Antiretroviral Therapy Resistance

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Overview

Antiretroviral therapy (ART) is a group of three or more medications to treat people affected by HIV (Human Immunodeficiency Virus). They primarily attack the CD4 cells, which are part of our immune system.

The ART drug regimen in HIV does not cure the disease but rather helps the patient to live longer and healthier lives. 

History of HIV/AIDS

A new syndrome affecting the immune system was found to have spread in the United States in 1981 among homosexual men. Later in 1983, the virus was identified as Human Immunodeficiency Virus.

By the mid-1980s, HIV/AIDS was largely spread among different parts of the world and the pandemic consisted of many separate epidemics. In 1985, the Food and Drug Administration (FDA) licensed the first commercial blood test to test for viral antibodies. 

Blood banks also began screening their blood samples for the virus to prevent transmission through blood transfusions. In March 1987 zidovudine was approved by the FDA as the first antiretroviral medication to treat HIV.

In 1988, the first World AIDS Day took place on December 1. By 1989, it was estimated that about one lakh people in the U.S. were reportedly living with AIDS, which develops from untreated HIV.

Importance of antiretroviral therapy (ART) in managing HIV

In the fight against HIV/AIDS, Antiretroviral Therapy (ART) stands as a powerful weapon in managing the virus and improving the quality of life for those affected. ART is crucial in the battle against HIV as it causes:

  • Viral Suppression:
    • ART suppresses the replication of the HIV virus within the body.
    • By inhibiting the virus, ART helps to reduce the viral load, which is the amount of HIV in the bloodstream.
  • Restoration of Immune Function:
    • ART works to restore and maintain a healthy immune system by allowing CD4 cell counts to increase.
    • With a strengthened immune system, individuals on ART are better equipped to fend off opportunistic infections and live healthier lives.
  • Prolonging Life Expectancy:
    • Before the advent of ART, an HIV diagnosis often meant a significantly shortened life expectancy.
    • ART has transformed HIV from a life-threatening condition to a manageable chronic illness, allowing individuals to lead long and fulfilling lives.
  • Improving Quality of Life:
    • ART helps alleviate symptoms, reduce the frequency of infections, and enhance general well-being.
  • Preventing Vertical Transmission:
    • Pregnant individuals with HIV can transmit the virus to their infants during pregnancy, childbirth, or breastfeeding.
    • ART has proven effective in preventing the vertical transmission of HIV (transmission from a mother to a newborn child), ensuring that newborns can start life without the virus.
    • This breakthrough has had a significant impact in reducing the number of children born with HIV.
  • Public Health Impact:
    • Widespread use of ART contributes to public health efforts to control the spread of HIV.
    • Plays a vital role in preventing and slowing the epidemic's progression.

What is antiretroviral therapy?

ART and its role in HIV treatment:

Antiretroviral Therapy (ART) has a major role in the comprehensive management of HIV, employing a combination of medications to control the replication of the virus within the body. This therapy does not offer a cure for HIV, but it serves as an effective means to manage the infection and enhance the well-being of individuals living with the virus. ART comprises different classes of drugs, based on clinical stages of HIV.

Table on widely used ART drugs:

ClassExamples of DrugsMechanism of Action
Nucleoside Reverse Transcriptase Inhibitors (NRTIs)Zidovudine (AZT), Lamivudine (3TC), Tenofovir (TDF)Inhibit reverse transcriptase, an enzyme needed for viral replication, by incorporating into the viral DNA chain and terminating its synthesis.
Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)Efavirenz, Nevirapine, RilpivirineBind directly to reverse transcriptase, preventing the enzyme from converting viral RNA into DNA.
Protease Inhibitors (PIs)Lopinavir, Atazanavir, DarunavirInhibit protease, an enzyme necessary for the final processing of viral proteins, preventing the production of infectious viral particles.
Integrase Strand Transfer Inhibitors (INSTIs)Raltegravir, Dolutegravir, ElvitegravirBlock the action of integrase, an enzyme that integrates viral DNA into the host cell's genome, preventing the virus from replicating.
Entry InhibitorsEnfuvirtide, MaravirocEnfuvirtide blocks the entry of the virus into the host cell by inhibiting the fusion of viral and cellular membranes. Maraviroc blocks the CCR5 co-receptor, preventing HIV entry into certain immune cells.

How ART works to suppress the HIV virus:

ART operates by disrupting various stages of the HIV life cycle, impeding the virus's ability to replicate and spread. Primarily, it targets key viral enzymes, such as reverse transcriptase, integrase, and protease, crucial for the virus's replication process. By inhibiting these enzymes, ART reduces the viral load in the bloodstream. Lowering the viral load not only alleviates symptoms and prevents disease progression, but also plays a pivotal role in minimizing the risk of transmitting the virus to others.

Understanding antiretroviral therapy resistance

Antiretroviral therapy (ART) is typically associated with the treatment of HIV/AIDS. Resistance to ART occurs when the virus (HIV) evolves or mutates in a way that makes it less susceptible to the effects of antiretroviral drugs. This can result in a decrease in the effectiveness of the treatment.

Factors contributing to the development of ART resistance include:

  • Adherence to Medication:
    • Inconsistent adherence to prescribed medication regimens is a major factor.
  • Drug Interactions:
    • Some medications can interact with antiretroviral drugs, affecting their absorption or efficacy. 
  • Drug Resistance Testing:
    • Delayed or inadequate testing to identify drug resistance can lead to continued use of ineffective drugs, allowing the virus to persist and mutate further.
  • Treatment Interruptions:
    • Stopping treatment without medical guidance can contribute to the development of resistance. It's important to maintain a consistent treatment schedule.
  • Pre-existing Drug Resistance
  • Genetic Factors
  • Viral Load:
    • Higher viral loads are associated with a greater risk of resistance. 

