HIV

I. Problem/Condition.

“Acute HIV”, or “acute retroviral syndrome”, is the clinical presentation of early HIV seroconversion and represents the time between initial infection and detection of HIV antibodies. Often undiagnosed, its non-specific presentation can make it a difficult diagnosis, particularly if no HIV exposure is identified.

In general, about 2/3 of patients acutely infected with HIV will exhibit symptoms, which typically last anywhere from 3 days to several weeks. Symptoms, which overlap with many other acute viral illnesses, include:

• fever (80-90%)

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• pharyngitis (+/- exudate)

• lymphadenopathy (generalized)/splenomegaly

• rash (erythematous, maculopapular, central > peripheral)

• mucosal ulcers

• fatigue/anorexia

• myalgia/arthralgia

• headache, retro-orbital pain

• neuro symptoms (aseptic meningitis, radiculitis, CN palsies, myelitis)

II. Diagnostic Approach.

A. What is the differential diagnosis for this problem?

Acute HIV symptoms often overlap with other viral illnesses:

• Mononucleosis

• Influenza

• Acute Hepatitis B

• Acute CMV

• Acute Toxoplasmosis

• Enterovirus

• Secondary Syphilis

B. Describe a diagnostic approach/method to the patient with this problem.

Early detection of HIV infection is essential for preventing further HIV infections and saving public health costs. Diagnosis of Acute HIV infection is particularly important because people who are at this phase of infection have higher viral loads and contribute disproportionally to new infections. Routine screening is recommended for most patients seen in the Emergency Department or admitted to the hospital because the symptoms of HIV infection can be non-specific and variable in presentation. Since 2006, the Centers for Disease Control and Prevention (CDC) has recommended routine, opt out HIV screening for all patients between the ages of 13-64 regardless of risk.

C. Historical information important in the diagnosis of this problem.

The spread of Human Immunodeficiency Virus (HIV), the causative agent of Acquired Immunodeficiency Syndrome (AIDS) throughout the world has resulted in one of the most devastating pandemics in history. Since the discovery of HIV in 1981, over 40 million people have died due to AIDS related causes. Millions of people are newly infected with HIV each year. However, the global incidence of HIV has fallen by 35% due to improved knowledge, safe sex practices and preventative treatment.

As of 2015, 1.7 million Americans have been infected and over 700,000 have died since the beginning of the HIV epidemic. Currently there are 1.2 million people living with HIV in the United States and of these about 55% are virally suppressed. An estimated 13% of people living with HIV are undiagnosed. There are approximately 40,000 new HIV diagnosis annually. New infections disproportionately affect African-Americans, Latinos, young adults, and gay and bisexual men. Patients with a history of intravenous drug use are also at risk.

D. Physical Examination maneuvers that are likely to be useful in diagnosing the cause of this problem.

Physical exam findings include:

• Fever

• Pharyngeal exudate

• Mucosal ulcers

• Diffuse lymphadenopathy

• Splenomegaly

• Generalized erythematous rash (usually central more than peripheral)

• Focal neurologic deficits.

Patients should also be evaluated for presence of AIDS defining illnesses or opportunist infections (OIs), including oropharyngeal candidiasis, Kaposi’s sarcoma, etc.

E. Laboratory, radiographic and other tests that are likely to be useful in diagnosing the cause of this problem.

Laboratory tests

In early infection, the immune system may not have had enough time to produce antibodies to HIV. The HIV ELISA, which was the most common test used to detect HIV antibodies may not be positive for the first 6-8 weeks of infection. Efforts to diagnosis acute HIV infection have focused on identifying HIV RNA or p24 antigen, both of which appear in the blood before HIV antibodies (Table I). Nucleic acid amplification testing (NAAT) is still the most sensitive and earliest method for detecting acute HIV infection as HIV RNA is detectable 5-7 days before p24 antigen is detectable. Unfortunately, NAAT is expensive and requires complex equipment and skilled technicians. Fourth generation laboratory assays that are highly accurate and less expensive than NAAT, are used to detect p24 antigen and HIV antibodies are now often used for HIV diagnosis. Counseling patients at the time of initial testing is recommended so that patients understand that a negative test does not ensure that a patient is not infected with HIV without repeat testing.

