A Review on Human Immuno Deficiency Virus and Acquired Immuno Deficiency Syndrome

Abstract

Human Immunodeficiency Virus (HIV) is a retrovirus that was first identified in humans in 1959, believed to have originated from chimpanzees through zoonotic transmission during hunting. The virus spreads through direct contact with infected bodily fluids, including blood, semen, vaginal fluids, and breast milk. HIV exists in two subtypes: HIV-1 and HIV-2, with HIV-1 being the more prevalent and virulent form. The infection progresses through three stages: acute infection, chronic infection, and acquired immunodeficiency syndrome (AIDS), ultimately compromising the immune system and leading to life-threatening opportunistic infections. Without treatment, HIV significantly reduces the lifespan of affected individuals. Currently, no definitive cure exists for HIV; however, Antiretroviral Therapy (ART) has revolutionized disease management. ART effectively suppresses viral replication, delays disease progression, and improves the quality of life and life expectancy of patients. Despite advancements, challenges remain, including drug resistance, treatment adherence, and accessibility, particularly in resource-limited settings. Ongoing research is focused on developing long-acting therapies, novel drug delivery systems, and potential curative strategies such as gene editing and immune-based interventions. Understanding the molecular mechanisms of HIV pathogenesis, transmission dynamics, and treatment strategies is crucial for developing improved therapeutic approaches. This review provides an overview of HIV’s origin, transmission, classification, disease progression, and current treatment strategies, with an emphasis on the role of ART in mitigating disease impact. Further research into innovative therapies is essential to achieve long-term viral suppression and ultimately find a functional or sterilizing cure for HIV.

Keywords

Introduction

Human Immunodeficiency Virus (HIV) is the causative agent of acquired immunodeficiency syndrome (AIDS), a life-threatening condition that severely weakens the immune system. The immune system plays a crucial role in defending the body against infections, but HIV specifically targets and destroys CD4 cells, a subset of T lymphocytes essential for immune function. If left untreated, the progressive loss of CD4 cells compromises the body’s ability to fight infections, making individuals highly susceptible to opportunistic infections and certain cancers.

As the immune system weakens, pathogens that would typically be controlled by a healthy immune response can cause severe complications, worsening the patient’s condition. The progression of HIV infection, if unmanaged, leads to AIDS, the most advanced stage of the disease, which significantly increases mortality risk. Despite the absence of a definitive cure, advancements in antiretroviral therapy (ART) have transformed HIV from a fatal disease into a manageable chronic condition, improving patient outcomes and life expectancy. Continued research and medical innovations remain essential in the pursuit of more effective treatments and potential cures for HIV/AIDS.

Transmission of Infection

HIV is transmitted when a healthy individual comes into direct contact with infected bodily fluids. The primary modes of transmission include:

1. Blood-to-blood contact
   • Sharing contaminated needles or syringes (common among intravenous drug users).
   • Receiving unscreened or improperly screened blood transfusions.
   • Occupational exposure in healthcare settings (e.g., accidental needle-stick injuries).
2. Sexual transmission
   • Unprotected vaginal, anal, or oral sex with an HIV-infected partner.
   • The risk is higher with multiple partners, untreated sexually transmitted infections (STIs), or in cases of mucosal injury.
3. Transmission through bodily fluids
   • Pre-seminal fluid, vaginal fluid, and rectal fluid can carry and transmit the virus.
   • Risk is increased during sexual contact without protection.
4. Mother-to-child transmission (Vertical Transmission)
   • HIV can be passed from an infected mother to her baby during pregnancy, childbirth, or breastfeeding.
   • The risk is significantly reduced if the mother takes antiretroviral therapy (ART) during pregnancy and avoids breastfeeding.
5. Transmission through contaminated medical equipment
   • Using unsterilized surgical instruments, dental tools, or tattoo needles.
   • Improper medical practices, such as reusing syringes, increase the risk.

Non-Transmission Facts

• HIV cannot spread through casual contact like hugging, shaking hands, sharing food, using public restrooms, or insect bites.
• Proper preventive measures, including safe sex practices, sterile medical procedures, and ART adherence, significantly reduce the risk of transmission.

