoretical

advantage of no clinical benefit.)

— One dose daily might improve adherence .

Disadvantages

— Drug is associated with rash (early onset) that can be severe and might rarely

progress to Stevens-Johnson syndrome.

— Differentiating between early drug-associated rash and acute seroconversion

can be difficult and cause extraordinary concern for the exposed person.

— Nervous system side effects (e.g., dizziness, somnolence, insomnia, and/or

abnormal dreaming) are common. Severe psychiatric symptoms are possible

(dosing before bedtime might minimize these side effects).

— Should not be used during pregnancy because of concerns about teratogenicity.

— Concomitant use of astemizole, cisapride, midazolam, triazolam, ergot

derivatives, or St. John’s Wort is not recommended because inhibition of the

metabolism of these drugs could create the potential for serious and/or lifethreatening

adverse events (e.g., cardiac arrhythmias, prolonged sedation, or

respiratory depression).

— Potential for oncogenic toxicity is unknown.

•

Abacavir (ZIAGEN™; ABC); available as TRIZIVIR™, a combination of ZDV, 3TC,

and ABC

— 300 mg twice daily.

Advantages

— potent HIV inhibitor, and

— well tolerated in patients with HIV infection.

Disadvantages

— Severe hypersensitivity reactions can occur, usually within the first 6 weeks

of treatment.

— Potential for delayed toxicity (oncogenic/teratogenic) is unknown.

ANTIRETROVIRAL AGENTS FOR USE AS PEP ONLY WITH EXPERT CONSULTATION

•

Ritonavir (NORVIR™; RTV)

Disadvantages

— difficult to take (requires dose escalation),

— poor tolerability, and

— many drug interactions.

•

Saquinavir (FORTOVASE™, soft-gel formulation; SQV)

Disadvantages

— Bioavailability is relatively poor, even with new formulation.

•

Amprenavir (AGENERASE™; AMP)

Disadvantages

— Dosage consists of eight large pills taken twice daily.

— Many drug interactions.

•

Delavirdine (RESCRIPTOR™; DLV)

Disadvantages

— Drug is associated with rash (early onset) that can be severe and progress to

Stevens-Johnson syndrome.

— Many drug interactions.

•

Lopinavir/Ritonavir (KALETRA™)

— 400/100 mg twice daily.

Advantages

— potent HIV inhibitor, and

— well tolerated in patients with HIV infection.

Disadvantages

— Concomitant use of flecainide, propafenone, astemizole, terfenadine,

dihydroergotamine, ergotamine, ergonovine, methylergonovine, rifampin,

cisapride, St. John’s Wort, lovastatin, simvastatin, pimozide, midazolam, or

triazolam is not recommended because inhibition of the metabolism of these

drugs could create the potential for serious and/or life-threatening adverse

events (e.g., cardiac arrhythmias, prolonged sedation, or respiratory

depression).

— May accelerate the clearance of certain drugs, including oral contraceptives

(requiring alternative or additional contraceptive measures for women taking

these drugs).

— Potential for delayed toxicity (oncogenic/teratogenic) is unknown.

ANTIRETROVIRAL AGENTS GENERALLY NOT RECOMMENDED FOR USE AS PEP

•

Nevirapine (VIRAMUNE™; NVP)

— 200 mg daily for 2 weeks, then 200 mg twice daily.

Disadvantages

— Associated with severe hepatotoxicity (including at least one case of liver

failure requiring liver transplantation in an exposed person taking PEP),

— Associated with rash (early onset) that can be severe and progress to Stevens-

Johnson syndrome,

— Differentiating between early drug-associated rash and acute seroconversion

can be difficult and cause extraordinary concern for the exposed person, and

— Concomitant use of St. John’s Wort is not recommended because this might

result in suboptimal antiretroviral drug concentrations.

 

24 hour free national PEPline (888.448.4911)

 