Table I.

• HIV Antibody test – negative in acute HIV; should be checked 4-6 weeks after acute HIV diagnosis to confirm seroconversion.

• HIV RNA viral load – usually greater than 100,000 in setting of acute HIV. False positives are seen in less than 5%, usually with viral loads only in the thousands.

• Absolute CD4 count – to help guide anti-retroviral therapy (ART) treatment and determine risk for opportunistic infections.

• HIV genotype – for confirmed positive acute HIV patients and all ART naive patients. Even if treatment is deferred initially, genotyping can help determine resistance patterns and guide future ART (mutations may be difficult to detect later).

Recommendations for laboratory testing for the diagnosis of HIV infection (2014 CDC guidelines)

• Laboratories should conduct initial testing for HIV with an FDA-approved antigen/antibody combination (4^th generation) immunoassay that detects HIV-1 and HIV-2 antibodies and HIV-1 p24 antigen to screen for established infection with HIV-1 or HIV-2 and for acute HIV-1 infection. No further testing is required for specimens that are nonreactive on the initial immunoassay.

• Specimens with a reactive antigen/antibody combination immunoassay result (or repeatedly reactive, if repeat testing is recommended by the manufacturer or required by regulatory authorities) should be tested with an FDA-approved antibody immunoassay that differentiates HIV-1 antibodies from HIV-2 antibodies. Reactive results on the initial antigen/antibody combination immunoassay and the HIV-1/HIV-2 antibody differentiation immunoassay should be interpreted as positive for HIV-1 antibodies, HIV-2 antibodies, or HIV-1 and HIV-2 antibodies, undifferentiated.

• Specimens that are reactive on the initial antigen/antibody combination immunoassay and nonreactive or indeterminate on the HIV-1/HIV-2 antibody differentiation immunoassay should be tested with an FDA-approved HIV-1 NAAT.

  A reactive HIV-1 NAAT result and non-reactive HIV-1/HIV-2 antibody differentiation immunoassay result indicates laboratory evidence for acute HIV-1 infection.

  A reactive HIV-1 NAAT result and indeterminate HIV-1/HIV-2 antibody differentiation immunoassay result indicates the presence of HIV-1 antibodies confirmed by HIV-1 NAAT.

  A negative HIV-1 NAAT result and non-reactive or indeterminate HIV-1/HIV-2 antibody differentiation assay result indicates a false-positive result on the initial immunoassay.

Imaging

As clinically indicated.

III. Management while the Diagnostic Process is Proceeding.

A. Management of Clinical Problem HIV.

Immediate management

The US Department of health and Human service guidelines from 2012 recommend starting anti-retroviral therapy in all patients with HIV regardless of the CD4 count. These recommendations are based on the improved safety and tolerability of antiretroviral therapy and data that supports early anti-retroviral therapy. Benefits of immediate treatment of HIV infection include reduced transmission of HIV and decreased chronic immune activation and dysfunction. Immediate treatment in the Emergency Department or Hospital with infectious disease consultation has been reported to be safe and feasible (See Table II for recommended first line antiretroviral regimens). Adherence challenges in the setting of a new diagnosis, potential medication toxicities and possibility for drug resistance must be weighed against the benefits.

Table II.

Laboratory tests

Per the guidelines for the use of antiretroviral agents in HIV-1 infected adults and adolescents, The following laboratory tests performed during initial patient visits can be used to stage HIV disease and to assist in the selection of ARV drug regimens:

• HIV antibody testing (if prior documentation is not available or if HIV RNA is below the assay’s limit of detection)

• CD4 T-cell count (CD4 count)

• Plasma HIV RNA (viral load)

• Complete blood count, chemistry profile, transaminase levels, blood urea nitrogen (BUN), and creatinine, urinalysis, and serological tests for hepatitis A, B, and C viruses

• Fasting blood glucose and serum lipids

• Genotypic resistance testing at entry into care, regardless of whether ART will be initiated immediately. For patients who have HIV RNA levels <500 to 1,000 copies/mL, viral amplification for resistance testing may not always be successful.

