Practice Guidelines

USPHS Releases Updated Guidelines for Management of Occupational Exposure to HIV

Am Fam Physician. 2005 Dec 1;72(11):2378-2384.

The U.S. Public Health Service (USPHS) has issued updated guidelines for prophylaxis of health care professionals with occupational exposure to blood and other body fluids that might contain human immunodeficiency virus (HIV). The recommendations, “Updated U.S. Public Health Service Guidelines for the Management of Occupational Exposures to HIV and Recommendations for Postexposure Prophylaxis,” were published in the Sept. 30, 2005, issue of Morbidity and Mortality Weekly Report Recommendations and Reports and are available online at http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5409a1.htm.

Although the principles of exposure management remain unchanged since the previous update in 2001, recommended drug regimens have changed based on new information about the use and safety of HIV postexposure prophylaxis and antiretroviral agents that have been approved by the U.S. Food and Drug Administration (FDA). The guidelines emphasize adherence to HIV postexposure prophylaxis; subspecialist consultation for management of HIV exposure; follow-up of exposed workers to improve prophylaxis adherence; and monitoring for adverse events, including seroconversion. To ensure timely postexposure management and administration of HIV postexposure prophylaxis, physicians should consider occupational exposures as urgent medical concerns.

Antiretroviral agents from five classes of drugs are available to treat HIV infection: nucleoside reverse transcriptase inhibitors, nucleotide reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors, protease inhibitors, and a single fusion inhibitor. The recommendations in this report provide guidance for prophylaxis regimens using two or more drugs based on the level of HIV transmission risk (Tables 1 and 2).

TABLE 1

HIV Postexposure Prophylaxis Regimens for Health Care Professionals

Exposure type Infection status of source
HIV-positive, class 1* HIV-positive, class 2* Unknown status Unknown source HIV-negative

Less severe percutaneous injury (e.g., solid needle or superficial injury)

Basic two-drug regimen recommended.

Expanded regimen, three or more drugs recommended.

Generally, no prophylaxis warranted; consider basic two-drug regimen if source has risk factors.§

Generally, no prophylaxis warranted; consider basic two-drug regimen in settings where exposure to HIV-infected persons is likely.

No prophylaxis warranted.

More severe percutaneous injury (e.g., large-bore hollow needle, deep puncture, visible blood on device, needle used in patient’s artery or vein)

Expanded three-drug regimen recommended.

Expanded regimen, three or more drugs recommended.

Generally, no prophylaxis warranted; consider basic two-drug regimen if source has risk factors.§

Generally, no prophylaxis warranted; consider basic two-drug regimen in settings where exposure to HIV-infected persons is likely.

No prophylaxis warranted.

Small-volume mucous membrane or nonintact skin exposure (e.g., a few drops of blood)

Consider basic two-drug regimen.

Basic two-drug regimen recommended.

Generally, no prophylaxis warranted.§

Generally, no prophylaxis warranted.

No prophylaxis warranted.

Large-volume mucous membrane or nonintact skin exposure (e.g., major blood splash)

Basic two-drug regimen recommended.

Expanded regimen, three or more drugs recommended.

Generally, no prophylaxis warranted; consider basic two-drug regimen if source has risk factors.§

Generally, no prophylaxis warranted; consider basic two-drug regimen in settings where exposure to HIV-infected persons is likely.

No prophylaxis warranted.


HIV = human immunodeficiency virus.

note: See Table 2 for preferred and alternate drug regimens.

*—HIV-positive, class 1 refers to persons with asymptomatic HIV infection or low viral load (i.e., less than 1,500 ribonucleic acid copies per mL). HIV-positive, class 2 refers to persons with symptomatic HIV infection, acquired immunodeficiency syndrome, acute seroconversion, or known high viral load. If drug resistance is a concern, consultation with a subspecialist is recommended, although initiation of postexposure prophylaxis should not be delayed pending consultation.

†—For example, source is deceased and no samples are available for HIV testing.

‡—For example, a needle from a sharps disposal container or a splash from improperly disposed blood.

§— If postexposure prophylaxis is initiated and the source is later determined to be HIV-negative, postexposure prophylaxis should be discontinued.

Adapted from Panlilio AL, Cardo DM, Grohskopf LA, Heneine W, Ross CS. Updated U.S. Public Health Service Guidelines for the management of occupational exposures to HIV and recommendations for postexposure prophylaxis. MMWR Recomm Rep 2005;54(RR09):3.

