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HIV / AIDS

Definition

Table Centers for Disease Control and Prevention 1993 Revised Classification System for HIV Infection in Adults and AIDS Surveillance Case Definition and Table Centers for Disease Control and Prevention 1994 Revised Classification System for HIV Infection in Children Younger than 13 Years present the revised classification systems for adult and child HIV infection.

HIV / AIDS

Pathogenesis

Transmission of HIV

  • Infection with HIV occurs through three primary modes: sexual, parenteral, and perinatal. Sexual intercourse, primarily receptive anal and vaginal intercourse, is the most common vehicle for transmission. The probability of HIV transmission from receptive anorectal intercourse is 0.1% to 3% per sexual contact and 0.1% to 0.2% per sexual contact for receptive vaginal intercourse. In general, the risk is increased when the index partner is in an advanced stage of disease. Persons at higher risk for heterosexual transmission include those with ulcerative sexually transmitted diseases, those with multiple sex partners, and sexual partners of intravenous drug users.
  • The use of contaminated needles or other injection-related paraphernalia by drug abusers has been the main cause of parenteral transmissions and currently accounts for one-fourth of AIDS cases reported in the United States.
  • Health care workers have a small risk of occupationally acquiring HIV, mostly through needlestick injury.
  • Perinatal infection, or vertical transmission, is the most common cause (greater than 90%) of pediatric HIV infection. The risk of mother-to-child transmission is approximately 25% in the absence of breast feeding or antiretroviral therapy. Breast feeding can also transmit HIV.

HIV / AIDS

Clinical presentation

  • Clinical presentations of primary HIV infection vary, but patients often have a viral syndrome or mononucleosis-like illness with fever, pharyngitis, and adenopathy (Table Clinical Presentation of Primary HIV Infection in Adults). Symptoms may last for 2 weeks.
  • Probability of progression to AIDS is related to RNA viral load; in one study, 5-year progression rates to AIDS were 8%, 26%, 49%, and 62% for RNA copies per milliliter of less than 4530, 4531 to 13,020, 13,021 to 36,270, and greater than 36,270, respectively.
  • The classification scheme of the Centers for Disease Control and Prevention  divides HIV infection into a matrix of nine categories based on the CD4 cell count (see «Diagnosis» below) and clinical conditions (see Table Centers for Disease Control and Prevention 1993 Revised Classification System for HIV Infection in Adults and AIDS Surveillance Case Definition).
  • Most children born with HIV are asymptomatic. On physical examination, they often present with unexplained physical signs such as lymphadenopathy, hepatomegaly, splenomegaly, failure to thrive and weight loss or unexplained low birth weight, and fever of unknown origin. Laboratory findings include anemia, hypergammaglobulinemia, altered mononuclear cell function, and altered T-cell subset ratios. The normal range for CD4 cell counts in children is much different than for adults (Table Centers for Disease Control and Prevention 1994 Revised Classification System for HIV Infection in Children Younger than 13 Years).
  • Clinical presentations of the opportunistic infections are presented in «Infectious Complications of HIV,» below.
TABLE. Centers for Disease Control and Prevention 1993 Revised Classification System for HIV Infection in Adults and AIDS Surveillance Case Definition
CD4 + T-Cell Categories (Absolute Number and Percentage) (A) Asymptomatic, Acute (Primary) HIV or PGLa (B) Symptomatic, not (A) or (C) Conditions (C) AIDS-Indicator Conditions
≥500/µL or ≥29% A1 B1 C1
200-499/ ВµL or 14-28% A2 B2 C2
<200/ВµL or <14% A3 B3 C3
AIDS-Indicator Conditions
Candidiasis of bronchi, trachea, or lungs Lymphoma, Burkitt's
Candidiasis, esophageal Lymphoma, immunoblastic
Cervical cancer, invasive Lymphoma, primary, or brain
Coccidioidomycosis, disseminated or extrapulmonary Mycobacterium avium complex or M. kansasii, disseminated or extrapulmonary
Cryptococcosis, extrapulmonary Mycobacterium tuberculosis, any site (pulmonary or extrapulmonary)
Cryptosporidiosis, chronic intestinal (duration >1 month) Mycobacterium, other species or unidentified species, disseminated or extrapulmonary
Cytomegalovirus disease (other than liver, spleen or nodes) Pneumocystis carinii pneumonia
Cytomegalovirus retinitis (with loss of vision) Pneumonia, recurrent
Encephalopathy, HIV-related Progressive multifocal leukoencephalopathy
Herpes simplex: chronic ulcer(s) (duration >1 month); or bronchitis, pneumonitis, or esophagitis Salmonella septicemia, recurrent
Histoplasmosis, disseminated or extrapulmonary Toxoplasmosis of brain
Isosporiasis, chronic intestinal (duration >1 month) Wasting syndrome due to HIV
Kaposi's sarcoma
aPCL, persistent generalized lymphadenopathy.
TABLE. Centers for Disease Control and Prevention 1994 Revised Classification System for HIV Infection in Children Younger than 13 Years
Immunologic Categories 12 Months Cells/ВµL (%)a 1-5 Years Cells/ВµL (%)a 6-12 Years Cells/ВµL (%)a
  1. No evidence of suppression
  2. Evidence of moderate suppression
  3. Severe suppression
1500 (25%) 750-1499 (15%-24%) <750 (<15%) 1000 (25%) 500-999 (15%-24%) <500 (<15%) 500 (25%) 200-499 (15%-24%) <200 (<15%)
Immunologic Categories N: No Signs/Symptoms A: Mild Signs/Symptoms B: Moderate Signs/Symptoms C: Severe Signs/Symptoms
1. No evidence of suppression N1 A1 B1 C1
2. Evidence of moderate suppression N2 A2 B2 C2
3. Severe suppression N3 A3 B3 C3
aPercentage of total lymphocytes.
TABLE. Clinical Presentation of Primary HIV Infection in Adults
Symptoms Fever, sore throat, fatigue, weight loss, and myalgia 40%-80% of patients will also exhibit a morbilliform or maculopapular rash usually involving the trunk Diarrhea, nausea, and vomiting Lymphadenopathy, night sweats Aseptic meningitis (fever, headache, photophobia, and stiff neck) may be present in a quarter of presenting cases Other High viral load (exceeding 50,000 copies/mL in the adult or 500,000 copies/mL in the child Persistent decrease in CD4 lymphocytes

