Specialisation: Acquired Immune Deficiency Syndrome

HIV/AIDS

Introduction

Human Immunodeficiency Virus (HIV) is an infectious agent that attacks the immune system, particularly the CD4 category of white blood cells (CD4 T lymphocyte), resulting in HIV disease (Lippincott & Wilkins, 2012). Losing T cells results in the body’s difficulties fighting infections and some cancers. Without effective treatment, HIV continuously destroys human immunity and advances to Acquired Immune Deficiency Syndrome (AIDS), the most advanced stage of HIV disease (National Institute of Health, 2023). Notably, an individual has AIDS when their CD4 cells count falls below 200 cells per every cubic millimeter of blood or they develop at least one opportunistic infection, regardless of the number of CD4 cells in their blood. Eventually, most individuals who get AIDS die from opportunistic diseases or infections (Lippincott & Wilkins, 2012). Although most experts believe HIV develops into AIDS in virtually all patients, early diagnosis and strict, effective treatment can prevent HIV patients from developing AIDS-related infections; hence they can lead a healthy life and attain a near-normal lifespan (National Health Service, 2021). However, the positive HIV status is currently irreversible. A dig deep into how HIV/AIDS affects the human body from the time of infection to the full-blown stage, and an exploration of available treatment for the condition is the perfect approach to understanding its anatomy and physiology.

How HIV Infection Happens

HIV is a retrovirus whose replication is only favorable in a human host. Once in the host’s body, the CD4 antigen receives the HIV, allowing it to invade the CD4 cells. Eventually, the RNA-based virus replicates within CD4 cells, causing death to the cells (Lippincott & Wilkins, 2012). This process interferes with the body’s normal immune response, considering CD4 cells are responsible for that action. Notably, body cells with CD4 antigen on their surface are at risk of HIV infection; some include macrophages, monocytes, epithelial, glial, gut, and bone marrow progenitor cells (Lippincott & Wilkins, 2012).

HIV Transmission

Considering initial misinformation that barely drew the line between myths and facts about HIV transmission, especially during the age of the first HIV/AIDS cases, researchers established the most common modes of transmission. According to the Centers for Disease Control and Prevention (2022), vaginal or anal sex, sharing of syringes, needles, and other injection equipment, and mother-to-child either during birth or breastfeeding contribute to the highest number of HIV infections. Lippincott and Wilkins (2012) classified the HIV modes of transmission into three broad categories. Firstly, the virus is transmitted through exposure to contaminated blood, for example, during tissue transplantation and blood transfusion or by sharing contaminated needles. Luckily, routine blood supply testing since 1985 reduced the first two instances of transmission in this category (Lippincott & Wilkins, 2012).

Secondly, HIV transmission occurs through exposure to infected body fluids, including vaginal and semen, during unprotected sex. Anal sex is the most dangerous considering the mucosal trauma during the act (Lippincott & Wilkins, 2012). Notably, in 2019, adolescent and adult bisexual and gay men contributed to approximately 69% of the United States’ new HIV diagnoses (National Institute of Health, 2021). Lastly, a fetus can get infected when the virus crosses from an infected mother through the placenta barrier or to an infant through breast milk or blood or cervical contact during delivery. Apart from the identified most common body fluids that transmit HIV, the virus is also found in saliva, tears, feces, and urine, regardless of the lack of evidence of transmission through these fluids (Lippincott & Wilkins, 2012).

The Stages of HIV Infection

Stage 1: Acute HIV Infection

The acute HIV infection stage develops within the first two to four weeks after the body receives the virus. The stage is marked by flu-like symptoms, such as headache, rash, and fever among some people (National Institute of Health, 2021). It is a means of the body’s reaction to a foreign virus. This stage is also marked by the rapid multiplication of the virus as it attacks and destroys CD4 cells while spreading across the body. Consequently, infected human bodies have the highest concentration of HIV in blood during this stage. Therefore, the risk of transmission is highest.

