You are in: eMedicine Specialties > Emergency Medicine > INFECTIOUS DISEASES HIV Infection and AIDSArticle Last Updated: Jul 10, 2008AUTHOR AND EDITOR INFORMATIONAuthor: Jeff Dubin, MD, Medical Director, Emergency Department, Washington Hospital Center, Assistant Professor, Department of Emergency Medicine, Georgetown University School of Medicine Editors: David S Howes, MD, Residency Program Director, Professor of Medicine, Section of Emergency Medicine, University of Chicago/Pritzker School of Medicine; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Eric L Weiss, MD, DTM&H, Director of Stanford Travel Medicine, Medical Director of Stanford Lifeflight, Assistant Professor, Departments of Emergency Medicine and Infectious Diseases, Stanford University School of Medicine; John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center; Steven C Dronen, MD, FAAEM, Director of Emergency Services, Director of Chest Pain Center, Department of Emergency Medicine, Ft Sanders Sevier Medical Center Author and Editor Disclosure Synonyms and related keywords: HIV infection, HIV, AIDS, STD, sexually transmitted disease, human immunodeficiency virus, acquired immune deficiency syndrome, highly active antiretroviral therapy, HAART, Lentivirus, retroviruses, HIV-related illnesses, Pneumocystis carinii pneumonia, P carinii pneumonia, PCP, cryptococcal meningitis, tuberculosis, TB, cytomegalovirus retinitis, CMV retinitis, CNS toxoplasmosis, central nervous system toxoplasmosis, toxoplasmosis, HIV-associated malignancies, oral candidiasis INTRODUCTIONBackgroundClinically apparent human immunodeficiency virus (HIV) infection first was recognized in 1981 in homosexual men in New York City who presented with evidence of a profound acquired immune deficiency syndrome (AIDS). We now appreciate that HIV infection is a worldwide health problem that affects millions of men and women. HIV has the capability to affect every organ system in the body by direct damage by the virus or by rendering the host susceptible to opportunistic infections. This article discusses some of the more common HIV-related illnesses that are seen frequently in the ED. PathophysiologyHIV is a Lentivirus, a subgroup of retroviruses. This family of viruses is known for latency, persistent viremia, infection of the nervous system, and weak host immune responses. HIV has high affinity for CD4 T lymphocytes and monocytes. HIV binds to CD4 cells and becomes internalized. The virus replicates itself by generating a DNA copy by reverse transcriptase. Viral DNA becomes incorporated into the host DNA, enabling further replication. HIV is transmitted primarily through sexual contact (>70%). Worldwide, it is more common in heterosexual men and women than in homosexual men. Although the majority of initial HIV-related AIDS cases in the United States were in homosexual men, more recently the majority of new cases of HIV infection are in the heterosexual population. Parenteral transmission occurs largely among intravenous drug users; transmission by contaminated blood products is rare in the United States, although this remains a serious problem in developing countries. Since the introduction of universal precaution practices, infection of health care workers through parenteral exposure remains rare. Children are infected primarily by perinatal transmission. FrequencyUnited StatesMore than 944,000 persons have been diagnosed with AIDS (cumulative estimate), and an estimated 1-1.2 million persons have asymptomatic HIV infection. InternationalSince the AIDS epidemic began, more than 20 million deaths have been attributed to AIDS. The current estimate of worldwide disease prevalence is more than 38 million HIV infections. Ninety-five percent of these cases are in developing countries, generally in sub-Saharan Africa and Southeast Asia. Mortality/MorbidityThe course of HIV infection is characterized primarily by latency. Unfortunately, profound immune suppression eventually develops and the illness appears to be almost uniformly lethal. More than 500,000 persons have died of AIDS in the United States. Progression from HIV infection to AIDS occurs at a median of 11 years after infection. In the recent past, most patients would not survive more than 1-2 years following diagnosis of AIDS. However, since the introduction of highly active antiretroviral therapy (HAART) and prophylaxis against opportunistic pathogens, death rates from AIDS have begun to decline significantly. RaceIn the United States, the breakdown of HIV infections by race is as follows:
SexMost HIV infections still occur in men via homosexual contact; however, the frequency of infection in women is increasing, especially in developing countries. In the United States, fewer than 19% of all HIV cases are in women, whereas worldwide an estimated 50% of all HIV patients are women. AgeMost AIDS cases occur in adults aged 25-44 years. Children represent fewer than 1% of AIDS cases in the United States. Internationally, children younger than 15 years are estimated to account for close to 10% of all HIV cases. CLINICALHistory
Physical
Causes
DIFFERENTIALSCandidiasis Cholecystitis and Biliary Colic Esophagitis Gastroenteritis Herpes Zoster Idiopathic Thrombocytopenic Purpura Meningitis Needle-stick Guideline Pancreatitis Pneumonia, Immunocompromised Pneumothorax, Iatrogenic, Spontaneous and Pneumomediastinum Shock, Septic Syphilis Tuberculosis
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| Drug Name | Trimethoprim/sulfamethoxazole (Bactrim) |
|---|---|
| Description | DOC for PCP. Inhibits bacterial synthesis of dihydrofolic acid by competing with para-aminobenzoic acid, inhibiting folic acid synthesis and, thus, bacterial growth. |
| Adult Dose | 2 double-strength tabs PO tid for 21 d 240 mg IV q6h |
| Pediatric Dose | <2 months: Not recommended >2 months: 15-20 mg TMP/kg/d IV divided q6h |
| Contraindications | Documented hypersensitivity; megaloblastic anemia caused by folate deficiency |
| Interactions | May increase PT when used with warfarin (perform coagulation tests and adjust dose accordingly); dapsone may increase blood levels of both drugs; diuretics increase incidence of thrombocytopenia purpura in elderly patients; may increase phenytoin levels; may potentiate effects of methotrexate in bone marrow depression; may increase hypoglycemic response to sulfonylureas; may increase levels of zidovudine |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Discontinue at first appearance of rash or sign of adverse reaction; obtain CBCs frequently—discontinue therapy if significant hematologic changes occur; goiter, diuresis, and hypoglycemia may occur with sulfonamides; prolonged IV infusions or high doses may cause bone marrow depression (if signs occur, give 5-15 mg/d leucovorin); caution in folate deficiency (eg, chronic alcoholism, elderly persons, those receiving anticonvulsant therapy, malabsorption syndrome); hemolysis may occur in G-6-PD–deficient individuals; AIDS patients may not tolerate or respond to TMP-SMZ; caution in renal or hepatic impairment (perform urinalyses and renal function tests during therapy); give fluids to prevent crystalluria and stone formation |
| Drug Name | Pentamidine (Pentam-300 injection, Pentacarinat) |
|---|---|
| Description | Inhibits growth of protozoa by blocking oxidative phosphorylation and inhibiting incorporation of nucleic acids into RNA and DNA, causing inhibition of protein and phospholipid synthesis. DOC for hospitalized patients with PCP who are allergic to TMP/SMZ. |
| Adult Dose | 4 mg/kg/d IV/IM qd for 10-14 d |
| Pediatric Dose | Administer as in adults |
| Contraindications | Documented hypersensitivity |
| Interactions | None reported |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Caution in diabetes mellitus, hypertension or hypotension, hepatic dysfunction, hypoglycemia, leukopenia, and thrombocytopenia |
These agents are used to treat patients with PCP and PaO2 <70 mm Hg. Early administration of corticosteroid therapy in the treatment of PCP decreases the risk of respiratory failure in patients with moderately severe to severe PCP infection, improving survival.