CDC Update 2005

Study Highlights

• HCP includes all paid and unpaid persons who have the potential for exposure to infectious materials and persons not directly involved in patient care potentially exposed to blood and body fluids.
• Exposures that might expose a person to risk of HIV infection are percutaneous injury (such as a needlestick) or contact of mucous membrane or intact skin (such as chapped skin).
• Semen and vaginal fluid, cerebrospinal, synovial, pleural, peritoneal, pericardial, and amniotic fluids are considered potentially infectious.
• Nasal or fecal secretions, saliva, sputum, sweat, tears, urine, and vomitus are not considered potentially infectious unless they are visibly bloody.
• Any direct contact to concentrated virus requires evaluation. For human bites, evaluation must account for both persons.
• The average risk of HIV transmission after a percutaneous exposure to HIV-infected blood is 0.3%.
• After a mucous membrane exposure, the risk is approximately 0.09%.
• The risk for exposures other than to HIV-infected blood has not been quantified but is considered lower.
• Increased risk of HIV infection is associated with exposure to a larger quantity of infected blood, reflecting higher viral titers in the source person. Such exposures include (1) needle placed in vein or artery, (2) deep injury, and (3) device visibly contaminated with the source blood.
• Rapid HIV testing after exposure is associated with decreased use of PEP. The median time to initiation of PEP is 2 hours.
• If PEP is offered and taken and the source is later determined to be HIV-negative, the PEP should be discontinued.
• Reevaluation of PEP should occur within 72 hours.
• Infectious disease consultation is recommended but should not delay PEP.
• 4 classes of antiretroviral agents are currently available: nucleoside reverse transcriptase inhibitors, nucleotide analogue reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and a single-infusion inhibitor.
• The new recommendations provide guidance for 2 or more drug PEP regimens based on level of risk of exposures.
• All persons receiving PEP should complete a 4-week regimen. However, adherence to 4 weeks of therapy is limited by toxicity with 17% to 47% of HCP not completing the full course.
• Symptoms most frequently reported resulting in premature termination of treatment are nausea (26.5%) and malaise and fatigue (22.8%).
• PIs are more likely to be associated with premature treatment termination.
• PIs and NNRTIs have the greatest potential for interactions with other drugs.
• Combinations of 3 or more antiretroviral agents have proven superior to monotherapy in HIV-infected patients.
• For higher-risk occupational exposures to HIV-infected sources, a 3- or 4-drug regimen is recommended. The PHS recommends that expanded PEP regimens include PIs.
• Offering a 2-drug regimen for lower-risk exposures is viable and associated with higher completion.
• There are currently 6 worldwide case reports of HIV seroconversion despite combination HIV PEP.
• Studies of the presence of drug resistance in HIV-exposed persons are scant because most persons are taking more than one drug.
• Drug resistance should be suspected when increasing viral load or decline in CD-4 or T-cell count occur despite therapy.
• Concerns about antiretroviral use during pregnancy have been raised by reports of neurologic disease and death among uninfected children whose mothers had taken antiretroviral drugs to prevent perinatal HIV transmission.

Pearls for Practice

• Exposures to HIV-infected blood, cerebrospinal, synovial, pleural, peritoneal, pericardial, amniotic, vaginal fluids, and semen are all considered potentially infectious for HCP. Larger quantities of blood pose a higher risk for infection also. Nasal or fecal secretions, saliva, sputum, sweat, tears, urine, and vomitus are not considered potentially infectious unless they are visibly bloody.
• HIV PEP should begin early in association with infectious disease consultation, and reevaluation should occur within 72 hours. Two-drug regimens are recommended for low-risk and three- or four-drug regimens for higher-risk exposures.

Basic and Expanded HIV Postexposure Prophylaxis Regimens

 

BASIC REGIMEN

• Zidovudine (Retrovir™; ZDV; AZT) + lamivudine (Epivir®; 3TC); available as Combivir™

Preferred dosing

— ZDV: 300 mg twice daily or 200 mg three times daily, with food; total: 600 mg daily — 3TC: 300 mg once daily or 150 mg twice daily — Combivir: one tablet twice daily

Dosage forms

— ZDV: 100 mg capsule, 300 mg tablet — 3TC: 150 or 300 mg tablet — Combivir: tablet, 300 mg ZDV + 150 mg 3TC

Advantages

— ZDV associated with decreased risk for HIV transmission — ZDV used more often than other drugs for PEP for health-care personnel (HCP) — Serious toxicity rare when used for PEP — Side effects predictable and manageable with antimotility and antiemetic agents — Can be used by pregnant HCP — Can be given as a single tablet (COMBIVIR™) twice daily

Disadvantages

— Side effects (especially nausea and fatigue) common and might result in low adherence — Source-patient virus resistance to this regimen possible — Potential for delayed toxicity (oncogenic/teratogenic) unknown

• Zidovudine (Retrovir®; ZDV; AZT) + emtrictabine (Emtriva™; FTC)

 

Preferred dosing

— ZDV: 300 mg twice daily or 200 mg three times daily, with food; total: 600 mg/day, in 2–3 divided doses — FTC: 200 mg (one capsule) once daily

