Drug Treatment of HIV and AIDS Complications
Medically reviewed by Leigh Ann Anderson, PharmD. Last updated on Oct 15, 2019.
Acquired immunodeficiency syndrome (AIDS) is a lifelong, and potentially life-threatening condition caused by the human immunodeficiency virus (HIV). You can acquire HIV by direct contact with body fluids that contain the HIV virus, such as blood, semen, vaginal fluids, mother-to-child transmission during pregnancy, labor and delivery, or via breast milk.
AIDS is an advanced stage of the HIV virus, where serious infections, called opportunistic infections may arise. Opportunistic infections occur in HIV because the virus interferes with your body's ability to fight the organisms that cause disease. AIDS-defining conditions include opportunistic infections and cancers that are life-threatening in a person with HIV/AIDS.
People living with a weakened immune system due to HIV/AIDS are susceptible to these opportunistic infections, cancers, and other AIDS-defining conditions. When someone with HIV is diagnosed with an AIDS-defining condition, they are then diagnosed with AIDS, the most advanced stage of HIV.
List of AIDS-defining conditions from the U.S. Centers for Disease Control and Prevention (CDC):
- Bacterial infections, multiple or recurrent
- Candidiasis of bronchi, trachea, or lungs
- Candidiasis of esophagus
- Cervical cancer, invasive
- Coccidioidomycosis, disseminated or extrapulmonary
- Cryptococcosis, extrapulmonary
- Cryptosporidiosis, chronic intestinal (>1 month's duration)
- Cytomegalovirus disease (other than liver, spleen, or nodes), onset at age >1 month
- Cytomegalovirus retinitis (with loss of vision)
- Encephalopathy, HIV-related
- Herpes simplex: chronic ulcers (>1 month's duration) or bronchitis, pneumonitis, or esophagitis (onset at age >1 month)
- Histoplasmosis, disseminated or extrapulmonary
- Isosporiasis, chronic intestinal (>1 month's duration)
- Kaposi sarcoma
- Lymphoma, Burkitt (or equivalent term)
- Lymphoma, immunoblastic (or equivalent term)
- Lymphoma, primary, of brain
- Mycobacterium avium complex or Mycobacterium kansasii, disseminated or extrapulmonary
- Mycobacterium tuberculosis of any site, pulmonary, disseminated, or extrapulmonary
- Mycobacterium, other species or unidentified species, disseminated or extrapulmonary
- Pneumocystis jirovecii pneumonia (previously known as Pneumocystis carinii)
- Pneumonia, recurrent
- Progressive multifocal leukoencephalopathy
- Salmonella septicemia, recurrent
- Toxoplasmosis of brain, onset at age >1 month
- Wasting syndrome attributed to HIV
Today, opportunistic infections are not as common as they were in the past due to advances in antiretroviral therapy (ART) used for HIV treatment. The best way to prevent an opportunistic infection is to get tested for HIV, and if needed, take your HIV medication without fail as directed by your healthcare provider.
Tuberculosis is a respiratory disease that is spread by breathing in the Mycobacterium tuberculosis bacteria from others with an active infection. When some with active TB sneezes, cough or speaks, someone close by can breath in the bacteria and become infected. TB usually affects the lungs and is the most common cause of death among people with AIDs.
If you have received an HIV or TB diagnosis you should be tested to see if you have both infections. Co-infection with HIV and TB can make both infections worse. TB is considered an “AIDS-defining condition” and is one of the leading causes of death among people with HIV. All patients with HIV and TB should be started on ART.
The treatment for tuberculosis depends on whether the infection is latent or active.
- People with latent TB infection do not have symptoms and cannot spread TB bacteria to others.
- People with active TB disease have symptoms of the disease and are contagious (meaning they can spread TB).
Your TB treatment regimen will depend upon your age, overall health, severity of TB, possible drug interactions with rifamycins, where you live, and if you have drug-resistant TB.
Common Tuberculosis (TB) Medications
|Generic name||Brand name examples|
|rifampin, rifapentine, or rifabutin (rifamycins)||Rifadin, Rimactane, others|
|pyrazinamide (PZA)||not available|
Treatment for latent TB is important to reduce the risk for worsening of your TB disease and to prevent spreading and will usually take at least 3 to 9 months. Treatment for active TB disease will usually take 6 to 9 months, but longer treatment may be needed.
If you have latent TB, you may only need to take 1 or 2 drugs. Active tuberculosis is usually treated with a combination of several drugs, especially if drug resistance is present.