TABLE 1   HIV Postexposure Prophylaxis Regimens for Health Care Professionals

View Table

TABLE 1

HIV Postexposure Prophylaxis Regimens for Health Care Professionals

Exposure type Infection status of source
HIV-positive, class 1* HIV-positive, class 2* Unknown status Unknown source HIV-negative

Less severe percutaneous injury (e.g., solid needle or superficial injury)

Basic two-drug regimen recommended.

Expanded regimen, three or more drugs recommended.

Generally, no prophylaxis warranted; consider basic two-drug regimen if source has risk factors.§

Generally, no prophylaxis warranted; consider basic two-drug regimen in settings where exposure to HIV-infected persons is likely.

No prophylaxis warranted.

More severe percutaneous injury (e.g., large-bore hollow needle, deep puncture, visible blood on device, needle used in patient’s artery or vein)

Expanded three-drug regimen recommended.

Expanded regimen, three or more drugs recommended.

Generally, no prophylaxis warranted; consider basic two-drug regimen if source has risk factors.§

Generally, no prophylaxis warranted; consider basic two-drug regimen in settings where exposure to HIV-infected persons is likely.

No prophylaxis warranted.

Small-volume mucous membrane or nonintact skin exposure (e.g., a few drops of blood)

Consider basic two-drug regimen.

Basic two-drug regimen recommended.

Generally, no prophylaxis warranted.§

Generally, no prophylaxis warranted.

No prophylaxis warranted.

Large-volume mucous membrane or nonintact skin exposure (e.g., major blood splash)

Basic two-drug regimen recommended.

Expanded regimen, three or more drugs recommended.

Generally, no prophylaxis warranted; consider basic two-drug regimen if source has risk factors.§

Generally, no prophylaxis warranted; consider basic two-drug regimen in settings where exposure to HIV-infected persons is likely.

No prophylaxis warranted.


HIV = human immunodeficiency virus.

note: See Table 2 for preferred and alternate drug regimens.

*—HIV-positive, class 1 refers to persons with asymptomatic HIV infection or low viral load (i.e., less than 1,500 ribonucleic acid copies per mL). HIV-positive, class 2 refers to persons with symptomatic HIV infection, acquired immunodeficiency syndrome, acute seroconversion, or known high viral load. If drug resistance is a concern, consultation with a subspecialist is recommended, although initiation of postexposure prophylaxis should not be delayed pending consultation.

†—For example, source is deceased and no samples are available for HIV testing.

‡—For example, a needle from a sharps disposal container or a splash from improperly disposed blood.

§— If postexposure prophylaxis is initiated and the source is later determined to be HIV-negative, postexposure prophylaxis should be discontinued.

Adapted from Panlilio AL, Cardo DM, Grohskopf LA, Heneine W, Ross CS. Updated U.S. Public Health Service Guidelines for the management of occupational exposures to HIV and recommendations for postexposure prophylaxis. MMWR Recomm Rep 2005;54(RR09):3.

TABLE 2

HIV Postexposure Prophylaxis Regimens

Agents Preferred dosing Dosage forms Advantages Disadvantages

Basic regimens (preferred)

Zidovudine (Retrovir) plus lamivudine (Epivir)

Zidovudine: 300 mg twice daily or 200 mg three times daily, with food

Zidovudine: 100-mg capsules and 300-mg tablets

Zidovudine associated with decreased risk of HIV transmission; serious toxicity is rare when used for postexposure prophylaxis; side effects are predictable and manageable with antimotility and antiemetic agents; can be used during pregnancy; can be given as a single tablet twice daily.

Side effects are common (especially nausea and fatigue) and may result in low adherence; potential source virus resistance; potential for delayed toxicity unknown.

Lamivudine: 300 mg daily or 150 mg twice daily

Lamivudine: 150- and 300-mg tablets

Combination therapy available(Combivir)

Combivir: one tablet twice daily

Combivir: tablets containing 300 mg zidovudine and 150 mg lamivudine

Zidovudine plus emtricitabine (Emtriva)

Zidovudine: 300 mg twice daily or 200 mg three times daily, with food

Zidovudine: see above

Zidovudine: see above

Zidovudine: see above

Emtricitabine: 200 mg daily

Emtricitabine: 200-mg capsules

Emtricitabine: once-daily dosing; well tolerated; long intracellular half-life (40 hours); tolerability and virologic response rates appear better than regimens containing didanosine (Videx) plus stavudine (Zerit).

Emtricitabine: rash may be more common than with lamivudine; cross-resistance with lamivudine; hyperpigmentation possible with long-term use in nonwhites.