Origin of Disease

HIV (Human Immunodeficiency Virus) is believed to have originated from non-human primates in Central and West Africa. Scientists trace its origins to the Simian Immunodeficiency Virus (SIV), which is found in chimpanzees and other primates. The transmission of SIV to humans likely occurred through bushmeat hunting, where hunters were exposed to the blood of infected animals during slaughter or consumption. Over time, SIV underwent genetic mutations, adapting to human hosts and evolving into HIV.

The first known case of HIV-1 in humans was identified in 1959 from a blood sample taken from a man in Kinshasa, Democratic Republic of Congo. Genetic studies suggest that HIV may have been circulating in humans as early as the late 1800s to early 1900s, long before its formal identification. The urbanization, increased travel, and medical practices such as unsterilized syringes in the mid-20th century contributed to the virus’s spread across Africa and eventually worldwide.

SIV-related strains have also been discovered in gorillas (SIVGOR) and other primates, indicating multiple cross-species transmissions. HIV/AIDS is classified as a zoonotic disease, meaning it originated in animals before jumping to humans.

Subtypes of HIV

HIV is primarily divided into two major types: HIV-1 and HIV-2, each with different characteristics in transmission, virulence, and geographical distribution.

1. HIV-1

• The most common and widespread form of HIV, responsible for 95% of global infections.
• Originated from chimpanzees (SIVcpz).
• Highly transmissible and more virulent, leading to faster disease progression.
• Divided into four groups (M, N, O, and P), with Group M being the most prevalent worldwide.
• Found in North America, Europe, Asia, and most parts of Africa.

2. HIV-2

• Less common and mostly restricted to West Africa.
• Originated from sooty mangabey monkeys (SIVsm).
• Less virulent, with slower disease progression and lower transmission rates.
• Less responsive to certain antiretroviral drugs, requiring specialized treatment.

Genetic Differences Between HIV-1 and HIV-2

• Research indicates that HIV-1 and HIV-2 have only 55% genetic similarity, meaning diagnostic tests and treatments designed for HIV-1 may not be fully effective against HIV-2.
• HIV-2 has a lower viral load, meaning infected individuals take longer to develop AIDS.
• Due to its lower transmission rate, HIV-2 is less studied than HIV-1, but it remains a concern in parts of Africa.

Global Spread and Evolution

• HIV-1 spread internationally during the 1960s and 1970s, reaching the U.S. in the early 1980s, where the first cases of AIDS were reported.
• The 1980s and 1990s saw a global pandemic, leading to widespread awareness and research into HIV/AIDS.
• Since the introduction of antiretroviral therapy (ART), HIV-related deaths have significantly declined, though a cure remains elusive.

Stages of HIV Infection

HIV infection progresses through three distinct stages, with severity increasing at each stage if left untreated. Proper medical intervention, particularly antiretroviral therapy (ART), can slow or even halt the progression of the disease.

Stage 1: Acute HIV Infection (Primary Stage)

• This stage typically develops 2 to 4 weeks after initial exposure to the HIV virus.
• It is characterized by rapid viral replication, leading to high levels of HIV in the bloodstream.
• HIV targets and begins destroying CD4 cells, weakening the immune system.
• Many individuals experience flu-like symptoms such as fever, fatigue, sore throat, swollen lymph nodes, and rash. This phase is also called acute retroviral syndrome (ARS).
• Since HIV levels in the blood are extremely high during this stage, the risk of transmission is significantly increased.
• Some individuals may not exhibit symptoms, making early detection through testing crucial.

Stage 2: Chronic HIV Infection (Clinical Latency Stage)

• Also referred to as asymptomatic HIV infection or clinical latency, this stage can last for several years.
• The virus remains active but reproduces at low levels, and individuals may not experience noticeable symptoms.
• Without ART, HIV continues to weaken the immune system gradually.
• If left untreated, this stage can progress to AIDS within approximately 10 years, though the timeline varies depending on the individual's immune response.
• With proper ART, people in this stage can live for decades without progressing to AIDS.

