02 April 2024 – The Hindu

Role of Anti-Retroviral Therapy in HIVAIDS Treatment

• An extremely significant day in the history of India’s reaction to the HIV/AIDS pandemic is April 1. Antiretroviral therapy (ART) for people living with HIV (PLHIV) was introduced by the Indian government on April 1, 2004, 20 years ago. This move has proven to be one of the most important and successful interventions in the battle against HIV/AIDS.

HIV/AIDS: What is it?

• HIV/AIDS is a virus that targets the immune system, particularly the T cells, or CD4 cells, which aid in the immune system’s ability to combat diseases.
• HIV lowers CD4 cells (T cells) in the body, increasing the risk of infections and malignancies linked to infections if treatment is not received.
• The last stage of HIV infection, known as AIDS, occurs when the immune system is so compromised that it is unable to fend off infections.

HIV/AIDS causes:

• The human immunodeficiency virus (HIV) causes HIV infection. Contact with infected body fluids, including blood, semen, vaginal, rectal, and breast milk, can spread the virus.
• It can be passed from mother to child during childbirth or nursing, through sharing needles or syringes, during intercourse, and in rare cases, through organ transplants or blood transfusions.

HIV/AIDS symptoms include:

HIV Acute Infection:

• The flu-like symptoms, such as fever, swollen lymph nodes, sore throat, rash, aches in the muscles and joints, and headaches, might also be present.
• Latent infection in clinical settings:
• Despite its low rate of reproduction, HIV is still active. Individuals may simply experience minor symptoms or none at all.

AIDS:

• Rapid weight loss, frequent fever or intense night sweats, extreme and inexplicable fatigue, prolonged swelling of the lymph glands in the armpits, groyne, or neck, prolonged diarrhoea lasting longer than a week, mouth, anus, or genital sores, pneumonia, and red, brown, pink, or purplish blotches on or under the skin or inside the mouth, nose, or eyelids are typical severe symptoms of AIDS.

HIV/AIDS diagnosis:

• HIV antibody/antigen tests: These assays, which are often performed on blood or oral fluid, identify antibodies or antigens generated by the virus.
• Tests called nucleic acid tests (NATs) can identify HIV infection earlier than antibody tests because they search for the virus itself.

Therapy and Administration:

• Antiretroviral therapy (ART): ART entails daily administration of a cocktail of HIV medications. Although antiretroviral therapy (ART) cannot cure HIV, it can manage the virus, extending the healthy life of those living with it and lowering the danger of infection infecting others.
• Pre-exposure prophylaxis, or PrEP, is a daily medication given to those who are not HIV positive but are at risk of contracting the virus. PrEP can lower the risk of HIV infection if taken regularly.

Antiretroviral Therapy (ART): What is it?

• One of the most important forms of treatment for HIV/AIDS, a long-term viral infection brought on by the human immunodeficiency virus (HIV), is antiretroviral therapy (ART).
• The goal of this therapy is to prevent HIV from replicating in the body, which will lower the viral load, maintain immunological function, and enhance the quality of life for those who are HIV/AIDS positive.

The way that antiretroviral therapy works:

• Antiretroviral medications block the HIV replication cycle at several stages, preventing the virus from entering cells, integrating its DNA into the host genome, reversing the transcription of its RNA into DNA, and assembling and releasing its viral particles.
• ART decreases viral replication and lowers the body’s viral burden by interfering with these mechanisms.
• Antiretroviral Therapy (ART) Components: ART usually consists of a mix of antiretroviral medications from several classes, such as:
• Nucleoside Reverse Transcriptase Inhibitors (NRTIs): These medications block the conversion of viral RNA into DNA by interfering with the reverse transcription process. Tenofovir, emtricitabine, and abacavir are a few examples.
• Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs): NNRTIs attach to the HIV reverse transcriptase enzyme and impede its function, preventing the spread of the virus. Nevirapine, efavirenz, and rilpivirine are a few examples.
• Protease Inhibitors (PIs): PIs stop the HIV protease enzyme from working, which stops the virus from cleaving its polyproteins and developing into infectious particles. Ritonavir, atazanavir, and darunavir are a few examples.
• Integrase Strand Transfer Inhibitors (INSTIs): INSTIs stop the permanent creation of a viral reservoir by blocking the integration of viral DNA into the host genome. Dolutegravir, bictegravir, and raltegravir are a few examples.
• Entry Inhibitors: To stop viruses from entering cells, entry inhibitors obstruct the connection between viral proteins and host cell receptors. Enfuvirtide and maraviroc are two examples.

Antiretroviral Therapy Benefits:

• Viral Suppression: ART lowers the body’s viral load, delaying the onset of illness and protecting immune system function.
• Prevention of Opportunistic Infections: ART aids in the prevention of opportunistic infections and problems associated with AIDS by reestablishing immune function.
• Enhancement of Quality of Life: By lowering morbidity and mortality, effective ART enables people living with HIV/AIDS to lead healthier and more fruitful lives.
• Prevention of Transmission: During pregnancy and childbirth, the risk of HIV transmission to sexual partners and vertical transmission from mother to child is greatly decreased by viral suppression obtained through antiretroviral therapy (ART).