Tenofovir (Viread) plus lamivudine

Tenofovir: 300 mg daily*

Tenofovir: 300-mg tablets

Tenofovir: once-daily dosing; resistance profile activity against certain thymidine analogue mutations; well tolerated

Tenofovir: same class warnings as nucleoside reverse transcriptase inhibitors; drug interactions; increased drug concentrations in persons taking atazanavir (Reyataz) and lopinavir/ritonavir (Kaletra); must monitor patients for toxicity.

Lamivudine: 300 mg daily or 150 mg twice daily

Lamivudine: see above

Lamivudine: see above

Tenofovir plus emtricitabine

Tenofovir: 300 mg daily*

Tenofovir: see above

Tenofovir: see above

Tenofovir: see above

Emtricitabine: 200 mg daily

Emtricitabine: see above

Emtricitabine: see above

Emtricitabine: see above

Combination therapy available (Truvada)

Truvada: one tablet daily*

Truvada: tablets containing 300 mg tenofovir and 200 mg emtricitabine

Basic regimens (alternate)

Lamivudine plus stavudine

Lamivudine: 300 mg daily or 150 mg twice daily

Lamivudine: see above

Lamivudine: see above

Potential source virus resistance; potential for delayed toxicity unknown.

Stavudine: 40 mg twice daily†; 30 mg twice daily in patients weighing less than 60 kg (132 lb)

Stavudine: 15-, 20-, 30-, and 40-mg tablets

Stavudine: GI side effects are rare

Emtricitabine plus stavudine

Emtricitabine: 200 mg daily

Emtricitabine: see above

Emtricitabine: see above

Potential source virus resistance; potential for delayed toxicity unknown.

Stavudine: 40 mg twice daily†; 30 mg twice daily in patients weighing less than 60 kg

Stavudine: see above

Stavudine: see above

Lamivudine plus didanosine

Lamivudine: 300 mg daily or 150 mg twice daily

Lamivudine: see above

Lamivudine: see above

Diarrhea more common with buffered preparation; associated with toxicity (i.e., peripheral neuropathy, pancreatitis, and lactic acidosis); must be taken on an empty stomach except when taken with tenofovir; drug interactions.

Didanosine: 400 mg daily or 200 mg twice daily‡; 125 mg twice daily or 250 mg daily in patients weighing less than 60 kg

Didanosine: 25-, 50-, 100-, 150-, and 200-mg buffered tablets

Didanosine: once daily dosing

Emtricitabine plus didanosine

Emtricitabine: 200 mg daily

Emtricitabine: see above

Emtricitabine: see above

Emtricitabine: see above

Didanosine: 400 mg daily or 200 mg twice daily‡; 125 mg twice daily or 250 mg daily in patients weighing less than 60 kg

Didanosine: see above

Didanosine: see above

Didanosine: see above

Expanded regimen (preferred)

Basic regimen plus lopinavir/ritonavir

Three capsules twice daily

Capsules containing 133 mg lopinavir and 33 mg ritonavir

Potent HIV protease inhibitor; generally well tolerated

Potential for serious or life-threatening drug interactions; may accelerate clearance of certain drugs, including OCPs (requiring additional or alternate contraceptive methods); may cause severe hyperlipidemia, especially hypertriglyceridemia; GI side effects common.

Expanded regimens (alternate)

Basic regimen plus one of the following drugs:

Atazanavir with or without ritonavir (Norvir)

Atazanavir alone: 400 mg daily*

Atazanavir: 100-, 150-, and 200-mg capsules

Potent HIV protease inhibitor; once-daily dosing; generally well tolerated

Hyperbilirubinemia and jaundice common; potential for serious or life- threatening drug interactions; must avoid coadministration with proton pump inhibitors; administration of antacids and buffered medications must be separated by two hours and histamine H2 antagonists by 12 hours to avoid decreasing atazanavir levels; caution must be used with products known to cause PR prolongation (e.g., diltiazem [Cardizem]).

Ritonavir: 100-mg capsules

Fosamprenavir (Lexiva) with or without ritonavir

Fosamprenavir alone: 1,400 mg twice daily

Fosamprenavir: 700-mg capsules

Once-daily dosing when taken with ritonavir

GI side effects common; multiple drug interactions; OCPs 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 may be difficult.

