Drug Treatment of AIDS Complications

Tuberculosis (TB)

The treatment for tuberculosis depends on whether the infection is latent or active.

Latent tuberculosis is treated with isoniazid (which is usually taken with pyridoxine to help prevent peripheral neuropathy) or the combination of rifampin and pyrazinamide. Active tuberculosis is usually treated with a combination of four drugs: isoniazid, rifampin, pyrazinamide and ethambutol. Rifabutin has fewer drug-drug interactions with protease inhibitors. Patients on protease inhibitor regimens should receive rifabutin instead of rifampin for TB treatment. Pyridoxine is also taken as an adjunct to isoniazid to prevent peripheral neuropathy.

Herpes Simplex Virus (HSV)

Herpes cannot be cured but it can be treated. There are three treatments available: acyclovir, valacyclovir and famciclovir. Therapy should be started within 48 to 72 hours of onset of symptoms and continued until lesions are healed, particularly in the immunocompromised, HIV population.

In some rare cases herpes does not respond to these drugs, possibly due to the emergence of resistant strains. The most common treatment for acyclovir-resistant herpes is foscarnet. Foscarnet is available in an intravenous form only and should be reserved for patients who have failed initial treatments of choice.

Therapy should be continued until all lesions are healed, particularly in the immunocompromised, HIV population. Treatment of genital herpes with topical antiviral creams is not recommended.

Candidiasis

There are three types of candidiasis: oral, vaginal and esophageal candidiasis. Oral candidiasis (thrush) is treated with liquids or lozenges containing clotrimazole, nystatin, or miconazole. If these drugs are unsuccessful in the HIV-patient, more potent systemic drugs such as itraconazole or fluconaozle oral suspension can be used. Ketoconazole and itraconazole capsules may be used as second-line therapy. Increasingly, azole resistance has been seen, and treatment with fluconazole higher doses (i.e., 800 mg/day) may be needed.

Uncomplicated vaginal candidiasis can be treated with a short course (1 to 3 days) of vaginal cream or vaginal suppository containing clotrimazole or other topical azole. If unsuccessful, more potent drugs such as oral fluconazole can be used.[1]

Esophageal candidiasis is considered to be more severe and harder to treat than either oral thrush or vaginal yeast infections. The drugs used are oral itraconazole or high dose oral or intravenous fluconazole. Drug-resistant candidiasis may need to be treated with intravenous amphotericin B. Caspofungin and voriconazole are other options.[2]

Non-Hodgkin's Lymphoma (NHL)

Non-Hodgkin’s Lymphomas are malignancies of the lymphoid system and include more than 30 different subtypes, with variable treatments. Standard treatments for lymphoma include surgery, radiation or chemotherapy. For more advanced stages, chemotherapy for Non-Hodgkin's Lymphoma almost always involves a combination of three or more compounds given in cycles, meaning that each treatment is followed by a period of rest. Effectives regimens include:

  • R-CHOP: a combination of rituximab, cyclophosphamide, doxorubicin, vincristine (Oncovin), and prednisone. Radiation therapy may be added in some circumstances.[3]

  • R-EPOCH: a combination of rituximab, etoposide, vincristine, cyclophosphamide, doxorubicin and prednisone.

  • Complete remission has been noted in 50-75 percent of patients with 2-year survival rates also approaching 75 percent.[1]

  • CNS Involvement: being HIV positive is a risk factor for central nervous system (CNS) relapses. Methotrexate or cytarabine are used for instances of bone marrow disease, Burkitt’s Lymphoma, or Epstein-Barr Virus. Hyper-CVAD is a chemotherapy regimen which involves alternating cycles of cyclophosphamide, vincristine, doxorubicin, and dexamethasone with methotrexate and cytarabine.

  • Peripheral-blood autologous stem-cell transplantation in patients with HIV-related lymphoma has been reported as a safe and useful procedure, and is increasingly being used in HIV+ patients with lymphoma.[4]

Chemotherapy can cause CD4 cells and other white blood cells to decrease. This can increase the risk of developing infections like Pneumocystis jiroveci pneumonia (formerly P. carini). It is recommended that all HIV-infected patients undergoing lymphoma chemotherapy receive antimicrobial prophylaxis to prevent PCP (i.e., trimethoprim/sulfamethoxazole).

