Introduction

HIV prophylaxis is divided into 2 categories: post-exposure prophylaxis (PEP) and pre-exposure prophylaxis (PrEP). PEP is the administration of antiretroviral therapy to an HIV-negative person who may be exposed to HIV. Exposure can be occupational (oPEP) or non-occupational (nPEP), with non-occupational exposure being related to sexual or intravenous (IV) drug exposures. PrEP is the use of antiretroviral drugs in a high-risk, HIV-negative patient to prevent future HIV infections.

Issues of Concern

Non-Occupational Post-Exposure Prophylaxis (nPEP)

Background

The risk of HIV transmission after exposure is variable and linked to viral load; higher viral load increases the risk of transmission. High viral loads can be seen in acute and early HIV infection. Coinfection with other sexual infections also increases the transmission of HIV infection. Although no prospective randomized clinical trial has been done to show the efficacy of PEP, some observational and case studies, along with expert opinion, have suggested that PEP might be useful in high-risk populations, and it has led to widespread acceptance.

In 1997, Cardo and collaborators published a case-control study on HIV prevention. They showed an 81% reduction in HIV transmission in healthcare workers when given zidovudine after percutaneous exposure.[1] Since then, many other clinical and observational studies have supported the use of PEP.

Risk of HIV transmission

The risk of HIV transmission differs and depends on the exposure route. It has done studies to estimate the per-act HIV transmission risk from an infected source to an HIV-negative person. The estimated highest per-act risk for acquiring HIV through a blood transfusion is 9250 per 10,000. Receptive anal intercourse (138 per 10,000), needle-sharing drug users (63 per 10,000), and percutaneous needle stick injuries (23 per 10,000) also had high levels of HIV transmission. Receptive penile-vaginal intercourse (8 per 10,000), insertive penile-vaginal intercourse (4 per 10,000), and oral sex (low) have much lower rates of transmission.[2]

Patient Evaluation

nPEP should start as soon as post-exposure has occurred for high-risk exposures and can start up to 72 hours after the event. It breaks exposure risks into 3 categories: negligible, intermediate, and substantial.

• Negligible risk is the exposure of vagina, rectum, eye, mouth, or other mucous membranes, intact or non-intact skin, or percutaneous contact with nasal secretions, urine, saliva, tears, or sweat if not visibly infected with blood, regardless of the contact HIV status. Negligible risk is not an indication for nPEP.
• Substantial risk is the exposure of the vagina, rectum, eye, mouth, or other mucous membranes, non-intact skin, or percutaneous contact with semen, blood, vaginal secretions, breast milk, and rectal secretions that can visibly contaminate the blood when the source is known to be HIV positive. For substantial risk, nPEP is recommended.
• Intermediate risk is the exposure of the vagina, rectum, eye, mouth, or other mucous membranes, non-intact skin, or percutaneous contact with blood, vaginal secretions, semen, rectal secretions, or any fluid visually contaminated with blood. When the source patient's HIV status is unknown, there is no recommendation for or against nPEP, but the risks and benefits should be tested on a case-by-case basis[3]. nPEP is not recommended if the patients present over 72 hours after exposure. 

Diagnostic Testing

HIV nPEP should only start in patients who are HIV-negative because a person presenting for nPEP treatment may already be HIV-positive and unaware of their status. Baseline HIV testing should be performed on all patients before starting nPEP. The CDC and NIH recommend the use of a rapid Ab or rapid Ag/Ab test. If early testing is unavailable, a non-rapid test should be performed, and nPEP can be offered while results are pending.

When a patient is being tested for nPEP, one should also offer to test for other sexually transmitted diseases, including hepatitis B, hepatitis C, syphilis, gonorrhea, and chlamydia. A pregnancy test should be done. Physicians should also test antiretroviral medications' renal and hepatic toxicity, a baseline creatinine, AST, and ALT.

It recommends follow-up labs at 4 to 6 weeks, including a repeat HIV test, creatinine, AST, ALT, syphilis test, and pregnancy test. Repeat HIV testing should also occur three months after exposure to determine if HIV infection has occurred. Additionally, it recommends testing at 6 months in patients with hepatitis C since this infection often has a delay in seroconversion.