With ritonavir: 1,400 mg fosamprenavir daily plus 200 mg ritonavir daily, or 700 mg fosamprenavir twice daily plus 100 mg ritonavir twice daily

Ritonavir: see above

Indinavir (Crixivan) with or without ritonavir

Indinavir: 800 mg twice daily

Indinavir: 200-, 333-, and 400-mg capsules

Potent HIV inhibitor

Potential for serious or life-threatening drug interactions; serious toxicity possible; consumption of eight glasses of water daily is required; hyperbilirubinemia is common; requires acid for absorption and cannot be taken simultaneously with didanosine.

Ritonavir: 100 mg twice daily

Ritonavir: see above

Saquinavir (Invirase) plus ritonavir

Saquinavir: 1,000 mg twice daily

Saquinavir: 200-mg capsules

Generally well tolerated, although GI events are common.

Potential for serious or life-threatening drug interactions; substantial pill burden

Ritonavir: 100 mg twice daily

Ritonavir: see above

Nelfinavir (Viracept)

1,250 mg twice daily with meals

250- and 625-mg tablets

Generally well tolerated

Diarrhea and other GI side effects common; potential for serious or life-threatening drug interactions; substantial pill burden

Efavirenz (Sustiva)

600 mg daily at bedtime

50-, 100-, and 200-mg capsules and 600-mg tablets

Once-daily dosing; does not require phosphorylation before activation; may be active earlier than other agents

Associated with rash that may progress to Stevens-Johnson syndrome; differentiating between early drug-associated rash and acute seroconversion can be difficult; CNS side effects; teratogenic; potential for serious or life-threatening drug interactions.


HIV = human immunodeficiency virus; GI = gastrointestinal; OCP = oral contraceptive pills; CNS = central nervous system.

*—If atazanavir is used in combination with tenofovir, ritonavir also should be used. The preferred daily dosages are 300 mg of atazanavir plus 100 mg of ritonavir plus 300 mg of tenofovir.

†—If toxicity occurs, dosage can be lowered to 20 to 30 mg twice daily. This dosage is equally effective but less toxic in patients infected with HIV who have peripheral neuropathy.

‡—Chewable buffered tablets can be taken on an empty stomach. Patients must take at least two of the appropriate strength tablets at each dose to provide adequate buffering and prevent gastric degradation of didanosine. Because of the need for adequate buffering, the 200-mg tablets should be used only as part of once-daily regimens.

HIV = human immunodeficiency virus; GI = gastrointestinal; OCP = oral contraceptive pills; CNS = central nervous system.

*—If atazanavir is used in combination with tenofovir, ritonavir also should be used. The preferred daily dosages are 300 mg of atazanavir plus 100 mg of ritonavir plus 300 mg of tenofovir. Adapted from Panlilio AL, Cardo DM, Grohskopf LA, Heneine W, Ross CS. Updated U.S. Public Health Service Guidelines for the management of occupational exposures to HIV and recommendations for postexposure prophylaxis. MMWR Recomm Rep 2005;54(RR09):13–7.

†—If toxicity occurs, dosage can be lowered to 20 to 30 mg twice daily. This dosage is equally effective but less toxic in patients infected with HIV who have peripheral neuropathy.

‡—Chewable buffered tablets can be taken on an empty stomach. Patients must take at least two of the appropriate strength tablets at each dose to provide adequate buffering and prevent gastric degradation of didanosine. Because of the need for adequate buffering, the 200-mg tablets should be used only as part of once-daily regimens.

TABLE 2   HIV Postexposure Prophylaxis Regimens

View Table

TABLE 2

HIV Postexposure Prophylaxis Regimens

Agents Preferred dosing Dosage forms Advantages Disadvantages

Basic regimens (preferred)

Zidovudine (Retrovir) plus lamivudine (Epivir)

Zidovudine: 300 mg twice daily or 200 mg three times daily, with food

Zidovudine: 100-mg capsules and 300-mg tablets

Zidovudine associated with decreased risk of HIV transmission; serious toxicity is rare when used for postexposure prophylaxis; side effects are predictable and manageable with antimotility and antiemetic agents; can be used during pregnancy; can be given as a single tablet twice daily.

Side effects are common (especially nausea and fatigue) and may result in low adherence; potential source virus resistance; potential for delayed toxicity unknown.

Lamivudine: 300 mg daily or 150 mg twice daily

Lamivudine: 150- and 300-mg tablets

Combination therapy available(Combivir)

Combivir: one tablet twice daily

Combivir: tablets containing 300 mg zidovudine and 150 mg lamivudine

Zidovudine plus emtricitabine (Emtriva)

Zidovudine: 300 mg twice daily or 200 mg three times daily, with food

Zidovudine: see above

Zidovudine: see above

Zidovudine: see above

Emtricitabine: 200 mg daily

Emtricitabine: 200-mg capsules

Emtricitabine: once-daily dosing; well tolerated; long intracellular half-life (40 hours); tolerability and virologic response rates appear better than regimens containing didanosine (Videx) plus stavudine (Zerit).

