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. Pyridoxine is also taken to prevent peripheral neuropathy.

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, probably 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

The three most common types of candidiasis are 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 higher fluconazole doses (i.e., 800 mg/day) may be needed.

Uncomplicated vaginal candidiasis can 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 is 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 includes more than 30 different subtypes, with variable treatments. The 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. Effective 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 being increasingly 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 (PCP) pneumonia (formerly P. carini). It is recommended that all HIV-infected patients undergoing lymphoma chemotherapy receive antimicrobial prophylaxis to prevent PCP (e.g. sulfamethoxazole/trimethoprim).

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 (Neupogen) or sargramostim (Leukine) 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 (food poisoning) is an infection caused by the salmonella bacterium, which is contracted from contaminated food or water. Symptoms include severe diarrhea, fever, chills, abdominal pain and sometimes vomiting. Salmonellosis is treated with antibiotics such as ciprofloxacin, ampicillin, ceftiraxone and sulfamethoxazole/trimethoprim. Resisitance 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 DF (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.^5,6

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 Carinii Pneumonia (PCP)

The most effective treatment for PCP is a combination of the drugs trimethoprim and sulfamethoxazole (TMP-SMX). Unfortunately, many people are allergic to the sulfur in sulfamethoxazole. Alternative treatments for PCP include pentamidine, clindamycin-primaquine, trimethoprim (TMP)-dapsone, Trimetrexate-leucovorin, aerosolized pentamidine (NebuPent) and prednisone, which can be taken to control the symptoms of PCP.

Kaposi's Sarcoma (KS)

KS cutaneous lesions of the skin do not necessarily need to be treated.

There are localized therapies available such as alitretinoin (Panretin Gel) or locally injected vinblastine, which treat the lesions, but are generally not effective in prevention. Systemic therapy can treat and prevent the lesions but has serious side effects. KS lesions in the digestive tract and in the lungs require systemic therapy such as antiretroviral therapy (HAART), Interferon alfa (Roferon-A, Intron A), liposomal chemotherapy (Doxil or DaunoXome) or standard chemotherapy (doxorubicin, vincristine, bleomycin, etoposide, paclitaxel).

Cryptococcal Meningitis

Drugs used in the treatment of Cryptococcal meningitis include amphotericin B, flucytosine and fluconazole.

Toxoplasmosis

Toxoplasmosis is treated with pyrimethamine and sulfadiazine.

Progressive Multifocal Leukoencephalopathy (PML)

Unfortunately, there are no treatments that have proven to be effective for PML.

Mycobacterium Avium Complex (MAC)

MAC is treated with the following drugs: clarithromycin, azithromycin, ethambutol, rifampin, rifabutin, ciprofloxacin, and amikacin.

Cytomegalovirus (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 foscarnet and ganciclovir (IV induction and oral maintenance) can be used to treat CMV retinitis and all other forms of CMV disease. IV cidofovir (probenecid must also be taken to prevent kidney damage) has been studied only for CMV retinitis but may also be effective for other forms of the disease.

Valganciclovir is the first oral treatment for CMV. 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. Fomivirsen is approved for injection into the eye when any of the previous therapies have failed.

Wasting Syndrome

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 have also been shown to help boost appetite.

For more information on new therapies, call the AIDS Clinical Trials Information Service at 800-TRIALS-A. If you'd like to find out more about federally approved treatment guidelines, contact the HIV/AIDS Treatment Information Service at 800-HIV-0440.