Dosage forms

— ZDV: see above — FTC: 200 mg capsule

FTC general comments

— Nucleoside analogue; same structure as 3TC, except fluoride residue at position 5 on pyrimidine ring — Same resistance and safety profile as 3TC — No apparent advantage over 3TC; tolerability and virologic response rates appear better than regimens containing ddI + d4T

Advantages

— ZDV: see above. — FTC

o Convenient (once daily) o Well tolerated o Long intracellular half-life (~40 hours)

Disadvantages

— ZDV: see above. — FTC

o Rash perhaps more frequent than with 3TC o No long-term experience with this drug o Cross resistance to 3TC o Hyperpigimentation among non-Caucasians with long-term use: 3%

• Tenofovir DF (Viread®; TDF) + lamivudine (Epivir®; 3TC)

Preferred dosing

— TDF: 300 mg once daily — 3TC: 300 mg once daily or 150 mg twice daily

Dosage forms

— TDF: 300 mg tablet — 3TC: see above

Advantages

— 3TC: see above — TDF

o Convenient dosing (single pill once daily) o Resistance profile activity against certain thymidine analogue mutations o Well tolerated

Disadvantages

— TDF

o Same class warnings as nucleoside reverse transcriptase inhibitors (NRTIs) o Drug interactions o Increased TDF concentrations among persons taking atazanavir and lopinavir/ritonavir; need to monitor patients for TDF-associated toxicities

— Preferred dosage of atazanavir if used with TDF: 300 mg + ritonavir 100 mg once daily + TDF 300 mg once daily

• Tenofovir DF (Viread®; TDF) + emtricitabine (Emtriva™; FTC); available as Truvada™

Preferred dosing

— TDF: 300 mg once daily — FTC: 200 mg once daily — As Truvada™: one tablet daily

Dosage forms

— TDF: 300 mg tablet — FTC: see FTC — Truvada™ (TDF 300 mg plus FTC 200 mg)

Advantages

— FTC: see above — TDF

o Convenient dosing (single pill once daily)

o Resistance profile activity against certain thymidine analogue mutations

o Well tolerated

Disadvantages

— TDF

o Same class warnings as NRTIs o Drug interactions o Increased TDF concentrations among persons taking atazanavir and lopinavir/ritonavir; need to monitor patients for TDF-associated toxicities o Preferred dosing of atazanavir if used with TDF: 300 mg + ritonavir 100 mg once daily + TDF 300 mg once daily

 

ALTERNATE BASIC REGIMENS

• Lamivudine (Epivir®; 3TC) + stavudine (Zerit®; d4T)

Preferred dosing

— 3TC: 300 mg once daily or 150 mg twice daily — d4T: 40 mg twice daily (can use lower doses of 20–30 mg twice daily if toxicity occurs; equally effective but less toxic among HIV-infected patients with peripheral neuropathy); 30 mg twice daily if body weight is <60 kg

Dosage forms

— 3TC: see above — d4T: 15, 20, 30, and 40 mg tablet

Advantages

— 3TC: see above — d4T: gastrointestinal (GI) side effects rare

Disadvantages

— Possibility that source-patient virus is resistant to this regimen — Potential for delayed toxicity (oncogenic/teratogenic) unknown  

• Emtricitabine (Emtriva™; FTC) + stavudine (Zerit®; d4T)

Preferrred dosing

— FTC: 200 mg daily — d4T: 40 mg twice daily (can use lower doses of 20–30 mg twice daily if toxicity occurs; equally effective but less toxic among HIV-infected patients who developed peripheral neuropathy); if body weight is <60 kg, 30 mg twice daily

Dosage forms

— FTC: see above — d4T: see above

Advantages

— 3TC and FTC: see above; d4T’s GI side effects rare

Disadvantages

— Potential that source-patient virus is resistant to this regimen — Unknown potential for delayed toxicity (oncogenic/teratogenic) unknown  

• Lamivudine (Epivir®; 3TC) + didanosine (Videx®; ddI)

Preferred dosing

— 3TC: 300 mg once daily or 150 mg twice daily — ddI: Videx® chewable/dispersible buffered tablets can be administered on an empty stomach as either 200 mg twice daily or 400 mg once daily. Patients must take at least two of the appropriate strength tablets at each dose to provide adequate buffering and prevent gastric acid degradation of ddI. Because of the need for adequate buffering, the 200-mg strength tablet should be used only as a component of a once-daily regimen. The dose is either 200 mg twice daily or 400 mg once daily for patients weighing >60 kg and 125 mg twice daily or 250 mg once daily for patients weighing >60 kg.