Stage 3: Acquired Immunodeficiency Syndrome (AIDS)

• AIDS is the most severe stage of HIV infection, occurring when the immune system is critically weakened.
• It is diagnosed when CD4 cell count drops below 200 cells/mm?3; or when the patient develops opportunistic infections (e.g., tuberculosis, pneumonia, certain cancers like Kaposi's sarcoma).
• Symptoms include chronic weight loss, persistent fever, night sweats, severe infections, and extreme fatigue.
• Individuals at this stage have a very high viral load, making transmission highly likely.
• Without treatment, life expectancy at this stage is typically around 3 years, but some may survive longer with intensive medical care.

Symptoms of HIV Infection

HIV symptoms vary depending on the stage of infection. In the early stage, symptoms are often mild and flu-like, while in later stages, they become more severe due to immune system deterioration.

Stage 1: Acute HIV Infection (Primary Stage)

• This is the initial phase that occurs 2–6 weeks after exposure.
• The virus rapidly multiplies, attacking the immune system and leading to high viral load in the blood.
• Many individuals experience symptoms similar to the flu or other viral infections.

Common Symptoms in Acute HIV Infection:

• Fever
• Headache
• Fatigue
• Swollen lymph nodes
• Muscle and joint pain
• Sore throat
• Non-itchy red rash (often on the upper body)

 These symptoms usually disappear within one to two weeks, but HIV remains active in the body. If left untreated, it progresses to the chronic stage.

Stage 2: Chronic HIV Infection (Clinical Latency Phase)

• Also known as the asymptomatic phase, this stage can last for years (typically 10+ years).
• HIV continues to replicate, but at a slower rate.
• Many individuals do not show noticeable symptoms, yet the virus gradually weakens the immune system.
  • Without treatment, the disease eventually progresses to AIDS.
  • People in this stage can still transmit the virus, even if they have no symptoms.
  •  Regular medical check-ups are essential to monitor CD4 count and viral load.

Stage 3: AIDS (Acquired Immunodeficiency Syndrome)

• This is the final and most severe stage of HIV infection.
• By this point, the immune system is critically weakened, making the body vulnerable to opportunistic infections and certain cancers.

Common Symptoms in AIDS Stage:

• Extreme fatigue (constant tiredness)
• Prolonged fever (lasting more than 10 days)
• Unexplained rapid weight loss
• Persistent diarrhea
• Night sweats
• Shortness of breath
• Purple or brown spots on the skin (Kaposi’s sarcoma)
• Chronic yeast infections (oral thrush, vaginal infections)
• Swollen lymph nodes (neck and groin)
• CD4 count falls below 200 cells/mm?3;, indicating severe immunosuppression.
•  Life expectancy without treatment is around 3 years.
• Opportunistic infections (OIs) such as tuberculosis (TB), pneumonia, and meningitis are common causes of death in AIDS patients.

HIV Diagnosis: Tests & Procedures

Early diagnosis of HIV is crucial for timely intervention and to prevent disease progression. Various tests help detect HIV at different stages.

1. Antigen/Antibody Test (4th Generation Test)

• Detects HIV antigens (p24 protein) and HIV antibodies.
• Can detect HIV within 2–6 weeks after exposure.
• Considered the most accurate early detection test.

2. ELISA Test (Enzyme-Linked Immunosorbent Assay)

• One of the most widely used HIV screening tests.
• Detects HIV antibodies in blood or saliva.
• If positive, the result must be confirmed with a Western Blot Test.

3. Western Blot Test

• A confirmatory test used after a positive ELISA test.
• Detects specific HIV proteins to rule out false positives.
• Considered the gold standard for HIV diagnosis.

4. HIV RNA (Viral Load) Test

• Measures the amount of HIV genetic material (RNA) in the blood.
• Used for early detection (within 10 days of infection).
• Helps monitor ART effectiveness by tracking viral load reduction.

5. Home-Based HIV Test Kits

• FDA-approved home tests allow individuals to test for HIV privately.
• Results are available within 20–40 minutes.
• Positive results must be confirmed through a laboratory test.

6. Saliva HIV Test

• A non-invasive test that detects HIV antibodies in saliva.
• Quick and simple, providing results in 20–30 minutes.
•  Less accurate than blood tests and should be confirmed with an ELISA or Western Blot Test.

HIV Prevention & Risk Reduction Strategies

Although there is no cure for HIV, preventive measures can significantly reduce the risk of transmission.