Impact of ART resistance

The development of antiretroviral therapy (ART) resistance in individuals living with HIV can have significant consequences, both on a personal level and on public health.

Consequences for individuals living with HIV:

Consequences of ART Resistance for Individuals Living with HIVDescription
Increased Viral LoadART resistance allows the virus to replicate more effectively, leading to a rise in viral load. Higher viral loads accelerate disease progression.
Progression of HIV/AIDSResistance compromises the effectiveness of treatment, potentially advancing HIV to AIDS more rapidly.
Limited Treatment OptionsDevelopment of resistance narrows the range of effective antiretroviral drugs, making it challenging to achieve viral suppression.
Increased Morbidity and MortalityAdvanced resistance may lead to higher morbidity and mortality rates due to opportunistic infections and HIV-related complications.
Transmission of Resistant StrainsIndividuals with resistant strains may transmit them, contributing to the spread of drug-resistant HIV in the community.
Challenges in Achieving Viral SuppressionART resistance hinders the sustained achievement of viral suppression, impacting overall health and transmission risk.

Detecting ART resistance

ART drug resistance testing assesses the susceptibility of HIV to antiretroviral drugs. This helps determine whether the virus has developed resistance to specific ART drugs.

Resistance testing

 Methods:

  • Genotypic Testing: Analyses the genetic code of the virus to identify mutations associated with drug resistance.
  • Phenotypic Testing: Measures how well the virus grows in the presence of different antiretroviral drugs to determine drug susceptibility.

 Timing:

  • Baseline Testing: Conducted at the start of treatment to identify pre-existing resistance.
  • Routine Monitoring: Periodic testing during treatment to detect emerging resistance.

Importance of routine monitoring

Regular monitoring and tests for HIV drug resistance help healthcare providers detect and intervene when required.

  • Early Detection
  • Guiding Treatment Decisions
  • Preventing Transmission: Helps prevent the spread of drug-resistant HIV strains to others.
  • Individualized care is based on the individual's drug resistance profile.

Prevention strategies

The crucial role of adherence counseling

  1. Education and Awareness: Conduct regular counselling sessions to explain the impact of adherence on treatment efficacy and overall health.
  2. Personalized Counseling: Offer one-on-one counselling to discuss the patient's specific challenges and strategies for adherence.
  3. Support Systems: Encourage patients to engage with support networks and provide resources for ongoing assistance.

Addressing barriers to adherence

Factors contributing to the development of ART resistance can include:

  • Adherence to Medication
  • Drug Interactions
  • Drug Resistance Testing
  • Treatment Interruptions
  • Pre-existing Drug Resistance
  • Genetic Factors
  • Viral Load
  • Access to Healthcare
  • Social and Stigma Issues

Overcoming stigma

Addressing misconceptions about HIV and ART

The stigma and misbeliefs associated with HIV are due to the preconceptions about the disease and the people who are infected by it. This can be overcome by encouraging open conversations about HIV and dismantling stigma through destigmatizing language, community dialogues, and media campaigns.

Healthcare professionals can make a huge impact in society through health literacy programs about HIV infection, comprehensive sexual education, and inclusive curricula that empower individuals with accurate information, promoting a deeper understanding of HIV transmission, prevention, and treatment. 

Potential new treatments and approaches

The treatment and the ART regimen is continuously transforming to serve people in a better way.

  1. The emergence of a single tablet regimen (STR) in ART has made the intake of pills easier thus increasing adherence to the treatment protocol.
  2. Long-Acting Antiretroviral Therapies (LAART)
  3. Broadly Neutralizing Antibodies (bNAbs)
  4. Immune Modulation
  5. Maturation Inhibitors: Investigation of maturation inhibitors that target the final stages of HIV replication, preventing the virus from becoming infectious.
  6. Two-drug regimens instead of the standard three-drug combinations, aiming to maintain efficacy while reducing potential side effects.
  7. Pre-Exposure Prophylaxis (PrEP) Innovations
  8. Personalized Medicine and Pharmacogenomics: Integration of genetic information to tailor HIV treatment regimens based on an individual's genetic profile, optimizing drug efficacy and minimizing side effects.

Summary

The goal behind using Antiretroviral therapy for HIV-positive people is to boost the immune system, reduce or stop the symptoms, and also to prevent the spread.

Taking the prescribed ART regimen does not cure the infection but increased longevity of life can be expected, thus making it a manageable disease.

The emergence of resistance to ART drugs has a negative impact on treating the infection. But as the drugs are taken by the patient throughout their life it's also impossible to completely avoid the drug resistance.

Research, continuous tests, and studies are carried out to develop and handle the drug-resistant strains of HIV/AIDS.

Successful ART not only transforms HIV from a life-threatening condition to a manageable chronic illness but also contributes significantly to public health efforts in controlling the spread of the virus.

Reference

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This content is purely informational and isn’t medical guidance. It shouldn’t replace professional medical counsel. Always consult your physician regarding treatment risks and benefits. See our editorial standards for more details.

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Keerthana Hareendran

Bachelor of Dental Surgery – BDS, Pondicherry University

Keerthana is a General Dentist with analytical skills who is passionate in crafting Dental as well as writing aesthetics.

She has several years of experience as a General Practice Dentist and also in the Oncology data analysis also in writing and editing articles.

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