Drug Treatment of AIDS Complications
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.
Drug-resistant tuberculosis is an increasing problem globally. These strains may have developed resistance to rifampin and isoniazid, and a combination of "second-line" tuberculosis treatments may be needed. Classes used second line might include the fluoroquinolones, such as levofloxacin or moxifloxacin, and the aminoglycoside class of drugs.
Herpes Simplex Virus (HSV)
Genital herpes simplex cannot be cured but it can be treated. There are three oral 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. For more severe forms of herpes, an IV formulation of acyclovir is available.
In some rare cases herpes does not respond to these drugs, possibly due to the emergence of resistant strains and occurring more frequently in patients with HIV. 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.
For HIV patients with recurrent genital herpes, oral antiviral therapy may be given episodically (eg, self-administered as outbreaks occur) or for ongoing suppression (eg, daily treatment to prevent episodes).
Treatment of genital herpes with topical antiviral creams is not recommended.
There are three types of candidiasis: oral, vaginal and esophageal candidiasis. Oral thrush is the most common opportunistic infection in persons with HIV infection. Oral candidiasis (thrush) is treated with liquids or lozenges containing clotrimazole, nystatin, or miconazole; however, nystatin has shown reduced effectiveness compared to clotrimazole 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 at higher doses (eg, up to 800 mg/day) may be needed, or selection of an alternate azole.
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.
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. Treatment may need to continue for up to 21 days. Drug-resistant candidiasis may need to be treated with intravenous amphotericin B, voriconazole, or an echinocandin such as caspofungin, anidulafungin, or micafungin.
Non-Hodgkin's Lymphoma (NHL)
Non-Hodgkin’s Lymphomas (NHL), called AIDS-related lymphoma in HIV, are malignancies of the lymphoid system and include more than 30 different subtypes, with variable treatments. Standard treatments for lymphoma include radiation or chemotherapy. Antiretroviral therapy (ART) should always be started or continued.
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. Therapy must be individualized based on CD4 count. Effective regimens might include:
R-EPOCH: a combination of rituximab, etoposide, vincristine, cyclophosphamide, doxorubicin and prednisone.
Rituximab is not used for NHL that lacks CD20 expression.
Complete remission has been noted in 50-75 percent of patients with 2-year survival rates also approaching 75 percent.
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.
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 is treated with antibiotics such as ciprofloxacin, levofloxacin, cefixime, azithromycin, and sulfamethoxazole/trimethoprim. Resistance may occur in some strains, so susceptibility should be checked.
Bacillary angiomatosis is a Bartonella infection that occurs primarily in immunocompromised persons. 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 for patients who cannot use doxycycline or erythromycin.
Viral Hepatitis B
Chronic viral hepatitis B is common among HIV+ patients due to shared modes of transmission. The antiretroviral drug tenofovir disoproxil fumarate (TDF or Viread) or tenofovir alafenamide (TAF or Vemlidy) can be effective in treating chronic hepatitis B virus.
A tenofovir-containing antiretroviral therapy (ART) regimen containing either tenofovir alafenamide-emtricitabine (Descovy) plus dolutegravir (Tivicay) or elvitegravir-cobicistat-emtricitabine-tenofovir alafenamide (Genvoya) is usually preferred, but TDF may also be used. In studies, TDF was linked with a greater risk of kidney and bone disease based on lab parameters. TAF and TDF should both be avoided in HIV patients with severe kidney impairment.
Hepatitis B vaccination is also indicated in HIV+ patients who are negative for the virus.
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. Patients with HIV infection may have a higher risk of anal cancer.
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 podofilox topical (Condylox), trichloroacetic acid, sinecatechins (Veregen) and imiquimod are used 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.
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.
HPV vaccination is recommended in those with HIV infection as normally indicated by age.
Usually in healthy individuals a cryptosporidium infection leads to watery diarrhea and the infection will resolve within a week or two. If you have a compromised immune system such as with HIV, a cryptosporidium infection can lead to severe diarrhea, weight loss and malabsorption and can be deadly unless proper treatment is given.