Diagnosis

  • The most commonly used screening method for HIV is an enzyme-linked immunosorbent assay (ELISA), which detects antibodies against HIV-1 and is both highly sensitive and specific. False positives can occur in multiparous women; in recent recipients of hepatitis B, HIV, influenza, or rabies vaccine; following multiple blood transfusions; and in those with liver disease or renal failure, or undergoing chronic hemodialysis. False negatives may occur if the patient is newly infected and the test is performed before antibody production is adequate. The minimum time to develop antibodies is 3 to 4 weeks from initial exposure.
  • Positive ELISAs are repeated in duplicate and if one or both tests are reactive, a confirmatory test is performed for final diagnosis. Western blot assay is the most commonly used confirmatory test.
  • The viral load test quantifies viremia by measuring the amount of viral RNA. There are several methods used for determining the amount of HIV RNA: reverse transcriptase-coupled polymerase chain reaction (RT-Polymerase chain reaction), branched DNA (bDNA), and transcription-mediated amplification. Each assay has its own lower limit of sensitivity, and results can vary from one assay method to the other; therefore, it is recommended that the same assay method be used consistently within patients.
  • Viral load can be used as a prognostic factor to monitor disease progression and the effects of treatment.
  • The number of CD4 lymphocytes in the blood is a surrogate marker of disease progression. The normal adult CD4 lymphocyte count ranges between 500 and 1600 cells/ВµL, or 40% to 70% of all lymphocytes.

Treatment of HIV/AIDS

Infectious complications of HIV

  • The development of certain opportunistic infections is directly or indirectly related to the level of CD4 lymphocytes.
  • The most common opportunistic diseases and their frequencies found before death in patients with AIDS between 1990 and 1994 were Pneumocystis carinii pneumonia, Mycobacterium avium complex, and cytomegalovirus disease.
  • The spectrum of infectious diseases observed in HIV-infected individuals and recommended first-line therapies are shown in Table Therapies for Common Opportunistic Pathogens in HIV-Infected Individuals.

Pneumocystis carinii

P. carinii pneumonia is the most common life-threatening opportunistic infection in patients with AIDS. The taxonomy of the organism is unclear, having been classified as both protozoan and fungal.