| Drug Name | Prednisone (Deltasone, Orasone, Sterapred) |
|---|---|
| Description | By reversing increased capillary permeability and suppressing PMN activity, may decrease inflammatory reactions. |
| Adult Dose | Days 1-5: 40 mg PO bid Days 6-10: 40 mg PO qd Days 11-20 or for duration of therapy: 20 mg PO qd |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity; viral, fungal, or tubercular skin infections |
| Interactions | Estrogens may decrease clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics |
| Pregnancy | B - Usually safe but benefits must outweigh the risks. |
| Precautions | Abrupt discontinuation may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur |
These agents are used to treat cryptococcal meningitis and oral candidiasis and to prevent relapse.
| Drug Name | Amphotericin B (AmBisome) |
|---|---|
| Description | DOC for treatment of cryptococcal meningitis. Depending on concentration attained in body fluids and on susceptibility of fungus, can be fungistatic or fungicidal. Polyene antibiotic produced by strain of Streptomyces nodosus. Changes membrane permeability by binding to sterols (eg, ergosterol) in fungal cell membrane, causing a variety of intracellular components to leak and leading to fungal cell death. |
| Adult Dose | 0.7-3 mg/kg/d IV for 14 d; infuse over 2-6 h |
| Pediatric Dose | Administer as in adults |
| Contraindications | Documented hypersensitivity |
| Interactions | Antineoplastic agents may enhance potential of amphotericin B for renal toxicity, bronchospasm, and hypotension; corticosteroids, digitalis, and thiazides may potentiate hypokalemia; cyclosporine increases risk of renal toxicity |
| Pregnancy | B - Usually safe but benefits must outweigh the risks. |
| Precautions | Monitor renal function, serum electrolyte levels (eg, magnesium, potassium), liver function, CBC, and hemoglobin concentrations; resume therapy at lowest level (eg, 0.25 mg/kg) if interrupted for more than 7 d; hypoxemia, acute dyspnea, and interstitial infiltrates may occur in neutropenic patients receiving leukocyte transfusions (amphotericin infusion should be separated in time from leukocyte transfusion); fever and chills not uncommon after first few administrations of drug; rare acute reactions may include hypotension, bronchospasm, arrhythmias, and shock |
| Drug Name | Flucytosine (Ancobon) |
|---|---|
| Description | Converted to fluorouracil after penetrating fungal cells and inhibits RNA and protein synthesis. Active against candidal and cryptococcal species, and generally used in combination with amphotericin B. |
| Adult Dose | 100 mg/kg/d IV for 2 wk |
| Pediatric Dose | Not established; suggested dose similar to adult dose |
| Contraindications | Documented hypersensitivity |
| Interactions | Amphotericin B may increase effects; cytosine may inactivate |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Caution in bone marrow suppression; adjust dose in patients with renal impairment |
| Drug Name | Clotrimazole (Femizole-7, Lotrimin AF, Mycelex) |
|---|---|
| Description | Broad-spectrum antifungal agent that inhibits yeast growth by altering cell membrane permeability. Pruritus usually relieved within first week of treatment. |
| Adult Dose | 10 mg PO 5 times/d for 14 d |
| Pediatric Dose | <3 years: Not established >3 years: Administer as in adults |
| Contraindications | Documented hypersensitivity |
| Interactions | None reported |
| Pregnancy | B - Usually safe but benefits must outweigh the risks. |
| Precautions | Not for treatment of systemic fungal infections; avoid contact with eyes; if irritation or sensitivity develops, discontinue use and institute appropriate therapy |
The goals in the use of antivirals are to shorten clinical course, prevent complications, prevent development of latency and/or subsequent recurrences, decrease transmission, and eliminate established latency.