• HLA-B501 testing if considering the use of abacavir in an antiretroviral regimen.

• Co-receptor tropism testing if considering the use of CCR% antagonist in an antiretroviral regimen.

• In addition, other tests (including screening tests for sexually transmitted infections and tests for determining the risk of opportunistic infections and need for prophylaxis) should be performed.

Long-term management

The number of people living with HIV continues to increase due to access to anti-retroviral therapy. HIV infection is now a manageable chronic disease resulting in near normal life expectancy for patients on anti-retroviral therapy. Hospital deaths among HIV-infected patients are now more often due to diseases other than AIDS. The most common causes of death among HIV-Infected patients include Non-HIV infections, cardiovascular disease, liver disease, and cancer. Factors associated to non-AIDS related deaths include older age, use of anti-retroviral therapy, CD4 count over 200 and suppressed HIV viral load.

HIV care follow-up, CD4 monitoring, opportunistic infection prophylaxis as indicated. Screening for cervical cancer, hepatitis B vaccine, hepatitis C antibody, lipid profile, dental oral exam, syphilis, tuberculosis infection (active or latent), chlamydia/gonorrhea, appropriate vaccinations, substance use, and toxoplasma antibody.

Renal insufficiency

Renal disease in patients with HIV can be primary (HIV associated nephropathy = HIVAN), secondary to systemic illness (e.g., diabetes mellitus, hypertension) or as an adverse event from medications. ARTs should be given to patients with renal disease according to usual ART recommendations, with specific medication recommendations based on the patient’s degree of renal failure and creatinine clearance.

The most notable medication to be aware of is tenofovir disoproxil which can cause renal insufficiency and Fanconi’s syndrome. Tenofovir alafenamide is a new formulation with less renal toxicity.

Most nucleoside reverse transcriptase inhibitors (NRTIs) need dose adjustment based on renal function, whereas protease inhibitors (PIs) and non-NRTIs do not (except with dialysis). Commonly used antiretroviral (ARV) medications that need to be dose-adjusted based on renal function include: emtricitabine, lamivudine, tenofovir and zidovudine.

The currently available fixed dose combination drugs; Atripla, Complera, Combivir, Epzicom,Truvada, Trizivir and, Genvoya should be substituted by the dose-appropriate individual component drugs.

Liver insufficiency

In the setting of liver insufficiency, medications should be monitored closely for hepatotoxicity. ARV medications that can cause hepatotoxicity or should be used cautiously include nevirapine, high-dose ritonavir, and tripanavir. Other medications, including fluconazole, isoniazid, and acetaminophen, should be used very cautiously as well.

All HIV-infected individuals should be tested for HBV, HCV and HAV infection and immunity. Among HIV/HCV co-infected individuals, liver disease is now the leading cause of death, having surpassed AIDS-related illnesses. The decision to initiate treatment for Hep B or Hep C in the setting of HIV infection is complicated, and specialist consultation is recommended.

Systolic/diastolic heart failure

Patients living with HIV are at higher risk of heart failure, subclinical impairment of the left ventricle mechanics, and myocardial fibrosis and steatosis. However, as of 2017, there are no published clinical trials pertaining to the treatment of heart failure in HIV-infected patients. Management for HIV infected patients with heart failure should be the same as management of heart failure in non-HIV infected patients.

Peripheral vascular disease (PVD)/coronary artery disease (CAD)

Patients with HIV are at increased risk for CAD due to HIV infection (as shown in SMART trial) and from ARV medications (D:A:D trial). HIV increases the likelihood of dyslipidemia and insulin resistance, and ARV meds also contribute to dyslipidemia. However, the risk of HIV-related CAD (from no ARV treatment) likely outweighs the risk of ARV-related CAD. Otherwise there is no change in standard management.

