Clinical Guide > Maintenance and Prevention > Nonoccupational PEP

# Nonoccupational Postexposure Prophylaxis

January 2011

### Chapter Contents

      - Background
      - S: SubjectiveO: ObjectiveA: AssessmentP: PlanPatient Education
ReferencesTable 1. Antiretroviral Regimens for Nonoccupational Postexposure Prophylaxis of HIV InfectionFigure 1. Exposure Risk AlgorithmBackground
Although avoiding exposure to HIV is the only reliable way of preventing HIV infection, postexposure prophylaxis (PEP) can decrease the risk of infection after exposure to HIV. Antiretroviral (ARV) therapy is an important prophylactic intervention for appropriate persons with nonoccupational exposures (e.g., sexual contact; sharing of injection drug needles or other equipment) as well as those with occupational exposures (e.g., needlesticks). The U.S. Department of Health and Human Services (DHHS) has developed recommendations for nonoccupational PEP (nPEP) based on data from animal models, perinatal clinical trials, and observational studies. Efficacy of nPEP remains hypothetical, and randomized clinical trials are not possible, but nPEP appears to be safe.

Overall, nPEP is more likely to be effective when the exposure is a single episode and nPEP is initiated in a timely manner. It is not appropriate for cases of multiple sexual exposures or injection drug use (IDU) exposures over time or for exposures that occurred >72 hours before starting nPEP treatment (see Figure 1).

The model for nPEP is derived in part from protocols for occupational PEP (e.g., in terms of risk stratification, pretreatment testing, timing of treatment, treatment regimens, and duration of treatment). However, the recommendations for PEP and nPEP are distinct and should not be confused. (For information on occupational PEP, see chapter *Occupational Postexposure Prophylaxis*.) One significant difference between the protocols is that nPEP protocols should include interventions to reduce the risk of HIV transmission. Although exposed individuals usually seek care because they are interested specifically in antiretroviral prophylaxis, the nPEP model takes advantage of a critical opportunity to provide risk-reduction counseling and education.

See chapter *Occupational Postexposure Prophylaxis* for further discussion of evaluating possible benefits and risks of PEP.
S: Subjective
The patient reports potential exposure to HIV through a sexual encounter or the sharing of needles or other equipment for IDU.

Take a thorough history of the specific sexual or drug-use activities, the time the exposure occurred, the HIV status of the source person (if known), and HIV risk factors of the source person (if HIV status is not known). In cases of sexual assault, evidence collection and specific paperwork may be required as well.
O: Objective
Examine for trauma and for signs or symptoms of sexually transmitted infections (STIs), which may increase the risk of HIV transmission. In injection drug users, examine for abscesses and signs or symptoms of infection. For women who may be pregnant, perform a pregnancy test.
A: Assessment
Assess for potential exposures to HIV and other bloodborne pathogens and for the presence of other STIs. The risk of HIV infection depends on the HIV status of the source and on the characteristics of the source (e.g., HIV viral load) and of the exposure (see Figure 1). The estimated risk of HIV exposure will determine whether nPEP should be offered. An algorithm for risk evaluation and treatment decisions is presented in Figure 1.
P: PlanLaboratory Testing- Perform a baseline HIV antibody test.
- Evaluate and test for other infections transmitted through sexual or IDU exposures, including chlamydia, gonorrhea, syphilis, herpes simplex virus infection, hepatitis B (HBV surface antigen, surface antibody, and core antibody), and hepatitis C (HCV antibody).
- Obtain complete blood count (CBC), liver function tests (LFTs), and creatinine and estimated glomerular filtration rate (GFR) at baseline before treatment with ARV medications.
Treatment
Follow the algorithm in Figure 1 to determine whether the patient should be offered nPEP medications. If the patient is a candidate for treatment, provide counseling about the potential risks and benefits of nPEP. Note that the current DHHS nPEP guidelines were last updated in 2005 and do not reflect current practice. **The recommendations presented here are drawn from the 2005 nPEP guidelines but have been adapted to reflect more recent nPEP strategies, the availability of newer ARVs, and current DHHS adult treatment guidelines** (see Table 1). A number of alternatives are available; consult with an expert. Note that, although these regimens are effective in treating HIV infection, their efficacy as prophylaxis has not been demonstrated.

If the source person is known or suspected to have infection with HIV that is resistant to ARV medications, seek expert consultation in selecting an appropriate nPEP regimen.

