- What is the medication for HIV/AIDS? |
- What is highly active antiretroviral therapy? |
- When should HAART be started? |
- What are the ARV combinations in HAART? |
- What is treatment failure? |
- What are the dangers of antiretroviral therapy? |
- What are the dangers of stopping antiretroviral therapy? |
- Ask a Doctor
What is the medication for HIV/AIDS?
The medication used to treat HIV/AIDS is known as antiretrovirals (ARVs). These drugs are not a cure for HIV infection and AIDS but helps suppress the virus for a period of time thereby allowing the immune system to recover to some extent. HIV (human immunodeficiency virus) infects a certain type of immune cell known as the CD4+ T-cell, replicates within it and then destroys it. By doing so the viral population increases within the body while the numbers of CD4 cells gradually declines.
This means that the virus grows in numbers infecting an ever increasing number of CD4 cells. At the same time the host defenses through the action of the CD4 cells is gradually diminished. This gives other types of infectious microbes the chance to infect the host and cause severe infections that can be fatal. Antiretrovirals are therefore the most effective way to manage HIV/AIDS by slowing down disease progression. It spares the immune system for long periods of time and ultimately prolongs one’s lifespan.
There are several types of antiretrovirals that works in different ways to counteract HIV replication. Highly active antiretroviral therapy (HAART) is a combination of three or more mutually compatible and synergistic antiretroviral agents belonging to different groups. Usually the drugs selected are from at least two different molecular mechanism of action meaning that it works in different ways to suppress HIV replication. The purpose of HAART is to :
- maximize the antiviral activity
- minimize the toxicity of ARVs
- restrict the development of drug resistance
In addition to initiation of HAART therapy, two important aspects are involved in treatment of AIDS patients namely the prophylaxis (preventative measures) against opportunistic infections and the treatment of AIDS-related complications.
When should HAART be started?
Although the combination of ARVs has several benefits, long term use is associated with toxicity. It is also costly and difficult to adhere to as there are several drugs that need to be simultaneously. Therefore HAART is recommended in the following :
- CD4 counts below 350 cells/mL and/or viral load greater than 100,000 copies/mL.
- Presence of HIV related opportunistic infection or HIV related cancers even if CD4 counts are above 350 cells/mL.
- In patients with acute HIV infection (first phase of HIV) and patients who have seroconverted in the previous 6 months.
- Pregnant HIV-positive patients.
- In patients who are also suffering from Hepatitis B or Hepatitis C infection
- Optionally in patients with CD4 counts between 350 to 500 cells/mL.
What are the ARV combinations in HAART?
HAART regimens are decided based on the antiviral activity, safety, ease of administration, potential for drug interactions, tolerability, drug availability and cost of each regimen. The regimen should also be compatible with the lifestyle of the patient, compatible with the drugs of other medical conditions of the patient. Three-drug regimens (using three drugs simultaneously) are usually preferred for initial treatment and are as effective as four-drug regimens.
Fixed Dose Combinations
Fixed dose combinations are where two or more drugs are combined into one dose. These fixed dose combinations for HAART includes :
- zidovudine + lamivudine
- lamivudine + abacavir
- zidovudine + lamivudine + abacavir
- emtricitabine + tenofovir
- emtricitabine + tenofovir + efavirenz
- lopinavir + ritonavir
First Time HIV Drug Use
The preferred drug regimens for treatment-naive HIV patients, who are HIV positive patients that have never used HIV drugs, includes :
- atazanavir with ritonavir + tenofovir/emtricitabine
- darunavir with ritonavir + tenofovir/emtricitabine
Pregnancy HIV Drug Use
The preferred regimen for pregnant women is as follows :
- lopinavir/ritonavir + zidovudine + lamivudine
- efavirenz + abacavir/lamivudine
- rilpivirine + abacavir/lamivudine
Read more on non-nucleoside reverse transcriptase inhibitors (NNRTIs).
Protease inhibitor based
- atazanavir/ritonavir + abacavir/lamivudine
- darunavir/ritonavir + abacavir/lamivudine
- fosamprenavir/ritonavir + abacavir/lamivudine or tenofovir/emtricitabine
- lopinavir/ritonavir + abacavir/lamivudine or tenovofir/emtricitabine
Read more on protease inhibitors.
- raltegravir + abacavir/lamivudine
Read more om HIV integrase inhibitors.
Combinations to Avoid
A few combinations are not recommended due to reduced efficacy or increased toxicity. The combinations not generally recommended include :
- two NRTIs regimen
- two NNRTIs regimens
- lamivudine with emtricitabine
- stavudine with didanosine
- stavudine with zidovudine
- lamivudine with zalcitabine
- amprenavir with lopinavir/ritonavir and atazanavir with indinavir
What is treatment failure?
Antiretroviral therapy failure may be primary or secondary.
- Primary treatment failure is where the HIV treatment regimen fails to reduce virus population (represented by plasma HIV RNA) significantly in a patient even after taking the prescribed regimen for more than 12 weeks.
- Secondary treatment failure is where there is a consistent increase in the virus population (plasma HIV RNA concentrations) despite continued treatment in a patient who had responded previously producing undetectable HIV RNA levels.
Failure is often evident as a deterioration in one’s health and with HIV there is also the aspect of repeated infections. Change of the treatment regimen to a completely new combination of drugs is required for further management of treatment failure in HIV infection. Three or four different drug class containing regimens are reserved for patients who have failed previous multiple regimens.
Antiretroviral medications are associated with a wide variety of toxicities but once started it should not be interrupted. A major toxicity of long-term therapy with majority of the current treatment regimens is :
- metabolic abnormalities like insulin resistance
- fat redistribution with loss of peripheral fat
- accelerated atherosclerosis
- abnormal lipid levels (HIV lipodystrophy syndrome)
- fatty liver disease
- decrease bone minerdal density
- avascular necrosis of hip bone
- lactic acidosis
Another major drawback of treating HIV with antiretroviral agents is that, once treatment is initiated, it has to be continued life long. Even if the therapy has been successful with undetectable virus population (HIV RNA in the blood), discontinuing the medication can quickly lead to the virus population returning to pre-treatment levels sometimes as soon as a few weeks.
Stopping or briefly discontinuing therapy in a patient with HIV who was on treatment may lead to a sudden increase in viral load and along with a fall in CD4 cell count. This dramatically increases the risk of disease progression.