Medical Drugs

HIV and AIDS Drug Medical Treatment

Introduction

Barely 25 years ago few people knew what the words AIDS and HIV meant. Now not only are red ribbons the standard attire on guests at television awards shows, but there are specific lines of clothing and cell phones dedicated to raise money and awareness of this deadly virus.

What is it?

AIDS stands for Acquired Immune Deficiency Syndrome. People with AIDS are infected with the human immunodeficiency virus (HIV), a virus that damages the immune system. Since the immune system protects the body from illness, people with AIDS are more susceptible to all sorts of other health problems. Currently, AIDS cannot be cured. However, AIDS has evolved from a relatively untreatable, almost always fatal disease into a complex, long-term illness for which patients and their caregivers have numerous treatment options. Therapies have been developed to treat both the virus itself and its associated complications.

What causes it?

Acquired Immune Deficiency Syndrome, or AIDS, is caused by an infection with a specific virus - human immunodeficiency virus (HIV). AIDS is the last stage of the HIV infection. When HIV enters the body, it attacks special white blood cells that are part of your body's immune system. These cells, called CD4 cells or T cells, play an important role in fighting infections as well as in directing other cells to find and destroy disease-causing organisms. After invading a cell, HIV releases an enzyme called reverse transcriptase that helps it grow and multiply inside the CD4 cell. HIV then uses another enzyme, protease, to make pieces of virus to spread throughout the body. As HIV disables and kills more and more CD4 cells, the body's ability to fight infection weakens.

AIDS is diagnosed when CD4 cell count drops below 200 cells per cubic millimeter of blood. (Healthy adults usually have CD4 counts of 1000 or more). A diagnosis of AIDS is also given when one or more of the 26 clinical conditions that often affect people with advanced HIV disease are present. Most of these conditions are infections that generally do not affect healthy people. In individuals with AIDS, these infections are often severe and sometimes fatal because the immune system is so weakened by HIV that the body cannot fight off certain bacteria, viruses, fungi, other microbes,and even certain cancers.

Who has it?

AIDS can strike individuals in all ethnic groups, ages, sexes, and sexual orientations. According to the World Health Organization (WHO), as of November, 2007, 33.2 million people worldwide were living with HIV/AIDS, with approximately 68% (22.5 million) of these people live in Sub-Saharan Africa and 50% being of the male gender. In the year 2006, 4.3 million individuals were diagnosed with HIV, which means that roughly 14,000 individuals were diagnosed each day. Approximately 95% of those new infections are occurring in developing countries such as: Bangladesh, Pakistan, Indonesia, Papua New Guinea, and Vietnam. Also, in the year 2006, there was an estimated 2.9 million deaths associated with HIV/AIDS.HIV continues to be one of the major causes of death globally, and it is the number one cause of death in sub-Sahara Africa.

As of March 2008, in the United States, it is estimated that 1.2 million residents are living with HIV/AIDS, 25% of whom are unaware that they are infected. Approximately 40,000 new cases are diagnosed each year, with 70% being males and 50% being individuals under the age of 25.

What are the risk factors?

HIV infection is spread by the transmission of body fluids from a person who is infected with HIV. Anybody, regardless of age, geographic location, gender, or sexual preference is at risk for HIV. For example, any of the following are ways of contracting HIV:

• Having unprotected sex, including vaginal, oral, and anal (without a latex condom) with a person who is infected with HIV whether they are heterosexual, homosexual, or bisexual.
• Having STI?s (sexually transmitted infections) such as syphilis, herpes, chlamydia, or gonorrhea.
• Sharing a needle or syringe with an HIV-positive individual.
• Receiving an HIV-contaminated blood transfusion or any blood product prior to 1985.
• Being born to or breastfeeding from an un-medicated HIV-positive woman.
• Breaking the skin with an injury from medical equipment that has been in contact with HIV-infected fluids. (eg. accidentally pricking the finger with a needle that was used in an HIV-positive patient)
• Receiving an HIV-contaminated organ transplant (very rare).
• Undergoing dental procedures done with improper sanitation of dental equipment that has been in contact with HIV (very rare).
• Getting a tattoo or body piercing with equipment that was not sanitized properly, or with needles that have been reused.

