Infectious Diseases HIV Notes PDF

# Infectious Diseases HIV ## Disclaimer These study notes on infectious diseases are based on my own research and understanding. Where information was omitted or unclear, AI assistance was used to fill in the gaps. While every effort has been made to ensure accuracy, these notes do not guarantee a...

# Infectious Diseases HIV ## Disclaimer These study notes on infectious diseases are based on my own research and understanding. Where information was omitted or unclear, AI assistance was used to fill in the gaps. While every effort has been made to ensure accuracy, these notes do not guarantee a pass or success in any examination or assessment. Always refer to official textbooks, peer-reviewed articles, and guidelines for comprehensive and authoritative information. ## What is HIV? - A rapidly multiplying virus - up to 1x10⁶(million) times a day. - This rapid multiplication leads to: - Genetic 'mistakes' during replication - Resulting in different types and strains of HIV ## 2 types of HIV: 1. **HIV-1 (Mr. worldwide)**: The most common and pathogenic type, consisting of 4 sub-groups, each with many sub types, but they are clinically identical. 2. **HIV2 (West-Africa)**: has lower pathogenicity and lower Mother-To-Child-Transmission risk (MTCT) ## Regardless of viral type, HIV is treated the same. - Different types of viruses may be important in development of future vaccines. ## Viral structure <start_of_image> където `gp 120 + gp 41 = 1 "spike"` - **Glycoprotein**: - **Capsid (p24)**: - **Error prone RNA**: - (two identical strands) - **Reverse transcriptase**: - **Envelope**: - **Matrix**: - **Viral core**: ## Replication cycle | Stage | Description | |---|---| | Binding | HIV binds to the host cell's membrane. | | Fusion and Entry | HIV fuses with the host cell's membrane and injects its genetic material into the cell. | | Reverse Transcription | HIV's RNA is converted into DNA. | | Integration | HIV's DNA integrates into the host cell's DNA. | | Transcription | HIV's DNA is used to create more viral RNA and proteins. | | Protein synthesis | Viral proteins are produced from the viral RNA. | | Assembly | New viral particles are assembled. | | Maturation | Viral particles mature and become infectious. | | Budding | New viral particles bud off from the host cell. | ## 1. Binding to cell: - **HIV Multiplication:** - HIV enters and uses host cells to multiply. - Host cells targeted: CD4 lymphocytes. - **Attachment and Entry:** - HIV attaches to CD4 receptors using its spike protein = gp120 + gp41 - **CD4 receptors**: CXCR4 or CCR5 (chemokine receptors) - These receptors are only found on CD4 cells - **Binding Process:** - Binding depends on the type of cell and the stage of the disease. - Binding causes a conformational change in gp120, allowing fusion and entry into the host cell. ## 2. Reverse Transcription: - **Post-Binding and Fusion:** - Capsid containing RNA strands and enzymes enters CD4 cells. - **RNA to DNA Conversion:** - RNA strands are converted to DNA in the cytoplasm (retroversion). - Single-stranded RNA is retroverted to double-stranded DNA by the reverse transcriptase enzyme. ## 3. Integration into host's DNA: - **RNA to DNA Integration:** - The virus retroverts RNA to DNA so that viral DNA can attach to host DNA. - This process occurs in the nucleus of the host cell. - Newly made HIV DNA moves to the nucleus. - **Integration Process:** - HIV DNA is spliced (integrated) into the host DNA. - The enzyme responsible for this process is integrase. - Integrated viral DNA is referred to as a provirus. ## 4. Transcription : - **Provirus Formation:** - The host cell nucleus now contains the genetic information of HIV, known as the provirus. - HIV uses the host cell to replicate itself. - **Replication Process:** - Viral DNA is transcribed into mRNA and genomic RNA using the host's enzymes - These RNA strands are transported out of the nucleus to