Clinical Presentation

  • Characteristic symptoms include fever and dyspnea; clinical signs are tachypnea, with or without rales or rhonchi, and a nonproductive or mildly productive cough. Chest radiographs may show florid or subtle infiltrates or may occasionally be normal, although infiltrates are usually interstitial and bilateral. Arterial blood gases may show minimal hypoxia (PaO2 80 to 95 mm Hg) but in more advanced disease may be markedly abnormal.
  • The onset of P. carinii pneumonia is often insidious, occurring over a period of weeks, although more fulminant presentations can occur.
TABLE. Therapies for Common Opportunistic Pathogens in HIV-Infected Individuals
Clinical Disease Selected Initial Therapies for Acute Infection in Adults Common Drug- or Dose-Limiting Adverse Reactions
Fungi
Candidiasis, oral Fluconazole 200 mg orally single dose or 100 mg orally for 5 days Taste, patient acceptance
or
Nystatin 500,000 units oral swish 4-6 times daily for 7-10 days,
or
Clotrimazole 10 mg (1 troche) orally 5 times daily for 7-10 days
Candidiasis, esophageal Fluconazole 200 mg orally or intravenously on the first day then 100 mg/day for 10-14 days or Ketoconazole 400 mg/day orally for 10-14 days Elevated liver function tests, hepatotoxicity, nausea and vomiting Elevated liver function tests, hepatotoxicity, rash, nausea and vomiting
Pneumocystis carinii pneumonia Trimethoprim-sulfamethoxazole intravenously or orally 12-20 mg/kg/day as trimethoprim component in 3-4 divided doses for 21 daysa Skin rash, fever, leukopenia Thrombocytopenia
or
Pentamidine intravenously 3-4 mg/kg/day for 21 daysa Mild episodes Azotemia, hypoglycemia, Hyperglycemia
Atovaquone suspension 750 mg (5 mL) orally twice daily with meals for 21 daysa Rash, elevated liver enzymes, diarrhea
Cryptococcal meningitis Amphotericin B 0.5-1 mg/kg/day intravenously for a minimum of 2 wk with or without flucytosine 100-150 mg/kg/day orally in 4 divided doses followed by Nephrotoxicity, hypokalemia, anemia, fever, chills Bone marrow suppression, Elevated liver enzymes Same as above
Fluconazole 100 to 200 mg/day, orallya
Histoplasmosis Amphotericin B 0.5-1 mg/kg/day intravenously for 6-8 wka Same as above
or
Itraconazole 200-400 mg/day orally for 3 monthsa Elevated liver function tests, hepatotoxicity, nausea and vomiting, hypertension
Coccidioidomycosis Amphotericin B 0.5-1 mg/kg/day intravenously for ≥6-8 wka Same as above
Protozoa
Toxoplasmic encephalitis Pyrimethamine 200 mg orally once then 50-100 mg/day Bone marrow suppression
+
Sulfadiazine 1-1.5 g orally 4 times daily Allergy, rash, drug fever
and
Folinic acid 10-20 mg orally daily for a minimum of 28 daysa
Isosporiasis Trimethoprim and sulfamethoxazole 1-2 double-strength tablets (160 mg trimethoprim and 800 mg sulfamethoxazole) orally twice daily for 2-4 wk Same as above
Bacteria
Organisms associated with T-cell defects:
Mycobacterium avium complex Clarithromycin 500 mg orally twice daily, + ethambutol 15 mg/kg/day orally to a maximum of 1000 mg/day, and Gastrointestinal intolerance Optic neuritis, peripheral neuritis
Rifabutin 300 mg/daya Rash, gastrointestinal intolerance
Neutropenia, discolored urine, uveitis
Salmonella enterocolitis or bacteremia Ciprofloxacin 500-750 mg orally twice daily for 14 days, Gastrointestinal intolerance
or
Trimethoprim (160 mg)-sulfamethoxazole (800 mg) 1 tablet orally twice daily for 14 days Same as above
Organisms associated with B-cell defects:
Campylobacter enterocolitis Ciprofloxacin 500 mg orally twice daily for 7 days Same as above
or
Erythromycin 250-500 mg orally four times daily for 7 days Gastrointestinal intolerance, colitis ototoxicity
Shigella enterocolitis Ciprofloxacin 500 mg orally twice daily for 5 days Same as above
Viruses
Mucocutaneous herpes simplex Acyclovir 1-2 g/day orally in 3-5 divided doses for 7-10 days Gastrointestinal intolerance
or
Valacyclovir 500 mg orally every 12 h for 7-10 days Gastrointestinal intolerance
or
Famciclovir 500 mg orally every 12 h for 7-10 days Headache, gastrointestinal intolerance
Varicella-zoster Acyclovir 30 mg/kg/day intravenously in 3 divided doses or 4 g/day orally for 7-10 days Obstructive nephropathy, central nervous system symptomatology
or
Valacyclovir, 1 g orally every 8 h for 7-10 days Gastrointestinal intolerance
or
Famciclovir 500 mg orally every 8 h for 7-10 days
Cytomegalovirus Ganciclovir 7.5-10 mg/kg/day in 2-3 divided doses intravenously for 14 daysa Neutropenia, thrombocytopenia
or
Foscarnet 180 mg/kg/day in 2 or 3 divided doses intravenously for 14 daysa Nephrotoxicity, hypohypercalcemia, hypohyperphosphatemia, anemia
Cytomegalovirus retinitis Ganciclovir intraocular implant
aMaintenance therapy is recommended.

