By Zara Saad
Abstract
HIV continues to pose a significant challenge to global public health, with an estimated 42.3 million fatalities attributed to the virus thus far. The transmission of HIV persists across all nations worldwide. Despite extensive research efforts, numerous misconceptions about the virus remain prevalent. Therefore, this paper seeks to develop a thorough understanding of the mechanisms and functions of HIV. It seeks to examine the related signs and symptoms, the various transmission methods, and associated risk factors and offers an in-depth discussion of the current treatments available.
Methodology
Formulating this paper employed research done utilizing online databases such as Google Scholar to locate articles about the immunological mechanisms and pathogenesis of HIV. The data collection process involved an examination of abstracts relevant to the topic and consulting official websites regularly updated by international health organizations, including WHO. Subsequently, articles that satisfied the metrics of this research paper were assessed rigorously. The selected studies underwent a meticulous evaluation of their soundness and precision of study, and their findings were integrated to elucidate the subject matter in question. The ethical considerations were centered around ensuring proper citation is practiced and plagiarism is prevented.
Introduction
Human immunodeficiency virus (HIV) is a viral infection that systematically destroys specific types of white blood cells and is managed with antiretroviral medications. In the absence of treatment, HIV can progress to acquired immunodeficiency syndrome (AIDS), a condition that is sometimes characterized as the terminal phase of HIV infection. The virus is transmitted through the exchange of infected bodily fluids, which include the likes of semen, vaginal secretions, blood, and breast milk. In addition, it is primarily via vaginal or anal intercourse, sharing of needles, or from an infected mother to her offspring during gestation, childbirth, or lactation. The diagnosis of HIV can be confirmed through blood tests that detect HIV antibodies and quantify the viral load [1].
Currently, there is no cure for HIV; however, with the provision of effective prevention, diagnostic strategies, treatment, and care – including for opportunistic infections – HIV can be effectively managed as a chronic health condition. This management allows individuals living with HIV to maintain long and healthy lives. Organizations such as WHO, the Global Fund, and UNAIDS have developed global strategies in response to HIV that are in line with the Sustainable Development Goal target 3.3, which aims to end the HIV epidemic by 2030. By 2025, it is anticipated that 95% of all individuals living with HIV will have received a diagnosis, of which 95% will be on life-saving antiretroviral treatment, and 95% of those receiving treatment will achieve a suppressed viral load. In 2023, the respective figures for these percentages were reported as 86%, 89%, and 93%. Additionally, WHO classifies Advanced HIV Disease (AHD) as having a CD4 cell count below 200 cells/mm3 or presenting with WHO stage 3 or 4 symptoms in both adults and adolescents. Children under the age of five diagnosed with HIV are automatically categorized as having AHD [2].
Signs and Symptoms
Upon initial infection (Stage 1), a significant number of individuals exhibit no prominent syndrome. However, within a timeframe of one to four weeks, manifestations such as fever, rashes, sore throat, swollen lymph nodes, and fatigue alongside a range of less prevalent symptoms may emerge in some individuals. Typically, the symptoms associated with the primary HIV infection endure for approximately three to fourteen days [2]. Following the resolution of the initial symptoms, the majority of individuals, even in the absence of treatment, either remain asymptomatic or experience only sporadic mild symptoms. This phase of minimal or absent symptoms can persist for an extended period, ranging from two to fifteen years. This is categorized as Stage 2. During this interval, symptoms often reminiscent of influenza may occur, including fever, muscle aches, headaches, night sweats, and oral lesions. Additional symptoms may consist of a sore throat, swollen lymph glands, and diarrhea. Many do not exhibit any symptoms at the initial time of HIV infection.
Nonetheless, if left untreated, nearly all individuals infected with HIV will progress to AIDS (Stage 3). Some may develop AIDS within a few years post-infection, while others may remain symptomatically healthy for periods extending to ten or even twenty years; these individuals are referred to as long-term nonprogressors [3]. The immune system of those with AIDS has been compromised by HIV placing them at a significantly heightened risk for infections that are infrequent among individuals with intact immune systems. These infections termed opportunistic infections, can impact body systems and may arise from bacteria and viruses. Notable examples of such are tuberculosis and certain skin cancers. Furthermore, common symptoms may encompass pneumonia, severe weight loss, and discolouration of skin [4].