In HIV patients, it is important to maximize antiretroviral therapy (ART) and restore immune function with CD4 counts to an appropriate level to help control cryptosporidiosis. Fluid replacement is important to prevent severe dehydration. You'll need to replace minerals such as sodium, potassium and calcium lost from severe diarrhea.
Nitazoxanide (Alinia), an antiparasitic, has been shown to be more effective than placebo in cryptosporidial diarrhea in HIV+ patients. Azithromycin (Zithromax) may also be used with an antiparasitic in severe diarrhea or recurrent disease.
Symptomatic treatment, such as atropine/diphenoxylate (Lomotil) or loperamide (Imodium AD) may also be prescribed, but slowing down the movement of the intestines can be dangerous in some instances, so only take antidiarrheal medication if it has been recommended by your doctor.
To help prevent a cryptosporidium infection, utilize good hygiene and avoiding swallowing water that can be contaminated with the one-celled cryptosporidium parasite. This includes water from pools, recreational water parks, lakes and streams. Cryptosporidium may also be found in improperly cooked, contaminated meat, hand to mouth contact, drinking well water, or by close contact with people or animals who have the parasite. Cryptosporidiosis is highly contagious.
Pneumocystis Jirovecci Pneumonia (PJP)
Patients with HIV may have symptoms or other risk factors that increase their susceptibility to Pneumocystis Jirovecci Pneumonia (PJP) - formerly known as Pneumocystis carinii (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 best to prevent PJP and any complications is by increasing the patient's immune function with ongoing antiretroviral therapy (ART). While immune function is recovering, antibiotic prophylaxis should be given.
The initial option for PJP prevention, in patients without contraindications or allergies, is a combination of the oral drugs trimethoprim and sulfamethoxazole (TMP-SMX), a sulfa-containing regimen. If the patient is not able to use TMP-SMX, other choices might include:
- aerosolized pentamidine.
Desensitization to TMP-SMX might be considered for patients with an appropriate history.
Secondary PJP prophylaxis should be started in HIV+ patients who have been treated for an active infection and continued unless the CD4 count recovers to >200 cells/microliter for three consecutive months.
In patients infected with mild to moderate PJP, 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: TMP + dapsone, clindamycin + primaquine, atovaquone (for more mild disease), or pentamidine (IV, for severe disease). Another option is desensitization to TMP-SMX. Antimicrobial therapy should continue for 21 days.
Glucocorticoids such as prednisone or methylprednisolone should be added to treatment based on lung function and severity of disease (moderate to severe).
AIDS-Related 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 antiretroviral therapy (ART), which may result in resolution of limited cutaneous or systemic disease.
- Injected vinblastine may result in good cosmetic outcome with roughly a 50% reduction in lesions.
- Topical alitretinion gel, applied 3 to 4 times a day, may need to be continued for 2 to 14 weeks. However, alitretinoin can cause skin pigment changes in dark-skinned patients and other options may be preferred.
- 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 liposomal (Doxil) or daunorubicin liposomal (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, or etoposide. Antiinflammatory corticosteroids may help prevent visceral swellings in airways or bowels.
Cryptococcal meningitis is a fungal infection in the lining of the brain caused by Cryptococcus neoformans. 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/mm3.
Preferred drugs used in the initial treatment phase of cryptococcal meningitis include
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 fluconazole may be preferred when possible.
ART should be started within 2 to 10 weeks after starting antifungal medications in patients with HIV infection to help lessen the possible occurrence of an immune reconstitution inflammatory syndrome (IRIS).
Long-term antifungal suppressive therapy with fluconazole should be continued for a minimum of one year after resolution.
Toxoplasmosis is an opportunistic infection due to Toxoplasma gondii, an obligate intracellular protozoan. Exposure commonly occurs due to oocysts from cat feces or consumption of undercooked meat. Toxoplasmosis is the most common nervous system infection in HIV patients with CD4 counts <100 cells/mm3.
Toxoplasmosis is initially treated with:
- pyrimethamine (Daraprim) and sulfadiazine
- leucovorin is given to prevent pyrimethamine-induced blood toxicity
Treatment should last for 6 weeks or longer if disease is extensive, followed by chronic maintenance therapy with the same agents. ART therapy should also be instituted if not currently ongoing. Alternative agents for toxoplasmosis might include clindamycin (Cleocon), given with sulfadiazine and leucovorin; or sulfamethoxazole-trimethoprin.
