Trimethoprim-sulfamethoxazole (TMP-SMZ;Bactrim, Septra) is an antibacterial agent for treating various or-ganisms causing infection. Persons with HIV infection who have a T-cell count of less than 200 should receive chemoprophylaxis against PCP with TMP-SMZ. PCP prophylaxis can be safely dis-continued in patients responding to HAART with a sustained in-crease in T lymphocytes. Its use also confers cross-protection against toxoplasmosis and some common respiratory bacterial in-fections (USPHS/IDSA, 2002). Patients with AIDS who are treated with TMP-SMZ experience a high incidence of adverse effects, such as fever, rashes, leukopenia, thrombocytopenia, and renal dysfunction. Reintroduction of TMP-SMZ using a gradual increase in dose (desensitization) may be successful in up to 70% of patients.
In the past several years, there have been many advances inthe treatment of PCP. TMP-SMZ, the drug of choice for PCP in patients with AIDS and in immunocompromised patients with-out HIV infection, is available in both intravenous (IV) and oral preparations. Pentamidine (Pentacarinat, Pentam 300, Nebu-Pent), an antiprotozoal medication, is used as an alternative agent for combating PCP. If adverse effects develop or if patients do not improve clinically when treated with TMP-SMZ, the health care provider may recommend pentamidine. Intramuscular adminis-tration is avoided because of the potential for painful sterile abscess formation. Also, IV pentamidine may cause severe hypo-tension if administered too rapidly. Other adverse effects include impaired glucose metabolism (with diabetes mellitus), renal dam-age, hepatic dysfunction, and neutropenia. Initially, the success of aerosolized pentamidine led to its use as a treatment for mild to moderate PCP. However, it has proved to be less effective and more costly than TMP-SMZ, and early relapses are common. Because of these limitations, the inhalant form of pentamidine is usually reserved for patients with mild to moderate PCP who are intolerant of other treatments. The combination of TMP-SMZ and pentamidine has shown no additional benefit and is avoided because of the cumulative toxic effects that may result.
Chemoprophylaxis against disseminated MAC disease isindicated for HIV-infected persons with T-cell counts less than (USOHS/IDSA, 2002). Treatment for MAC infections in-volves use of either clarithromycin (Biaxin) or azithromycin (Zithromax). The combination of azithromycin with rifabutin (Mycobutin) is more effective but the additional cost, increased occurrence of adverse effects, potential for drug interactions, and absence of differences in survival do not warrant the recommen-dation of both medications (USPHS/IDSA, 2002). Secondary prophylaxis for disseminated MAC may be discontinued in pa-tients with sustained increases (eg, longer than 6 months) in CD4 counts greater than 100 in response to HAART, if they have completed 12 months of MAC therapy and have no signs or symptoms attributable to MAC. Primary prophylaxis for dis-seminated MAC may be discontinued in patients who have re-sponded to HAART with CD4 counts of 100 or more for at least 3 months and reintroduced if counts decrease to 50 to 100 (USPHS/IDSA, 2002).
Current primary therapy for cryptococcal meningi-tis is IV amphotericin B with or without oral flucytosine (5-FC, Ancobon) or fluconazole (Diflucan). Serious potential adverse ef-fects of amphotericin B include anaphylaxis, renal and hepatic impairment, electrolyte imbalances, anemia, fever, and severe chills. Intrathecal administration of amphotericin B has been used in place of or in combination with IV administration in pa-tients who have failed to respond to the latter. Until fluconazole,an antifungal agent, was approved and used for lifelong suppres-sive therapy, frequent relapses and high mortality rates often ne-cessitated prolonged therapy with amphotericin B. In some instances, the patient continues to receive IV amphotericin in the home setting. Oral fluconazole is used as suppressive therapy when the CSF tests negative for the organism. This medication is less toxic and better tolerated than amphotericin B.
Retinitis caused by CMV is a leadingcause of blindness in patients with AIDS. Prophylaxis with oral ganciclovir may be considered for HIV-infected persons with T-cell counts of less than 50. Two antiviral agents, ganciclovir (DHPG, Cytovene, Vitrasert) and foscarnet (Foscavir), offer ef-fective treatment but not a cure for CMV retinitis. Because gan-ciclovir and foscarnet do not kill the virus but rather control its growth, they must be taken lifelong. Relapse rates of the two agents are similar. Discontinuation of the medication is associ-ated with the relapse of retinitis within 1 month.
A common adverse reaction to ganciclovir is severe neutrope-nia, which limits the concomitant use of zidovudine (AZT, Com-pound S, Retrovir). For patients who cannot tolerate systemic ganciclovir because of severe neutropenia, infection at the venous access site, or the need to take zidovudine, intravitreal injections of ganciclovir have been effective. Zidovudine can be given with foscarnet (Foscavir). Common adverse reactions to foscarnet are nephrotoxicity, including acute renal failure, and electrolyte im-balances, including hypocalcemia, hyperphosphatemia, and hypo-magnesemia, which can be life-threatening. Other common adverse effects include seizures, GI disturbances, anemia, phlebitis at the infusion site, and low back pain. Possible bone marrow suppression (producing a decrease in white blood cell and platelet counts), oral candidiasis, and liver and renal impairments require close patient monitoring.