Nonetheless, the CD4 count of a person with HIV at the first stage of infection is the same as that of a healthy person, with at least 500 cells per cubic milliliter of blood, and accounts for 29% or more of all lymphocytes (Healthwise Staff, 2021). Therefore, individuals at this stage do not have any AIDS-related conditions. According to Lippincott and Wilkins (2012), individuals at this stage only have documented HIV infection. However, regardless of patients being asymptomatic at this stage, they may experience generalized lymph node enlargement. This stage is identified as category A in clinical categorization. Patients may benefit significantly if they start Antiretroviral Treatment (ART) during this stage (National Institute of Health, 2021).

Stage 2: Chronic HIV Infection

Also referred to as category B, according to clinical classification, most patients in this stage still do not notice any AIDS-related symptoms, regardless of the absence of ART (Frysh, 2022). The patient may not notice any symptoms for a decade or more. People who take ART may sustain the stage for several decades. Due to this fact, the stage is also called the clinical latency or the asymptomatic HIV stage. Diversely, HIV continues its multiplication in the body, but at a lower rate. At this stage, the CD4 count ranges between 350 to 499 cells per cubic milliliter of blood, and the percentage of CD4 cells ranges between 14% and 28% of the total count of lymphocytes in blood (Healthwise Staff, 2021). Transmission to other people is still possible at this stage; however, a patient can take ART effectively and according to the prescription, attain the undetectable viral load and eliminate the transmission of the virus through sex (National Institute of Health, 2021).

Still, in some cases, infected individuals show defects in cell-mediated immunity or have a clinical management course that is complicated by the HIV infection. For instance, some patients may experience persistent vulvovaginal candidiasis, diarrhea or fever lasting more than a month, angiomatosis, idiopathic thrombocytopenic purpura, peripheral neuropathy, and pelvic inflammatory disease (Lippincott & Wilkins, 2012). According to Frysh (2022), some patients may also have pneumonia, shingles, weight loss, oral yeast infections, and tiredness.

Stage 3: Acquired Immune Deficiency Syndrome

AIDS is the final and most severe HIV infection stage. The body lacks defense against opportunistic infections or diseases, considering that HIV has severely destroyed the immune system. A person with HIV is diagnosed with AIDS when they have a CD4 count of fewer than 200 cells per cubic milliliter of blood, and the cells are less than 14% of the total lymphocyte count in blood (Healthwise Staff, 2021). Alternatively, if one has more than 200 CD4 cells per microliter of blood but has any opportunistic infections, they have AIDS. The viral load at this stage is very high in the body; therefore, the HIV transmission risk is at its highest. Without treatment, the patient can only survive about three years (National Institute of Health, 2021).

HIV’s Physiological Process from Stage 1 to Stage 3

After infection, when HIV comes in contact and penetrates the host T cells through chemokine receptors and CD4 molecules, several HIV-encoded enzymes and HIV RNA enter the host cell (Cachay, 2023). A viral replication process starts whereby reverse transcriptase, a DNA polymerase dependent on an RNA, copies HIV RNA to produce pro-viral DNA. However, this process is prone to errors, resulting in recurrent mutations and, ultimately, the emergence of novel HIV genotypes. Through mutation, HIV gains the ability to resist control by antiretroviral drugs or the human immune system.

Eventually, the pro-viral DNA penetrates the host cell’s nucleus and integrates with the cell through a process involving the HIV enzyme integrase. Every cell division process after the integration results in the duplication of the pro-viral DNA alongside the host DNA (Cachay, 2023). Subsequently, the pro-viral DNA can undergo transcription to HIV RNA before it is translated to HIV protein, for instance, envelope glycoproteins 120 and 41. The HIV proteins assemble into virions in the inner membrane of the host cell and are budded from the host cell’s surface within an enclosure of an altered human cell membrane (Cachay, 2023). Notably, each affected human cell may generate thousands of virions. After the budding process, the HIV enzyme protease splits viral proteins and converts immature non-infectious virions into mature infectious ones.