In general, the recommendations for nPEP involve three-drug combination therapy and are more aggressive than the occupational PEP recommendations. However, if the HIV status of the source person is unknown and the exposure is thought to be of relatively low risk, consider two-drug nPEP (e.g., tenofovir + emtricitabine) to minimize toxicity.
Figure 1. Exposure Risk AlgorithmU.S. Department of Health and Human Services. *Antiretroviral postexposure prophylaxis after sexual, injection-drug use, or other nonoccupational exposure to HIV in the United States*. MMWR Recomm Rep. 2005 Jan 21;54(RR02);1-20. 
Select a regimen that is likely to be effective but tolerable; consider the potential adverse effects of ARV agents. Certain ARVs are not recommended for PEP, including abacavir, delavirdine, nevirapine, and the combination of didanosine + stavudine. The 2005 DHHS guidelines list lopinavir/ritonavir as the preferred third agent for the expanded PEP regimen, and it still is commonly used. Newer protease inhibitors (i.e., atazanavir, darunavir) or the integrase inhibitor raltegravir may be appropriate for certain individuals, and should particularly be considered if exposure factors (e.g., comorbidities or interacting drugs) or source patient factors (e.g., concern for resistance) make therapy with lopinavir/ritonavir problematic. Although the 2005 guidelines designate it as a preferred agent, efavirenz may have a higher rate of significant adverse effects than other listed agents. Additionally, efavirenz should not be used with pregnant women, because of							possible teratogenicity. Refer to the appendix in the updated DHHS adult treatment guidelines for more complete information on the dosing, advantages, and disadvantages of the various ARV agents. Consider consultation with experts (see "Expert Consultation," below).
Table 1. Antiretroviral Regimens for Nonoccupational Postexposure Prophylaxis of HIV Infection
* Unboosted atazanavir cannot be coadministered with tenofovir (use atazanavir + ritonavir)

Abbreviations: NNRTI = nonnucleoside reverse transcriptase inhibitor; NRTI = nucleoside analogue reverse transcriptase inhibitor; PI = protease inhibitor

Adapted from U.S. Department of Health and Human Services. *Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents*. January 10, 2011. and U.S. Department of Health and Human Services. *Antiretroviral Postexposure Prophylaxis After Sexual, Injection-Drug Use, or Other Nonoccupational Exposure to HIV in the United States--January 21, 2005*. 
 Preferred Regimens  PI based Lopinavir/ritonavir (Kaletra) 400/100 mg BID + 2-NRTI combination (see below) Alternative Regimens **PI based**
Atazanavir 300 mg once daily + ritonavir 100 mg once daily + 2-NRTI combination (see below) 

Darunavir 800 mg once daily + ritonavir 100 mg once daily + 2-NRTI combination (see below)

Atazanavir 400 mg once daily*
**Integrase inhibitor based**Raltegravir 400 mg BID + tenofovir/emtricitabine 1 tablet once daily NRTI combinations (to be used with Preferred or Alternative third agents listed above) 
Tenofovir 300 mg once daily + emtricitabine 200 mg once daily (available as Truvada, 1 tablet once daily) 

Zidovudine 300 mg BID + lamivudine 150 mg BID (available as Combivir, 1 tablet BID)

Once the decision is made to institute nPEP, do the following:
- Begin ARV prophylaxis as soon as possible after the exposure, but always within 72 hours. Treatment should be continued for 28 days, unless the source person is determined to be HIV negative.
- Provide counseling about the efficacy of nPEP, including the importance of protection against future HIV exposures, timely initiation of nPEP medications, and adherence to these medications for 28 days.
- Counsel exposed patients to use latex barriers with their sexual partners until transmission of HIV infection has been ruled out.
- Counsel patients, as appropriate, about ways to reduce risks of future exposure to HIV.
- In cases of sexual assault, refer the patient to a rape counselor.
Follow-Up
Patients should be evaluated at 1 week for review of all test results and further risk-reduction counseling. For patients taking nPEP, this follow-up should include adherence assessment and evaluation of any adverse effects. A 2-week blood screening (CBC, LFTs, and creatinine) should be checked for patients on the 28-day nPEP regimen to monitor for nPEP toxicity. Follow-up testing for HIV antibody in patients with a negative baseline HIV antibody test should be done at 6 weeks, 3 months, and 6 months after the exposure.

Patients need health education and risk-reduction counseling and emotional support during their follow-up visits. Nonoccupational PEP programs should focus efforts on risk-reduction counseling rather than the continued use of medicines for prevention. To this end, many programs have case managers, social workers and health educators as the key providers of follow-up and counseling after an exposure, with referral to clinicians as needed.

