175 Human Immunodeficiency Virus Infection
• In the United States, more than 1.1 million people are estimated to be living with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), and approximately 50,000 new infections occur each year.
• When the CD4 cell count falls to less than 200 /µL (from a normal level of approximately 1000 cells/µL), opportunistic infections are more likely to develop.
• The Centers for Disease Control and Prevention continue to emphasize “opt out” routine HIV screening during any health care encounter, including in the emergency department, for patients between the ages of 13 and 64 years, to allow for earlier detection and treatment and to prevent transmission.
• Current treatment recommendations include early initiation of antiretroviral therapy in asymptomatic patients with CD4 cell counts of up to 500/µL.
The mainstay of transmission of HIV infection is sexual exposure. The sharing of needles for illicit drug use also leads to transmission of HIV. An HIV-infected mother has approximately a 30% chance of passing the virus to her newborn, but with treatment, the risk plummets to less than 1%. Health care workers have a less than 0.3% chance of becoming infected with HIV following an accidental stick with a contaminated needle. Only in rare cases is HIV now transmitted through infected blood products (estimated to be less than 1 transmission per 500,000 blood transfusions) (Table 175.1).
Table 175.1 Risk of Human Immunodeficiency Virus Infection
ROUTE OF TRANSMISSION | PER 10,000 EXPOSURES | PERCENTAGE OR INCIDENCE |
---|---|---|
Transfusion of contaminated blood | 9000 | Almost 100% |
Transfusion of blood after screening | — | 1/500,000 |
Mother-to-child without treatment | 3000 | 30% |
Mother-to-child with treatment | — | <0.01% |
Needle stick in health care worker | 30 | 0.3% |
Unprotected receptive penile-vaginal intercourse | 10 | — |
Unprotected insertive anal intercourse | 6 | 0.01-1.0% |
Unprotected insertive vaginal intercourse | 5 | 0.01-1.0% |
Unprotected receptive penile-vaginal intercourse with genital ulcers | 100 | 0.1-10% |
Unprotected receptive oral intercourse | 1 | — |
Unprotected insertive oral intercourse | 0.5 | — |
Testing
Rapid Assays
Rapid assays for detecting HIV-specific antibodies in serum can yield results in less than 30 minutes. These tests have high sensitivity and specificity and have proven effective for screening. HIV-specific antibodies may be detected in oral fluids, whole blood, serum, and plasma. Many people find oral fluid testing more acceptable than blood testing. Unfortunately, the rapid tests suffer from the same limitation as ELISA. They produce false-negative results during the window period. Positive results on rapid assays require confirmation with the Western blot.1
Opt-Out Testing
In 2006, the U.S. Centers for Disease Control and Prevention (CDC) revised the recommendations for HIV screening to include routine (i.e., nontargeted) testing in all health care settings, including emergency departments (EDs). Understanding that an estimated 20% of patients infected with HIV are unaware of their status and that ongoing HIV transmission continues at a steady rate, the new recommendations highlight the need to expand screening. Additionally, the number of persons who are newly diagnosed with HIV and who already have advanced disease is unacceptably high. Routine testing will also decrease the number of “late testers” and provide earlier entry to care. Testing now should be done on all patients 13 to 64 years old, regardless of risk factors, at all health care facilities where the prevalence of undiagnosed HIV infection is greater than 0.1%. Patients are to be informed of the testing and have the opportunity to decline or opt out of it. General consent for medical care is sufficient for testing, and special written consent for HIV testing is not required, except in the few states that continue to require written consent. Pretest and post-test counseling is no longer required.2
Acute Infection
Acute HIV infection, also termed acute retroviral syndrome or primary HIV infection, is a self-limited stage that develops in the first few weeks following initial infection. During this period, viral replication is rapid and ongoing, leading to high viral loads. The CD4 cell count may decrease transiently during the acute phase. The signs and symptoms are nonspecific and most commonly include fever and rash (Box 175.1). Approximately one third of patients are asymptomatic. The average duration of illness is 14 days, but this stage may last from a few days to more than 10 weeks.3
Opportunistic Infections
Antiretroviral Therapy
Currently, 23 antiretrovirals are available (Box 175.2). The early initiation of ART can prevent the progressive destruction of the immune system that occurs even when a patient is asymptomatic and has been shown to reduce mortality markedly. Safety and tolerability of new ART regimens and increasing evidence of the detrimental effects of uncontrolled viremia led to changes in the latest management guidelines. The 2010 International AIDS Society-USA Panel revised recommendations for adults with HIV infection to include initiating ART for all asymptomatic patients with a CD4 cell count of up to 500/µL.4 Additionally, ART is recommended, regardless of CD4 cell count, for all symptomatic patients, as well as those who are pregnant, those with hepatitis B or C coinfection, patients with HIV-associated nephropathy, persons with active or high-risk coronary artery disease, persons more than 60 years old, patients with acute HIV infection, or persons with a high risk of HIV transmission.