After CD4 lymphocytes are infected, they produce more than 98% of HIV virions plasma. Notably, an infected CD4 lymphocytes subset has an HIV reservoir that can reactivate, for instance, when a patient stops using ART. According to Cachay (2023), CD4 cells create and remove between 10and 10virions per day in moderate (Stage 2) to heavy (Stage 3) infection. The average HIV half-life in blood plasma is approximately thirty-six hours, twenty-four hours as an intracellular virus, and about six hours extracellularly (Cachay, 2023). Eventually, infected individuals experience a 30% turnover of the total HIV burden. Also, five to seven percent of CD4 cells turn over daily, while the whole CD4 cell pool turns over in approximately 48 hours (two days) (Bonhoeffer et al., 1997).

Eventually, the consistent and persistent HIV replication leading to the death of CD4 lymphocytes through immune-mediated and viral attacks results in AIDS. Also, extreme replication of HIV volume in blood and high transcription error frequency by the reverse transcriptase enzyme elevated the number of mutations, skyrocketing the instances of immunity and drug-resistance strains production (Cachay, 2023).

Subsequently, this stage is marked by opportunistic infections in the human body, which can eventually result in death. Categories of opportunistic diseases include bacterial infections such as Tuberculosis, Mycobacterium avium complex, and salmonellosis; fungal infections including cryptococcosis, coccidioidomycosis, Histoplasmosis, and candidiasis; protozoan infections such as cryptosporidiosis, pneumocystis jirovecii pneumonia; and viral infections including Herpes Zoster, Cytomegalovirus, Progressive multifocal leukoencephalopathy and Herpes Simplex Virus (Lippincott & Wilkins, 2012).

Throughout the process, the immune system tries to control the virus by producing more T cells. However, it fails to produce them fast enough; hence the amount of virus increases relative to the number of CD4 cells. The immune system weakens, opening up the body to higher chances of infections. Therefore, HIV patients require ART to help them lead healthier and longer lives.

Testing for HIV

Currently, there exist three types of HIV tests; the nuclei acid test (NAT), antibody tests, and the antigen/antibody test. Based on the Centers for Disease Control and Prevention (2022), the last two tests are based on the immune system’s reaction to viruses. Notably, the system produces antibodies when the host body comes into contact with HIV. Diversely, antigens activate the immune system, considering they are foreign substances in the body. When an individual has HIV, their body produces the p24 antigen even before developing antibodies.

While the antibody test searches for antibodies related to HIV in people’s blood, antigen/antibody tests search for both HIV-related antigens and antibodies, the antibody test is the most rapid and the only test approved by the Food and Drugs Administration (FDA) for self-administration (Centers for Disease Control and Prevention, 2022). Diversely, the antigen/antibody test is commonly performed in labs. However, in both cases, tests conducted on blood produce results sooner than when conducted on other body fluids.

Ultimately, the NAT test for the actual virus in human blood. In this case, the healthcare provider draws blood from the individual’s vein and sends it to the lab for testing. Apart from telling the HIV status of an individual, NAT also reveals the amount of virus in the blood. Consequently, NAT detects the presence of HIV infection faster than the other two methods (Centers for Disease Control and Prevention, 2022). It is also the only way patients can confirm their HIV status after exposure to the virus, yet they keep testing negative for the infection through the other two tests.

Treating HIV Disease

The Incurable Nature of HIV

The HIV pathophysiological process results in the formation of a latent viral reservoir. In detail, HIV merges with the host DNA during its lifecycle. Subsequently, a subset of the merged pro-virus maintains a transcriptional silence, producing neither viral progeny nor viral protein until it is reactivated by some physiological stimuli (Cummins & Badley, 2015). The latency status of HIV makes some infected cells invincible; hence they escape immune elimination and detection; instead, they constitute the viral reservoir. Although incurable, several drug types are used to treat HIV disease and allow patients to lead healthier and prolonged lives.

Antiretrovirals

Antiretrovirals (ARVs) drugs control the reproduction of HIV in body cells and slow HIV-related disease progression. According to Lippincott and Wilkins (2012), a combination of ARVs referred to as Highly Active Antiretroviral Therapy (HAART) is the most effective and recommended HIV infection treatment. Patients need to take at least three antiretroviral medications per day to follow through with the therapy perfectly. Notably, the Food and Drug Administration (FDA) approves five categories of antiretrovirals.