Treatment

  • Treatment with trimethoprim-sulfamethoxazole or parenteral pentamidine is associated with a 60% to 100% response rate. Trimethoprim-sulfamethoxazole is the regimen of choice for treatment and subsequent prophylaxis of P. carinii pneumonia in patients with and without HIV.
  • Trimethoprim-sulfamethoxazole is given in doses of 15 to 20 mg/kg/day (based on the trimethoprim component) as three to four divided doses for the treatment of P. carinii pneumonia.
  • Trimethoprim-sulfamethoxazole is usually initiated by the intravenous route, although oral therapy (as oral absorption is high) may suffice in mildly ill and reliable patients or to complete a course of therapy after a response has been achieved with intravenous administration.
  • For treatment of HIV-associated P. carinii pneumonia, pentamidine isethionate is administered intravenously, usually in doses of 4 mg/kg /day.
  • The optimum length of therapy for treatment of P. carinii pneumonia with either agent is not known, but 21 days is commonly recommended.
  • The more common adverse reactions seen with trimethoprim-sulfamethoxazole are rash, fever, leukopenia, elevated serum transaminases, and thrombocytopenia. The incidence of these adverse reactions is higher in HIV-infected individuals than in those not infected with HIV.
  • For pentamidine, side effects include hypotension, tachycardia, nausea, vomiting, severe hypoglycemia or hyperglycemia, pancreatitis, irreversible diabetes mellitus, elevated transaminases, nephrotoxicity, leukopenia, and cardiac arrhythmias.
  • The early addition of adjunctive glucocorticoid therapy to anti-P. carinii pneumonia regimens has been shown to decrease the risk of respiratory failure and improve survival in patients with AIDS and moderate to severe P. carinii pneumonia (PaO2 less than or equal to ≤ 0 mm Hg or [A-a] gradient ≥ reater than or equal to 35 mm Hg). The regimen currently recommended is 40 mg of prednisone orally twice daily during days 1 through 5; 40 mg once daily on days 6 through 10; and 20 mg once daily on days 11 through 21, or for the duration of therapy. In general, adjunctive glucocorticoid therapy should be initiated when antipneumocystis therapy is started, as the data supporting the use of glucocorticoids are based on initiation within the first 24 to 72 hours of the start of antipneumocystis therapy.

Prophylaxis

  • Currently, P. carinii pneumonia prophylaxis is recommended for all HIV-infected individuals who have already had previous P. carinii pneumonia. Prophylaxis is also recommended for all HIV-infected persons who have a CD4 lymphocyte count of less than 200 cells/ВµL (i.e. their CD4 cells are less than 20% of total lymphocytes), unexplained fever (greater than 100В° F) for more than 2 weeks, or a history of oropharyngeal candidiasis. Patients on P. carinii pneumonia prophylaxis whose CD4 counts increase above 200 cells/ВµL antiretroviral therapy should not discontinue P. carinii pneumonia prophylaxis at this point (Table 39-7).
  • Trimethoprim-sulfamethoxazole is the preferred therapy for both primary and secondary prophylaxis of P. carinii pneumonia in adults and adolescents. The recommended dose in adults and adolescents is one double-strength tablet daily.
  • Trimethoprim-sulfamethoxazole is also the recommended drug of choice for P. carinii pneumonia prophylaxis in children. The trimethoprim-sulfamethoxazole regimen recommended (although other acceptable alternatives exist) is 150 mg/m2/day of trimethoprim and 750 mg/m2/day of sulfamethoxazole given in divided doses twice daily, 3 times weekly on consecutive days (e.g., Monday, Tuesday, and Wednesday). The total daily dose of trimethoprim-sulfamethoxazole in children should not exceed 320 mg of trimethoprim with 1600 mg of sulfamethoxazole.

