HIV Page 3

Introduction
Opportunistic infections: complication of advanced HIV disease (CD4 T cells less than 200 per microliter. Major opportunistic infections include: Pneumocystis carinii Cytomegalovirus (CMV) Mycobacterium avium About 80% of AIDS patients die as a result of an opportunistic infection. return to main menu

Clinical Features
- "The symptoms of P. carinii pneumonia (PCP) include dyspnea, non-productive cough, and fever. Chest radiography demonstrates bilateral infiltrates. Extrapulmonary lesions occur in a minority (<3%) of patients, involving most frequently the lymph nodes, spleen, liver and bone marrow. Typically, in untreated PCP increasing pulmonary involvement leads to death"-CDC
Laboratory Diagnosis:
- "The specific diagnosis is based on identification of P. carinii in bronchopulmonary secretions obtained as induced sputum or broncho-alveolar lavage (BAL) material.
  - In situations where these two techniques cannot be used, transbronchial biopsy or open lung biopsy may prove necessary.
  - Microscopic identification of P.carinii trophozoites and cysts is performed with stains that demonstrate either the nuclei of trophozoites and intracystic stages (such as Giemsa) or the cyst walls (such as the silver stains).
  - In addition, immunofluorescence microscopy using monoclonal antibodies can identify the organisms with higher sensitivity than conventional microscopy."-CDC
- Pneumocystis carinii trophozoites in broncho-alveolar lavage (BAL) material
- Pneumocystis carinii cysts:B: 3 cysts in bronchoalveolar material, Giemsa stain
- Cysts in lung tissue, silver stain
- Pneumocystis carinii cysts in broncho-alveolar lavage material; silver stain

Pneumocystis carinii (P. carinii): common HIV infection -declining incidence.
P. carinii pneumonia (PCP): AIDS-defining illness in about 20% of HIV patients.
About 50% of HIV patients will contract PCP pneumonia at least once.
PCP pneumonia, because of HIV, is now a growing cause of community acquired pneumonia.
Risk of PCP pneumonia increases as CD4 T cell counts decline.
Patients with CD4 T cell accounts less than 200/microliter have a significantly higher likelihood of contracting PCP.
With prophylaxis against Pneumocystis carinii, PCP is now occurring when the median CD4 T cell count is about 36/microliter.
PCP definitive diagnosis requires and demonstration of trophozoite or cyst form of the organism in samples from sputum, bronchoalveolar lavage or opened lung biopsy.

Standard therapy: trimethoprim-sulfamethoxazole (Bactrim) [IV and oral formulation]
- High incidence of side effects (about 50 % -- 65%) in HIV patient population.
  - rash, fever, leukopenia, thrombocytopenia, and hepatitis
  - More serious hypersensitivity reactions possible including Stevens-Johnson syndrome
- Possibly advisable not to prescribe zidovudine or ganciclovir, because of cumulative myelotoxic effects.

Pneumocystis prophylaxis its central in management of HIV-infected patients.
Pneumocystis prophylaxis is indicated when:
- previous PCP infection has occurred
- patient's CD₄ T cell level < 200 per microliter
- presence of unexplained fever (> 100^o F)
- history of oropharyngeal candidiasis.
Preferred medication for prophylaxis: trimethoprim-sulfamethoxazole (Bactrim)
- aerosolized pentamidine (Pentam) was associated with increased jeopardy of recurrence
- aerosolized pentamidine use is associated with increased likelihood of disseminated pneumocystosis.
- Combination of dapsone, pyrimethamine, and leucovorin may be the alternative for patients intolerant of trimethoprim (generic) sulfamethoxazole (Gantanol); aerosolized pentamidine (Pentam) remains an option.

Toxoplasma gondii second most common cause of secondary CNS infections in AIDS patients (about 40 percent of all CNS infections)
Accounts for over 50% of CNS mass lesions.
Responsible for about 3% of first seizures.
Toxoplasmosis present is about 15% of HIV patients.
Usually a late complication of HIV disease.
Most common clinical presentation:
- fever
- headache
- focal neurologic deficits (90% of patients)
- Diagnosis usually based on MRI (preferred) or double-dose contrast computed tomography.
- Definitive diagnosis: brain biopsy.
  - typically biopsy will not be performed (because of perioperative morbidity) unless patient is unresponsive to treatment. Treatment is initiated based on imaging and seropositivity.

Standard treatment: combination therapy with pyrimethamine and sulfadiazine
Response rate: 90% -- Relapse rate within six months-about 50%.
Therapeutic complications with Pyrimethamine (Daraprim) and sulfadiazine combination:
- Leukopenia -- main side effect
- Dosages of myelosuppressive antiviral agents, such as zidovudine (Retrovir, AZT, azidothymidine) or ganciclovir (DHPG, Cytovene)r, may have to be reduced.
- Fever
- rash
- thrombocytopenia
- renal failure, secondary to sulfadiazine crystalluria.
- Side effects are common (45% -- 70%).
Alternative therapy:
- Clindamycin (Cleocin) and pyrimethamine (Daraprim): almost as effective as pyrimethamine (Daraprim) and sulfadiazine.
- Atovaquone (Mepron) and pyrimethamine (Daraprim)
- Azithromycin (Zythromax) plus rifabutin (Mycobutin) plus pyrimethamine (Daraprim).
- Atovaquone: broad anti-protozoal activity; effective alternative therapy for patients who have been unresponsive or who have significant adverse reactions to standard therapy.

Patients receiving and trimethoprim/sulfamethoxazole or dapsone and pyrimethamine for Pneumocystis carinii prophylaxis, also are decreased risk for toxoplasmosis.
Adverse effects associated with drugs used to treat toxoplasmosis are sufficiently serious to make those drugs (perhaps with the exception of atovaquone) questionable choices for prophylaxis