Dosage forms

— 3TC: 150 or 300 mg tablets — ddI: 25, 50, 100, 150, or 200 mg buffered white tablets

Advantages

— ddI: once daily dosing option — 3TC: see above

Disadvantages

— Tolerability: diarrhea more common with buffered preparation than with enteric-coated preparation — Associated with toxicity: peripheral neuropathy, pancreatitis, and lactic acidosis — Must be taken on empty stomach except with TDF — Drug interactions — 3TC: see above  

• Emtricitabine (Emtriva™; FTC) + didanosine (Videx®; ddI)

Preferred dosing

— FTC: 200 mg once daily — ddI: see above

Dosage forms

— ddI: see above — FTC: see above

Advantages

— ddI: see above — FTC: see above

Disadvantages

— Tolerability: diarrhea more common with buffered than with enteric-coated preparation — Associated with toxicity: peripheral neuropathy, pancreatitis, and lactic acidosis — Must be taken on empty stomach except with TDF — Drug interactions — FTC: see above

 

PREFERRED EXPANDED REGIMEN

Basic regimen plus:

• Lopinavir/ritonavir (Kaletra®; LPV/RTV)

Preferred dosing

— LPV/RTV: 400/100 mg = 3 capsules twice daily with food

Dosage form

— LPV/RTV: 133/33 mg capsules

Advantages

— Potent HIV protease inhibitor — Generally well-tolerated

Disadvantages

— Potential for serious or life-threatening drug interactions (see Table 4) — Might accelerate clearance of certain drugs, including oral contraceptives (requiring alternative or additional contraceptive measures for women taking these drugs) — Can cause severe hyperlipidemia, especially hypertriglyceridemia — GI (e.g., diarrhea) events common

 

ALTERNATE EXPANDED REGIMENS

Basic regimen plus one of the following:

• Atazanavir (Reyataz®; ATV) + ritonavir (Norvir®; RTV)

Preferred dosing

— ATV: 400 mg once daily, unless used in combination with TDF, in which case ATV should be boosted with RTV, preferred dosing of ATV 300 mg + RTV: 100 mg once daily

Dosage forms

— ATV: 100, 150, and 200 mg capsules — RTV: 100 mg capsule

Advantages

— Potent HIV protease inhibitor — Convenient dosing — once daily — Generally well tolerated

Disadvantages

— Hyperbilirubinemia and jaundice common — Potential for serious or life-threatening drug interactions (see Table 4) — Avoid coadministration with proton pump inhibitors — Separate antacids and buffered medications by 2 hours and H2-receptor antagonists by 12 hours to avoid decreasing ATV levels — Caution should be used with ATV and products known to induce PR prolongation (e.g., diltiazem)  

• Fosamprenavir (Lexiva®; FOSAPV) + ritonavir (Norvir®; RTV)

Preferred dosing

— FOSAPV: 1400 mg twice daily (without RTV) — FOSAPV: 1400 mg once daily + RTV 200 mg once daily — FOSAPV: 700 mg twice daily + RTV 100 mg twice daily

Dosage form

— FOSAPV: 700 mg tablets — RTV: 100 mg capsule

Advantages

— Once daily dosing when given with ritonavir

Disadvantages

— Tolerability: GI side effects common — Multiple drug interactions. Oral contraceptives decrease fosamprenavir concentrations — Incidence of rash in healthy volunteers, especially when used with low doses of ritonavir. Differentiating between early drug-associated rash and acute seroconversion can be difficult and cause extraordinary concern for the exposed person  

• Indinavir (Crixivan®; IDV) + ritonavir (Norvir®; RTV)

Preferred dosing

— IDV 800 mg + RTV 100 mg twice daily without regard to food

Alternative dosing

— IDV: 800 mg every 8 hours, on an empty stomach

Dosage forms

— IDV: 200 mg, 333, and 400 mg capsule — RTV: 100 mg capsule

Advantages

— Potent HIV inhibitor

Disadvantages

— Potential for serious or life-threatening drug interactions (see Table 4) — Serious toxicity (e.g., nephrolithiasis) possible; consumption of 8 glasses of fluid/day required — Hyperbilirubinemia common; must avoid this drug during late pregnancy — Requires acid for absorption and cannot be taken simultaneously with ddI, chewable/dispersible buffered tablet formulation (doses must be separated by >1 hour)  

• Saquinavir (Invirase®; SQV) + ritonavir (Norvir®; RTV)

Preferred dosing

— SQV: 1,000 mg (given as Invirase) + RTV 100 mg, twice daily — SQV : five capsules twice daily + RTV: one capsule twice daily