Toxoplasma gondii

T. gondii can infect any organ of the body and cause an acute infection; it has a predilection for the brain and the eye.

Clinical Presentation

  • The clinical signs and symptoms of toxoplasmosis are most frequently associated with involvement of the central nervous system and, less commonly, the lungs and eyes, although any organ can be affected. Clinical presentation often includes fever, headache, seizures (in approximately 10% to 25% of patients), focal neurologic abnormalities (in approximately 60% to 90%), and mental status changes.
  • Brain biopsy is required to make a definitive diagnosis of toxoplasmic encephalitis, although presumptive diagnosis is commonly made in T. gondii-seropositive patients with typical central nervous system lesions.

Treatment

  • The initial treatment of central nervous system toxoplasmosis is usually empiric. Antitoxoplasmosis therapy is usually initiated in patients with AIDS who are seropositive for Toxoplasma, have clinical symptoms suspicious for toxoplasmosis, and have characteristic findings on neuroradiographic studies.
  • The combination of pyrimethamine and sulfadiazine is considered the most effective regimen for acute therapy of AIDS-related central nervous system toxoplasmosis.
  • Pyrimethamine loading doses of 75 mg orally on the first day followed by 25 mg/day thereafter have been commonly used. Others have recommended larger loading doses of 100 to 200 mg followed by daily oral doses of 1 to 1.5 mg/ kg/day (50 to 100 mg/day).
  • The usual dose of sulfadiazine is 1 to 1.5 g every 6 hours (4 to 8 g/day).
  • Folinic acid, in doses of 10 to 20 mg/day (although doses as high as 50 mg/day have been used) is usually added to the combination to reduce the pyrimethamine-induced bone marrow toxicity.
  • Acute therapy with this combination should be continued for at least 3 weeks, but 6 weeks of treatment is recommended for more severely ill patients.
  • The combination of pyrimethamine and clindamycin appears to be less toxic, but less effective, than that of pyrimethamine and sulfadiazine.
  • The discontinuation of pyrimethamine and sulfadiazine after successful initial therapy may be considered in persons who have a sustained CD4 cell count of greater then 200 cells/ВµL, for at least 6 months and have completed initial therapy and are asymptomatic.
  • A regimen of pyrimethamine (25 to 50 mg/day with leukovorin 10 to 25 mg orally once dialy) and sulfadiazine (500 to 1000 mg four times daily) is recommended for maintenance therapy.

Cryptococcus neoformans

Cryptococcal infection is now uncommon and occurs primarily in those with limited access to health care.