Chemotherapy can have a serious effect on white blood cell counts (WBCs) and red blood cell counts (RBCs). There are treatments available to help manage these two serious side effects during chemotherapy. For decreased WBCs, filgrastim or sargramostim are usually started within days after chemotherapy is initiated. RBCs can be decreased during chemotherapy, which can cause anemia and fatigue. Blood transfusions are sometimes recommended, along with the drugs leucovorin calcium (Leukovorin) and/or epoetin-alfa (Procrit).

Salmonellosis

Salmonellosis is treated with antibiotics such as ciprofloxacin, ampicillin, ceftiraxone and sulfamethoxazole/trimethoprim. Resistance may occur in some strains, so susceptibility should be checked.

Bacillary Angiomatosis

Bacillary angiomatosis is treated first-line with antibiotics such as erythromycin or doxycycline, usually for a period of at least three months. Azithromycin and clarithromycin are alternatives. If there is CNS involvement in an HIV+ patient, doxycycline with or without rifampin may be used.[5]

Viral Hepatitis B

Chronic viral hepatitis B is common among HIV+ patients due to shared modes of transmission. The usual treatment of interferon alfa 2b is not approved for HIV patients and has not been well studied. The antiretroviral drug tenofovir (TDF or Viread) can be effective in treating chronic hepatitis B, and may be combined with lamivudine (3TC) or emtricitabine (FTC) plus one other HIV treatment. Vaccination is indicated in HIV+ patients who are negative for hepatitis B.

Human Papillomavirus (HPV) - Genital Warts

Immunocompromised patients can be resistant to standard HPV treatment and recurrence is possible. It is important to treat HPV in HIV+ patients to lessen the likelihood of development of squamous cell carcinoma. Treatment depends upon extent of lesions and location (internal or external). Extended treatment periods, a combination of drugs, cryotherapy, or surgical removal may be required in this patient population.

Topical medications such as podophyllotoxin, trichloroacetic acid, and imiquimod are used only for the treatment of genital warts. Podophyllum is not recommended for use anymore due to mutagenic potential. The quadrivalent HPV vaccine Gardasil is currently being investigated for use in HIV+ women.[6]

Other treatments available for refractory HPV in HIV+ patients are procedures to remove or destroy irregular cells such as those that make up genital warts or cervical cancer. Treatment depends on the location and the severity of the disease and can include cryotherapy, laser treatment, LEEP (loop electrical excision procedure), surgery/cold-knife cone biopsy or radical surgery/radiation/chemotherapy.

Cryptosporidiosis

In HIV patients, it is important to maximize highly active antiretroviral therapy (HAART) and restore immune function with CD4 counts above 100 to help control cryptosporidiosis. Nitazoxanide (Alinia) has been shown to be more effective than placebo in cryptosporidial diarrhea in HIV+ patients.[7] Many antiretroviral agents are not well absorbed in HIV patients with cryptosporidiosis. Some clinicians use antiparasitic drugs such as nitazoxanide (Alinia) for treatment of cryptosporidial diarrhea to enhance HAART, but nitazoxanide should not be used alone. Symptomatic treatment, such as atropine/diphenoxylate (Lomotil) or loperamide (Imodium) may also be prescribed. Rehydration and correction of electrolytes may be needed in severe disease.

Pneumocystis Jirovecci Pneumonia (PCP)

Patients with HIV may have symptoms or other risk factors that increase their susceptibility to Pneumocystis Jirovecci Pneumonia (PCP), including: a CD4 count <200 cells/microliter; oropharyngeal candidiasis; a CD4 percentage less than 15%; or a history of an AIDS-defining illness. The initial option for PCP prevention, in patients without contraindications or allergies, is a combination of the oral drugs trimethoprim and sulfamethoxazole (TMP-SMX).

If the patient is not able to use TMP-SMX, other choices might include dapsone, trimethoprim, atovaquone or pentamidine.

Secondary prophylaxis should be started in HIV+ patients who have been treated for an active PCP infection and continued for life unless the CD4 count recovers to >200 cells/microliter for three consecutive months.

In patients infected with mild to moderate PCP, the first-line treatment is also TMP-SMX (oral or IV depending upon symptoms); however, some patients may be allergic, intolerant, or fail treatment with TMP-SMX. In those patients, alternative treatments to TMP-SMX include clindamycin-primaquine (oral), trimethoprim (TMP)-dapsone (oral), or atovaquone (oral). In more severe PCP, IV TMP-SMX is still considered first-line treatment, but other options include clindamycin-primaquine, pentamidine (IV). A corticosteroid taper should also be utilized in PCP.