Pyridoxine (25 mg/day) is also taken with isoniazid to prevent peripheral neuropathy. Rifabutin has fewer drug interactions with antiretroviral agents than rifampin, but may not be as accessible or affordable.
According to the CDC, twelve weeks of once-weekly isoniazid and rifapentine is recommended for persons with latent TB infection and HIV and who are taking ART with acceptable drug interactions with rifapentine.
For active TB disease in adults infected with HIV, the CDC recommends a 6 to 9-month daily regimen consisting of:
- isoniazid (INH), a rifamycin, pyrazinamide, and ethambutol (EMB) for the first 2 months (given five to seven days per week)
- a continuation phase of INH and a rifamycin for the last 4 or 7 months (given five to seven days per week).
Drug-resistant tuberculosis is an increasing problem globally, with resistance growing to rifampin and isoniazid. Treatment of drug-resistant, multi-drug resistant, or extensively drug-resistant strains may require 5 or more drugs and last for 20 to 30 months. Drugs that may be included for treatment of resistant TB infections include:
- fluoroquinolones (levofloxacin or moxifloxacin)
- amikacin, an aminoglycoside
- capreomycin (Capastat)
- bedaquiline (Sirturo)
- linezolid (Zyvox)
In August 2019, the FDA approved oral pretomanid tablets, an antimycobacterial, used in combination with bedaquiline (Sirturo) and linezolid (Zyvox) for the treatment of adults with extensively drug resistant (XDR), treatment-intolerant or nonresponsive multidrug-resistant (MDR) pulmonary tuberculosis (TB). Pretomanid comes from The Global Alliance for TB Drug Development.
- MDR TB and XDR TB are difficult to treat due to drug resistance and lack of effective options.
- In studies, 95/107 patients (89%) had success with the 3-drug combination, which significantly exceeded the historical success rates for treatment of XDR TB.
- Side effects reported were nerve damage (peripheral neuropathy), acne, anemia, nausea, vomiting, headache, increased liver enzymes, indigestion (dyspepsia), and rash, among others.
Genital herpes simplex virus (HSV) cannot be cured but it can be treated. Genital herpes is most commonly caused by the HSV-2 virus. HSV-1 more commonly causes sores on the face, mouth, and lips. The virus spreads through sexual contact and skin-to-skin contact, even if you do not have an open sore. In HIV-infected patients who are highly immunosuppressed, HSV recurrences are a common problem. Drugs used in the treatment of HSV in patients with HIV generally follows the same recommendations as non-HIV patients.
There are three antiviral oral treatments available:
Effectiveness is similar among these agents, and these agents are usually well-tolerated.
- For an initial episode genital HSV infection, 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 recurrent episodes, start treatment within 24 hours of symptom onset. For more severe forms of HSV, such as severe ulceration or CNS involvement, an IV formulation of acyclovir is available.
In some rare cases HSV does not respond to these drugs due to the emergence of resistant strains. Drug resistance should be suspected if there is no improvement in lesions after one to two weeks of drug therapy. Resistance to one antiviral usually means resistance all oral antiviral treatments, as they all work the same way.
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 (self-administered as outbreaks occur) or for ongoing suppression (eg, daily treatment to prevent episodes). Drug doses for episodic or suppressive therapy may need to be higher for HIV-infected patients. Patients with HIV and an occurrence of acyclovir-resistant herpes should be maintained on daily suppressive antiviral therapy.
There are several types of candidiasis: oral, vaginal and esophageal candidiasis. Oral candidiasis (also known as thrush) is the most common opportunistic infection in patients with HIV. It is usually caused by the Candida albicans organism, but other Candida species have been identified. In HIV-infected patients, oral candidiasis is most often observed in patients with CD4 counts <200 cells/µL.
The incidences of oral thrush and esophageal candidiasis have dramatically declined since the introduction of antiretroviral therapy. Being on effective HIV treatment will lower your risk for candidiasis and recurrent infections.
The initial episode of mild thrush in patients with HIV can be treated for 7 to 14 days with liquids or lozenges containing:
Nystatin suspension has shown reduced effectiveness for oral thrush when compared to clotrimazole or miconazole.
Other options may be needed for recurrent thrush, more severe disease, with advanced immunosuppression, or for those at risk of esophageal candidiasis. These agents include:
- fluconazole tablets are often selected as a drug of first choice due to effectiveness, tolerability, and lower cost. It also provides coverage for esophageal candidiasis.