Transmission and Associated Risk Factors
The transmission of HIV necessitates the exposure of an open wound, such as a cut, in an infected individual to a body fluid that harbors the virus. While HIV can be found in nearly all body fluids, the primary modes of transmission are through blood, semen, vaginal secretions, and breast milk. Although fluids like tears, saliva, and urine may contain trace amounts of HIV, the likelihood of transmission through these fluids is exceedingly low if it occurs at all. HIV is not transmitted through non-fluid exchange contact, such as touching, holding, or making contact with surfaces or objects. There are no documented cases of HIV transmission resulting from the coughing or sneezing of an infected individual or from mosquito bites. Instances of transmission from a healthcare provider to a patient are also exceedingly rare [3].
The primary routes of HIV transmission include: engaging in sexual activities with an infected individual, where mucous membranes in the mouth, vagina, penis, or rectum come into contact with body fluids like semen or vaginal secretions containing HIV, particularly during unprotected sexual intercourse. Moreover, it can be transmitted via the injection of contaminated blood which can occur through sharing needles by drug addicts or accidental pricks from HIV-infected needles by healthcare workers. Maternal transmission can occur to a child during pregnancy, childbirth, or through breastfeeding. Medical procedures that involve the transfusion of HIV-infected blood, the use of inadequately sterilized instruments, or the transplantation of infected organs or tissues also pose a risk [1, 2, 5]. The likelihood of HIV transmission increases if the skin or mucous membranes are compromised even to a minimal extent. During intercourse, small tears may occur in the genital area or surrounding skin, often without the individual’s awareness [1, 5].
Mechanism - The CD4+ Lymphocyte Dysfunction
HIV is responsible for the development of AIDS by engaging with a diverse array of cells within the host and evading the immune system’s defenses. The infection process entails the interaction of HIV with the CD4 receptor on target cells, as well as with other recently identified cellular receptors. This is followed by the fusion of the virus with the host cell and subsequent entry of HIV. Once inside, various intracellular mechanisms influence the expression of viral regulatory and accessory genes, which can lead to either productive or latent infections. In the case of CD4+ lymphocytes, HIV replication can result in the formation of syncytia and subsequent cell death; conversely, in other cell types such as macrophages, the virus can establish persistent infections, creating reservoirs in multiple tissues and cell types [6].
The progressive reduction of CD4+ T cells observed during HIV infection may be partially attributed to the immune system’s compromised ability to replenish the CD4+ T cell population. Two primary mechanisms are thought to contribute to this impaired regeneration during HIV or simian immunodeficiency virus (SIV) infection: (a) the destruction of lymphoid precursor cells, potentially due to infection as these cells become activated and begin to divide, and (b) the disruption of the microenvironment necessary for the effective regeneration of immune-competent cells [7]. HIV strains exhibit significant genetic diversity, and specific biological and serological characteristics linked to particular genetic sequences can be associated with pathogenic mechanisms and immune evasion. The host’s immune response to HIV, which includes the production of neutralizing antibodies and robust cellular immune responses, can effectively suppress the virus for extended periods. Long-term survival is often associated with infection by a relatively low-virulence strain that remains susceptible to immune responses, particularly the antiviral activity of CD8+ T cells. Various therapeutic strategies have been explored, with additional approaches currently under investigation [7].
Diagnosis
The evolution of HIV diagnostic testing has held significance since its debut in the early 1908s. Modern enzyme immunoassays possess the sensitivity to locate antibodies within one to two weeks post-infection. A range of supplementary assays are crucial for confirming positive antibody screenings, including Western blot and polymerase chain reaction (PCR) tests. Additionally, these assays can complement antibody testing (such as p24 antigen and PCR) or furnish further insights for clinicians managing HIV-positive patients through both, qualitative and quantitative PCR and genotyping [1, 8]. Most diagnostic laboratories implement intricate and meticulous testing algorithms to guarantee result accuracy and optimize laboratory resource utilization. The selection of assays is influenced by initial screening outcomes and clinical contests provided by the physician, both of which are vital for the laboratory’s capacity to deliver precise diagnoses.
Furthermore, laboratories must offer detailed guidance on specimen collection, storage, and transport to maintain specimen integrity, thereby ensuring the reliability of laboratory findings. Studies in recent years illustrate that Point of Care tests have gained considerable traction in the US and regions of Canada, offering quick, on-site HIV results in a format that is straightforward for clinic personnel to administer.
Nonetheless, the efficacy of these tests relies on strict adherence to quality control protocols, alongside the support of a licensed diagnostic laboratory for the clarification and confirmation of positive or indeterminate results. Quality assurance programs in laboratories and participation in HIV proficiency testing initiatives are highly critical in ensuring that diagnostic laboratories yield accurate, timely, and clinically pertinent results [8].