Dosage forms

— SQV (Invirase): 200 mg capsule — RTV: 100 mg capsule

Advantages

— Generally well-tolerated, although GI events common

Disadvantages

— Potential for serious or life-threatening drug interactions (see Table 4) — Substantial pill burden  

• Nelfinavir (Viracept®; NFV)

Preferred dosing

— NFV: 1,250 mg (2 x 625 mg or 5 x 250 mg tablets), twice daily with a meal

Dosage forms

— NFV: 250 or 625 mg tablet

Advantages

— Generally well-tolerated

Disadvantages

— Diarrhea or other GI events common — Potential for serious and/or life-threatening drug interactions (see Table 4)  

• Efavirenz (Sustiva®; EFV)

Preferred dosing

— EFV: 600 mg daily, at bedtime

Dosage forms

— EFV: 50, 100, 200 capsules — EFV: 600 mg tablet

Advantages

— Does not require phosphorylation before activation and might be active earlier than other antiretroviral agents (a theoretic advantage of no demonstrated clinical benefit) — Once daily dosing

Disadvantages

— Drug associated with rash (early onset) that can be severe and might rarely progress to Stevens-Johnson syndrome — Differentiating between early drug-associated rash and acute seroconversion can be difficult and cause extraordinary concern for the exposed person — Central nervous system side effects (e.g., dizziness, somnolence, insomnia, or abnormal dreaming) common; severe psychiatric symptoms possible (dosing before bedtime might minimize these side effects) — Teratogen; should not be used during pregnancy — Potential for serious or life-threatening drug interactions (see Table 5)

 

ANTIRETROVIRAL AGENTS GENERALLY NOT RECOMMENDED FOR USE AS PEP

• Nevirapine (Viramune®; NVP)

Disadvantages

— Associated with severe hepatotoxicity (including at least one case of liver failure requiring liver transplantation in an exposed person taking PEP) — Associated with rash (early onset) that can be severe and progress to Stevens-Johnson syndrome — Differentiating between early drug-associated rash and acute seroconversion can be difficult and cause extraordinary concern for the exposed person — Drug interactions: can lower effectiveness of certain antiretroviral agents and other commonly used medicines  

• Delavirdine (Rescriptor®; DLV)

Disadvantages

— Drug associated with rash (early onset) that can be severe and progress to Stevens-Johnson syndrome — Multiple drug interactions  

• Abacavir (Ziagen®; ABC)

Disadvantages

— Severe hypersensitivity reactions can occur, usually within the first 6 weeks — Differentiating between early drug-associated rash/hypersensitivity and acute seroconversion can be difficult  

• Zalcitabine (Hivid®; ddC)

Disadvantages

— Three times a day dosing — Tolerability — Weakest antiretroviral agent

ANTIRETROVIRAL AGENT FOR USE AS PEP ONLY WITH EXPERT CONSULTATION

• Enfuvirtide (Fuzeon™; T20)

Preferred dosing

— T20: 90 mg (1 ml) twice daily by subcutaneous injection

Dosage forms

— T20: Single-dose vial, reconstituted to 90 mg/ml

Advantages

— New class — Unique viral target; to block cell entry — Prevalence of resistance low

Disadvantages

— Twice-daily injection — Safety profile: local injection site reactions — Never studied among antiretroviral-naïve or HIV-negative patients — False-positive EIA HIV antibody tests might result from formation of anti-T20 antibodies that cross-react with anti-gp41 antibodies

PHS Working Group on Occupational Postexposure Prophylaxis: Adelisa L Panlilio, Denise M. Cardo, Division of Healthcare Quality Promotion, National Center for Infectious Diseases, CDC; Lisa A. Grohskopf; Walid Heneine, Division of HIV/AIDS Prevention, National Center for HIV, STD, and TB Prevention, CDC; Clara Sue Ross, Ahmed Gomaa; Division of Surveillance and Hazard Evaluations, and Field Studies, National Institute for Occupational Safety and Health, CDC; Kimberly A. Struble, Center for Drug Evaluation and Research, FDA; Abe Macher, HIV/AIDS Bureau, HRSA; David K Henderson, Clinical Center, National Institutes of Health.

External Consultants: Henry M. Blumberg, Grady Memorial Hospital; Betty Dong, National Clinicians’ Postexposure Prophylaxis Hotline (PEPline); Ron Goldschmidt, University of California, San Francisco; Michael Saag, University of Alabama, Birmingham; Michael Tapper, Lenox Hill Hospital.

Box 1Return to top. Box 2Return to top. Table 1Return to top. Table 2Return to top. Table 3Return to top. Table 4Return to top. Table 5Return to top. Table 6  

 

 

 

 

 

 

    |      |      |