Recommended Treatment

Once starting with nPEP, the recommended protocol is a 28-day course of 3 medications. The preferred medication regimen for adults and adolescents aged older than 13 years, with normal renal function (creatinine clearance equal to 60 mL per min), including pregnant women, is tenofovir DF 300 mg and fixed-dose combination emtricitabine 200 mg (Truvada) once daily with raltegravir 400 mg twice daily or dolutegravir 50 mg once daily. Alternative regimens are available for patients with renal dysfunction and children 12 years and younger.[3]

Adherence plays a vital role in effectiveness. Patients with suboptimal adherence have higher rates of failure. Studies comparing tenofovir-containing regimens with zidovudine-containing regimens have shown that patients given tenofovir-containing regimens do well. They can tolerate it with fewer side effects and have higher completion rates.[4]

It should provide additional treatment for other STIs, including hepatitis B, syphilis, gonorrhea, and chlamydia when the diagnosis is confirmed.

If nPEP fails, patients may develop signs and symptoms of acute HIV infection. Patients should know the signs and symptoms of acute HIV infection and be instructed to return if they become symptomatic. It usually associates acute HIV infection with a high viral load. Common symptoms include fever, fatigue, myalgia, and a skin rash. Less common symptoms include headaches, pharyngitis, cervical adenopathy, arthralgia, night sweats, and diarrhea.

Occupational Post-Exposure Prophylaxis (oPEP)

Risk of Transmission

The average risk of HIV transmission after occupational exposure is 0.3%. Risk varies depending on the exposure. It estimates the risk of percutaneous exposure at 0.23%, mucous membrane exposure at 0.09%, and cutaneous exposure at less than 0.09%. Several factors may be associated with an increased risk of HIV transmission, including injuries from hollow-bore needles, visibly bloody devices, deep tissue injuries, and injuries during procedures involving a needle or device being positioned in an artery or vein.[1]

Patient Evaluation

oPEP should start as soon as possible, ideally within 2 hours. It should not delay the initiation of oPEP while waiting for information or test results from the source patient. If oPEP is started and later determined by the source patient to be negative, then oPEP can be discontinued, and no further evaluation or treatment is necessary.

Diagnostic Testing

Source Patient Testing

It recommends HIV testing of the source patient whenever possible. Voluntary testing of the source patient is required, and laws on consent for testing differ by state. A rapid test is mandatory where available. If the source patient reports a high-risk exposure within the preceding six weeks, some guidelines (though not the CDC) recommend HIV RNA assay. HIV RNA can test the patient for infection during the "window period," which is the time frame between contracting the virus and developing an antibody response. However, there have been no documented cases of transmission during this window period. The source patient may test for hepatitis C (HCV) RNA and hepatitis B (HBV) surface antigen.

Patient Testing

Baseline HIV testing of the exposed worker should be done after occupational exposure, even if the exposed worker declines PEP. It can then perform repeat HIV testing at 4 weeks, 12 weeks, and 6 months post-exposure. Other baseline tests conducted on the patient at the time of the initial presentation should include HCV antibody and HBV if the individual has not been vaccinated against hepatitis B.

Recommended Treatment

• It recommends a 28-day course of a 3-drug regimen for HIV-negative patients who need oPEP. The recommended regimen includes tenofovir DF 300 mg and a fixed-dose combination of emtricitabine 200 mg once daily with raltegravir 400 mg twice daily.
• Wound treatment: The wound from a needle stick should be washed with soap and running water. Splashes to the eyes, mouth, or skin should be irrigated with water or saline. Avoid using caustic agents like bleach. There is no evidence that using antiseptics reduces the risk of HIV transmission.

Follow-up

It should also advise patients to avoid donating plasma, blood, tissue, or semen until confirmatory negative testing. They should also avoid unprotected sex and pregnancy. Breastfeeding should be temporarily discontinued. Milk can be pumped and stored until testing confirms a noninfectious state.

Pre-Exposure Prophylaxis (PrEP)

Background

In 2015, about 1.1 million people aged 13 and older in the United States were living with HIV. The number of new HIV diagnoses in the United States in 2015 was 38,500, which has declined since 2010. Although rates are falling overall, rates of new HIV diagnoses in specific subpopulations are not following this trend. Black men (especially males having sex with males-MSM) have shown no change, and rates among Hispanic MSM are increasing.

HIV seems to affect specific subsets of the population disproportionately. In 2015, 67% of newly diagnosed HIV cases were among MSM. 55% of new diagnoses were among adolescents and young adults (age 13 to 34), and 44% of new diagnoses were among blacks.

It developed PrEP to help reduce the number of new HIV diagnoses. PrEP therapy includes tenofovir-emtricitabine, a single pill taken daily to prevent HIV infection. Multiple clinical studies have shown this regimen to be useful for PrEP. Overall, when taken as prescribed, PrEP has been found PrEP to be over 90% effective in preventing HIV infection. Based on that, the FDA approved the use of tenofovir-emtricitabine for PrEP in 2012, and in 2014, PrEP clinical practice guidelines were developed by the CDC.

