Department of Pharmacy Practice, Bharathi College of Pharmacy, Bharathinagara.
Forty years after the first cases of HIV were reported, treatment and prevention strategies continue to improve. People diagnosed with HIV should start treatment as soon as possible. If they have another infection, antiretroviral therapy (ART) should begin soon after treating the infection. The first ART options typically involve a daily pill, often including an integrase strand transfer inhibitor (InSTI). For patients who have controlled the virus, there is also an option of a long-acting injectable treatment (cabotegravir and rilpivirine [RPV]) that is given every two months. Along with treatment progress, there have been major advancements in HIV prevention, including preexposure prophylaxis (PrEP), which now includes daily pills and, for the first time, a long-acting injectable version of cabotegravir. As treatment and prevention improve, new challenges and opportunities arise. Since people with HIV are living longer, aging-related issues need special attention and care. It is also important to provide comprehensive care for people with substance use problems to get the best results in treating and preventing HIV. Other infectious diseases, like COVID-19 and monkeypox, also create challenges for both doctors and people with HIV. To overcome these issues and end the HIV epidemic, efforts must increase, with a focus on fairness and equality.
Human immunodeficiency virus (HIV) is a virus that attacks the body’s immune system. Acquired immunodeficiency syndrome (AIDS) occurs at the most advanced stage of infection. HIV targets the body’s white blood cells, weakening the immune system. This makes it easier to get sick with diseases like tuberculosis, infections and some cancers. HIV is spread from the body fluids of an infected person, including blood, breast milk, semen and vaginal fluids. It is not spread by kisses, hugs or sharing food. It can also spread from a mother to her baby. HIV can be prevented and treated with antiretroviral therapy (ART). Untreated HIV can progress to AIDS, often after many years.
Antiretroviral therapy (ART) is treatment of people infected with human immunodeficiency virus (HIV) using anti-HIV drugs. The standard treatment consists of a combination of drugs (often called "highly active antiretroviral therapy" or HAART) that suppress HIV replication. The combination of drugs is used in order to increase potency and reduce the likelihood of the virus developing resistance. ART reduces mortality and morbidity rates among HIV-infected people, and improves their quality of life. The benefits of ART also include the prevention of HIV transmission by suppressing HIV replication in persons living with the virus. This benefit of ART is also defined as “undetectable equal untransmittable”.
HIV can be transmitted via the exchange of body fluids from people living with HIV, including blood, breast milk, semen, and vaginal secretions. HIV can also be transmitted to a child during pregnancy and delivery. People cannot become infected with HIV through ordinary day-to-day contact such as kissing, hugging, shaking hands, or sharing personal objects, food or water.
People living with HIV who are taking ART and have an undetectable viral load will not transmit HIV to their sexual partners. Early access to ART and support to remain on treatment is therefore critical not only to improve the health of people living with HIV but also to prevent HIV transmission.
The symptoms of HIV vary depending on the stage of infection.
HIV spreads more easily in the first few months after a person is infected, but many are unaware of their status until the later stages. In the first few weeks after being infected people may not experience symptoms. Others may have an influenza-like illness including:
The infection progressively weakens the immune system. This can cause other signs and symptoms:
Without treatment, people living with HIV infection can also develop severe illnesses:
HIV causes other infections to get worse, such as hepatitis C, hepatitis B and mpox
HIV can be diagnosed through rapid diagnostic tests that provide same-day results. This greatly facilitates early diagnosis and linkage with treatment and prevention. People can also use HIV self-tests to test themselves. However, no single test can provide a full HIV positive diagnosis; confirmatory testing is required, conducted by a qualified and trained health worker or community worker. HIV infection can be detected with great accuracy using WHO prequalified tests within a nationally approved testing strategy and algorithm.
Most widely used HIV diagnostic tests detect antibodies produced by a person as part of their immune response to fight HIV. In most cases, people develop antibodies to HIV within 28 days of infection. During this time, people are in the so-called “window period” when they have low levels of antibodies which cannot be detected by many rapid tests, but they may still transmit HIV to others. People who have had a recent high-risk exposure and test negative can have a further test after 28 days. Following a positive diagnosis, people should be retested before they are enrolled in treatment and care to rule out any potential testing or reporting error. While testing for adolescents and adults has been made simple and efficient, this is not the case for babies born to HIV-positive mothers. For children less than 18 months of age, rapid antibody testing is not sufficient to identify HIV infection – virological testing must be provided as early as birth or at 6 weeks of age. New technologies are now available to perform this test at the point of care and enable same-day results, which will accelerate appropriate linkage with treatment and care.1
Home Test
A Food and Drug Administration-approved home test. To do the test, you swab fluid from your upper and lower gums. If the test is positive, you need to see your doctor to confirm the diagnosis. If the test is negative, it needs to be repeated in three months to confirm the results.
Tests To Tailor Treatment
If you receive a diagnosis of HIV/AIDS, several types of tests can be done. These tests include:
CD4 cells are a type of white blood cell that's specifically targeted and destroyed by HIV.