Box 175.2 Antiretrovirals
Adverse Effects
Investigators have estimated that approximately 25% of all patients will discontinue ART because of side effects. Adverse reactions may be mild to potentially life-threatening (Table 175.2). Distinguishing between these adverse effects and possible symptoms of infection with HIV or opportunistic pathogens is often difficult for clinicians. Emergency physicians must be familiar with the frequently encountered, and possibly deadly, adverse effects of ART.
AGENTS | ADVERSE EFFECTS* |
---|---|
Nucleoside Reverse Transcriptase Inhibitors | |
Abacavir | Rash Hypersensitivity* |
Didanosine | Pancreatitis* Peripheral neuropathy Transaminitis |
Emtricitabine | Headache Rash Hyperpigmentation |
Lamivudine | Headache |
Stavudine | Peripheral neuropathy |
Zidovudine | Headache Myalgias Anemia (elevated mean corpuscular volume) |
Non-nucleotide Analogue Reverse Transcriptase Inhibitors | |
Tenofovir | Lactic acidosis* Hepatitis Renal insufficiency |
Non-nucleoside reverse transcriptase inhibitors | Rash |
Delavirdine | Severe rash* Hepatitis Fatigue |
Efavirenz | Hepatitis* Severe rash Central nervous system effects or abnormal dreams |
Etravirine | Elevation of liver function tests |
Nevirapine | Stevens-Johnson syndrome* Severe rash* Hepatitis* Fever Headache |
Protease Inhibitors | Dyslipidemia Lipodystrophy Hyperglycemia Elevations of liver function tests |
Atazanavir | Jaundice |
Darunavir | Rash |
Fosamprenavir | Rash |
Indinavir | Nephrolithiasis |
Lopinavir/ritonavir | Taste perversion |
Nelfinavir | Enteritis |
Ritonavir | Taste perversion |
Saquinavir | Oral ulcers |
Tipranavir | Rash |
Fusion Inhibitors | |
Enfuvirtide | Injection site reactions Neutropenia |
Maraviroc | Hepatitis Myalgias or arthralgias |
Integrase Inhibitor | |
Raltegravir | Elevation of liver function tests Rash |
* Severe adverse effect warrants discontinuation of all antiretrovirals.
Prophylaxis Against Common Opportunistic Infection
Patients infected with HIV infection and who are severely immunosuppressed are at risk for many opportunistic infections. Long-term antimicrobial prophylaxis has been demonstrated to be beneficial in preventing several common opportunistic infections (Table 175.3).
OPPORTUNISTIC INFECTION | INDICATION | RECOMMENDED ANTIMICROBIAL |
---|---|---|
Pneumocystis pneumonia | CD4 cell count < 200 cells/µL or history of oropharyngeal candidiasis |
TMP/SMX 1 DS/day PO |
Toxoplasmosis | CD4 cell count < 100 cells/µL | TMP/SMX 1 DS/day PO |
Disseminated Mycobacterium avium complex |
CD4 cell count < 50 cells/µL | Azithromycin 1200 mg/wk PO |
DS, double strength; PO, orally; TMP/SMX, trimethoprim-sulfamethoxazole.
Postexposure Prophylaxis
Occupational Exposure
Although the risk of occupational transmission of HIV to health care workers is quite small, it is not zero. Percutaneous exposure to blood from an HIV-infected patient carries an estimated risk of transmission of approximately 0.3%. Similar exposures to mucous membranes are associated with a 0.09% risk of transmission, and the risk of transmission following exposure to nonintact skin is even lower. The CDC provides recommendations for the management of health care workers exposed to HIV and for postexposure prophylaxis (PEP). These recommendations are based on the severity of the exposure and the viral load of the source patient (Box 175.3).5 Health care workers with low-risk exposures are recommended to take the basic two-drug regimens. A small-volume blood exposure to mucous membranes or nonintact skin from a source patient who is asymptomatic or who has a low viral load (<1500 RNA copies/mL) represents a low risk of infection (Box 175.4). Those with high-risk exposures are recommended to take the expanded three-drug regimen of PEP. Percutaneous exposure to a source patient with a high viral load is considered to carry a higher risk.
Box 175.3 Occupational Transmission of Human Immunodeficiency Virus to Health Care Workers
No PEP is recommended for any type of exposure if the source patient is HIV negative. Saliva, tears, nasal secretions, sputum, gastric fluids, urine, and feces are not infectious unless they are visibly bloody. All medications should be initiated as soon as possible, and all regimens should be continued for 28 days. Initiating PEP 72 hours after exposure is not effective, and it is generally not recommended. Available resources include a 24-hour telephone help line (PEPline: 888-448-4911) and online information from the National HIV/AIDS Clinicians’ Consultation Center at www.nccc.ucsf.edu.
