HIV antiretrovirals or ARV's are drugs used to treat HIV. ARV's interrupt the replication cycle of HIV preventing the virus from replicating and infecting new cells. The goal of ARV's is to lower the amount of HIV in the body allowing the immune system to recover. The two main ways we measure how well ARV's are working is by measuring viral load and CD4 cell count. When ARV's are working properly a raise in CD4 cells are usually seen and the viral load level decreases to undetectable levels in the blood.
How do you know if ARV's are working?
Viral load
A viral load assay is used to measure the amount of virus in the blood. Evidence shows that keeping HIV viral load levels as low as possible, for as long as possible, decreases the complications of HIV disease, slows the progression from HIV infection to AIDS, and prolongs life. This does not mean that HIV is not replicating, only that HIV RNA is not present in the blood at the time of testing or it is below the level of detection. HIV continues to be present in other cells and tissue throughout the body. This is called 'HIV provirus'. HIV provirus refers to virus that has moved into cells and into the nucleus, where it has become integrated with the DNA of the host cell. This is also call “HIV proviral DNA.”
CD4 Cells
CD4 cells are white blood cells responsible for fighting infection. They are also called T-cells or T-helper cells. A normal CD4 count is from 500 to 1200 cells. CD4 cells travel through the body searching for invading pathogens such as germs, viruses and bacteria. HIV enters and infects the T-cell by binding to the viral envelope called GP120 thus crippling the immune system and disabling it from killing off and protecting the body from invading pathogens which could make us sick. By measuring the CD4 cell count we are able to tell determine whether ARV's are working properly. Once the CD4 count falls below 200 the person is considered to have AIDS. A CD4 test measures the amount of functioning T-cells.
Antiretroviral Drugs
There are several classes of HIV antiretrovirals available. It is recommended that a combination of at least 3 drugs be used. ART (antiretroviral therapy) is a combination of 2 or more antiretrovirals and HAART (highly active antiretroviral therapy) is a combination of 3 or more anitretrovirals.
The World Health Organization's (WHO) 'Antiretroviral Therapy for HIV Infection in Adults and Adolescents' provides updated guidelines on issues such as when to initiate therapy, which combinations should be used, preferred first line therapies, recommendations for pregnant women and people co-infected with HBV or TB and other clinical considerations. The guidelines can be found at: http://whqlibdoc.who.int/publications/2010/9789241599764_eng.pdf
The United States Department of Health and Human Services (DHHS) also released guidelines for treating HIV infected adults and adolescents. They can be found at: http://aidsinfo.nih.gov/Guidelines/GuidelineDetail.aspx?MenuItem=Guidelines&;Search=Off&GuidelineID=7&ClassID=1
HIV antiretroviral drugs and classes of drugs
Nucleoside reverse transcriptase inhibitors
Also known as: NRTI's, nucleoside analogs or nukes
Function: NRTI's block HIV's ability to copy a cell's DNA which the virus needs to make copies of itself (replicate).
Available Nucleoside reverse transciptase inhibitors:
Abacavir (ABC) (Ziagen)
possible side effects may include:
Severe allergic reactions which can be life threatening, call your doctor immediately if you experience:
fever, rash, severe nausea, diarrhea, abdominal pain, sore throat, cough, shortness of breath
Other side effects include: lactic acidosis (a buildup of acid in the blood), fatty liver, headache, depression, anxiety, difficulty falling asleep or staying awake, hives itching, chills, difficulty breathing
Didanosine (ddl) (Videx)
possible side effects may include:
Should be used carefully by people with hepatitis.
pancreatitis, buildup of acid in the blood, fatty liver, peripheral neuropathy (numbness, tingling, or pain in the hands or feet), nausea, diarrhea and anemia
Emtricitabine (FTC) (Emtriva)
possible side effects may include:
Buildup of acid in the blood, fatty liver: should be used carefully by people with hepatitis B.
headache, diarrhea, nausea, rash, darkening of the skin on the palms and the soles of the feet
Lamivudine (3TC) (Epivir)
possible side effects may include:
buildup of acid in the blood, fatty liver: should be used carefully by people with hepatitis B. anemia, headache, nausea, vomiting, diarrhea, fever, fatigue, hair loss, insomnia, malaise, nasal symptoms, cough, peripheral neuropathy, low white blood cell count
Stavudine (d4T) (Zerit)
possible side effects may include:
peripheral neuropathy, facial wasting, mitochondrial toxicities, lipodystrophy, pancreatitis, upset stomach, diarrhea, abdominal pain, headache, chills/fever, malaise, insomnia, anxiety, depression, rash, blood lipid increases
Zidovudine (ZDV) (AZT) (Retrovir)
possible side effects may include:
anemia, damage to muscle, nausea, vomiting, stomach discomfort, buildup of acid in the blood, fatty liver: should be used carefully by people with hepatitis B, headache, insomnia, weakness
Non-nucleoside reverse transcriptase inhibitors
Also known as: NNRTI's
Function: NNRTI's bind to and disable reverse transcriptase, a protein that HIV needs to make copies of itself. NNRTIs block the same protein as the NRTI, but are chemically different. Resistance to this class of medications develops quickly if not used in combination with an NRTI.