Emtricitabine: rash may be more common than with lamivudine; cross-resistance with lamivudine; hyperpigmentation possible with long-term use in nonwhites.

Tenofovir (Viread) plus lamivudine

Tenofovir: 300 mg daily*

Tenofovir: 300-mg tablets

Tenofovir: once-daily dosing; resistance profile activity against certain thymidine analogue mutations; well tolerated

Tenofovir: same class warnings as nucleoside reverse transcriptase inhibitors; drug interactions; increased drug concentrations in persons taking atazanavir (Reyataz) and lopinavir/ritonavir (Kaletra); must monitor patients for toxicity.

Lamivudine: 300 mg daily or 150 mg twice daily

Lamivudine: see above

Lamivudine: see above

Tenofovir plus emtricitabine

Tenofovir: 300 mg daily*

Tenofovir: see above

Tenofovir: see above

Tenofovir: see above

Emtricitabine: 200 mg daily

Emtricitabine: see above

Emtricitabine: see above

Emtricitabine: see above

Combination therapy available (Truvada)

Truvada: one tablet daily*

Truvada: tablets containing 300 mg tenofovir and 200 mg emtricitabine

Basic regimens (alternate)

Lamivudine plus stavudine

Lamivudine: 300 mg daily or 150 mg twice daily

Lamivudine: see above

Lamivudine: see above

Potential source virus resistance; potential for delayed toxicity unknown.

Stavudine: 40 mg twice daily†; 30 mg twice daily in patients weighing less than 60 kg (132 lb)

Stavudine: 15-, 20-, 30-, and 40-mg tablets

Stavudine: GI side effects are rare

Emtricitabine plus stavudine

Emtricitabine: 200 mg daily

Emtricitabine: see above

Emtricitabine: see above

Potential source virus resistance; potential for delayed toxicity unknown.

Stavudine: 40 mg twice daily†; 30 mg twice daily in patients weighing less than 60 kg

Stavudine: see above

Stavudine: see above

Lamivudine plus didanosine

Lamivudine: 300 mg daily or 150 mg twice daily

Lamivudine: see above

Lamivudine: see above

Diarrhea more common with buffered preparation; associated with toxicity (i.e., peripheral neuropathy, pancreatitis, and lactic acidosis); must be taken on an empty stomach except when taken with tenofovir; drug interactions.

Didanosine: 400 mg daily or 200 mg twice daily‡; 125 mg twice daily or 250 mg daily in patients weighing less than 60 kg

Didanosine: 25-, 50-, 100-, 150-, and 200-mg buffered tablets

Didanosine: once daily dosing

Emtricitabine plus didanosine

Emtricitabine: 200 mg daily

Emtricitabine: see above

Emtricitabine: see above

Emtricitabine: see above

Didanosine: 400 mg daily or 200 mg twice daily‡; 125 mg twice daily or 250 mg daily in patients weighing less than 60 kg

Didanosine: see above

Didanosine: see above

Didanosine: see above

Expanded regimen (preferred)

Basic regimen plus lopinavir/ritonavir

Three capsules twice daily

Capsules containing 133 mg lopinavir and 33 mg ritonavir

Potent HIV protease inhibitor; generally well tolerated

Potential for serious or life-threatening drug interactions; may accelerate clearance of certain drugs, including OCPs (requiring additional or alternate contraceptive methods); may cause severe hyperlipidemia, especially hypertriglyceridemia; GI side effects common.

Expanded regimens (alternate)

Basic regimen plus one of the following drugs:

Atazanavir with or without ritonavir (Norvir)

Atazanavir alone: 400 mg daily*

Atazanavir: 100-, 150-, and 200-mg capsules

Potent HIV protease inhibitor; once-daily dosing; generally well tolerated

Hyperbilirubinemia and jaundice common; potential for serious or life- threatening drug interactions; must avoid coadministration with proton pump inhibitors; administration of antacids and buffered medications must be separated by two hours and histamine H2 antagonists by 12 hours to avoid decreasing atazanavir levels; caution must be used with products known to cause PR prolongation (e.g., diltiazem [Cardizem]).