Nonoccupational Exposure
In 2005, the CDC published recommendations for antiretroviral PEP following sexual exposure, injection drug use, or other nonoccupational exposure to HIV.6 A 28-day course of ART is now recommended for persons seeking care less than 72 hours after nonoccupational exposure to blood, genital secretions, or other potentially infectious bodily fluid from a source known to be HIV positive.
Substantial exposure risk is defined as exposure of vagina, eyes, rectum, mouth, or other mucous membranes, or nonintact skin, or percutaneous contact, with blood, semen, vaginal secretions, rectal secretions, breast milk, or any bodily fluid that is visibly contaminated with blood from a source that is HIV positive. Negligible exposure risk is defined as exposure of vagina, eyes, rectum, mouth, or other mucous membranes, or nonintact skin, or percutaneous contact, with urine, nasal secretions, saliva, sweat, or tears if not visibly contaminated with blood, regardless of the known or suspected HIV status of the source. If the source’s HIV status is unknown, the source should be tested, if possible. The first dose of nPEP may be given initially, and no further doses are given if the source is determined to be HIV negative. If the source’s HIV status cannot be determined and the person seeking care had a substantial risk exposure, consideration of the source patient’s risk of having HIV is warranted. High-risk populations include men who have sex with men, commercial sex workers, those who inject drugs, those with history of incarceration, persons from countries where the HIV seroprevalence is at least 1%, or sexual partners of persons at high risk. Perpetrators of sexual assault are considered to have a high risk for HIV. Substantial exposure to high-risk populations warrants nPEP (Box 175.5).
Once the decision has been made to initiate nPEP, ART should be administered promptly. The basic regimens recommended for occupational PEP are also recommended for nPEP (see Box 175.4).7 The expanded regimens are reserved for patients exposed to a source population in which background resistance of HIV to ART is high.
Prevention of HIV Infection
Exciting data have revealed fundamentally new, effective approaches to prevent HIV transmission. The Center for the AIDS Program of Research in South Africa (CAPRISA) study demonstrated the effectiveness and safety of a 1% vaginal gel formulation of tenofovir for the prevention of HIV acquisition in women.8 A double-blind, randomized controlled trial comparing tenofovir gel with placebo demonstrated a reduction in risk of HIV transmission by more than one half. This microbicide gel allows women around the world to play a greater role in HIV prevention when compared with relying on their partners to use condoms.
The second landmark report was the Preexposure Prophylaxis Initiative (iPreEx) trial.9 This study, conducted in six countries, included 2499 HIV-negative men who had sex with men to evaluate whether antiretroviral medications could prevent the transmission of HIV. A once-daily antiretroviral combination pill of emtricitabine and tenofovir was compared with placebo. The participants were followed for an average of 14 months. The antiretroviral group demonstrated a 44% reduction in the incidence of HIV compared with the placebo group, and a subset of participants with enhanced compliance had an even greater risk reduction of 73%. This trial clearly showed that preexposure prophylaxis is generally safe, well tolerated, and effective. Together, these two reports demonstrate significant advances in the prevention of HIV transmission.
1 Greenwald JL, Burstein GR, Pincus J, Branson B. A rapid review of rapid HIV antibody tests. Curr Infect Dis Rep. 2006;8:125–131.
2 Branson BM, Handsfield HH, Lampe MA, et al. Revised recommendations for HIV testing of adults, adolescents, and pregnant women in health-care settings. MMWR Morb Mortal Wkly Rep. 2006;55:1–17.
3 Kahn JO, Walker BD. Acute human immunodeficiency virus type 1 infection. N Engl J Med. 1998;339:33–39.
4 Thompson MA, Aberg JA, Cahn P, et al. Antiretroviral treatment of adult HIV infection: 2010 recommendations of the International AIDS Society-USA Panel. JAMA. 2010;304:321–333.
5 Panlilio AL, Cardo DM, Grohskopf LA, et al. Updated U.S. Public Health Services guidelines for the management of occupational exposures to HIV and recommendations for postexposure prophylaxis. MMWR Morb Mortal Wkly Rep. 2005;54:1–17.
6 Smith DK, Grohskopf LA, Black RJ, et al. Antiretroviral postexposure prophylaxis after sexual, injection-drug use, or other nonoccupational exposure to HIV in the United States. MMWR Morb Mortal Wkly Rep. 2005;54:1–20.
7 Landovitz RJ, Currier JS. Postexposure prophylaxis for HIV infection. N Engl J Med. 2009;361:1768–1775.
8 Karim QA, Karim SSA, Frohlich JA, et al. Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women. Science Express on behalf of the CAPRISA 004 Trial Group http://www.sciencemag.org/cgi/rapidpdf/science.1193748.pdf, 2010.
9 Grant RM, Lama JR, Anderson PL, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med. 2010;363:2587–2599.