- Other azole options include: itraconazole, voriconazole, and posaconazole.
- itraconazole capsules should not be used because they have variable absorption which may affect efficacy.
- posaconazole (Noxafil) oral suspension is indicated for the treatment of oropharyngeal candidiasis, including cases that do not respond to itraconazole and/or fluconazole, in patients 13 years or older.
Note - Boxed Warning: Because ketoconazole tablets have been associated with serious adverse effects, ketoconazole tablets are not indicated for the treatment of onychomycosis, cutaneous dermatophyte infections, or Candida infections. Use ketoconazole only when other effective antifungal therapy is not available or tolerated and the potential benefits are considered to outweigh the potential risks. Cases of hepatotoxicity, including fatal cases and cases requiring liver transplantation, have occurred with use of ketoconazole.
Prevention: Oral fluconazole is an effective prophylactic therapy for prevention of oropharyngeal candidiasis; however most clinicians do not recommend this option. Treatment for acute infection is very effective and oral candidiasis is not linked with frequent complications, but side effects may occur.
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. A one or 3-day course of oral fluconazole can also be used.
Esophageal candidiasis is considered to be more severe and harder to treat than either oral thrush or vaginal yeast infections. It should only be treated with systemic therapy; not local agents.
- Oral fluconazole is often selected as a drug of first choice; itraconazole, voriconazole or posaconazole may also be options. Treatment may need to continue for up to 21 days.
- Drug-resistant esophageal candidiasis may need to be treated with intravenous amphotericin B or an echinocandin such as caspofungin, anidulafungin, or micafungin.
Chronic hepatitis B virus (HBV) is a serious liver infection caused by the hepatitis B virus (HBV) that lasts for more than six months. Your risk of developing liver failure, liver cancer, or liver cirrhosis - a permanent scarring of your liver - is increased with chronic HBV. A vaccine is available to prevent hepatitis B virus.
Hepatitis B is transmitted via blood, semen, or another body fluid from sexual contact, sharing needles and syringes, or from mother to baby at birth.
Chronic HBV is common among patients with HIV due to shared modes of transmission, such as sexual contact or drug use. Chronic HBV can lead to serious health issues, like cirrhosis or liver cancer. Patients with HIV should receive treatment to treat both HIV and HBV, both of which are life-long treatments.
- The antiretroviral drug tenofovir disoproxil fumarate (TDF or Viread) or tenofovir alafenamide (TAF or Vemlidy) are effective in treating chronic hepatitis B virus.
- A tenofovir-containing antiretroviral therapy (ART) regimen containing these agents is often preferred:
TDF has a greater risk of bone and kidney toxicity than TAF, as well as a possibility of more drug interactions. In general, TAF-based regimens may be preferable in those who have concerns with renal dysfunction or bone marrow density.
Hepatitis B vaccination is also indicated in patients with HIV who are negative for the virus. Alcohol use should be avoided if you have HBV as it will worsen your liver damage.
Patients with HIV/AIDS may have symptoms or other risk factors that increase their susceptibility to Pneumocystis pneumonia (also called PCP or PJP). This lung infection is caused by a fungus called Pneumocystis jirovecii.
People with a healthy immune system rarely get Pneumocystis pneumonia, as the fungus can live in their lungs without causing symptoms. Up to one-fifth of adults might carry this organism at any one time, but healthy immune systems are able to clear the fungus.
Today, most patients with HIV/AIDS who develop Pneumocystis pneumonia have a weakened immune system (i.e., CD4 counts <100 cells/mm3) and are not following an ART regimen for HIV treatment. Other risk factors include:
- a CD4 count <200 cells/microliter
- oropharyngeal candidiasis, an oral fungus infection
- a low CD4 cell percent <14%
- a history of an AIDS-defining illness.
In people with HIV/AIDS, Pneumocystis pneumonia symptoms usually develop over several weeks and may include a cough, fever, chills, fatigue, chest pain, and trouble breathing. While immune function is recovering, antibiotic prophylaxis (prevention) should be given.
Treatment for Pneumocystis pneumonia
The initial, preferred option for Pneumocystis pneumonia prevention, in patients without contraindications or allergies, is a combination of the oral drugs trimethoprim and sulfamethoxazole (TMP-SMX), a sulfa-containing regimen. Based on severity of disease patients may receive oral or intravenous treatment. Therapy is typically given for 3 weeks, and drug resistance with TMP-SMX is uncommon. Outpatient therapy with oral TMP-SMX is highly effective in patients with mild-to-moderate disease. Adjust doses of TMP-SMX with kidney impairment.