Within the past 15 years, many efforts have been made to reduce the risk of being infected with HIV. For instance, since 1985 the American blood supply has been tested for HIV, making infections through blood transfusions very rare. HIV infection is NOT spread by:

• Air
• Food
• Water
• Insects (including mosquitoes and bedbugs)
• Animals
• Non-infected people wanting to donate blood
• Everyday, casual contact with people who are HIV-positive (eg. sharing food, utensils, towels, bedding, telephones, toilet seats, swimming pools, and hand shaking)
• Saliva from kissing, sweat, tears, urine, feces

What are the symptoms?

A person who has been infected with HIV is usually referred to as being "HIV-positive". The time between a diagnosis of HIV and the onset of AIDS can vary greatly. Whereas many HIV-positive individuals remain symptom-free for several years, most will develop at least some AIDS-related condition within 10 years.

Many people do not develop any symptoms when they first become infected with HIV. Others may suffer a brief flu-like illness, with symptoms that may include the following:

• Fever
• Headaches
• Tiredness
• Sore throat
• Swollen glands
• Muscle and joint pain

As the immune system loses its ability to fight infection, serious illnesses, called opportunistic infections, may appear. Opportunistic infections result when microorganisms that do not ordinarily cause problems in healthy people take advantage of a weakened immune system and attack the body. Common sites for some of these infections are the following:

• Esophagus
• Lungs
• Brain or spinal cord
• Retina (an organ located behind the eye that is ultimately responsible for vision)

Symptoms of opportunistic infections can include the following:

• Upset stomach
• Vomiting
• Diarrhea
• Stomach cramps
• Coughing
• Fever
• Headaches
• Vision loss
• Weight loss
• Tiredness, lack of energy
• Painful swallowing
• Mental symptoms including confusion and forgetfulness
• Seizures, lack of coordination

How is it treated?

AIDS has no cure and there are currently no FDA-approved vaccines to protect against HIV, but there are vaccines that are currently being studied. However, medications can slow the progress of the disease, which allows patients to stay healthier and live longer. The drugs used to treat HIV infection are called antiretrovirals, because they fight HIV, which is a type of "retrovirus."

The goals of therapy are to:

• Suppress viral load (or the amount of HIV in a sample of blood)
• Restore or preserve immune function
• Improve quality of life
• Reduce morbidity (the occurrence of opportunistic infections or number of hospitalizations) and mortality (death)
• Reduce the transmission of HIV/AIDS

The six types of currently FDA-approved antiretroviral medications used to treat HIV and AIDS are:

1. Nucleoside Reverse Transcriptase Inhibitors (NRTIs), which includes Nucleotide Analogs
2. Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
3. Protease Inhibitors
4. Fusion Inhibitors, sometimes also referred to as Entry Inhibitors
5. CCR5 Entry Inhibitors, sometimes also referred to as CCR5 Co-receptor Antagonist
6. Integrase Inhibitors

How These Drugs Work:

Antiretroviral drugs inhibit the growth and replication of HIV at various stages of its life cycle. NRTIs interrupt an early stage of the virus replication process (or interrupt the virus from making copies of itself). NRTIs help to slow the spread of HIV in the body and delay the start of other opportunistic infections. NNRTIs keep the enzyme called "reverse transcriptase" from working so viral cells cannot reproduce. Protease Inhibitors interrupt virus replication at a later step in the HIV life cycle. Nucleotide Analogs prevent the HIV cells from producing new virus and decrease the amount of HIV in the body. Fusion Inhibitors bind to HIV and prevent the virus from infecting healthy cells in the body. CCR5 Entry Inhibitors work by binding to CD4 cells and prevent the HIV virus from entering CD4 cells. Integrase Inhibitors work by stopping viral genetic material from being integrated into healthy host cell genetic material.