Treatment
Upon the diagnosis of HIV infection, it is imperative to conduct regular blood tests to monitor two critical parameters: the CD4 count and viral load. A diminished CD4 count indicates an increased susceptibility to severe infections and other HIV-related complications, including specific types of cancer. The viral load serves as a predictive measure for the potential decline of the CD4 count over the subsequent years. These two indicators are essential for healthcare providers to ascertain the appropriate timing for initiating antiretroviral therapy, to evaluate the anticipated effects of treatment, and to determine the necessity for additional medications to avert opportunistic infections. With effective treatment, the viral load can decrease to minimal levels within a matter of weeks, while the CD4 count gradually trends toward normalcy [1].
There exists a diverse array of antiretroviral medications categorized into seven distinct classes based on their mechanisms of action against HIV. The selection of a treatment regimen is tailored to the unique requirements of each individual. In this decision-making process, individuals living with HIV and their healthcare professionals take into account various factors, including the potential side effects of the medications and the likelihood of drug interactions. Antiretroviral medications reduce the amount of HIV in the body by preventing its replication. A lower viral burden promotes immune system recovery and increases CD4 cell production. A strong enough immune system can fight infections and some HIV-associated cancers, even if remnants of the virus persist in the body.
Furthermore, antiretroviral drugs lessen the risk of HIV transmission by lowering the viral load. The major goal of HIV treatment is to attain an undetectable viral load which essentially translates to there not being a sufficient amount of HIV present in the bloodstream to be detected by a routine viral load test. When HIV-positive individuals maintain an undetectable viral load, they do not pose a danger of spreading the virus to HIV-negative partners for the most part [9].
Conclusion
Human immunodeficiency virus (HIV) represents a significant public health challenge due to its detrimental impact on the immune system, ultimately progressing to AIDS. It is a notable concern as the virus can manifest and present itself as a plethora of diseases and symptoms whose cause remain undetected until tested for HIV specifically. Although a definitive cure for HIV remains elusive, the implementation of effective prevention and treatment methods enables
control over its spread and for HIV-positive individuals to live a healthy life. Ongoing research and the efforts of global health organizations are focused on the goal of eradicating this virus entirely.
Sources:
Human Immunodeficiency Virus (HIV) Infection By Edward R. Cachay, MD, MAS, University of California, San Diego School of Medicine Reviewed/Revised May 2024 - https://www.msdmanuals.com/home/infections/human-immunodeficiency-virus-hiv-infection/human-immunodeficiency-virus-hiv-infection
World Health Organization’s official website - https://www.who.int/news-room/fact-sheets/detail/hiv-aids?gad_source=1&gclid=Cj0KCQjww5u2BhDeARIsALBuLnOqnxqEm9aG9RpgM2qOXyX63R8cwbUNtCpAV-C04XumwKy_MAjC3MoaAuLAEALw_wcB
What is HIV and AIDS? Reviewed by Jatin M. Vyas, MD, PhD, Associate Professor in Medicine, Harvard Medical School; Associate in Medicine, Division of Infectious Disease, Department of Medicine, Massachusetts General Hospital, Boston, MA. Also reviewed by David C. Dugdale, MD, Medical Director, Brenda Conaway, Editorial Director, and the A.D.A.M. Editorial team. - https://www.pennmedicine.org/for-patients-and-visitors/patient-information/conditions-treated-a-to-z/aids-and-hiv
What are the signs and symptoms of HIV and AIDS (stage 3 HIV)? Medically reviewed by Michaela Murphy, PA-C — Written by Joana Cavaco Silva: https://www.medicalnewstoday.com/articles/321920
Estimating per-act HIV transmission risk a systematic review by Patel, Pragna; Borkowf, Craig B.; Brooks, John T.; Lasry, Arielle; Lansky, Amy; Mermin, Jonathan - https://journals.lww.com/aidsonline/abstract/2014/06190/estimating_per_act_hiv_transmission_risk__a.14.aspx
Pathogenesis of human immunodeficiency virus infection by J A Levy, Department of Medicine, University of California School of Medicine, San Francisco - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC372905/
Immunopathogenic Mechanisms of HIV Infection - Retroviruses by Coffin JM, Hughes SH, Varmus HE, editors.Cold Spring Harbor (NY) - https://www.ncbi.nlm.nih.gov/books/NBK19451/
The Laboratory Diagnosis of HIV Infections - Margaret Fearon, Medical Microbiology, Canadian Blood Services, Toronto, Ontario - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2095005/
https://hivinfo.nih.gov/understanding-hiv/fact-sheets/hiv-treatment-basics
great work!
Really informative!