the cytoplasm. - mRNA is translated into new viral proteins using the host's enzymes and ribosomes. - **Activation:** - Cytokines, which are secreted during an immune reaction against opportunistic infections, may activate this replication step. ## 5. Assembly and Budding: - **Assembly of New Virions:** - Newly made HIV core proteins, enzymes, and genomic RNA move towards the surface of the cell. - New, immature viral particles (virions) assemble. - These virions bud off from the host cell, taking some of the cell membrane with them. - Virions are not infectious outside the host. - **Protease Processing:** - The protease enzyme starts processing proteins in the newly formed virus. - It finishes by cutting HIV processing proteins in the protein chains into individual proteins. - These proteins combine to make a new, working virus. - The process is completed by the formation of the capsid core & lipid envelope. ## Dynamics of HIV | Parameter | Value | |---|---| | Extracellular half-life| < 6 hours | | Production cycle | ± 2.6 days | | Infected CD4 cell half-life | ± 1.6 days | | Virions produced per day | ± 4-10 billion | | Virions produced over 10 years | ± 37.6 trillion | | CD4 cells destroyed per day | ± 1.8 billion | ## Transmission of HIV - **Blood or blood products (Plasma)** - **Semen** - **Vaginal secretions** - **Breast milk** - **Other body fluids containing blood** ## Unique features of HIV: - Binds to: - Immune cells - CD4 T cells (primary target) - Also, monocytes, macrophages and other WBCs. - Other cells - Microglia, gastro-intestinal epithelium, lungs, heart and kidneys ## Effect differs depending on the cell infected: - Kills CD4 T-cells - Keeps macrophages alive = serves are reservoir for virus - **HIV escapes the body's immune response:** - **HIV mutates due to reverse-transcriptase being error-prone:** - Mutation can be lethal to the virus, - Causes a more virulent virus, which is not recognized by host's antibodies or immune cells. - **Immune cells become dysfunctional or are killed** - **HIV inserts itself into cell's genome, where anti-retroviral drugs can't reach it** - Viral DNA is not permanently incorporated however and cannot be inherited by offspring - **Heterogeneity of viral strains cause different strains to infect different persons & different cell types** ## How does HIV cause immune-deficiency and diseases? ### Recap immunology: | Immune System | Components | Functions | |---|---|---| | **Innate Immunity** | Skin, Natural killer cells, Phagocytic cells, Various blood borne molecules | Acts as the first line of defense, Provides physical barriers | | **Acquired Immunity** | T-cells, B-cells, Antibodies, Lymphocyte-derived cytokines | Distinguishes between self and foreign entities, Has memory responses, Provides cell-mediated and humorally (anti-bodies) mediated immunity | ### Lymphocytes: - Are type of white blood cell crucial for the acquired immune response. ### T Cells: - T Helper (CD4): Synthesize and release cytokines to regulate other immune cells. (TARGET OF HIV!) - T Cytotoxic (CD8): Kill virus-infected cells and cancer cells. ### NK (Natural Killer) Cells: - Kill virus-infected cells and cancer cells. ### B Cells: - Produce antibodies that help in the destruction of viruses and assist in killing bacteria. ### Macrophages and Dendritic Cells: - Interact with T Helper (CD4) cells, influencing their activity. - Present antigens to T -Helper cells, activating them. - Release cytokines that promote the differentiation and activation of T cells & B cells. ### CD4 T cells: - **Immune Response:** - Produce lymphokines upon contact with antigens. - Function as memory cells. - Activate B cells for long-term immune response. - Act as reservoirs for HIV, continuing the infection - **Clinical Significance:** - Used for clinical staging and assessing the need for prophylaxis (treatment that prevents a disease) against opportunistic infections. - Crude