Clinical Presentation

  • The usual clinical presentation of cryptococcal infection is meningitis. The clinical features of cryptococcal meningitis may be subtle, nonspecific, and not localized to the central nervous system. Fever, headache, and malaise are the most frequent symptoms.
TABLE. Therapies for Prophylaxis of First Episode Opportunistic Diseases in Adults and Adolescents
Pathogen Indication First Choice
I. Standard of Care
Pneumocystis Carinii CD4 + count <200ВµL or oropharyngeal candidiasis Trimethoprim-sulfamethoxazole, 1 double-strength tablet orally once daily or 1 single-strength tablet orally once daily
Mycobacterium tuberculosis Isoniazid-sensitive TST reaction ≥5 mm or prior positive TST result without treatment or contact with case of active tuberculosis Isoniazid 300 mg orally + pyridoxine, 50 mg orally once daily for 9 months, or isoniazid 900 mg orally + pyridoxine 50 mg orally twice weekly x 12 months
Isoniazid-resistant Same as isoniazid-sensitive; high probability of exposure to isoniazid-resistant tuberculosis Rifampin 600 mg orally once daily + pyrazinamide 200 mg/kg orally once daily for 2 months
Toxoplasma gondii immunoglobulin G antibody to Toxoplasma and CD4 + count <100/ВµL Trimethoprim-sulfamethoxazole 1 double-strength tablet orally once daily
Mycobacterium avium complex CD4 + count <50 ВµL Azithromycin, 1200 mg orally once weekly or clarithromycin, 500 mg orally twice daily
Varicella zoster virus Significant exposure to chickenpox or shingles for patients who have no history of either condition or, if available, negative antibody to Varicella zoster virus Varicella zoster immune globulin, 5 vials (1.25 mL each) intramuscularly administered ideally within 48 h of exposure but ≤96 h.
II. Usually Recommended
Streptococcus pneumoniae CD4 count of ≥200 cells µL 23-valent polysaccharide vaccine, 0.5 mL intramuscularly
Hepatitis B virus All susceptible (antihepatitis B core antigen negative) patients Hepatitis B vaccine, 3 doses
Influenza virus All patients (annually, before influenza season) Inactivated trivalent influenza virus vaccine: 0.5 mL intramuscularly
Hepatitis A virus All susceptible (anti-hepatitis A-negative) patients at increased risk for hepatitis A infection (e.g., illegal drug users, men who have sex with men, hemophiliacs) or Patients with chronic liver disease Including chronic hepatitis B or C Hepatitis A vaccine: 2 doses
III. Indicated for Use Only in Selected Circumstances
Bacteria Neutropenia Granulocyte-colony-stimulating factor (G-cerebrospinal fluid), 5-10 mcg/kg subcutaneously once daily for 2-4 wk; or granulocyte-macrophage colony-stimulating factor (GM-cerebrospinal fluid), 250 mcg/m2 subcutaneously for 2-4 wk.
Cryptococcus neoformans CD4 + count <50ВµL Fluconazole, 100-200 mg orally once daily
Histoplasma capsulatum CD4 + count < 100/ВµL, endemic Geographic area Itraconazole capsule, 200 mg orally once daily
Cytomegalovirus CD4 + count <50/ВµL and cytomegalovirus antibody positivity Oral ganciclovir, 1 g orally 3 times daily
From Centers for Disease Control and Prevention. Guidelines for Preventing Opportunistic Infections Among HIV-Infected Persons – 2002 Recommendations of the USPHS/IDSA. MMWR 2002;51:1-52.
  • Methods for diagnosis of cryptococcal infection include serum and cerebrospinal fluid (cerebrospinal fluid) testing for cryptococcal antigen and fungal cultures. Detection of cryptococcal antigen in serum and cerebrospinal fluid is the most sensitive and specific test; an antigen titer greater than 1:8 should be regarded as evidence of infection.

Treatment

  • The standard therapeutic approach has been amphotericin B for both acute and maintenance therapy.
  • Fluconazole is also effective for treatment of cryptococcal meningitis; however, the combination of amphotericin B and flucytosine was found to be superior.
  • Most patients with cryptococcal meningitis should receive amphotericin B in an intravenous dose of at least 0.5 mg/kg/day for a minimum of 2 weeks as acute therapy. Flucytosine in doses of 100 to 150 mg/kg/day can be considered for combination with amphotericin B.
  • Serum concentrations of flucytosine should be monitored, and peak levels kept below 100 mcg/mL to minimize hematologic adverse reactions.
  • Maintenance therapy is necessary to prevent relapse. Fluconazole is the drug of choice to prevent relapse of cryptococcal meningitis.

Mycobacterium infections

Clinical Presentation

  • The clinical syndrome associated with Mycobacterium avium complex (Mycobacterium avium complex) includes high spiking fevers, diarrhea, night sweats, malaise, weight loss, anemia, and neutropenia. Persistent diarrhea and abdominal pain, a malabsorption syndrome, and extrahepatic biliary obstruction are manifestations associated with Mycobacterium avium complex gastrointestinal infection.
  • Diagnosis of Mycobacterium avium complex infection is usually based on culture of the organisms from the blood, although biopsies of the liver, bone marrow, and lymph nodes are also highly sensitive and specific.