Ritonavir: 100-mg capsules

Fosamprenavir (Lexiva) with or without ritonavir

Fosamprenavir alone: 1,400 mg twice daily

Fosamprenavir: 700-mg capsules

Once-daily dosing when taken with ritonavir

GI side effects common; multiple drug interactions; OCPs 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 may be difficult.

With ritonavir: 1,400 mg fosamprenavir daily plus 200 mg ritonavir daily, or 700 mg fosamprenavir twice daily plus 100 mg ritonavir twice daily

Ritonavir: see above

Indinavir (Crixivan) with or without ritonavir

Indinavir: 800 mg twice daily

Indinavir: 200-, 333-, and 400-mg capsules

Potent HIV inhibitor

Potential for serious or life-threatening drug interactions; serious toxicity possible; consumption of eight glasses of water daily is required; hyperbilirubinemia is common; requires acid for absorption and cannot be taken simultaneously with didanosine.

Ritonavir: 100 mg twice daily

Ritonavir: see above

Saquinavir (Invirase) plus ritonavir

Saquinavir: 1,000 mg twice daily

Saquinavir: 200-mg capsules

Generally well tolerated, although GI events are common.

Potential for serious or life-threatening drug interactions; substantial pill burden

Ritonavir: 100 mg twice daily

Ritonavir: see above

Nelfinavir (Viracept)

1,250 mg twice daily with meals

250- and 625-mg tablets

Generally well tolerated

Diarrhea and other GI side effects common; potential for serious or life-threatening drug interactions; substantial pill burden

Efavirenz (Sustiva)

600 mg daily at bedtime

50-, 100-, and 200-mg capsules and 600-mg tablets

Once-daily dosing; does not require phosphorylation before activation; may be active earlier than other agents

Associated with rash that may progress to Stevens-Johnson syndrome; differentiating between early drug-associated rash and acute seroconversion can be difficult; CNS side effects; teratogenic; potential for serious or life-threatening drug interactions.


HIV = human immunodeficiency virus; GI = gastrointestinal; OCP = oral contraceptive pills; CNS = central nervous system.

*—If atazanavir is used in combination with tenofovir, ritonavir also should be used. The preferred daily dosages are 300 mg of atazanavir plus 100 mg of ritonavir plus 300 mg of tenofovir.

†—If toxicity occurs, dosage can be lowered to 20 to 30 mg twice daily. This dosage is equally effective but less toxic in patients infected with HIV who have peripheral neuropathy.

‡—Chewable buffered tablets can be taken on an empty stomach. Patients must take at least two of the appropriate strength tablets at each dose to provide adequate buffering and prevent gastric degradation of didanosine. Because of the need for adequate buffering, the 200-mg tablets should be used only as part of once-daily regimens.

HIV = human immunodeficiency virus; GI = gastrointestinal; OCP = oral contraceptive pills; CNS = central nervous system.

*—If atazanavir is used in combination with tenofovir, ritonavir also should be used. The preferred daily dosages are 300 mg of atazanavir plus 100 mg of ritonavir plus 300 mg of tenofovir. Adapted from Panlilio AL, Cardo DM, Grohskopf LA, Heneine W, Ross CS. Updated U.S. Public Health Service Guidelines for the management of occupational exposures to HIV and recommendations for postexposure prophylaxis. MMWR Recomm Rep 2005;54(RR09):13–7.

†—If toxicity occurs, dosage can be lowered to 20 to 30 mg twice daily. This dosage is equally effective but less toxic in patients infected with HIV who have peripheral neuropathy.

‡—Chewable buffered tablets can be taken on an empty stomach. Patients must take at least two of the appropriate strength tablets at each dose to provide adequate buffering and prevent gastric degradation of didanosine. Because of the need for adequate buffering, the 200-mg tablets should be used only as part of once-daily regimens.

Because all antiretroviral agents have been associated with side effects, the toxicity profile of these agents, including the frequency, severity, duration, and reversibility of side effects, is an important consideration in selection of an HIV postexposure prophylaxis regimen. The majority of data about adverse events have been reported primarily for persons with established HIV infection who are receiving prolonged antiretroviral therapy. Therefore, these data may not reflect the experience of uninfected persons who take postexposure prophylaxis. Anecdotal evidence indicates that antiretroviral agents are tolerated more poorly by health care professionals taking HIV postexposure prophylaxis than by patients infected with HIV who are taking antiretroviral medications.