If patients develop acute HIV infection or are discovered to be HIV seropositive at follow-up testing, refer to an HIV specialist for evaluation and care (see chapter *Primary HIV Infection*).
Expert Consultation
For consultation on the treatment of exposures to HIV (and HBV and HCV), the clinician managing the exposed person can call the National HIV/AIDS Clinicians' Post-Exposure Prophylaxis Hotline (PEPline) at 888-HIV-4911 (888-448-4911). This service is available 24 hours a day at no charge. (However, 24-hour availability may be temporarily interrupted. Additional information on the Internet is available at the PEPline website.) PEPline support may be especially useful in challenging situations, such as when drug-resistant HIV strains are suspected to be involved in the exposure or when the exposed person is pregnant.
Prophylaxis Against HBV and HCV
Prophylaxis against HBV is recommended for patients with potential exposure to HBV who do not have not have immunity against HBV. Give HBV immune globulin (HBIG) as a 0.06 mL/kg IM injection and initiate the vaccination series. For patients who received the vaccine series but did not develop protective antibody (HBV sAb+), give HBIG at the time of the postexposure workup and initiate revaccination; consider repeat of HBIG in 1 month. For patients with immunity to HBV (HBV sAb+), no treatment is indicated.

For HCV, no prophylactic treatments are recommended. After potential exposure, conduct a baseline HCV antibody test. If the source is known to have HCV infection, consider alanine aminotransferase (ALT) and HCV viral load testing at 4-6 weeks. HCV antibody testing should be repeated at 4-6 months. If HCV seroconversion occurs (indicated by ALT elevation, detectable HCV viral load, or confirmed positive HCV antibody test result), refer the patient to a hepatologist because early treatment of acute HCV may be indicated.
Note on Preexposure Prophylaxis
A number of investigations have been undertaken to evaluate the efficacy of ARV medications as preexposure prophylaxis (PrEP)--that is, oral ARVs taken by at-risk HIV-uninfected individuals with the goal of preventing HIV infection. Other studies are examining ARV-based microbicides, topical preparations applied before HIV exposure, with the same goal. Two recent studies have shown that these approaches can reduce the risk of sexual acquisition of HIV. In one, oral tenofovir + emtricitabine (Truvada), taken daily, reduced the risk of HIV acquisition in high-risk MSM and transgender women who have sex with men. In another, tenofovir vaginal gel (available only through research studies), used before and after vaginal intercourse, reduced the rate of HIV infection in high-risk heterosexual women in South Africa. In both studies, the ARV prophylaxis was given *in conjunction with* other risk-reduction interventions, including counseling, condom provision, and STI testing and treatment. This and other studies will explore the efficacy and safety, and possible effects on risk of various types of PrEP and microbicides in different populations. The CDC has issued interim guidelines on the use of oral tenofovir-emtricitabine as PrEP in MSM (see "References," below); until more data are available, alternative approaches to PrEP should not be undertaken.
Patient Education- Persons who have possible exposures to HIV should contact a medical provider or go to an emergency room as soon as possible after the potential exposure has occurred. PEP may be effective if it is started within 72 hours of exposure, but the sooner medications are initiated, the better the chance for preventing HIV transmission.
- PEP medications should be taken as directed for a full 28-day course. Adherence to PEP medications is essential for successful treatment.
- If patients are experiencing uncomfortable adverse effects, they should contact their care provider. Providers may prescribe medications to alleviate the adverse effects or select other PEP medications.
- Until HIV infection has been ruled out, exposed persons should be advised to use latex barriers to prevent transmission of HIV to their sex partners.
- Exposed persons should be counseled about the symptoms of primary HIV infection and instructed to contact their care provider immediately if symptoms develop.
- The most effective way to prevent HIV infection is to prevent exposure to HIV by practicing safer sex and safer IDU techniques. Using condoms and avoidance of needle sharing are successful preventive measures. If patients have questions about access to condoms or clean needles, they should contact their care provider for assistance.
References- Bryant J, Baxter L, Hird S.  Non-occupational postexposure prophylaxis for HIV: a systematic review . Health Technol Assess. 2009 Feb;13(14):iii, ix-x, 1-60.
- Centers for Disease Control and Prevention.  Interim Guidance: Preexposure Prophylaxis for the Prevention of HIV Infection in Men Who Have Sex with Men . MMWR Recomm Rep. 2011 Jan 28;60(RR-3):65-69.
- Panlilio AL, Cardo DM, Grohskopf LA, et al; U.S. Public Health Service.  Updated U.S. Public Health Service guidelines for the management of occupational exposures to HIV and recommendations for postexposure prophylaxis . MMWR Recomm Rep. 2005 Sep 30;54(RR-9):1-17.
- U.S. Department of Health and Human Services.  Antiretroviral postexposure prophylaxis after sexual, injection-drug use, or other nonoccupational exposure to HIV in the United States . MMWR Recomm Rep. 2005 Jan 21;54(RR02);1-20. 
- U.S. Department of Health and Human Services.  Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents . January 10, 2011.
- U.S. Department of Health and Human Services.  Updated U.S. Public Health Service Guidelines for the Management of Occupational Exposures to HBV, HCV, and HIV and Recommendations for Postexposure Prophylaxis . MMWR Recomm Rep. 2001 Jun 29;50(RR11).