Diabetes/endocrine

Along with traditional risk factors (obesity, family history) and comorbidities, certain ARV medications can lead to hyperglycemia and increase the risk of diabetes. In particular, some PIs and prolonged NRTI exposure have been implicated. Consider treatment regimens without a PI (NNRTI instead) or a PI with a favorable metabolic profile. Otherwise there is no change to standard management.

Other endocrine: ritonavir is a potent inhibitor of CYP 450 3A4, which happens to be the same target for fluticasone (inhaled or intranasal). When taken concomitantly, patients can develop significant steroid accumulation, adrenal suppression, and Cushing’s syndrome. Consider a significant dose reduction of fluticasone, substituting a safer steroid (such as budesonide, beclomethasone, flunisolide, or triamcinolone), changing to oral montelukast, or substituting ritonavir. At a minimum, patient receiving ritonavir and any form of steroids should be monitored for both steroid accumulation and withdrawal.

Immunosuppression

Depending on CD4 levels or evidence of AIDS defining illnesses, HIV-infected individuals are at increased risk of opportunistic infections (OIs). Prophylaxis is given to prevent a first episode (primary prophylaxis) or recurrence of an OI (secondary prophylaxis). Prophylaxis is continued until CD4 counts improve and remain stable for a certain duration, usually anywhere from 3-12 months, depending on primary or secondary prophylaxis.

Table III reflects general guidelines for management; please consult a specialist as needed for specific management issues.

Table III.

In addition to the above opportunistic infections, HIV-infected individuals are at risk for fungal infections depending on their geographic region, their degree of environmental exposure, and positive serologies confirming exposure. The guidelines below can be considered for individuals who meet the above criteria. Again, specialist consultation may be warranted for specific management considerations. (See Table IV)

Table IV.

With regards to organ transplants and immunosuppression in HIV-infected individuals, there is no change in standard management other than to account for any drug-drug interactions with immunosuppressive medications.

Primary lung disease

For patients with airway disease, as noted in the Endocrine section, ritonavir is a potent inhibitor of CYP450-3A4, which happens to be the same target for fluticasone (inhaled or intranasal). When taken concomitantly, patients can develop significant steroid accumulation, adrenal suppression, and Cushing’s syndrome. Patients need to be assessed for bacterial and other infections, particularly OIs.

Tuberculosis (TB) is the leading cause of death in patients with HIV worldwide. Patients with HIV and latent TB infection are 20-30 times more likely to have TB reactivate compared to the general population and precautions should be taken to evaluate HIV-infected patients with pulmonary disease. Additionally, pneumococcal pneumonia risk is 150-fold higher than the general population and may cause repeated episodes of lung infection.

GI/Nutritional Issues

Patients with HIV should be carefully screened for any oral disease and gastrointestinal (GI) malignancies, especially anal carcinoma for those co-infected with HPV/HIV. Involuntary weight loss is associated with disease progression and is an independent predictor of death.

Hematologic/coagulation

Patients with HIV often have a macrocytosis without anemia. This can also be seen with ART, particularly zidovudine and stavudine.

While yet to be well established, it appears that HIV-infected individuals are at slightly increased risk of venous thromboembolism compared to the general population.

Dementia/psychiatric illness

Altered mental status: a patient with HIV presenting with altered mental status has a broad range of biologic causes which need to be ruled out, including psychological disorders, substance abuse, metabolic derangements, infections (systemic versus CNS), malignancy, medications (of note, some ARV medications, especially Efavirenz, can cause delirium), and toxicology.

The HIV-related neurocognitive disorders (HAND) is a common with a prevalence of 20% to 69% in different populations. Subtypes of HAND include asymptomatic neurocognitive impairment (ANI), mild neurocognitive dementia (MND) and HIV-associated dementia (HAD). MND and HAD are considered AIDS-defining conditions and are diagnoses of exclusion. HIV is a neurotropic virus and enters the brain with infection where it can lead to deficits in cognition, behavior and motor functioning. ANI, MND and HAD reflect the clinical effects of this process, respectively reflecting increasing severity.