Treatment

  • Treatment regimens should contain at least two antimycobacterial agents.
  • Every regimen should contain either clarithromycin or azithromycin, with clarithromycin (500 mg twice daily) being the preferred agent. For the second agent, numerous choices are available, although ethambutol (15 mg/kg/day) is preferred by many experts. Many clinicians would add a third (such as rifabutin), and some, a fourth drug to this regimen.
  • Clinical responses usually occur within 2 to 8 weeks of the start of therapy. If a clinical and microbiologic response is observed, therapy should continue for the duration of the patient's life.
  • Mycobacterium avium complex prophylaxis is now strongly recommended for all HIV-infected adults and adolescents with a CD4 count less than 50 cells/ВµL. The first-line choices are either azithromycin (1200 mg once weekly) or clarithromycin (500 mg twice daily). Rifabutin is an alternative.

Herpes virus infections

Herpes Simplex Virus

  • The manifestations of Herpes Simplex Virus disease observed in persons with AIDS include orolabial, genital, and anorectal mucocutaneous disease; esophagitis; and less commonly, encephalitis. Ulcerative Herpes Simplex Virus lesions present for longer than 1 month in an individual with laboratory evidence of HIV infection, or no other apparent cause for immunodeficiency, are considered an AIDS-defining condition.
  • Symptoms of anorectal lesions, the most common clinically evident Herpes Simplex Virus disease causing morbidity in homosexual men, include pain, itching, and painful defecation.
  • Acyclovir is the drug of choice for treatment of Herpes Simplex Virus disease. For mild to moderate mucocutaneous disease, oral acyclovir in doses of 200 mg five times daily or 400 mg three times daily are used, although 400 mg five times daily may be necessary. Intravenous acyclovir (15 mg/kg/day) should be used in those settings where absorption of an oral drug is questionable, oral tolerance is unlikely (Herpes Simplex Virus esophagitis), or perhaps when severe mucocutaneous disease is present.
  • Treatment of mucocutaneous disease should be continued until all lesions have crusted.
  • Intravenous acyclovir (30 mg/kg/day) should also be used for viscerally disseminated disease and for Herpes Simplex Virus encephalitis.
  • Recurrent Herpes Simplex Virus disease can often be managed with low-dose suppressive oral acyclovir therapy, 200 mg four times daily, 400 mg twice daily, or 800 mg once daily.

Varicella-Zoster Virus

  • Zoster usually begins as radicular pain followed by localized erythematous rash and characteristic vesicles. Zoster will usually remain confined to a limited number of dermatomes, but complications such as widespread cutaneous involvement and disseminated visceral zoster may occur.
  • Acyclovir is the drug of choice for Varicella zoster virus infections. While an oral acyclovir regimen of 4 g/day has been shown effective for the treatment of zoster in immunocompetent adults, the drug has not been fully evaluated in immunocompromised patients such as those with AIDS.
  • AIDS patients with disseminated cutaneous or visceral zoster should receive treatment with intravenous acyclovir in doses of 30 mg/kg/day for at least 7 days or until all lesions are crusted.

Cytomegalovirus

  • Manifestations of cytomegalovirus infection include retinitis, esophagitis, hepatitis, gastrointestinal involvement, and less commonly radiculopathy, encephalitis, and pneumonitis. cytomegalovirus retinitis is usually associated with a painless progressive loss of vision. Patients may initially complain of blurry vision, loss of visual acuity, or «floaters.»
  • Ganciclovir therapy for cytomegalovirus disease has traditionally been divided into two phases – induction and maintenance – because high relapse rates are found after discontinuation of the drug following successful completion of a 2- to 3-week course of initial therapy. Induction regimens are typically 7.5 to 10 mg/kg/day intravenously in two or three equally divided doses for 14 days, or longer if there is a slow clinical response. Maintenance therapy is usually 5 to 6 mg/kg once daily, although doses of 10 mg/kg have been used, 5 to 7 days/wk for an indefinite period of time.
  • Foscarnet is an alternative to ganciclovir that appears less likely to cause neutropenia; however, it has a variety of potential adverse effects, including renal insufficiency and metabolic disturbances (both increases and decreases) in calcium and phosphorus.
  • Prophylaxis with oral ganciclovir should be considered in HIV-infected adults and adolescents who have a CD4 cell count of less than 50 cells/ВµL; ganciclovir prophylaxis is not a recommended standard of care.
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