| Drug Name | Zidovudine (Retrovir) |
|---|---|
| Description | Nucleosidase (thymidine) analog that inhibits viral replication by blocking reverse transcriptase. |
| Adult Dose | 200 mg PO tid 1-2 mg/kg/dose IV q4h |
| Pediatric Dose | 90-180 mg/m2/dose PO q6h 1-2 mg/kg/dose IV q4h |
| Contraindications | Documented hypersensitivity |
| Interactions | Acetaminophen may decrease bioavailability; amphotericin B, flucytosine, Adriamycin, vincristine, vinblastine, doxorubicin, cimetidine, indomethacin, probenecid, lorazepam, aspirin, acyclovir, ganciclovir, dapsone, and pentamidine may increase toxicity |
| Pregnancy | B - Usually safe but benefits must outweigh the risks. |
| Precautions | Caution in impaired hepatic or renal function; reduce or stop therapy in hematologic disorders, such as thrombocytopenia, granulocytopenia, and severe anemia |
| Drug Name | Lamivudine (Epivir) |
|---|---|
| Description | Nucleosidase (thymidine) analog that inhibits viral replication by blocking reverse transcriptase. |
| Adult Dose | 150 mg PO bid |
| Pediatric Dose | 4 mg/kg PO bid |
| Contraindications | Documented hypersensitivity |
| Interactions | TMP/SMZ increases bioavailability; increases zidovudine concentrations |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Adjust dose in renal impairment; caution in children with history of pancreatitis |
| Drug Name | Abacavir, lamivudine, and zidovudine (Trizivir) |
|---|---|
| Description | Nucleoside reverse transcriptase inhibitor, which interferes with HIV viral RNA-dependent DNA polymerase, and inhibits viral replication. Lamivudine and zidovudine are thymidine analogs that inhibit viral replication. |
| Adult Dose | <40 kg: Not recommended >40 kg: 1 tab PO bid |
| Pediatric Dose | <12 years: Not recommended >12 years: Administer as in adults |
| Contraindications | Documented hypersensitivity |
| Interactions | Ethanol may increase risk of toxicity of abacavir; methadone concentrations may decrease with concomitant administration of abacavir Trimethoprim/sulfamethoxazole increases bioavailability of lamivudine; lamivudine increases concentration of zidovudine when administered concurrently Acetaminophen may decrease bioavailability of zidovudine; zidovudine toxicity increases when administered concurrently with amphotericin B, flucytosine, Adriamycin, vincristine, vinblastine, doxorubicin, cimetidine indomethacin, probenecid, lorazepam, aspirin, acyclovir, ganciclovir, dapsone, and pentamidine |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Fatal hypersensitivity may occur with abacavir following reintroduction of therapy; caution in hepatic dysfunction, prior liver disease, and prolonged use With lamivudine, adjust dose in renal impairment; caution in history of pancreatitis With zidovudine, caution in impaired hepatic or renal function; reduce or stop therapy in hematologic disorders, such as thrombocytopenia, granulocytopenia, and severe anemia |
| Drug Name | Nevirapine (Viramune) |
|---|---|
| Description | Nonnucleoside reverse transcriptase inhibitor that limits virus replication by mechanism different from that of nucleosidase inhibitors such as zidovudine and lamivudine. |
| Adult Dose | 200 mg tab PO bid (should take 1 tab/d for first 2 wk to decrease risk of rash) |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity |
| Interactions | Rifampin and rifabutin may decrease effects; decreases concentrations of protease inhibitors; may decrease effectiveness of oral contraceptives |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Resistant HIV may emerge rapidly when administered as monotherapy; high incidence of rash (especially early in treatment); Stevens-Johnson syndrome, severe skin reactions, and hepatotoxicity may occur |
| Drug Name | Ganciclovir (Cytovene, Vitrasert) |
|---|---|
| Description | Synthetic guanine derivative active against CMV. Acyclic nucleoside analog of 2'-deoxyguanosine inhibits replication of herpes viruses both in vitro and in vivo. Levels of ganciclovir-triphosphate are as much as 100-fold greater in CMV-infected cells than in uninfected cells. This may be result of preferential phosphorylation of ganciclovir in virus-infected cells. For patients who experience progression of CMV retinitis while receiving maintenance treatment with either dosage form of ganciclovir, administer reinduction regimen. |