Indications

Physicians show PrEP in high-risk populations.

High-Risk MSM

• An HIV-negative man with having anal sex without condoms (receptive or insertive) within the past 6 months
• A bacterial STI (syphilis, gonorrhea, or chlamydia) was diagnosed or reported within the past 6 months.

Heterosexually Active Men and Women

• An HIV-negative person who has had sex with both women and men.
• Infrequent use of condoms during sex with 1 or more high-risk partners of unknown HIV status
• An ongoing sexual relationship with an HIV-positive partner
• A bacterial STI (syphilis, gonorrhea, or chlamydia) was diagnosed or reported within the past 6 months

Men and Women Who Use Injectable Drugs

• An HIV-negative person who has shared needles or drug preparation equipment within the past 6 months

Diagnostic Testing

PrEP is indicated for only HIV-negative patients; thus, an initial HIV test should always be performed. A physician can examine the patients for signs and symptoms of acute HIV infection. Primary HIV infection symptoms include fever, fatigue, myalgia, rash, headache, pharyngitis, cervical lymphadenopathy, arthralgia, night sweats, and diarrhea. If signs of acute HIV are present and the initial HIV test is negative, the patient may still be infected with HIV but have no detectable HIV antibodies (the "window period"). Recommended evaluation for patients possibly in the window period includes HIV antigen/antibody test, checking viral load, or rechecking HIV status in 1 month.

Renal function testing: Because tenofovir-emtricitabine can cause a decrease in renal function, it is recommended to get a baseline creatine clearance before starting PrEP.

Hepatitis B and hepatitis C testing: Infection with hepatitis B or C viruses is not a contraindication for starting PrEP. Individuals who do not test positive for Hepatitis B should administer the HBV vaccination at the initiation of PrEP.

Pregnancy and STI: Pregnancy is not a contraindication for PrEP, but risks and benefits should be discussed with the patient, and STI testing should be done.  

Recommended Treatment

Tenofovir disoproxil fumarate (TDF) 300 mg plus emtricitabine (FTC) 200 mg. This regimen is available as a combination pill.

Patient Follow-up

After starting PrEP, patients need to be followed every three months for repeating HIV and STI testing. It should test women for pregnancy. Besides, healthcare workers should educate patients about the signs and symptoms of acute HIV infection and medication side effects. A physician should also monitor renal function.

nPEP Risks

Risks include adverse reactions, the potential for selection of drug-resistant HIV, and the possibility of increased high-risk behavior by the patient.

Adverse reactions: The most common side effects of nPEP medications include fatigue, nausea, vomiting, headache, diarrhea, and other gastrointestinal (GI) complaints.[1] These can often be treated with additional anti-emetic or anti-diarrheal medications. Severe reactions, including nephrolithiasis and hepatitis, have been occasionally reported.[2]

Potential for selection for drug-resistant strains of HIV: This is another potential concern, but the frequency at which resistant strains develop is unknown. The potential risk can be decreased by only prescribing nPEP to HIV-negative individuals and stressing the importance of adherence to treatment regimens.

The possibility of continuing or increasing high-risk behavior: High-risk behavior includes condom-less sex, multiple partners, and insertive anal intercourse. Studies investigating this idea have shown mixed results. The majority showed no increase in high-risk behavior after receiving nPEP; however, a few studies showed nPEP users being more likely to have multiple partners or to engage in condom-less sex. Two of these studies showed that nPEP users were more likely to become HIV positive than patients who did not receive nPEP.[3]

Clinical Significance

The emotional effects of HIV exposure can be substantial, and proper follow-up and counseling can benefit all patients. Prompt follow-up provides an opportunity for patients to ask questions, ensures education, can increase compliance, and can help the patient with managing side effects. Once antiretroviral therapy has started, the pharmacist should always monitor for adverse effects, which often lead to a drop in compliance.

It has been well established that an interprofessional approach to HIV-positive patients will increase adherence and allow for better outcomes. Expanding this interprofessional approach to encompass HIV prevention will help decrease HIV transmission rates and end the AIDS epidemic.[4]

Enhancing Healthcare Team Outcomes

 An interprofessional approach, including physicians, nurses, and pharmacists assisting patients with appropriate and regular medical dosing, will lead to the best outcomes. [Level 5]