Oral acyclovir, famciclovir, or valacyclovir canbe used to treat infections caused by herpes simplex or herpes zoster. Esophageal or oral candidiasis is treated topically with clo-trimazole (Mycelex) oral troches or nystatin suspension. Chronic refractory infection with candidiasis (thrush) or esophageal in-volvement is treated with ketoconazole (Nizoral) or fluconazole (Diflucan).
Although many forms of diarrhea respond to treatment, it is not unusual for this condition to recur and become a chronic prob-lem for the patient. Therapy with octreotide acetate (Sando-statin), a synthetic analog of somatostatin, has been shown to be effective in managing chronic severe diarrhea. High concentra-tions of somatostatin receptors have been found in the GI tract and other tissues. Somatostatin inhibits many physiologic func-tions, including GI motility and intestinal secretion of water and electrolytes.
Management of KS is usually difficult be-cause of the variability of symptoms and the organ systems in-volved. KS is rarely life-threatening except when there is pulmonary or GI involvement. The treatment goal is reduction of symptoms by decreasing the size of the skin lesions, reducing discomfort as-sociated with edema and ulcerations, and controlling symptoms associated with mucosal or visceral involvement. No one treat-ment has been shown to increase survival. Localized treatmentincludes surgical excision of the lesions or application of liquid nitrogen to local skin lesions and injections of intraoral lesions with dilute vinblastine. Injection of intraoral lesions has been as-sociated with local pain and skin irritation. Radiation therapy is effective as a palliative measure to relieve localized pain due to tumor mass (especially in the legs) or for KS lesions that are in sites such as the oral mucosa, conjunctiva, face, and soles of the feet.
Interferon is known for its antiviral and antitumor effects. Patients with cutaneous KS treated with alpha-interferon have experienced tumor regression and improved immune system function. Positive responses have been observed in 30% to 50% of patients, with the best responses seen in those with limited disease and no OIs. Alpha-interferon is administered by the IV, intramuscular, or subcutaneous route. Patients may self-administer interferon at home or receive it in an outpatient setting.
Successful treatment of AIDS-related lymphomashas been limited because of the rapid progression of these ma-lignancies. Combination chemotherapy and radiation therapy regimens may produce an initial response, but it is usually short-lived. Because standard regimens for non-AIDS lymphomas have been ineffective, many clinicians suggest that AIDS-related lym-phomas be studied as a separate group in clinical trials.
Treatment for depression in people with HIV infection involves psychotherapy integrated with pharmacology. If depressive symp-toms are severe and of sufficient duration, treatment with anti-depressants may be initiated. Antidepressants such as imipramine (Tofranil), desipramine (Norpramin), and fluoxetine (Prozac) may be used because these medications also alleviate the fatigue and lethargy that are associated with depression. A psychostimu-lant such as methylphenidate (Ritalin) may be used in low doses in patients with neuropsychiatric impairment. Electroconvulsive therapy may be an option for patients with severe depression that has not responded to pharmacologic interventions.
Malnutrition increases the risk for infection and may also increase the incidence of OIs. Nutrition therapy should be integrated into the overall management plan and should be tailored to meet the nutritional needs of the patient, from oral diet to enteral tube feedings through parenteral nutritional support if needed. As with all patients, a healthy diet is essential for the patient with HIV infection. Calorie counts should be obtained for all patients with AIDS with unexplained weight loss to evaluate nutritional status and to initiate appropriate therapy. The goal is to maintain the ideal weight and, when necessary, to increase weight.
Appetite stimulants have been successfully used in patients with AIDS-related anorexia. Megestrol acetate (Megace), a syn-thetic oral progesterone preparation used to treat breast cancer, promotes significant weight gain and inhibits cytokine IL-1 syn-thesis. In patients with HIV infection, it increases body weight primarily by increasing body fat stores. Dronabinol (Marinol), synthetic tetrahydrocannabinol (THC), the active ingredient in marijuana, has been used to relieve nausea and vomiting associ-ated with cancer chemotherapy. Preliminary results show that after beginning Marinol therapy, almost all patients with HIV in-fection experience a modest weight gain. The effects on body composition are unknown.
Oral supplements may be used to supplement diets deficient in calories and protein. Ideally, oral supplements should be lactosefree (many people with HIV infection are intolerant to lactose), high in calories and easily digestible protein, low in fat with the fat easily digestible, palatable, inexpensive, and tolerated without causing diarrhea. Advera is a nutritional supplement that has been developed specifically for people with HIV infection and AIDS. Parenteral nutrition is the final option because of the costs and associated risks, including infections.