| Adult Dose | Initial dose: 5 mg/kg IV bid for 14 d Maintenance: 5 mg/kg IV qd for 5-7 d/wk; alternative, 500 mg PO q4h or 1 g tid for life |
| Pediatric Dose | <3 months: Not established >3 months: Administer as in adults |
| Contraindications | Documented hypersensitivity; severe thrombocytopenia or neutropenia |
| Interactions | Cytotoxic drugs such as dapsone, vinblastine, Adriamycin, pentamidine, flucytosine, vincristine, amphotericin B, TMP/SMZ combinations, or other nucleoside analogs may result in additive toxicity in bone marrow, spermatogonia, and germinal layers of skin and GI mucosa (coadminister only if potential benefits outweigh risks); imipenem-cilastatin may cause generalized seizures (use only if potential benefits outweigh risks); concurrent cyclosporine or amphotericin B may increase serum creatinine level; probenecid reduces renal clearance; administration of didanosine within 2 h before or simultaneously with ganciclovir may increase bioavailability; zidovudine may decrease bioavailability, while ganciclovir may increase bioavailability of zidovudine |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Clinical toxic effects of ganciclovir include granulocytopenia, anemia, and thrombocytopenia; because oral ganciclovir is associated with a higher rate of CMV retinitis progression than IV formulation, use only when benefits outweigh risks (in advanced HIV disease); half-life and plasma/serum concentrations may be increased as a result of reduced renal clearance; dosages > 6 mg/kg IV may result in increased toxicity; rapid infusions may result in increased toxicity; initially, reconstituted solutions of IV ganciclovir have high pH (eg, 11); phlebitis or pain may occur at site of IV infusion despite further dilution in IV fluids; administration should be accompanied by adequate hydration; photosensitization (photoallergy or phototoxicity) may occur |
| Drug Name | Tenofovir disoproxil fumarate (Viread) |
|---|---|
| Description | Antiretroviral agent used in the treatment of AIDS. Inhibits activity of HIV reverse transcriptase by competing with the natural substrate deoxyadenosine 5'-triphosphate and, after incorporation into DNA, by DNA chain termination. Administered as prodrug bis-isopropoxycarbonyloxymethyl ester derivative of tenofovir, which is converted, through various enzymatic processes, to tenofovir, an acyclic nucleoside phosphonate (nucleotide) analog of adenosine 5'-monophosphate. Bioavailability is enhanced by a high fat meal. Prolonged intracellular distribution allows for once-daily dosing. |
| Adult Dose | 300 mg PO qd pc |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity |
| Interactions | Coadministration with drugs eliminated by active tubular secretion in the kidney may increase serum concentrations of either tenofovir or the coadministered drug; drugs that decrease renal function (eg, acyclovir, ganciclovir, cidofovir) may increase serum concentrations of tenofovir |
| Pregnancy | B - Usually safe but benefits must outweigh the risks. |
| Precautions | The CDC recommends women with AIDS not to breastfeed due to potential HIV transmission to infant; lactic acidosis and hepatomegaly with steatosis reported with nucleoside analogs (suspend treatment if clinical or laboratory findings suggest presence of lactic acidosis or pronounced hepatotoxicity); peripheral wasting, facial wasting, breast enlargement, and cushingoid appearance reported with antiretroviral therapy; common adverse effects include GI complaints (eg, nausea, diarrhea, vomiting, flatulence); monitor for changes in serum creatinine and serum phosphorus levels in patients at risk or with history of renal dysfunction |
These agents block the modification of precursor polyproteins responsible for synthesis of reverse transcriptase and HIV-1 protease itself. These agents are used for treatment of HIV infection and postexposure prophylaxis.