Kaposi's Sarcoma (KS)

Options for treatment of Kaposi’s Sarcoma (KS) includes antiretroviral therapy, surgery, radiation, and/or chemotherapy. Patients with AIDS-related Kaposi’s Sarcoma should receive highly active antiretroviral therapy (HAART), which may result in resolution of limited cutaneous or systemic disease.

Localized therapies such as topical alitretinoin (Panretin Gel) or locally injected vinblastine treat the lesions, but are generally not effective in prevention. Injected vinblastine may result in excellent cosmetic outcome. Topical alitretinion, applied 3 to 4 times a day, may need to be continued for 2 to 14 weeks. Surgical excision may be used if lesions are cosmetically unacceptable, painful or if spread needs to be controlled. Laser therapy or cryotherapy are alternatives. Lesions which are ulcerated or infected may need to be treated with radiation therapy.

Widespread lesions and/or systemic disease, including lymphatic involvement may require systemic chemotherapy with liposomal anthracyclines, such as doxorubicin (Doxil) or daunorubicin (Daunoxome), which are used as first-line treatment, but myelosuppression may be the main dose-limiting side effect. Paclitaxel or vinorelbine may be appropriate second or third-line options, but due to toxicity are not typically used first-line.

Other systemic visceral treatments include interferon-alpha and single agent chemotherapy such as pegylated liposomal doxorubicin, paclitaxel http://www.drugs.com/mtm/paclitaxel.html, or etoposide http://www.drugs.com/mtm/etoposide.html. Antiinflammatory corticosteroids http://www.drugs.com/drug-class/glucocorticoids.html may help prevent visceral swellings in airways or bowels.

Cryptococcal Meningitis

Cryptococcal meningitis is a fungal infection in the lining of the brain. Immunocompromised patients, such as those with AIDS, are at higher risk of Cryptococcal meningitis, and it is the most common cause of meningitis in AIDS patients who have a CD4 count less than 100 cells/mL.

Preferred drugs used in the initial treatment phase of Cryptococcal meningitis include amphotericin B, flucytosine and fluconazole. Liposomal amphotericin B may be preferred in patients with renal impairment. Fluconazole is also used in the maintenance phase of treatment for Cryptococcal meningitis; itraconazole may be used in patients intolerant of fluconazole, although experience is limited. HAART should be started within 2 to 10 weeks after starting antifungal medications in patients with HIV infection.

Toxoplasmosis

Toxoplasmosis is an opportunistic infection due to Toxoplasma gondii, an obligate intracellular protozoan. Exposure often occurs due to oocysts from cat feces or consumption of undercooked meat. Toxoplasmosis is often the most common nervous system infection in HIV patients with CD4 counts <100 cells/mL.

Toxoplasmosis is initially treated with pyrimethamine, sulfadiazine and leucovorin. Treatment should last for 6 weeks or longer if disease is extensive, followed by chronic maintenance therapy with the same agents.

Progressive Multifocal Leukoencephalopathy (PML)

Progressive multifocal leukoencephalopathy (PML) is a rare and possibly fatal brain disorder due to damaged myelin that covers and shields the nerves in the brain. The JC virus (JCV) leads to PML but most people have this virus by age ten and do not acquire PML; people with compromised immune systems, like AIDS patients are at greater risk for PML.

In people with AIDS, adequate antiretroviral therapy and immune system recovery can lessen the symptoms of PML. No other treatments have proved effective for PML.

Mycobacterium Avium Complex (MAC)

HIV-infected patients with CD4 cell count <50 cells/mL are at increased risk of severe infection with Mycobacterium Avium Complex (MAC), which requires multiple agents for drug treatment. Combined treatment helps to prevent drug resistance and maximizes therapy. Patients with HIV and MAC that have low CD4 counts may present with fevers, sweating, lethargy or exhaustion, stomach pain, and diarrhea. MAC may be treated with the following drugs: clarithromycin, azithromycin, ethambutol, rifampin, rifabutin, ciprofloxacin, and amikacin.

