Session 10: ART Initiation

Introduction to Antiretroviral Therapy

In this session, we will discuss the benefits of antiretroviral therapy, how to assess client readiness for ART in various populations, the appropriate ART regimen and dosage, and effective adherence support interventions and strategies for supporting adherence to ART.

Learning Objectives

By the end of this session, you will be able to:

• Describe the goals of ART.
• Discuss the benefits of ART.
• Describe how ARVs work.
• Explain the principles of ARV treatment.
• Discuss the characteristics of ARVs.
• Explain the classes of ARVs.

Learning Activities

• Introduction to ART (5 min)

  Watch this video for an introduction to ART.
• Targeting HIV Replication (10 min)

  Watch this video on how ART targets HIV replication.

  After watching the video, write out any key points in your workbook that you will want to remember. Then tap the compare answer button below.

  Clear Compare Answer

  Key Points:

  1. ARV medicines DO NOT kill the virus
  2. ART helps to reduce the HIV transmission risk and hence reduce HIV in the community
  3. The main classes of ARVs in Zimbabwe are: protease inhibitors, reverse transcriptase inhibitors and Integrase inhibitors
• Principles of ARV Treatment (5 min)

  ART reduces the amount of HIV in the blood and other parts of the body, lowering what’s known as the viral load.

  An antiretroviral (ARV) regimen generally consists of two nucleoside or nucleotide reverse-transcriptase inhibitors (N(t)RTIs) in combination with a third active ARV drug from one of the two drug classes: a non-nucleoside reverse-transcriptase inhibitor (NNRTI), a protease inhibitor (PI), or dolutegravir (DTG).

  

  It is important to understand that only a triple combination will achieve a sufficient drop in viral load in a majority of clients.

  Often the medicines can lower the viral load so much that HIV becomes undetectable by current technology. An undetectable viral load can be achieved and maintained if a client consistently maintains an adherence of greater than 95%. We will talk more about adherence later in this session.

  Note!

  The undetectable level depends on the sensitivity of the viral load assay that is used (sensitive assays have a lower limit of detection below 50 copies/ml).

  Antiretroviral Medicines (ARVs)

  By prescribing and dispensing fixed dose combinations (FDCs), the client’s pill burden can be reduced, and adherence can be improved.

  

  Classes of antiretroviral medicines that are often used to treat HIV include:

  • Nucleoside and Nucleotide Reverse Transcriptase Inhibitors (NRTIs/NtRTIs): Tenofovir (TDF) (NtRTI), Zidovudine (AZT, ZDV), Stavudine (D4T), Lamivudine (3TC), Didanosine (ddl), Abacavir (ABC), Emtricitabine (FTC)
  • Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs): Efavirenz (EFV), Nevirapine (NVP), Delavirdine, Etravirine, Rilpivirine
  • Protease Inhibitors: Atazanavir/ritonavir (ATV/r), Lopinavir/ritonavir (LPV/r), Ritonavir (RTV), Saquinavir, Indinavir, Nelfinavir, Fosamprenavir, Tiprinavir, Darunavir
  • Integrase Inhibitors: Raltegravir, Elvitegravir, Dolutegravir
  • Antiretroviral Metabolic Inhibitors: Cobicistat, Ritonavir
  • CCR5 Inhibitor (Co-receptor blockers): Maraviroc
  • Fusion inhibitors: Enfuvirtide

  Source

  Guidelines for Antiretroviral Therapy for the Prevention and Treatment of HIV in Zimbabwe, 2016, Table 4, page 19.

  Characteristics of ARVs

  The table below illustrates ARVs used in most programmes in Zimbabwe. The table details their classes and how they work.

  ARV	How it Works
  Available in Zimbabwe
  Nucleoside reverse transcriptase inhibitors (NRTIs)	These medicines block the HIV reverse transcriptase enzyme and prevent the copying of the viral RNA into the DNA of infected host cells by imitating the building blocks of the DNA chain. The resulting DNA chain is incomplete and cannot create new viruses.
  Nucleotide reverse transcriptase inhibitors (NtRTIs)	These medicines act at the same stage of the viral life cycle as do NRTIs.
  Non-nucleoside reverse transcriptase inhibitors (NNRTIs)	These medicines also block the HIV reverse transcriptase enzyme, but have a different mechanism of action than the NRTIs and the NtRTIs.
  Protease inhibitors (PIs)	These medicines block the enzyme protease and prevent the assembly and release of HIV particles from infected cells.
  Integrase inhibitors (IIs)	These medicines target HIV’s integrase protein, blocking its ability to integrate its genetic code into human cells.
  Fusion inhibitors (FIs)	These work by preventing HIV from entering healthy CD4 cells by blocking proteins on the surface of CD4 cells.
  CCR5 inhibitors	These block the CCR5 co-receptor that HIV uses to enter and infect the cell. CCR5 inhibitors work specifically against CCR5-tropic HIV. Before treating a client with a CCR5 inhibitor, a test to determine the strain of virus is necessary.
  Source Guidelines for Antiretroviral Therapy for the Prevention and Treatment of HIV in Zimbabwe, 2016.

