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Highly Active Antiretroviral Therapy (HAART)

Antiretroviral therapy is the treatment used in people who are infected with human immunodeficiency virus (HIV). This treatment is commonly known as Highly Active Antiretroviral Therapy or abbreviated as HAART.¹ HAART consists of a combination of at least 3 antiretroviral drugs from at least 2 different antiretroviral classes. This combination is required in order to successfully suppress the HIV replication. ¹ ²

Goals of treatment: ¹²³

  • Maximally and durably suppress plasma HIV viral load
  • Reduce HIV-associated morbidity and prolong survival
  • Improve quality of life
  • Restore and preserve immunologic function
  • Prevent HIV transmission

Classes of Antiretrovirals

  • Nucleoside Reverse Transcriptase Inhibitors (NRTI)
  • Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI)
  • Protease Inhibitor (PI)

Antiretroviral Drugs Available in the Ministry of Health, Malaysia (4)

NRTI
NNRTI
PI
Stavudine Nevirapine (Hirapine ®) Indinavir (Crixivan ®)
Lamivudine (3TC ®) Efavirenz (Stocrin ®) Ritonavir (Norvir ®)
Zidovudine (Retrovir ®) Lopinavir (Kaletra ®)
Didanosine (Dinex EC ®) Darunavir (Prezista ®)
Tenofovir (Tenvir ®)
Abacavir (Ziagen ®)

When to Start Antiretroviral Therapy

HAART is started when CD4 cell counts are less than 350cells/mm³. CD4 is a laboratory marker that is used to assess one’s immune status, with a normal CD4 counts to be between 500-1000 cells/mm³. Evidence states that there is a higher likehood of CD4 normalisation if HAART is initiated earlier.

The first line treatment consists of 2 drugs from the NRTI group and 1 drug from the NNRTI group. This set of medications will be supplied by the Ministry of Health for life if patients are successfully treated on the first line treatment. Second-line treatment consists of 2 NRTIs and 2 PIs, but one of the PI drugs will have to be purchased by the patient, whilst the remaining medications will be supplied by the Ministry of Health. ² ³

The selection of the antiretroviral regimen is based on several factors including comorbid conditions such as cardiovascular disease, liver disease or tuberculosis, pregnancy, potential drug interactions, gender, baseline CD4 counts and patient adherence potential. ² ³

Common Adverse Effects of Antiretrovirals ² ³

Class
Drug Name
Common Adverse Effects
NRTI
Stavudine Nausea, vomiting, nerve pain, sunken face
Lamivudine Nausea, vomiting, headache, fatigue
Zidovudine Anemia, nausea, vomiting
Didanosine Headache, nausea, vomiting, diarrhea, nerve pain, sunken face
Tenofovir Rash, diarrhea, nausea, vomiting, kidney problems,
Abacavir Diarrhea, nausea, vomiting, liver problems
NNRTI
Nevirapine Rash, allergic reaction, hepatitis, headache, fatigue
Efavirenz Dizziness, nightmares, rash, insomnia, depression
PI
Indinavir Nausea, vomiting, increased bilirubin levels, kidney problems
Ritonavir Raised cholesterol levels, nausea, vomiting, altered sense of taste
Lopinavir Diarrhea, bloating, increased triglyceride and cholesterol levels, may cause or worsen diabetes
Darunavir Nausea, diarrhea, increased triglyceride and cholesterol levels, headache

Importance of Compliance & Adherence to Antiretrovirals

Definition of compliance and adherence.

  • Compliance is the patients’ doing what they have been told by the doctor/pharmacist
  • Adherence is defined as the extent to which a patient’s behavior coincides with the prescribed health care regimen as agreed upon through a shared decision-making process between the patient and the health care provider

Adherence is an extremely important factor in maintaining successful virological suppression and an increase in CD4 counts. Antiretrovirals are normally taken twice daily (e.g. 8am and 8pm) and should not be missed or delayed as far as possible. If a delay does occur, a delay of a half hour will not affect the efficacy of the antiretrovirals.

Predictors of medication success ²

Viral load reduction to below detectable limits usually occurs within the first 12-24 weeks of therapy. Factors that determine virological success are as follows:

  • high potency of antiretroviral regimen,
  • excellent adherence to treatment regimen,
  • low baseline viremia,
  • higher baseline CD4 T-cell count (>200 cells/mm3),and
  • rapid reduction of viremia in response to treatment.

Successful outcomes are usually observed although adherence difficulties may lower the success rate in clinical practice to below the 90% rate commonly seen in clinical trials

Tips to remember

  • Use an alarm clock or set a reminder on your handphone mobile phone to help you remember to take your medications.
  • If you happen to forget/delay the time of your medication, take it as soon as you remember.
  • Avoid taking traditional medications or herbal supplements with HAART as there may be drug-drug interactions that could affect the efficacy of HAART.
  • Ensure that you have sufficient amount of medication with you at all times, especially before you travel.
  • If you are going overseas, take your medication following the Malaysian time.
  • Whenever you face any problems with your medications, consult a pharmacist or doctor – DO NOT stop the medications without the doctor’s advice.

References

  1. WHO
  2. Guidelines for the Use of Antiretroviral Agents in HIV-1 Infected Adults and Adolescents, Panel on Antiretroviral Guidelines for Adults and Adolescents – A Working Group of the Office of AIDS Research Advisory Council, January 29, 2008.
  3. John Hopkins HIV Guide
  4. Malaysian HIV CPG
  5. Grabar S et.al, Clinical Outcome of Patients with HIV-1 Infection according to Immunologic and Virologic Response after 6 months of Highly Active Antiretroviral Therapy, Annals of Internal Medicine, American College of Physicians 2000.
Last reviewed : 23 April 2014
Writer : Cheang Lai Fong
Accreditor : Dr. Roshayati Mohd Sani
Reviewer : Che Pun bt. Bujang

 

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