Desensitization to TMP-SMX in patients with non-life threatening allergies might be considered. Desensitization is the process of safely administering a medication to an allergic patient to eliminate the allergic response.
Second line choices, all given for 21 days, include:
- trimethoprim (TMP) + dapsone - (oral)
- use dapsone with caution in patients with hypersensitivity to other sulfonamides; sulfone reactions may also occur as potentially fatal hypersensitivity reactions, requiring drug discontinuation
- atovaquone suspension - oral, for mild-to-moderate disease
- clindamycin (oral) + primaquine (intravenous or oral) for moderate-to-severe disease
- pentamidine (intravenous) for severe disease; do not use aerosolized pentamidine for treatment due to limited efficacy.
Patients with severe symptoms may need to stay in the hospital for treatment.
Glucocorticoids such as prednisone or methylprednisolone should be added to treatment based on lung function and severity of disease. Corticosteroids will help to decrease swelling and make it easier to breathe. Added oxygen may be needed as well.
Test patients receiving dapsone or primaquine for G6PD deficiency due to risk of hemolytic anemia.
Prevention of Pneumocystis pneumonia (prophylaxis)
Pneumocystis pneumonia prophylaxis (prevention) should be started in HIV/AIDS patients who have been treated for an active infection and continued unless the CD4 count recovers to >200 cells/microliter and viral load is undetectable for three consecutive months. The risk for a recurrent episode of Pneumocystis pneumonia is over 60% in patients who are not receiving ART and who do not receive prophylaxis.
- In patients with mild to moderate disease, the first-line treatment is TMP-SMX (oral or IV depending upon symptoms); however, some patients may be allergic, intolerant, or fail treatment with TMP-SMX.
- Doses include either one double strength TMP-SMX daily, one single-strength TMP-SMX daily, or one double strength TMP-SMX three times weekly, based on tolerance.
- Treatment with TMP-SMX should be permanently stopped if instances of severe adverse reactions, such as Stevens-Johnson syndrome or toxic epidermal necrolysis, occur. Alternate treatments should be used.
- In those patients, alternative treatments to TMP-SMX for prophylaxis include:
- Patients receiving pyrimethamine and sulfadiazine for treatment or suppression of toxoplasmosis do not require additional prophylaxis for Pneumocystis pneumonia.
The best way to prevent Pneumocystis pneumonia and any complications is by increasing immune function with ongoing antiretroviral therapy (ART) and adherence to treatment. If not already started, ART should be initiated in patients, when possible, within 2 weeks of diagnosis of Pneumocystis pneumonia.
Paradoxical immune reconstitution inflammatory syndrome (IRIS) following an episode of PCP is rare but has been reported. Symptoms include cough and worsening of pulmonary symptoms. IRIS tends to occur within week of diagnosis. Use of corticosteroid therapy may be indicated, although, treatment is not well defined.
Kaposi sarcoma (KS), also called Kaposi's sarcoma, is the most common AIDS-related cancer. It is caused by a herpes virus which lead to cancer of the blood capillary vessel wall. Abnormal growth of these vessels leads to symptoms like pink, red or purple lesions on the skin, mouth, genital area, or lymph nodes. Lesions can occur internally in organs, too, such as the lungs. As with other AIDS-related opportunistic infections, the incidence of KS has dramatically fallen since the introduction of ART regimens.
Options for treatment of Kaposi sarcoma includes antiretroviral therapy, surgery, radiation, and/or chemotherapy. Patients with AIDS-related Kaposi sarcoma should start antiretroviral therapy (ART), if they are not on treatment, which may result in full resolution of KS lesions, and no other treatments may be needed.
Local treatments for small skin lesions include:
- Minor surgery (excision)
- Burning (electrodessication) or freezing (cryotherapy)
- Low-dose radiation for ulcerated lesions or for multiple skin lesions
- Injection of the chemotherapy drug vinblastine directly into lesions
- Application of a topical vitamin A-like drug (retinoid) known as alitretinoin (Panretin Gel), for 2 to 14 weeks.
- Alitretinoin can cause skin pigment changes in dark-skinned patients.
Localized therapies such as topical alitretinoin (Panretin Gel) or locally injected vinblastine treat the lesions, but are generally not effective in prevention.