1. Safe Sexual Practices

• Use condoms consistently and correctly.
• Consider Pre-Exposure Prophylaxis (PrEP) for high-risk individuals.\
• Limit multiple sexual partners to reduce exposure risk.

2. Safe Needle Use

• Avoid sharing needles (common in intravenous drug use).
• Use sterile and disposable syringes.

3. Prevention of Mother-to-Child Transmission (PMTCT)

• Pregnant women with HIV should take ART to prevent transmission to the baby.
• Avoid breastfeeding if an alternative (formula feeding) is available.

4. Post-Exposure Prophylaxis (PEP)

• Emergency medication taken within 72 hours of possible HIV exposure.
• Reduces the risk of HIV infection by over 80%.

5. Regular Testing & Early Detection

• Routine HIV screening for high-risk individuals.
•  Early diagnosis allows timely ART initiation to suppress the virus.

Treatment: Antiretroviral Therapy (ART)

Antiretroviral Therapy (ART) is a combination treatment strategy that uses at least three antiretroviral (ARV) drugs to maximize the suppression of HIV in the body, prevent its progression, and maintain viral load at undetectable levels. ART has revolutionized the management of HIV, improving survival rates and reducing transmission. The therapy is aimed at reducing viral replication, improving immune function, and preventing complications associated with HIV infection.

Classification of Antiretroviral Drugs

1. Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs)

Mechanism of Action:
NRTIs work by inhibiting the reverse transcriptase enzyme, which is responsible for converting the viral RNA into DNA. They are incorporated into the growing viral DNA chain, resulting in premature chain termination, thereby halting viral replication.

Example Drugs:

• Abacavir
• Zidovudine
• Stavudine
• Didanosine
• Emtricitabine
• Lamivudine
• Tenofovir alafenamide
• Tenofovir disoproxil fumarate

2. Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)

Mechanism of Action:
NNRTIs directly bind to the reverse transcriptase enzyme, altering its structure and preventing it from converting the viral RNA into DNA, which is necessary for HIV replication.

Example Drugs:

• Delavirdine
• Rilpivirine
• Etravirine
• Doravirine
• Efavirenz
• Nevirapine

3. Protease Inhibitors (PIs)

Mechanism of Action:
Protease inhibitors block the HIV protease enzyme, which is responsible for processing viral proteins necessary for assembling new HIV particles. By inhibiting this enzyme, protease inhibitors prevent the formation of mature, infectious virions.

Example Drugs:

• Atazanavir
• Darunavir
• Tipranavir
• Ritonavir
• Lopinavir + ritonavir
• Fosamprenavir
• Indinavir
• Nelfinavir
• Saquinavir

4. Integrase Strand Transfer Inhibitors (INSTIs)

Mechanism of Action:
INSTIs block the HIV integrase enzyme, which is responsible for inserting the viral DNA into the host cell’s genome. This prevents the virus from replicating and establishing infection in new cells.

Example Drugs:

• Bictegravir
• Dolutegravir
• Elvitegravir
• Raltegravir

5. Fusion Inhibitors (FIs)

Mechanism of Action:
Fusion inhibitors prevent HIV from entering healthy host cells by blocking the fusion of the virus with the cell membrane. This is an early step in the HIV infection process, which makes FIs distinct from other ARVs that act on post-entry processes.

Example Drugs:

• Enfuvirtide

6. CCR5 Antagonists

Mechanism of Action:
CCR5 antagonists block the CCR5 receptor on the surface of CD4 cells, which is one of the receptors used by HIV to enter and infect the cells. By preventing this interaction, the drug inhibits HIV entry into the host cell.

Example Drugs:

• Maraviroc

Novel Capsid Inhibitors for HIV-1 Infection: Lenacapavir

Mechanism of Action:
Lenacapavir works by binding to the HIV-1 capsid protein, preventing the virus from uncoating and replicating inside host cells.

Marketed As:
Lenacapavir is marketed under the brand name Sunlenca.

Main Use:

It is primarily used for the treatment of HIV-1 infection in adults, especially for those who are heavily treatment-experienced or have multidrug-resistant strains. It offers a long-acting formulation that requires only biannual injections.

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