Available non-nucleoside reverse transciptase inhibitors:
Efavirenz (EFV) (Sustiva)
possible side effects may include:
rash, central nervous system symptoms such as drowsiness, insomnia, confusion, inability to concentrate, dizziness, and vivid dreams, increased liver enzymes, false-positive drug testing (marijuana) and birth defects if taken during pregnancy.
Etravirine (ETR) (Intelence)
possible side effects may include:
nausea, rash
Nevirapine (NVP) (Viramune)
possible side effects may include:
severe liver problems mostly among women with CD4 counts greater then 250, severe skin reactions
Delaviridine (Rescriptor)
possible side effects:
rash, headaches, increased liver enzymes
Etravirine (Intelence):
possible side effects
rash, nausea
Nucleotide reverse transciptase inhibitor
Also known as: NtRTI's
Function: Like NRTIs, NtRTIs block HIV's ability to copy a cell's DNA, preventing the virus from replicating. NtRTIs (unlike NRTIs) are chemically per-activated.
Available Nucleotide Reverse Transciptase Inhibitors:
Tenofovir (TDF) (Viread)
possible side effects may include:
headache, weakness, diarrhea, vomiting, nausea, intestinal gas, kidney problems, fatty liver, build up of acid in the blood
NRTI fixed dose combinations:
Combovir – 3TC/AZT
possible side effects may include:see 3TC and AZT
Trizivir – 3TC/abacavir/AZT
possible side effects may include: see 3TC, abacavir and AZT
Kivexa (EU) - 3TC/abacavir
possible side effects may include:see 3TC and abacavir
NRTI/NtRTI fixed dose combinations:
Truvada – FTC/tenofovir
possible side effects may include:see FTC and tenofovir
NRTI/NtRTI/NNRTI fixed dose combinations:
Atripla – FTC/tenofovir/efavirenz
possible side effects may include:see FTC and tenofovir
Protease inhibitors
Also known as: PI's. protease
Function: PI's block protease, an enzyme that the HIV virus needs to make copies of itself.
Available protease inhibitors:
Atazanavir (ATZ) (Rayataz)
possible side effects may include:
lipodystrophy, nausea, rash, stomach pain, vomiting, diarrhea, depression, increased bleeding in people with hemophilia
Darunavir (DRV) (Prezista)
possible side effects may include:
rash, headache, diarrhea, increased bleeding in people with hemophilia
Fosamprenavir (FPV) (Telzir) (Lexiva)
possible side effects may include:
rash, diarrhea, nausea, stomach discomfort, headache, lipodystrophy, icreased liver enzymes, numbness around mouth, increased bleeding in people with hemophilia
Indinavir (IDV) (Crixivan)
possible side effects may include:
kidney stones, diarrhea, vomiting, nausea, lipodystrophy, headache, blurred vision, rash, metallic taste, low platelets, anemia
Nelfinavir (NFV) (Viracept)
possible side effects may include:
diarrhea, increased cholesterol, increased liver enzymes levels, increased bleeding in people with hemophilia
Ritonavir (RTV) (Norvir)
possible side effects may include:
diarrhea, nausea, stomach discomfort, paresthesias (tingling or numbness in limbs or around the mouth), increased liver enzymes levels, increased bleeding in people with hemophilia
Saquinavir (SQV) (Invirase)
possible side effects may include:
diarrhea, nausea, stomach discomfort, headache, lipodystrophy, increased liver enzymes levels, increased bleeding in people with hemophilia
Tipranavir (TPV) (Aptivus)
possible side effects may include:
diarrhea, rash, nausea, stomach discomfort, vomiting, bleeding in the brain
Kaletra (LPV) (Aluvia) – Loprenivir/ritonnavir
possible side effects may include:
diarrhea, fatigue, headache, nausea, rash, weakness, increased liver enzyme levels, increased bleeding in people with hemophilia
Fusion inhibitor
Also known as: FI. Entry inhibitors
Function: FIs block HIV's entry into the cell. This medication must be administered by injection.
Available fusion inhibitors:
Enfuvirtide (T-20) (Fuzeon)
possible side effects may include:
local injection site reactions, nausea, diarrhea, fatigue, flu-like symptoms
CCR5 inhibitors
Function: CCR5 inhibits viral infection before it enters the cell at the point of attachment
Available CCR5 inhibitors:
Maviroc (Selzentry)
possible side effects may include:
body aches or pain, burning or stinging of the skin, chills, cough producing mucus, coughing, difficulty in breathing, dizziness when getting up suddenly from a lying or sitting position, ear congestion, headache, loss of voice, nasal congestion
Intergrase Inhibitors
Function: Integrase inhibitors interfere with the integrase enzyme, which HIV needs to insert its genetic material into human cells.
Available intergrase inhibitors:
Raltegravir (Isentress)
possible side effects may include:
Isentress may cause problems for patients who are at increased risk for muscle problems like myopathy and rhabdomyolysis, which includes patients using other medications known to cause these conditions. diarrhea, nausea, headache