Toxoplasmosis is an opportunistic infection due to Toxoplasma gondii, a common parasite. Exposure or reactivation of the latent organism in patients with HIV/AIDS often leads to symptoms within the central nervous system (CNS). Exposure commonly occurs due to oocysts from cat feces or consumption of undercooked meat. Toxoplasmosis is the most common CNS infection in patients living with HIV/AIDS with CD4 counts <100 cells/mm3.
Symptoms in patients with HIV/AIDS include:
- lung problems that resemble Pneumocystis pneumonia
- blurred vision
- First-line oral therapy as recommended by the CDC: pyrimethamine (Daraprim) + sulfadiazine + leucovorin. Pyrimethamine may prevent your body from absorbing the B vitamin folate (folic acid) so leucovorin (folinic acid) is given to prevent blood toxicity.
- Alternative agents for toxoplasmosis in patients who fail or cannot use first-line treatment includes clindamycin (Cleocin), given with pyrimethamine and leucovorin (if the patient has a hypersensitivity reaction to sulfa drugs. Clindamycin is available orally or parenterally.
- TMP-SMX (intravenous) can be used in severely ill patients who cannot take oral therapy.
- Atovaquone + pyrimethamine + leucovorin; or atovaquone + sulfadiazine are also options.
Treatment should last for 6 weeks or longer if disease is extensive. An ART regimen should also be instituted if not currently ongoing.
Prophylaxis against Toxoplasma gondii encephalitis
- TMP-SMX double-strength (DS), one tablet daily, is recommended by the CDC as the preferred regimen (also effective for Pneumocystis pneumonia prophylaxis). TMP-SMX DS, three times weekly, is an alternative.
- Dapsone + pyrimethamine + leucovorin is an alternative in patients who cannot tolerate TMP-SMX (also effective against Pneumocystis pneumonia).
- Atovaquone with or without pyrimethamine/leucovorin also can be considered.
- Aerosolized pentamidine is not recommended for prophylaxis.
Prophylaxis against toxoplasmosis should be discontinued among patients who have responded to an ART regimen with an increase in CD4+ counts to >200 cells/µL for at least 3 months.
Cytomegalovirus (CMV) is a mild disease that usually does not cause any serious problems in patients with an intact immune system. The CMV virus can lie latent (inactive) in the body and then lead to infection, such as AIDS-related CMV retinitis when immunosuppression occurs. CMV can affect not only the eyes, but other organs such as the lungs, digestive tract, and brain.
CMV retinitis can lead to blurring, progressive loss of vision, and blindness if not treated. Complications due to CMV in patients with HIV/AIDS are uncommon today since the advent of antiretroviral therapy should (ART). However, because CMV can lead to loss of vision, it is important for people with HIV/AIDS with weak immune systems to schedule regular eye exams to detect CMV early. The best way to prevent complications from CMV is to take your antiretroviral therapy daily as prescribed.
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)
- maintenance therapy (to prevent the virus from causing future disease)
Drug Treatment of CMV Retinitis:
- Initial systemic treatment of non-sight threatening CMV disease is usually started with oral valganciclovir.
- For patients with CMV retinitis that is sight-threatening, local ocular therapy (intravitreal injections of ganciclovir or foscarnet) as well as systemic therapy, such as oral valganciclovir, is preferred.
- Oral ganciclovir should be avoided when possible for CMV treatment due to poor bioavailability. Oral valganciclovir, a prodrug of ganciclovir, has better oral absorption.
- Ganciclovir implants (Vitrasert) have been discontinued by the manufacturer.
Ganciclovir gel (Zirgan ophthalmic gel) is not used to treat CMV retinitis; it is used to treat eye ulcers caused by the herpes simplex virus (HSV).
Induction antiviral therapy for CMV retinitis is typically given for 2 to 3 weeks. Maintenance therapy is recommended until the disease is stable, antiviral treatment has continued for 12 weeks, AND the CD4 count is ≥100 cells/mm3 for at least three months.
Intravenous cidofovir is an option for severe CMV disease, but is associated with significant renal toxicity. In patients receiving cidofovir, probenecid must be given with adequate hydration to help prevent kidney damage. Kidney function should be monitored. Cidofovir is usually only considered if other options are not tolerated or available.
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.
|For more information and dosing options: Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV|
Learn More: Slideshow - HIV & AIDS Update: New Treatments, Easier Options
For more information on AIDS/HIV treatment guidelines or clinical trials go to AIDSInfo sponsored by the National Institutes of Health (NIH). You may also contact them at 1-800-HIV-0440 (1-800-448-0440).
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