• Knowledge Check (5 min)

  1Goals of ART include all of the following except:

  1. Reduce morbidity and mortality due to HIV and AIDS.
  2. Improve the quality of life of PLHIV.
  3. Greatest possible reduction in viral load for as long as possible.
  4. Elimination of HIV entirely from the body.

  Clear Feedback

  D is correct.

  2Which of the following statements is false about ART?

  1. ART reduces HIV-transmission.
  2. ART reduces hospitalization.
  3. ART increases survival rate.
  4. ART is a cure for AIDS.

  Clear Feedback

  D is correct.

  3Match the 3 key viral enzymes that are targeted by ARVs with the correct mode of action:

  Enables integration of the HIV DNA into the host’s DNA. - select - Converts viral single-stranded RNA into a single strand deoxyribonucleic acid (DNA). - select - Splits macro-proteins into smaller viral proteins, which are then incorporated into the new viral particles. - select -

  Clear Feedback

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  4Match the ART Classes listed below with the correct ARVs.

  Tenofovir (TDF) - select - Enfurvirtide - select - Nevirapine (NVP), efavirenz (EFV), etravirine - select - Raltegravir, dolutegravir - select - Maraviroc - select - Lopinavir/ritonavir (LPV/r), atazanavir/ritonavir (ATV/r), darunavir, ritonavir (RTV) - select - Zidovudine (AZT, ZDV), lamivudine (3TC), emtricitabine (FTC), abacavir (ABC), didanosine (ddl), stavudine (d4T) - select -

  Clear Feedback

  feedback_text

  5Which statement about ART regimen is true?

  1. ART must be given in 3-drug combination.
  2. Use AZT + 3TC + NVP in patients with Hb <8 g/dL.
  3. Give only 1 or 2 ARVs if intolerance is present.
  4. Give only 1 ARV in asymptomatic (WHO stage 1) patients.

  Clear Feedback

  A is correct. It is important to understand that only a triple combination will achieve a sufficient drop in viral load in a majority of clients.

  6ARVs kill the HIV virus.

  1. True
  2. False

  Clear Feedback

  The answer is false. ART does not cure the HIV infection; it halts viral replication, preventing further disease progression and damage to the immune system. The body’s defense or immune system gets a chance to recover, and fewer opportunistic infections occur.

  7Match the ARV with the correct characteristics of how they work:

  These medicines target HIV’s integrase protein, blocking its ability to integrate its genetic code into human cells. - select - These medicines act at the same stage of the viral life cycle as do NRTIs. - select - These block the CCR5 co-receptor that HIV uses to enter and infect the cell. CCR5 works specifically against CCR5-tropic HIV. Before treating a client with a CCR5 inhibitor, a test to determine the strain of virus is necessary. - select - These medicines block the HIV reverse transcriptase enzyme and prevent the copying of the viral RNA into the DNA of infected host cells by imitating the building blocks of the DNA chain. The resulting DNA chain is incomplete and cannot create new viruses. - select - These work by preventing HIV from entering healthy CD4 cells by blocking proteins on the surface of CD4 cells. - select - These medicines also block the HIV reverse transcriptase enzyme, but have a different mechanism of action than the NRTIs and the NtRTIs. - select - These medicines block the enzyme protease and prevent the assembly and release of HIV particles from infected cells. - select -

  Clear Feedback

  feedback_text

  8Effectiveness of antiretroviral therapy is measured by:

  1. A fall in the plasma viral load and an increase in the CD4 count.
  2. A rise in red blood cell count and hemoglobin level.
  3. A rise in plasma HIV antibodies level.
  4. A reduction in opportunistic infections.

  Clear Feedback

  A is correct.

  9What happens if patients do not take the combination of several antiretroviral drugs? Type your answer in the box, then tap the compare answer button.

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  Without ART, most individuals with HIV will eventually develop progressive immunodeficiency marked by CD4 T lymphocyte (CD4) cell depletion leading to AIDS-defining illnesses and premature death.

• Key Points (5 min)
  • The primary goal of ART is to reduce morbidity and mortality due to HIV and AIDS, as well as to improve the quality of life of PLHIV.
  • ART helps reduce HIV transmission risk and hence reduces HIV in the community.
  • The three key viral enzymes that are targeted by ARVs are: reverse transcriptase, integrase, and protease.
  • ARVs interfere with key enzymatic steps in viral replication; they do NOT kill the virus.
  • Standard ART consists of the combination of at least three ARV medicines to maximally suppress the HIV virus and stop the progression of HIV disease.
  • There are several classes of ARVs depending on which stage of the viral life cycle they target.