Nonnucleoside reverse transcriptase inhibitor is the first category; it works to disable the reverse transcriptase HIV enzyme by binding it. Eventually, it limits HIV’s capability to make more viral copies. Some of the drugs in this category include efavirenz, nevirapine, and delavirdine. The second category, including drugs such as didanosine, lamivudine, Abacavir, emtricitabine, stavudine, zidovudine, tenofovir, and zalcitabine is the Nucleoside reverse transcriptase inhibitors (Lippincott & Wilkins, 2012). These are faulty building block versions required by HIV to replicate itself. Notably, when an individual uses this category of ARVs, HIV reproduction comes to a stop courtesy of the faulty perception that replication building blocks already exist.

The third category, Protease inhibitors, act almost the same as Nucleoside reverse transcriptase inhibitors; they disable the HIV protein, protease needed for the virus to replicate (Lippincott & Wilkins, 2012). Notably, these inhibitors bind the enzyme protease’s active part, preventing viral peptide cleavage. Therefore, Protease inhibitors are best for reducing the viral load and slowing the progression of HIV (Yetman, 2021). The enzyme is also essential in protein sample preservation from dehydration, through the deactivation of enzyme protease in cell lysate. Succinctly, in the presence of these inhibitors, HIV produces only non-infectious particles. This category of ARVs include atazanavir, amprenavir, lopinavir, fosamprenavir, saquinavir, nelfinavir, indinavir and lopinavir (Lippincott & Wilkins, 2012). This category of inhibitors aids patients attains long life, almost similar to healthy people, free from the virus.

The other important category is the Fusion inhibitors. These inhibitors, such as Enfuvirtide, block the virus from entering the host cells. Notably, they stop the merging of the HIV envelope with the cell membrane of the CD4 cell. Since HIV cannot replicate outside the host cell, the fusion inhibitors lower the viral load in the infected human body (editorial Team, 2019).

Last but not least of the ARVs category is the Integrase inhibitors. Based on their names, inhibitor, such as Raltegravir, bictegravir, elvitegravir, and dolutegravir, is responsible for inhibiting HIV DNA insertion into the human DNA through enzyme integrase. HIV cannot enter CD4 cells and multiply without enzyme integrase; therefore, the presence of the inhibitor in the body denies the virus access to the cells, limiting its action against the human body’s defense system (Jennifer, 2018). If a patient takes integrase inhibitors according to plan, they can have their HIV levels reduced to undetectable levels. Subsequently, the patient cannot transmit the virus to uninfected individuals. Also, with a combination of the other ARVs categories, the patient can lead a quality life, like individuals living without the virus.

Antineoplastic and Anti-infectives

In addition to the ARVs, HIV-positive individuals, especially at the AIDS stage, need antineoplastic and anti-infective interventions to simultaneously treat associated cancers and opportunistic diseases (Lippincott & Wilkins, 2012). Cancer treatment for HIV and AIDS patients is similar to the treatment of healthy individuals. Notably, antineoplastics can be the primary cancer treatment therapy or used alongside other interventions, such as surgery, hormone therapy, radiation therapy, targeted therapy, and immunotherapy, as secondary treatment interventions. For instance, Yetman (2021) revealed that antineoplastic is necessary for shrinking cancerous tumors before or after the administration of other treatment interventions.

Conclusion

The anatomy and physiology or pathophysiology of HIV are evident in all aspects of the HIV disease. Notably, the explanation of the HIV infection, transmission, progression, testing, and treatment depend on the virus’s structure and how it interacts with the CD4 cells and affects immunity. Considering HIV treatment, enzyme, and process inhibition were the focus of drug development to treat the virus. However, the disease is incurable due to its physiological process, notably the latent viral reservoir. Also, the HIV tests emanate from a good understanding of HIV action in blood, hence the detection of HIV-related antigens and antibodies. Diversely, considering the complexity of the virus’s anatomy and physiology, it is incredible how medicine can help manage the disease to levels of HIV becoming undetectable and subsequently eliminating transmission. It is crucial for anyone to keep checking their HIV status, and possibly apply all three testing methods to confirm their HIV status. Upon discovering the virus in an individual’s body, it is recommended that they start ART immediately to increase their chances of living a longer and healthier life.

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