ART is the treatment of choice for HIV-associated neurocognitive disorders, and can reverse effects of disease (Table II). Appropriate ART that maintains low viral loads is optimal. By suppressing HIV RNA in the serum, you can often decrease HIV in CNS. While ART reduces the incidences of the more severe forms of dementia (HAD), the prevalence of milder neurocognitive disorders, ANI and MND, is increasing.

The CNS penetration effectiveness of antiretroviral therapy is important and limited data suggest ARV medications with good CNS penetration can be more effective in treating HAND. These include abacavir, emtricitabine, zidovudine (NRTIs); nevirapine (NNRTI); indinavir/ritonavir and lopinavir/ritonavir (PIs) and maraviroc (CCR5 antagonist). Alternatively, zidovudine and lamivudine may not penetrate the CNS as well and therefore not adequately treat the CNS reservoir of HIV.

Depression/anxiety: check for interactions between ARV and anti-depressant medications. PIs (including ritonavir-boosted PIs) in particular need careful monitoring. Ritonavir affects cytochrome P450 and can often significantly increase serum levels of tricyclic antidepressants, leading to potential toxicity (routine TCA blood level monitoring recommended). Most antidepressants should be started at low dosages and titrated slowly.

Conversely, some PIs decrease paroxetine, sertraline, and bupropion levels; efavirenz also lowers sertraline and bupropion levels. St John’s Wort decreases many ARV serum levels – it should be avoided.

PIs and NNRTIs increase blood concentration of many benzos: start low and titrate. Note that midazolam is contraindicated with PIs, efavirenz and delavirdine.

Transitions of care

A) Sign-out – patients should continue on ART unless there is a specific contraindication.

B) Anticipated length of stay – pending work-up to ensure no other infectious processes present (OIs, TB etc. as indicated). Hospital stay may depend on patient’s access to follow-up care.

C) Readiness for discharge – when appropriate treatment plan has been instituted.

D) Arranging clinical follow-up:

• When/with whom (general medicine physician – preferably with certification in HIV medicine; infectious disease; case management – patients without insurance may be eligible for the AIDS Drug Assistance Program (ADAP) for medications and other funds (Ryan White Federal Funds) for care. HIV support/counseling is helpful as many patients may also be dealing with adjustment disorder, other psychiatric illness, or drug/alcohol addiction issues.

• Tests prior to discharge. See below.

• Outpatient tests prior to clinic visit: complete blood count (CBC) with differential, basic metabolic panel (BMP), liver function tests (LFT), hepatitis A antibody, hepatitis C antibody, hepatitis B surface antibody (HBV sAb), hepatitis B surface antigen (HBV sAg), hepatitis B core antibody (HBV cAb), toxoplasma antibody immunoglobulin G (IgG), rapid plasma reagin (RPR), urinalysis, HIV viral load, HIV genotype, CD4 count, chlamydia/gonorrhea screen.

E) Placement considerations – none specifically. If non-home placement, then likely PPD required (place on hospital day 1).

F) Prognosis and patient counseling – patients diagnosed with HIV need intensive support and education about the diagnosis, course of disease progression, prognosis, risk/benefit of ART treatment. Counseling should include safe sex/safe injection techniques. In the acute HIV stage, patients are highly infectious and need to be counseled about high risk of infecting others.

IV. Patient safety/quality measures

A. Core indicator standards and documentation –

The Health Resources and Services Administration’s HIV/AIDS Bureau (HAB) is committed to improving the quality of HIV care and treatment services for people living with HIV. Under the Ryan White HIV/AIDS Program, quality management is a series of activities that focus on enhancing the quality of HIV care provided and increasing access to services.

HAB has developed an online data system for use by all Ryan White HIV/AIDS Program (RWHAP) recipients called the HIV Quality Measures Module (HIVQM Module).

The HIVQM Module is an online tool that allows recipients to enter aggregate data on the HAB performance measures and then generate reports to assess their performance. Recipients may also compare their performance regionally and nationally against other recipients who submit data. The HAB performance measures comprise the following categories: 1) core, 2) all ages, 3) adolescent/adult, 4) HIV-infected children, 5) HIV-exposed children, 6) medical case management, 7) oral health, 8) AIDS Drug Assistance Program (ADAP), and 9) systems-level. The HIVQM Module facilitates recipients in meeting clinical quality management program requirements. The use of the module is voluntary for RWHAP recipients, but strongly encouraged.