Cytomegalovirus (CMV)

Preventive therapy is key for CMV disease in transplant and HIV patients. Antiviral prophylaxis may be used, and highly active antiretroviral therapy should be used in HIV patients. A specialist consult may be required to determine appropriate therapy or prophylaxis in patients at risk of CMV.

CMV is treated using powerful antiviral drugs. In most cases CMV treatment consists of two phases: induction therapy (to treat the disease) and maintenance therapy (to prevent the virus causing disease again in the future). Intravenous (IV) foscarnet and ganciclovir (IV induction and oral maintenance) can be used to treat CMV retinitis and all other forms of CMV disease. Ganciclovir is the preferred treatment due to lower risk of kidney toxicity compared to foscarnet. Intravenous cidofovir is a third-line option for severe CMV disease, but probenecid must also be taken to prevent kidney damage. Immunoglobulins may also be used as a treatment adjunct in severe CMV cases.

Valganciclovir is the first oral treatment for CMV, but should not be used first-line in the treatment of severe CMV. It may be used as a step-down therapy after initial treatment with IV ganciclovir. Oral ganciclovir should be avoided for CMV treatment due to poor bioavailability.

Ganciclovir implants are used only for the treatment of CMV retinitis and do not prevent CMV disease occurring in other parts of the body, including the other eye. Ganciclovir implants may be used with concomitantly with IV ganciclovir or oral valganciclovir. Fomivirsen is approved for injection into the eye when any of the previous therapies have failed; also used in combination with intravenous ganciclovir or valganciclovir, foscarnet or cidofovir. Fomivirsen is not currently available for prescribing in the US.

AIDS Wasting Syndrome (Cachexia)

AIDS wasting syndrome is the loss of at least 10 percent of your body weight accompanied by at least a month of diarrhea, or weakness and fever. Since the use of highly active antiretroviral medications (HAART), the incidence of AIDS wasting syndrome has dramatically decreased, but patients can still be at risk, especially with the loss of a significant amount of muscle tissue. Continuing on successful antiretroviral medications and lowering the viral load to undetectable levels can lead to increased weight of 10 to 20 percent in one year for many AIDS patients.

There are a number of treatments available to control symptoms of reduced appetite. Drugs commonly used include antiemetics to control nausea and vomiting, antidiarrheals for diarrhea, and appetite stimulants. Treatments such as Marinol (gel-caps containing THC, the active ingredient in marijuana) and megestrol acetate (Megace), a synthetic progesterone, have also been shown to help boost appetite. Megace may lead to increased levels of fat and hypogonadism (lack of sexual hormone) so it is not often recommended. Marinol may lead to drowsiness, dizziness or confusion. AIDS activists has also been instrumental in the legalization of medical marijuana, as it is effective in controlling nausea and stimulating appetite.

Other measures to control diarrhea and boost absorption of nutrients may be added as well. Nutritional supplement drinks such as Ensure or Juven may be helpful.

For more information on new therapies, or to find out more about federally approved treatment guidelines, contact the HIV/AIDS Treatment Information Service at 800-HIV-0440.

See Also:

References

  1. Sexually transmitted diseases treatment guidelines 2002. Centers for Disease Control and Prevention. MMWR Recomm Rep 2002; 51:1
  2. Pappas PG et al: Guidelines for treatment of candidiasis. Clin Infect Dis 2004;38:161
  3. Boué F et al: Phase II trial of CHOP plus rituximab in patients with HIV-associated non-Hodgkin's lymphoma. J Clin Oncol 2006;24:4123-8.
  4. Balsalobre P, Díez-Martín JL, Re A, et al. Autologous stem-cell transplantation in patients with HIV-related lymphoma. J Clin Oncol 2009;27:2192-8.
  5. Kaplan JE et al: Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. MMWR Recomm Rep 2009;58:1.
  6. Kahn J. HPV vaccination in HIV-infected young women: risk perceptions, HPV epidemiology, and immune response. 2nd International Workshop on HIV & Women. January 9-10, 2012, Bethesda, Maryland.
  7. Rossignol JF, et al. A double-blind placebo-controlled study of nitazoxanide in the treatment of cryptosporidial diarrhea in AIDS patients in Mexico. Trans R Soc Trop Med Hyg 1998;92:663–6.

Last updated: 2013-09-20 by Leigh Anderson, PharmD

Hide
(web2)