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, starting or optimizing antiretroviral therapy (ART) to allow immune system recovery can lessen the symptoms of PML. No other treatments have been proven effective for PML.
Mycobacterium Avium Complex (MAC)
HIV-infected patients with CD4 cell count <50 cells/mm3 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 is preferentially treated with clarithromycin plus ethambutol; studies have shown clarithromycin to have better efficacy over azithromycin plus ethambutol. Multi-drug treatment is preferred based on susceptibility testing. MAC may also be treated with the following drugs: azithromycin, rifabutin, ciprofloxacin, levofloxacin, or amikacin.
Prophylaxis for MAC is recommended if CD4 counts are below 50 cell/mm3. Azithromycin or clarithromycin are options for prophylaxis; azithromycin can be dosed weekly and may be a preferred regimen.
Cytomegalovirus is a mild disease that usually does not cause any serious problems in patients with an intact immune system. However, CMV and AIDS-related CMV retinitis can affect patients with immunosuppression and HIV. Preventive therapy is key for CMV disease in transplant and HIV patients. Antiviral prophylaxis may be used, and active antiretroviral therapy should (ART) be used early in HIV patients. CMV retinitis can lead to blindness if not treated. A specialist consult may be required to determine appropriate therapy or prophylaxis in patients at risk of CMV.
Healthy people with no immunosuppression generally do not need any specific drug treatment for CMV. In HIV/AIDS patients, 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). Drugs used in the treatment of CMV include:
- ganciclovir (generics, Vitrasert)
- valganciclovir (Valcyte)
- cidofovir (Vistide)
- foscarnet (Foscavir).
Initial systemic treatment of non-sight threatening CMV disease is usually with oral valganciclovir, as it as effective as the IV therapy. Valganciclovir is the first oral treatment for CMV, but should not be used alone as a treatment of severe, sight-threatening CMV. Intravenous ganciclovir or foscarnet are also options for initial treatment.
For patients with CMV retinitis that is sight-threatening, local ocular therapy as well as systemic therapy is preferred. Local intravitreal injections of ganciclovir or foscarnet plus systemic therapy can be used for sight-threatening disease. Ganciclovir implants (Vitrasert) are used only for the local 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 concomitantly with IV ganciclovir or oral valganciclovir.
Oral ganciclovir should be avoided when possible for CMV treatment due to poor bioavailability; valganciclovir, an orally administered prodrug of ganciclovir, has better oral absorption.
Intravenous cidofovir is another option for severe CMV disease, but probenecid must also be used to prevent kidney damage. It may be considered a 4th line agent if ganciclovir, valganciclovir, or foscarnet cannot be given or tolerated.
Induction antiviral therapy for CMV retinitis is typically given for 2 to 3 weeks. Maintenance therapy is recommended until:
- the patient has dormant retinitis disease
- at least 12 weeks of antiviral treatment of local ocular lesions
- HIV viral load is suppressed, AND
- the CD4 count is ≥100 cells/mm3 for at least three months
Side effects of CMV antivirals can include suppression of white blood cells, red blood cells, and platelets. Kidney function should be closely followed with the use of cidofovir and foscarnet.
AIDS Wasting Syndrome (Cachexia)
The main therapy for AIDS wasting is continued treatment with antiretroviral medications (ART). Since the use of ART, 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. 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. 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)
- Megestrol acetate (Megace), a synthetic progesterone
are approved to treat loss of appetite and weight loss in people with acquired immunodeficiency syndrome (AIDS). These agent have been shown to help boost appetite. Choice may depend upon patient and clinician preferences.
Megace or other steroids may lead to increased levels of fat and hypogonadism (lack of sexual hormone). Marinol may lead to drowsiness, dizziness, confusion and even hallucinations. AIDS activists have 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.
Exercise has been shown to boost lean muscle mass and should be recommended to patients who are able to exercise. In male patients with hypogonadism, testosterone supplementation may increase muscle mass and strength.
For more information on new therapies, or to find out more about federally approved treatment guidelines, access AIDSInfo or call 1- 800-448-0440.
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