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.
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
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).
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
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
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
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.
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.