measurement of immunological health, but still used clinically. - **Factors Affecting CD4 Count:** - Intercurrent illnesses (other ongoing illnesses). - Time of venesection (blood draw). - Recent vaccinations. - Nutritional status. ### When HIV attacks and destroys CD4 cells this happens: - ↓ CD4 levels = ↑ vulnerability to various infections and cancers. - Activation of dormant infections - TB and Herpes zoster (shingles = adult chicken pox). - ↑ risk of developing certain cancers e.g. Kaposi's Sarcoma - HIV also causes micro inflammation of blood vessels (arteritis) and other tissue. ## Transmission of HIV - **HIV Entry and Initial Capture:** - HIV enters the body through the genital epidermal layer during sexual transmission. - Dendritic Cells: The virus is captured by dendritic cells via specific receptors on their surface. - These cells act as messengers in the immune system. - Capturing pathogens like HIV and presenting them to other immune cells to initiate a response. - However, HIV can exploit this mechanism to spread within the body. - **Transport to Lymph Nodes:** - Movement: The dendritic cells transport HIV to lymph nodes located within the genital tract and rectal wall (in cases of anal infection). - Lymph nodes are small, bean-shaped structures that act as filters for foreign particles and are crucial in the immune response. - **Activation of Immune Cells:** - B and T Cells: Within the lymph nodes, B cells and T cells are activated in response to the presence of HIV. - B cells are responsible for producing antibodies, while T cells can directly kill infected cells or help other immune cells respond to the infection. - HIV targets CD4+ T cells(a subset of T cells) which are crucial for orchestrating the immune response. - **Dissemination (act or process of spreading something widely):** - Spread: HIV spreads throughout the body via the lymphatic system → leading to systemic infection. - The lymphatic system is a network of tissues and organs that help rid the body of toxins and waste, including the lymph nodes, spleen, and thymus. - HIV uses this system to disseminate throughout the body, leading to widespread infection. ## Course of HIV infection - **Early Phase: Acute Infection (Seroconversion)** - HIV Entry: HIV enters the bloodstream, causing a high viral load within days to weeks, accompanied by a decline in CD4 levels. - **Acute Infection Phase:** - Seroconversion: HIV antibodies are produced, and CD8 cells proliferate to reduce viral levels in the blood. - Timeline: Approximately 4-6 weeks post-infection, CD4 counts begin to recover, and the HIV viral load slowly declines. - **Set Point:** HIV is never completely eliminated but declines to a maximal level, known as the set point. - **Window Period:** The time between initial infection and the development of HIV antibodies - **Acute Infection Syndrome:** During this phase, HIV+ patients may experience flu-like symptoms such as fever, sore throat, headache, body aches, swollen lymph nodes, and rash. Generally not considered serious, brushed off as common flu. - **Post Seroconversion/Latent Phase** - Viral Load: Drops to a plateau (set point) and persists for years. - Duration: Typically, 10-12 years, but varies widely. ### Systemic: - Elevated body temperature (Fever) - Weight loss - thrush - Pharyngitis - Oesophagus: Sores - Mouth: Sores, Thrush - Muscles (and joints): Sore/painful ache - Liver and Spleen: enlarge ### Central: - Malaise - Headaches - Lymph Nodes: Swollen, Tender - Skin: rash ### Gastric: - Nausea - Vomiting - 10% progress to AIDS within 2 years. - 5% maintain normal CD4 counts after >12 years. - **CD4 Count:** Gradually declines over time. ### Viral Load Set Point - **Determination:** By host immune response. - **Disease Progression Marker:** - Higher set point → Rapid CD4 decline → Faster progression to AIDS. - Lower set point → Slower progression. ### Duration of Latent Phase Influences - **Factors:** - Age (shorter in children). - Host factors (genetic mutations like CCR5, immune activation). - Viral factors (type, strain, virulence, viral load). - Co-infections. - Access to treatment for early opportunistic infections. ### Clinical Latency - **Active Viral Replication:** - Accumulation of viruses in CD4 cells and dendritic cells. - Reservoirs in lymph nodes and lymphoid organs. - Breakdown of lymph node structure, not recovered with ARVs. - **Immune System Involvement:** - Cytokine dysregulation and immune hyperactivation. - Activated CD4 cells allow greater HIV replication. - Activated B cells may impair antibody synthesis. - Chronic immune activation leads to apoptosis and increased pro-inflammatory cytokines. ### Later Phase: Immune Deficiency and Organ Involvement - **HIV Infection:** Damages immune cells (CD4). - **CD4 Cells:** - Vital for immune system regulation and control. - Protect against infections and newly developed cancer cells. - Produce cytokines (ILs and IF). - Influence development and function of other immune cells (macrophages, monocytes). ### How HIV Destroys Cells - **Direct Cell Killing:** Disrupts cell membrane when large amounts of virus particles bud out or interfere with cellular machinery. - **Apoptosis:** Induces “cell suicide” in infected and uninfected cells due to abnormal cellular activation. - **Antibody-Dependent Cellular Toxicity:** Cells marked by HIV are destroyed by T cytotoxic lymphocytes (CD8), even without virus entry. - **Damage to Precursor Cells:** Affects bone marrow and leads to lymph node destruction. - **CD4 Count Drop:** After 5-10 years, CD4 count drops to critical levels, impairing immune function. - **Asymptomatic HIV Phase:** Some individuals show no symptoms, while others may have symptoms earlier or much later. - **Emerging Evidence:** HIV stimulates micro-inflammatory processes, causing diseases in various organs (kidneys, liver, heart, brain). ### Immune Deficiency - **Long-Term Infection:** After 3-7 years, large numbers of viral particles destroy immune cells, leading to immune deficiency. - **Monitoring:** Progress can be tracked by measuring CD4 count and viral load. - **ARVs:** Antiretroviral drugs can prevent, delay, or reverse the process. ### Natural Response to HIV Infection - **Variation in Response:** Some people experience damage and illness earlier than others. ### Slow Progressors: - Remain well and active for 10-15 years or more with little to no immune deficiency. ### Rapid Progressors: - Develop immune deficiency within 3-7 years due to aggressive viral strains. ### Factors Influencing Progression: - Type of Viral strain, infection dosage, body's response, general health, and genetics. ## 4. AIDS (Acquired Immune Deficiency Syndrome) - **Definition:** - **Acquired Immune Deficiency Syndrome** - **CDC:** CD4 count < 200 cells/µl or presence of one of the defining illnesses. - **WHO:** Stage 3 or 4 of HIV infection. - **Prognosis:** Without treatment, life expectancy is approximately 18 months in settings with sophisticated healthcare. ### Examples of AIDS-Defining Illnesses (CDC) - Candidiasis: Of bronchi, trachea, lungs, oesophagus. - HIV-Related Encephalopathy. - Herpes (HSV): Chronic ulcer >1 month. - Kaposi's Sarcoma. - Extrapulmonary or Disseminated Tuberculosis. - Mycobacterium Avium Complex. - Pneumocystis Carinii. - Recurrent Pneumonia. - Toxoplasmosis of the Brain. - Wasting Syndrome Due to HIV. ### AIDS-Associated Infectious Diseases - **Depends On:** - Latent infections (e.g., VZV, CMV, TB). - Exposure to different germs (e.g., TB). ### Examples: - **Bacteria:** Pneumocystis carinii, Mycobacterium tuberculosis. - **Viruses:** HSV, CMV. - **Parasites:** Toxoplasmosis. - **Fungi:** Candida albicans. ### Systems Affected by AIDS - **Infectious, Auto-immune, and Cancerous Diseases.