Side effects often are reported by persons taking antiretroviral agents for postexposure prophylaxis. A substantial proportion of health care professionals who took antiretroviral agents after occupational exposures to HIV-positive sources did not complete a full four-week course of therapy because they were not able to tolerate the drugs (range: 17 to 47 percent). Nausea was the most commonly reported symptom (26.5 percent), followed by malaise and fatigue (22.8 percent). Because side effects are common, and particularly because they are cited as a major reason for not completing postexposure prophylaxis regimens as prescribed, the selection of regimens should be heavily influenced toward regimens that are tolerable for short-term use.

Determining which agents to use, how many to use, and when to alter a postexposure prophylaxis regimen is primarily empiric. Guidelines for treating HIV infection, which typically involves a high total body burden of the virus, recommend the use of three or more drugs. However, the applicability of these recommendations to postexposure prophylaxis is unknown. In patients infected with HIV, combination regimens with three or more antiretroviral agents have proved superior to monotherapy and dual-therapy regimens in reducing viral load, reducing the incidence of opportunistic infections and death, and delaying the onset of drug resistance. In theory, a combination of drugs with activity at different stages of the viral replication cycle (e.g., nucleoside analogues with a protease inhibitor) may offer an additive preventive effect in postexposure prophylaxis, particularly for occupational exposures that pose an increased risk of transmission or transmission of a resistant virus. Although the use of three or more drugs may be justified for exposures that pose an increased risk of transmission, whether the potential added toxicity of a third or fourth drug is justified for lower-risk exposures is uncertain, especially in the absence of data supporting increased effectiveness of more drugs in the context of occupational postexposure prophylaxis. Offering a two-drug regimen is a viable option, primarily because the benefit of completing a full course of medication exceeds the benefit of adding a third agent and risking noncompletion. In addition, the total body burden of HIV is substantially lower in health care professionals exposed to HIV than in persons with established HIV infection. For these reasons, the USPHS recommendations provide guidance for post-exposure prophylaxis regimens with at least two drugs, depending on the level of HIV transmission risk. Empiric decisions about the presence of antiretroviral drug resistance can be difficult because patients often take more than one antiretroviral agent. Resistance should be suspected in a source patient when clinical progression of disease or a persistently increasing viral load or decline in CD4+ T-cell count occurs despite therapy, or when no virologic response to therapy occurs. However, resistance testing of the source virus at the time of exposure is impractical because the results will not be available in time to influence the choice of the initial prophylaxis regimen. No data suggest that modifying a postexposure prophylaxis regimen after resistance testing results become available (usually one to two weeks) improves the effectiveness of the regimen.

The USPHS recommendations apply to situations in which health care professionals have been exposed to a person who is known to have or is considered likely to have HIV infection. If postexposure prophylaxis is offered and taken, and the source later is determined to be HIV-negative, prophylaxis should be discontinued. Reevaluation of exposed health care professionals should be strongly encouraged within 72 hours of exposure, especially as additional information about the exposure or source becomes available.

Postexposure prophylaxis should be initiated as soon as possible, preferably within hours rather than days of exposure. If there is a question about which antiretroviral drugs to use, or whether to use a basic or expanded regimen, the basic regimen should be started immediately rather than delaying prophylaxis. The optimal duration of postexposure prophylaxis is unknown, but a four-week course of antiretroviral agents is recommended based on results from occupational and animal studies.

The selection of a drug regimen for postexposure prophylaxis must balance the risk of infection against the potential toxicities of the medications. Because postexposure prophylaxis can be toxic, its use is not justified for exposures that pose a negligible risk of transmission. Because of the complexity of choosing and administering an HIV postexposure prophylaxis regimen, consultation with an infectious diseases subspecialist or another physician who has experience with antiretroviral agents is recommended (Table 3). However, a consultation should not delay timely initiation of postexposure prophylaxis.

Health care professionals with occupational exposure to HIV should receive follow-up counseling, postexposure testing, and medical evaluation regardless of whether they receive postexposure prophylaxis (Table 4). HIV-antibody testing by enzyme immunoassay should be used to monitor exposed persons for seroconversion for more than six months after occupational HIV exposure. After baseline testing at the time of exposure, follow-up testing could be performed at six weeks, 12 weeks, and six months after exposure. Extended HIV follow-up (e.g., for 12 months) is recommended for health care professionals who become infected with hepatitis C virus (HCV) after exposure to a person coinfected with HIV and HCV. Whether extended follow-up is indicated in other circumstances (e.g., exposure to a person coinfected with HIV and HCV in the absence of HCV seroconversion) is unclear.