How Has ART Changed to Ensure Treatment Is Effective?

• When HIV/AIDS first became known in the early 1980s, there was a great deal of fear, stigma, and discrimination around the illness. It was also seen as a death sentence.
• Three more antiretroviral medications were approved by the US FDA in 1988, despite the fact that the first medication, AZT (zidovudine), was approved in March 1987. Protease inhibitors, a novel family of antiretroviral medications, were first made available in 1995. With a few notable exceptions, most people on the planet still have restricted access to these medications.

Worldwide Initiatives:

• Acknowledging this problem, world leaders adopted a specific aim to stop and reverse the spread of HIV during the Millennium Summit of the UN General Assembly in 2000.
• After its founding in 2002, the Global Fund to Fight AIDS, Tuberculosis and Malaria promoted universal access to HIV prevention, treatment, care, and support services.
• With a population incidence of 0.4%, the estimated number of PLHIV in India in 2004 was 5.1 million. Few of them were on antiretroviral medication. Merely 7,00 PLHIV were on ART by the end of 2004.

Obstacles to the Evolution of ART:

• Geographic availability to treatment and the high expense of ART for individuals constituted the main obstacles to its use.
• Actually, since 1996, HAART (highly active antiretroviral therapy), often known as “cocktail therapy,” has been accessible. However, the cost of this treatment, which consists of three or more antiretroviral medications, has been prohibitively exorbitant (USD 10,000 annually).
• HIV-positive individuals suffered from stigma and passed away, and medical professionals felt powerless since ARTs were unavailable or too expensive.

Need for Free Medical Care:

• It was a revolutionary move to offer free ART to any adult living with HIV. Children might now receive the free ART as of November 2006.
• Over the course of the free ART effort, which has lasted for 20 years, the number of institutions administering ART has increased from less than 10 to almost 700 ART centres. Of these, 1,264 Link ART centres have given free ART medications to about 1.8 million PLHIV who are undergoing treatment.

ART’s effectiveness:

• ART involves more than just getting an HIV-positive person started on medication. Maintaining a low and suppressed viral load is equally crucial for stopping the spread of illnesses.
• As a result, in 2023, the predicted number of people living with HIV (PLHIV) decreased to 2.4 million, and the prevalence of HIV in those aged 15 to 49 dropped to 0.20 (confidence interval 0.17%-0.25%).

Benefits to the Indian Community:

• India’s proportion of PLHIV cases worldwide has decreased to 6.3% from over 10% twenty years ago. By the end of 2023, 82% of PLHIV were predicted to be aware of their status, 72% to be receiving antiretroviral therapy, and 68% to be virally suppressed.
• India’s yearly rate of new HIV infections has decreased by 48% compared to the 31% global average (2010 served as the baseline). Compared to the global average of 47% (the baseline year of 2010), the annual mortality rate from AIDS-related causes has decreased by 82%.

What Elements of the ART Intervention Made It Successful?

Patient-First, Service-Oriented Approach:

• It would be unjust to attribute the achievement to free ART alone. The HIV epidemic has been stopped thanks to a number of complementing actions.
• These include offering free diagnostic services, focusing on HIV prevention programmes for parents and children, and managing co-infections like tuberculosis (TB) in addition to preventing, diagnosing, and treating opportunistic infections.

Including Dynamic Adjustments:

• The programme has demonstrated adaptability and dynamic changes. Over time, the Treat All policy and early ART commencement were modified, with the ART eligibility requirements being loosened from less than 200 cells/mm3 in 2004 to less than 350 cells/mm3 in 2011, and finally less than 500 cells/mm3 in 2016.
• The ‘Treat All’ strategy, which was introduced in 2017, guarantees that ART be started regardless of CD4 count. This has been a true universalization that has helped lower the amount of viruses spreading inside communities as well as among individuals.
• Along with offering two to three months of medication to PLHIV in a stable state, the initiative also introduced a free viral load test for all PLHIV undergoing treatment. This approach minimises the number of patient visits to ART clinics, saving money and time for the patients.
• In addition to freeing up ART clinics, this strategy improves treatment adherence by lowering the average daily OPD, which frees up medical staff members’ time for other patients.

Including New Pharmaceuticals:

• India kept expanding the plan to include stronger and more recent medications when they became available. For instance, in 2020, Dolutegravir (DTG), a novel medication with exceptional virological potency and no side effects, was released.
• An individual receiving an HIV diagnosis must begin taking antiretroviral therapy (ART) within seven days, and in certain situations, on the same day, according to a policy India implemented in 2021.

Issues with ART Therapy:

• First, the largest obstacle facing the national programme is the delayed enrollment in ART facilities. In India, over one-third of all patients who visit ART clinics do so with a CD4 level of less than 200.
• Second, the patient begins to feel better after beginning and continuing ART. However, as soon as this occurs, individuals begin to miss doses, forget to take their medications for months, or stop altogether. Resistance also develops as a result of this. It is necessary to remedy this “loss to follow up.”