Recommended Treatment Options:

According to the guidelines for the use of antiretroviral agents,

• treatment is typically not started in individuals who have a CD4+ T cell count of greater than 350 cells/mm3 and plasma HIV RNA levels of less than 100,000 copies/mL.
• clinicians may consider starting therapy for individuals who have a CD4+ count of more than 350 cells/mm3 and a plasma HIV RNA level of more than 100,000 copies/mL and are not showing signs or symptoms of HIV, whereas some clinicians may choose to delay starting therapy.
• individuals who have a CD4+ count of 201to 350 cells/mm3 and any level of plasma HIV RNA are offered the option to start treatment, but it is up to the individual.
• treatment is recommended in those individuals who have a CD4+ count of less than 200 cells/mm3 even if they are not showing signs or symptoms of HIV/AIDS.
• treatment is recommended in those individuals who have severe symptoms of HIV infection or who have a history of AIDS-defining illnesses (such as multiple/recurrent bacterial infections, recent pneumonia, fungal infection in the esophagus, herpes simplex virus, kaposi's sarcoma-a type of skin cancer, burkitt's lymphoma-a type of cancer, invasive cervical cancer, as well as any other opportunistic infections just to name a few) no matter what their CD4+ count is.

Highly Active Anti-Retroviral Therapy (HAART) is a combination of different classes of drugs that are used to treat HIV/AIDS. This therapy focuses on maximizing suppression of the individual's symptoms of HIV and prolonging the development of opportunistic infections. The treatment guidelines recommend two different types of regimens for those individuals who have not been placed on HAART before. Both regimens include the use of 2 NRTIs as the basis of therapy. One of the regimens recommends the additional use of 1 NNRTI agent (so, 2 NRTIs plus 1 NNRTI) while the other recommends the additional use of 1 to 2 PIs (so, 2 NNRTIs plus 1 to 2 PIs). Studies have shown that the combination of zidovudine, lamivudine (both are NRTIs ), and efavirenz (an NNRTI) is a regimen that is superior over other regimens for initial therapy.Fusion inhibitors, CCR5 Co-Receptor Antagonists, and Integrase Inhibitors are typically used in place of protease inhibitors, NRTIs, or NNRTI in cases of resistant HIV.

Unfortunately, the HIV/AIDS virus typically becomes resistant to medications due to viral mutations or changes. Also, over time, individuals may become intolerant to the medication or the medication?s side effects which can be very unpleasant. With resistance developing or if medication intolerance occurs, 1 to 2 medications might have to changed at some point during therapy.

Combination Medications:

Due to the need of a large number of medications used to treat HIV, drug companies have started to create combination medications. Some of these combination medications contain up to three different HIV medication ingredients to help reduce the number of pills taken per day and to help individuals remember to take all medications. Here is a list of all currently available combination medications: Trizivir, Epzicom, Truvada, Combivir, and Atripla. Some of the combination medications contain drugs from the same class, but not all of them.

Resistance Testing:

When individuals who are infected with HIV become resistant to a particular treatment regimen, a new regimen should be tried. But how do doctors know if the new treatment will work? Persons who fail a certain combination of antiretroviral drugs can undergo resistance testing (sometimes called genotype testing) before starting a new treatment regimen. This type of testing may help health care providers find the most effective treatment regimen for the resistant infection. Also, since resistant HIV can be transmitted to others, some newly diagnosed patients who have not been on antiretroviral drugs previously may also undergo resistance testing to find the most appropriate drugs even before beginning treatment.

The treatment guidelines provide recommendations on when an individual should have resistance testing done. Resistance testing should be performed in those individuals who:

• have an acute HIV infection and therapy is going to be started (often times an acute infection goes unrecognized as it presents with similar symptoms to the flu and other illnesses, symptoms include: fever, rash, headache, nausea/vomiting, weight loss. HIV RNA tests are done to then confirm diagnosis.)
• have a chronic HIV infection and therapy is going to be started
• have suboptimal viral load reduction

Resistance testing should be considered in those individuals who have an acute HIV infection, but therapy is going to be started at a later time. However, resistance testing may not be beneficial for all patients with HIV/AIDS. Your doctor can decide if resistance testing is right for you.