B. The HIV/AIDS Bureau encourages Ryan White HIV/AIDS Program recipients to use the revised performance measures, including the core performance measures.

• Pregnant women with HIV prescribed ART

• CD4 measurements at least twice a year

• Medical visits in HIV care setting at least twice a year

• ART therapy prescribed for patients with AIDS

• CD4 count less than 200 prescribed pneumocystis pneumonia prophylaxis

• Adherence assessment and counseling at least twice yearly

• Cervical cancer screening yearly

• Hepatitis B vaccination

• Hepatitis C screening at least once

• HIV risk counseling yearly

• Lipid panel yearly

• Oral examination by dentist at least once yearly

• Syphilis screening yearly

• Tuberculosis screening since HIV diagnosis

• Chlamydia/gonorrhea screening yearly for patients at risk for sexually transmitted infections

• Hepatitis B screening

• Alcohol counseling for HIV-infected patients with hepatitis B or C

• Influenza vaccination yearly

• CD4 count less than 50 prescribed Mycobacterium avium complex (MAC) prophylaxis

• Mental health screening

• Pneumococcal vaccination

• Substance use screening

• Tobacco cessation counseling yearly

• Toxoplasma screening at least once since HIV diagnosis

C. Prophylaxis/other measures to prevent readmission – no change in standard management.

• Vaccines: avoid live vaccines unless benefit outweighs risk. In general, vaccines may not be effective – and for live vaccines, safe – unless CD4 count is greater than 200. If vaccines are given when the CD4 count is less than 200, consider follow-up vaccination when CD4 rises above 200 or evaluating for immunity before considering re-vaccination.

• Pneumococcal: all HIV-infected patients who have never received a pneumococcal vaccine should receive a 13-valent pneumococcal vaccine. Patients should receive a dose of the 23-valent pneumococcal vaccine 8 weeks after the 13-valent vaccine; one-time repeat vaccination with 23 valent vaccine at age 65 years. If the 23 valent pneumococcal vaccine is given first, then the 13 valent vaccine should be given 1 year later.

• Influenza: all patients; yearly (most effective when CD4 > 100; live vaccine contraindicated).

• Hepatitis B: all patients unless documented immunity or active infection (surface antigen + or core antibody+ with HBV viremia). High dose (40mcg) vaccine likely improves immune response. Monitor response (HBV sAb).

• Hepatitis A: consider for all; recommended for liver disease, IV drug use, MSM, international travel, hemophilia. Monitor response (HAV Ab).

• MMR (live vaccine): for all non-immune with CD4 greater than 200; contraindicated with CD4 less than 200.

• VZV (live vaccine): consider for non-immune with CD4 greater than 200; contraindicated with CD4 less than 200. Monitor for infection, treat with acyclovir as needed. VZ immune globulin for non-immune patients with recent (<96 hours) exposure.

• Human papillomavirus (HPV): per usual guidelines (female or male age 9-26). Limited data with HIV population; no data for preventing anal dysplasia.

• TDaP/Meningococcal: per usual guidelines.

• Guidance: medication adherence and ART.

V. Common Pitfalls and Side-Effects of Management of this Clinical Problem

A common pitfall in the diagnosis of HIV is failure to re-check HIV ELISA when acute HIV seroconversion is suspected (i.e. just testing once). Other tests may be helpful in acute HIV infection before seroconversion such as nucleic acid amplification testing (like PCR viral load test or bDNA viral load test) and P24 antigen testing.

Another pitfall includes checking CD4 counts before the establishment of HIV as a diagnosis. CD4 counts are very helpful to establish disease severity and patient risk once HIV has been diagnosed, however checking CD4 counts on their own (based on suspicion for opportunistic infection etc.) is of little clinical benefit. In addition, in the setting of acute bacterial infection and rheumatologic disease CD4 counts may be falsely low and not a good indicator of immune status.