| Drug Name | Lopinavir and ritonavir (Kaletra) |
|---|---|
| Description | Inhibits HIV protease and renders the enzyme incapable of processing polyprotein precursor, which leads to production of noninfectious immature HIV particles. Ritonavir inhibits CYP3A metabolism of lopinavir, which increases plasma levels of lopinavir. |
| Adult Dose | 400 mg lopinavir/100 mg ritonavir PO bid |
| Pediatric Dose | <6 months: Not established 6 months to 12 years: 7-15 kg: 12 mg/kg PO bid 15-40 kg: 10 mg/kg PO bid >40 kg or >12 years: Administer as in adults |
| Contraindications | Documented hypersensitivity; concomitant administration with benzodiazepines, narcotics, anesthetics, antiarrhythmics, and amiodarone |
| Interactions | Coadministration with quinidine, amiodarone, encainide, bepridil, flecainide, rifabutin, and propafenone may cause arrhythmias Toxicity of alprazolam, propoxyphene, bupropion, clorazepate, diazepam, estazolam, meperidine, flurazepam, midazolam, triazolam, and zolpidem may significantly increase with concomitant use of lopinavir Carbamazepine, phenobarbital, dexamethasone, phenytoin, rifampin, efavirenz, and nevirapine may decrease levels of lopinavir |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Pancreatitis may occur (suspend therapy if symptoms of pancreatitis occur); may exacerbate diabetes mellitus; caution in hepatic impairment; large increases of total cholesterol and triglycerides reported; hemophilia type A and type B reported with protease inhibitors |
| Drug Name | Indinavir (Crixivan) |
|---|---|
| Description | Prevents formation of protein precursors necessary for HIV infection of uninfected cells and viral replication. |
| Adult Dose | 800 mg PO q8h |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity |
| Interactions | Increases blood concentrations of astemizole, cisapride, midazolam, isoniazid, stavudine, trimethoprim, terfenadine, triazolam, and oral contraceptives; fluconazole and rifampin decrease blood concentrations; quinidine and ketoconazole increase blood concentrations; decreases blood concentration of lamivudine |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Caution in hepatic impairment |
These agents are indicated for treatment of toxoplasmosis. Therapy usually is initiated in patients with AIDS who test positive for Toxoplasma gondii, in those who have clinical symptoms suggestive of toxoplasmosis, or when neuroradiography studies show findings consistent with toxoplasmosis.
| Drug Name | Pyrimethamine (Daraprim) |
|---|---|
| Description | Folic acid antagonist that selectively inhibits plasmodial dihydrofolate reductase. Highly selective against plasmodia and T gondii. Does not destroy gametocytes but arrests sporogony in mosquito. Possesses blood schizonticidal and some tissue schizonticidal activity against malaria parasites of humans. Extend regimens to include suppressive cure through any characteristic periods of early recrudescence and late relapse for at least 6-10 wk in each case. |
| Adult Dose | 50-75 mg PO qd |
| Pediatric Dose | Loading dose: 1-2 mg/kg/d PO divided bid for 1-3 d, followed by 1 mg/kg/d bid for 4 wk; not to exceed 25 mg/d |
| Contraindications | Documented hypersensitivity; megaloblastic anemia resulting from folate deficiency |
| Interactions | Concurrent use of antifolic acids, such as methotrexate, may increase risk of bone marrow suppression; discontinue if signs of folate deficiency develop; lorazepam may cause mild hepatotoxicity |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | If signs of folate deficiency develop, reduce dose or discontinue drug depending on patient response; caution in hepatic or renal impairment; monitor for toxoplasmosis by performing semiweekly CBC, including platelet counts; may precipitate hemolytic anemia in G-6-PD deficiency, generally in presence of other stressful events |
| Media file 1: HIV infection and AIDS. Pneumocystis carinii pneumonia. Bilateral interstitial infiltrates. | |
![]() | View Full Size Image | Media type: X-RAY |
| Media file 2: HIV infection and AIDS. CNS toxoplasmosis. Multiple ring-enhancing lesions with edema and midline shift. | |
![]() | View Full Size Image | Media type: CT |
HIV Infection and AIDS excerpt
Article Last Updated: Jul 10, 2008