TABLE 3

Situations in Which Expert Consultation for HIV Postexposure Prophylaxis Is Advised

Antiretroviral resistance in the source

Breastfeeding in the exposed person

Delayed exposure report (i.e., more than 24 to 36 hours’ postexposure)

Known or suspected pregnancy in the exposed person

Toxicity of the initial postexposure prophylaxis regimen

Unknown source (e.g., needle in sharps disposal container or laundry)


HIV = human immunodeficiency virus.

Adapted from Panlilio AL, Cardo DM, Grohskopf LA, Heneine W, Ross CS. Updated U.S. Public Health Service Guidelines for the management of occupational exposures to HIV and recommendations for postexposure prophylaxis. MMWR Recomm Rep 2005;54(RR09):10.

TABLE 3   Situations in Which Expert Consultation for HIV Postexposure Prophylaxis Is Advised

View Table

TABLE 3

Situations in Which Expert Consultation for HIV Postexposure Prophylaxis Is Advised

Antiretroviral resistance in the source

Breastfeeding in the exposed person

Delayed exposure report (i.e., more than 24 to 36 hours’ postexposure)

Known or suspected pregnancy in the exposed person

Toxicity of the initial postexposure prophylaxis regimen

Unknown source (e.g., needle in sharps disposal container or laundry)


HIV = human immunodeficiency virus.

Adapted from Panlilio AL, Cardo DM, Grohskopf LA, Heneine W, Ross CS. Updated U.S. Public Health Service Guidelines for the management of occupational exposures to HIV and recommendations for postexposure prophylaxis. MMWR Recomm Rep 2005;54(RR09):10.

TABLE 4

Follow-up of Health Care Professionals Exposed to HIV

Exposed persons should be advised to use precautions (e.g., avoid blood or tissue donations, breastfeeding, and pregnancy) to prevent secondary transmission, especially in the first six to 12 weeks’ postexposure.

When postexposure prophylaxis is prescribed, counsel exposed persons about possible drug toxicity and the need for monitoring, possible drug interactions, and the need for adherence to postexposure prophylaxis regimens.

Consider reevaluation of exposed persons 72 hours postexposure, especially after additional information about the exposure or source becomes available.


HIV = human immunodeficiency virus.

Adapted from Panlilio AL, Cardo DM, Grohskopf LA, Heneine W, Ross CS. Updated U.S. Public Health Service Guidelines for the management of occupational exposures to HIV and recommendations for postexposure prophylaxis. MMWR Recomm Rep 2005;54(RR09):11.

TABLE 4   Follow-up of Health Care Professionals Exposed to HIV

View Table

TABLE 4

Follow-up of Health Care Professionals Exposed to HIV

Exposed persons should be advised to use precautions (e.g., avoid blood or tissue donations, breastfeeding, and pregnancy) to prevent secondary transmission, especially in the first six to 12 weeks’ postexposure.

When postexposure prophylaxis is prescribed, counsel exposed persons about possible drug toxicity and the need for monitoring, possible drug interactions, and the need for adherence to postexposure prophylaxis regimens.

Consider reevaluation of exposed persons 72 hours postexposure, especially after additional information about the exposure or source becomes available.


HIV = human immunodeficiency virus.

Adapted from Panlilio AL, Cardo DM, Grohskopf LA, Heneine W, Ross CS. Updated U.S. Public Health Service Guidelines for the management of occupational exposures to HIV and recommendations for postexposure prophylaxis. MMWR Recomm Rep 2005;54(RR09):11.

If postexposure prophylaxis is used, the exposed person should be monitored for drug toxicity by testing at baseline and again two weeks after the onset of postexposure prophylaxis. The scope of testing should be based on medical conditions in the exposed person and the toxicity of drugs included in the antiretroviral regimen. Minimally, laboratory monitoring for toxicity should include a complete blood count and renal and hepatic function tests. Monitoring for evidence of hyperglycemia should be included for persons whose regimens include a protease inhibitor; if the exposed person is receiving indinavir (Crixivan), monitoring for crystalluria, hematuria, hemolytic anemia, and hepatitis also should be included. If toxicity is noted, modification of the regimen should be considered after consultation with a subspecialist; further diagnostic studies may be indicated.

Health care professionals often fail to complete the recommended regimen because they experience side effects (e.g., nausea or diarrhea). These symptoms often can be managed with antimotility and antiemetic agents or other agents that target specific symptoms without changing the antiretroviral regimen. In other situations, modifying the dose interval (i.e., administering a lower dose more frequently throughout the day, as recommended by the manufacturer) may facilitate adherence to the regimen. Serious adverse events should be reported to the FDA’s MedWatch program.


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