Immune reconstitution inflammation syndrome (IRIS) – starting ART will improve the immune system’s response to pathogens, including partially or successfully treated OIs or previously undiagnosed OIs, and potentially release inflammatory mediators. A small percentage of patients will be diagnosed clinically with IRIS; an exacerbation of partially or fully treated OI, or unmasking of a sub-clinical OI. IRIS develops in response to many pathogens, notably Mycobacteria tuberculosis (TB), Mycobacterium avium complex (MAC), cytomegalovirus, Cryptococcus neoformans, Pneumocystis pneumonia (PCP), Toxoplasmosis, hepatitis B and Varicella zoster virus (VZV). IRIS is seen weeks to months after the initiation of ART, and usually in the context of a marked rise in CD4 count from low pre-treatment levels (CD4 <100).

Severity can vary significantly, but rarely is IRIS fatal. Mainstay of treatment is to continue ART if possible, treating opportunistic infections as indicated and starting anti-inflammatory medications (non-steroidal anti-inflammatory drugs, steroids) as needed. Consult with a specialist for questions about timing for initiation of ART in setting of active opportunistic infections. Ideally, ART should be started within 2 weeks of an AIDS defining illness. Of note, IRIS is not unique to HIV and can be seen with treatment of other infectious diseases.

VI. Post-exposure Prophylaxis

Post-exposure prophylaxis (PEP) with anti-retroviral drugs to prevent transmission of HIV following sexual or injection drug use exposures or occupational exposures (needle sticks and splashes to eye, nose or oral cavity) to blood or body fluids is an essential intervention that should occur within 72 hours of the exposure (Table II). The risk of HIV transmission after a percutaneous exposure to HIV-infected blood is estimated to be about 0.3%. Indications for non-occupational PEP include: exposure to a potentially infectious fluid such as semen, vaginal secretions, rectal secretions, breast milk, cerebrospinal fluid, amniotic fluid, peritoneal fluid, synovial fluid, pericardial fluid, pleural fluid, blood or body fluid contaminated with blood. Non-bloody saliva, urine, feces, vomitus, sputum, nasal secretions, sweat, and tears are not considered infectious. Source person testing should be obtained if possible using a fourth-generation HIV antigen-antibody test. If the source person’s HIV status is not known, then risk is estimated based on known or suspected risk factors. There are three recommended PEP regimens:

• Preferred: Tenofovir disoproxil, 300 mg/Emtricitabine, 200 mg (Truvada) once daily plus Raltegravir (Isentress) 400 mg daily

• Preferred: Tenofovir disoproxil, 300 mg/Emtricitabine, 200 mg (Truvada) once daily plus Doutegravir (Tivicay), 50 mg daily

• Alternative: Tenofovir disoproxil, 300 mg/Emtricitabine, 200 mg (Truvada) once daily plus Darunavir (Prezista) 800 mg daily plus Ritonvir (Norvir), 100 mg daily

Pep should be given for 28 days. The exposed person should have HIV testing done at initial screening and again at four to six weeks and at three months.

Expert advice should be sought if there is delayed exposure (>72 hours), regency or breast feeding in an exposed patient, known HIV resistance of the source patient, toxicity or drug interactions of PEP regimen, or serious medical illness including renal or liver disease in the exposed patient.

VII. Pre-Exposure Prophylaxis

Despite advances in HIV treatment, infection remains a significant burden worldwide. The use of Pre-Exposure Prophylaxis (PrEP) in HIV negative patients who are at risk of HIV acquisition has been well studied. PrEP has been licensed in the United States for 4 years. The CDC recommends daily Truvada-based PrEP for men who have sex with men (MSM), heterosexual men and women who are at on-going risk for HIV acquisition (HIV-discordant couples), and active injecting drug users. Truvada- based prep has potential renal and bone toxicity due to the tenofovir formulation. PrEP has been calculated to be cost effective. Condom use should still be advised to prevent infection with other sexually transmitted diseases.

The national Pepline (888-448-4911) and National PrEPline (855-448-7737) are available to answer questions/consultations about PEP and PrEP for challenging case.

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