Finally, it is important to note that individuals who are infected with HIV should seek medical care from doctors who are specially trained and have expertise in treating HIV/AIDS. We are learning more and more about HIV/AIDS on a daily basis. Research into new drug therapies and treatments is ongoing. Seeking medical care from an HIV/AIDS specialist will help you ensure that you are receiving the most cutting-edge therapy and care. An HIV/AIDS specialist will best be able to determine when to start HIV treatment and what HAART regimen is best.

Drug classes used to treat HIV and AIDS

1. Combination Antiretroviral Medications

• Combination antiretroviral medications have been developed to help reduce the number of pills that HIV/AIDS individuals need to take. This development will hopefully help HIV/AIDS individuals be compliant with their medications and to help reduce the development of drug resistance. Some combination medications contain drugs in the same class, whereas others combine two different classes together.

Drugs in the class

• Emtricitabine and Tenofovir (Truvada)
• Abacavir, Zidovudine and Lamivudine (Trizivir)
• Lamivudine and Zidovudine (3TC and AZT, 3TC and ZDV, Combivir)
• Abacavir and Lamivudine (Abacavir and 3TC, Epzicom)
• Efavirenz; emtricitabine; tenofovir tablets (Atripla)

2. Fusion Inhibitors

• Fusion Inhibitors bind to HIV and prevent the virus from infecting healthy cells in the body. They are used along with other antiretroviral medications to treat HIV.

Drugs in the class

• Enfuvirtide (Fuzeon)

3. Non-Nucleoside Reverse Transcriptase Inhibitors

• NNRTIs keep the enzyme reverse transcriptase from working so viral cells cannot reproduce.

Drugs in the class

• Delavirdine (Rescriptor)
• Nevirapine (Viramune)
• Efavirenz (Sustiva)

4. Nucleoside Reverse Transcriptase Inhibitors (NRTIs)

• By taking the place of essential viral parts during division, NRTIs prevent viral cells from copying properly. This allows NRTIs to block the replication of viruses and slow the progression of viral infections such as HIV and hepatitis B.

Drugs in the class

• Zalcitabine (Hivid, ddC, dideoxycytidine)
• Stavudine Oral Solution (Zerit Oral Solution, d4T Oral Solution)
• Abacavir tablets (Ziagen)
• Emtricitabine capsules (Emtriva capsules)
• Stavudine (Zerit, d4T)
• Zidovudine Injection (AZT Injection, Azidothymidine Injection, Compound S, Retrovir Injection)
• Didanosine (DDI, Videx)
• Lamivudine (3TC, Epivir, Epivir-HBV)

5. Nucleotide Analogs

Drugs in the class

• Tenofovir (PMPA, TDF, Tenofovir Disoproxil Fumarate, Viread)

6. Protease Inhibitors

• Protease inhibitors are a newer class of antiretroviral drugs. They interrupt virus replication at a later step in the HIV life cycle. HIV can still divide to make copies of itself, but the new viral particles are unable to infect additional CD4 cells. Protease inhibitors can reduce the amount of virus in the blood and increase CD4 cell counts, helping to preserve or even restore immune system function. The chance of getting opportunistic infections is less, too.

  Most of the protease inhibitors interact with other medications, so they require careful monitoring to avoid serious complications. A unique adverse effect of the protease inhibitors is called lipodystrophy?the redistribution of body fat from the face, arms, and legs to the stomach, breasts, and upper back. Although it is not dangerous, lipodystrophy can be annoying or embarrassing enough to make some HIV/AIDS patients stop taking protease inhibitors. Another complication of these drugs is extremely high cholesterol that occurs in some patients and can lead to serious health complications, including heart disease. Researchers are not sure why this occurs but some evidence points to genetics. Future research may include testing to determine which patients would be at increased risk for developing this complication.

Drugs in the class

• Atazanavir (Reyataz)
• Amprenavir (Agenerase)
• Indinavir (Crixivan)
• Ritonavir (Norvir)
• Amprenavir Oral Solution (Agenerase Oral Solution)
• Lopinavir and Ritonavir (Kaletra)
• Ritonavir Oral Solution (Norvir Oral Solution)
• Nelfinavir (Viracept)
  Fosamprenavir Calcium (Lexiva)
• Tipranavir (Aptivus)
• Saquinavir (Invirase)
• Darunavir tablets (Prezista)