This test measures the amount of virus in your blood. Studies have shown that people with higher viral loads generally fare more poorly than do those with a lower viral load.2
HIV is a preventable disease. Reduce the risk of HIV infection by:
Doctors may suggest medicines and medical devices to help prevent HIV infection, including:
ARVs can also be used to prevent mothers from passing HIV to their children.
People taking antiretroviral therapy (ART) and who have no evidence of virus in the blood will not pass HIV to their sexual partners. Access to testing and ART is an important part of preventing HIV.
Antiretroviral drugs given to people without HIV can prevent infection
When given before possible exposures to HIV it is called pre-exposure prophylaxis (PrEP) and when given after an exposure it is called post-exposure prophylaxis (PEP). People can use PrEP or PEP when the risk of contracting HIV is high.1
During the first stage of HIV’s life cycle, the virus binds to receptors on the surface of CD4 cells. CD4 cells, also called helper T cells, are a type of white blood cell that alerts other immune cells that there’s an infection in your body.
2. Fusion
HIV is an enveloped virus, meaning that its genetic information is protected by both a protein shell and a lipid layer called an envelope. Once HIV binds to receptors on CD4 cells, it initiates the fusion of its envelope with the membrane of the CD4 cell using a glycoprotein. Glycoproteins are molecules made of chains of carbohydrates and proteins.
Fusing with the membrane of your CD4 cells allows the virus to enter the cell.
3. Reverse transcription
Reverse transcription is a process of converting genetic information in the form of RNA into DNA.
The virus converts its RNA into DNA by releasing an enzyme called reverse transcriptase. This process allows the virus’ genetic information to enter the nucleus of your CD4 cell.
4. Integration
Once HIV has converted its RNA into DNA, it then releases another enzyme called integrase inside the nucleus of CD4 cell. The virus uses this enzyme to combine its DNA into the DNA of CD4 cell. At this point, the infection is still considered latent and is difficult to detect even with sensitive laboratory tests.
5. Replication
Because HIV is now integrated into the CD4 cell’s DNA, it can use that cell’s machinery to generate viral proteins. During this time, it can also produce more of its genetic material (RNA). These two things allow it to create more viral particles.
6. Assembly
In the assembly stage, new HIV proteins and RNA are sent to the edge of CD4 cell and become immature HIV. These viruses are non-infectious in their current form.
7. Budding
During the budding stage, the immature viruses push out of CD4 cell. They then release an enzyme called protease that modifies proteins in the virus and creates a mature and infectious version.3
There are two main types of human immunodeficiency virus -- HIV-1 and HIV-2. Both can lead to AIDS. HIV-1 is the most common type. HIV-2 occurs in a much smaller number of people. It's harder to transmit HIV-2 from person to person, and it takes longer for the infection to turn into AIDS. Both HIV-1 and HIV-2 have multiple groups within them. Those groups branch out even further into subtypes, or strains. HIV constantly makes copies of itself. Some strains multiply faster and can be passed from person to person more easily than others.4
There are many types of antiretroviral therapy (ART) regimens, including first-line, second-line, and third-line regimens:
These regimens vary depending on the age and health of the patient:
For example, LPV/r + 2 NRTIs is a preferred second-line regimen for patients who were not exposed to ARV.
There are concerns about high mortality among patients who fail second-line therapy. Many countries also have financial constraints that limit the use of third-line regimens.
Review
Link between ART REGIMEN and HIV
Anti Retroviral Therapy (ART) is the use of a combination of HIV medicines to treat HIV infection. People on ART take a combination of HIV medicines (called an HIV treatment regimen) every day. HIV medicines protect the immune system by blocking HIV at different stages of the HIV life cycle. HIV medicines are grouped into different drug classes according to how they fight HIV. Each class of drugs is designed to target a specific step in the HIV life cycle.
Because an HIV treatment regimen includes HIV medicines from at least two different HIV drug classes, ART is very effective at preventing HIV from multiplying. Having less HIV in the body protects the immune system and prevents HIV from advancing to acquired immunodeficiency syndrome (AIDS).ART cannot cure HIV, but HIV medicines help people with HIV live longer, healthier lives. HIV medicines also reduce the risk of HIV transmission (the spread of HIV to others).
Initiation of ART
Initiating ART as soon as possible after an HIV diagnosis is a high priority to improve the health and life expectancy of people with HIV and to eliminate HIV transmission to sexual and injection drug use partners, as well as to infants. Rapid ART initiation (within 7 days of diagnosis), including same-day initiation of ART on the day of diagnosis or the first clinic visit, improves the likelihood of persons linking to HIV care and the likelihood of and time to viral suppression. In resource-limited settings, rapid ART initiation improved survival and longitudinal engagement in care. In highly resourced settings, there are limited clinical and long-term outcomes from randomized clinical trials of rapid ART initiation. Based on the totality of evidence, ART initiation is recommended within 7 days of diagnosis, including on the day of diagnosis or the first clinic visit, if the patient is ready and there is no evidence of a co-occurring opportunistic infection that might affect the timing of initiation of treatment. Timing and choice of initial therapy in the presence of an acute opportunistic infection is discussed in the Initiating ART in the Setting of Active Opportunistic Infections.
Recommended for Most People With HIV
Recommended During Pregnancy
Not Recommended to Initiate During Pregnancy Because of Inadequate Data to Support Use.
If patient is already taking, and stable while taking, bictegravir- or doravirine-containing regimens or the 2-drug regimens DTG/3TC or DTG/RPV and wishes to continue, counsel patient about uncertainties regarding safety during pregnancy and monitor HIV RNA more frequently Should Not Be Used During Pregnancy Because of Inadequate Drug Levels
Recommended During Tuberculosis Treatment (in Alphabetical Order by Anchor Drug)
There is a pharmacokinetic interaction between rifampin and tenofovir alafenamide; clinical data with coadministration are limited. Tenofovir alafenamide (TAF) or tenofovir disoproxil fumarate (TDF) (herein TXF)/emtricitabine (FTC) or lamivudine (3TC) (herein XTC) are recommended as nucleoside reverse transcriptase inhibitor (NRTI) components of initial ART regimens (when DTG/3TC is not used). Abacavir is no longer recommended as initial therapy in most people with HIV owing to concerns about its association with cardiovascular disease, the risk of abacavir hypersensitivity, the burden of HLA B*5701 testing, and no substantial advantage over DTG/3TC alone. DTG/3TC is the only 2-drug regimen currently recommended for initial therapy, but it should only be used when HIV RNA level is less than 500?000 copies/mL and neither hepatitis B coinfection nor lamivudine resistance is present. Accordingly, DTG/3TC should not be used for rapid ART initiation when these laboratory results are not yet available. Long-acting cabotegravir with rilpivirine is not recommended for initial ART, although its use has been explored in a small demonstration project (see Switches to Long-acting Cabotegravir and Rilpivirine section below).Although InSTIs and tenofovir alafenamide have been implicated in weight gain for some individuals and preliminary data raise concern about metabolic adverse effects with InSTIs, such concerns do not override the potential benefit of these drugs. Clinicians should provide resources and counsel patients regarding lifestyle changes that may ameliorate weight gain and other metabolic concerns.5
Investigations
People with certain risk factors should get tested more often. You should get tested at least once a year if:
Sexually active gay or bisexual men may benefit from more frequent testing (every 3 to 6 months). Talk to your health care provider about your risk factors and what testing options are available to you.
Pregnant people should get tested for HIV during each pregnancy. Testing pregnant people and treating those who have HIV is a highly effective way to prevent babies being born with HIV.
Types of tests:
There are three types of HIV tests: antibody tests, antigen/antibody tests, and nucleic acid tests (NAT). Antibodies are produced by your immune system when you're exposed to viruses like HIV. Antigens are foreign substances that cause your immune system to activate. If you have HIV, an antigen called p24 is produced even before antibodies develop.
HIV tests are typically performed on blood or oral fluid. They may also be performed on urine.
An antibody test looks for antibodies to HIV in your blood or oral fluid. Most rapid tests and the only HIV self-test approved by the U.S. Food and Drug Administration (FDA) are antibody tests. Antibody tests that use blood from a vein can detect HIV sooner than tests done with blood from a finger stick or with oral fluid.
An antigen/antibody test looks for both HIV antibodies and antigens. Antigen/antibody tests are recommended for testing done in labs and are common in the United States. This lab test involves drawing blood from a vein. There is also a rapid antigen/antibody test available that is done with blood from a finger stick.
A NAT looks for the actual virus in the blood. With a NAT, the health care provider will draw blood from your vein and send the sample to a lab for testing. This test can tell if a person has HIV or how much virus is present in the blood (HIV viral load test). A NAT can detect HIV sooner than other types of tests. This test should be considered for people who have had a recent exposure or a possible exposure and have early symptoms of HIV and who have tested negative with an antibody or antigen/antibody test.
CONCLUSION:
This review paper discusses about the effectiveness of the current ART regimen and a short detailed view of HIV/AIDS.
Current HIV drugs work well, but long-term side effects and sticking to the treatment remain challenges. New drugs in traditional classes are offering hope for both new and experienced patients. These new options give experienced patients more choices for second-line treatments. However, we still don't know the long-term safety of these drugs or how they interact with others. Many new drugs in different classes are being studied, but none have been proven to completely get rid of the virus or avoid side effects. This means we still need to look for new drugs and use existing ones carefully to fight drug-resistant strains and stop the virus from spreading. In addition to treating HIV, antiretroviral drugs (ARVs) have also been shown to reduce the chance of HIV being passed through sex. As a result, ARVs are recommended as a prevention method before exposure to reduce the risk of sexual transmission. Developing an effective microbicide or vaccine to prevent HIV remains a key area for future research.
REFERENCES
Sandeep S.*, Divyashree N, Basil Kuruvila, Diffy C John, Shanih T., Bhoomika S., A Narrative Review on HIV and Effectiveness of ART Regimen, Int. J. of Pharm. Sci., 2024, Vol 2, Issue 12, 107-114. https://doi.org/10.5281/zenodo.14258776
10.5281/zenodo.14258776