** - **Affected Systems:** - Nervous system (central and peripheral). - Digestive system. - Skin. - All other systems. ### Types of Germs: - Opportunistic and “normal” bacteria, viruses, fungi, and parasites. ## Relationship Between CD4 Count and Risk of Opportunistic Infections and Cancers - **CD4 Count:** Lower counts increase the risk of infections and cancers. ### Common Infections and Conditions: - Herpes simplex, fatigue, TB, lymphadenopathy, skin infections, vaginal candidiasis, CMV, MAC, CNS lymphoma, toxoplasmosis, oesophageal candidiasis, cryptococcosis, herpes zoster, bacterial pneumonia, oral hairy leukoplakia, thrush, fever, diarrhoea, weight loss, Kaposi's sarcoma, non- Hodgkin's lymphoma, Pneumocystis jirovecii pneumonia. ### Relationship CD4 / risk of developing opportunistic infections and cancers - **Early HIV infection; seroconversion illness** - **'Silent' or latent phase** - **Minor symptomatic phase** - **AIDS-defining diseases** - **AIDS-severe opportunistic diseases** ### Natural Resistance to HIV Infection - Genetic Mutations: Certain mutations in the chemokine co-receptor (e.g., CCR-5 gene) may confer resistance. - Homozygous Deletion: Total resistance. - Heterozygous Deletion: Slower disease progression. - Limited to HIV-1: Evidence of resistance without this deletion exists. ## ARVs (Anti Retro Viral Drugs) - **Function:** Interfere with the virus's reproduction cycle by inhibiting viral enzyme action at specific sites, preventing replication. - **Limitations:** Cannot destroy viral cDNA once integrated into host cells. ### Benefits: - Reduce immune cell destruction, indirectly protecting against opportunistic infections. - Prevent the development of AIDS, but do not cure HIV infection. ### Administration: - Oral drugs with challenges in bioavailability and distribution to tissues (e.g., lymph nodes, brain, testes). ## Antiretroviral Drugs (ARVs) - **Purpose:** Interfere with the HIV virus reproduction cycle, inhibiting viral enzyme action to prevent replication. ### Function: - Stop the virus from being made but cannot destroy viral cDNA once integrated into host cells. - Limit immune cell destruction, indirectly protecting the body from opportunistic infections. - Prevent the development of AIDS but do not cure HIV infection. ### Administration: - Oral drugs - Challenges in bioavailability and distribution to tissues (e.g., lymph nodes, brain, testes). - While ARVs are effective in managing HIV, their oral administration can pose challenges in ensuring that enough of the drug reaches all the necessary tissues in the body to fully combat the virus. ## Classes of ARVS ### 1. Nucleoside Reverse Transcriptase Inhibitors (NRTIs) - Target the HIV-specific reverse transcriptase enzyme. - Mimic natural nucleosides, blocking enzyme action and terminating DNA chain elongation. ### Examples: 1. Zidovudine (AZT) - Thymidine analogue 2. Stavudine (D4T) - Thymidine analogue (NB) 3. Lamivudine (3TC) - Cytosine analogue 4. Didanosine (ddi) - Guanosine analogue 5. Tenofovir (TDF) – Adenosine analogue ### 2. Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs) - Bind directly to the catalytic centre of the reverse transcriptase enzyme. - Hamper nucleotide binding, slowing or stopping DNA synthesis. ### Examples: Efavirenz (EFV) (NB), Nevirapine (NVP). ### 3. Protease Inhibitors (PIs) - Target the HIV-specific protease enzyme. - Inhibit enzyme action, hampering the formation of new virus particles ### Example: Lopinavir/ritonavir – LPV/r (Kaletra/Alluvia). ### 4. Integrase Strand Transfer Inhibitors (INSTIs) - Target the HIV-specific integrase enzyme. - Inhibit enzyme action, preventing the integration of viral DNA into the host cell DNA. ### Example: Dolutegravir (DTG) ### 5. Capsid inhibitors ### 6. Fusion inhibitors ### 7. CCR5 (co-receptor) antagonists ### 8. Post-attachment inhibitors - Entry inhibitors (attachment inhibitors) ## HAART - **Highly Active Antiretroviral Treatment** ### Consist of administering 3 or more ARVs - why: - Using a combination of three or more antiretroviral drugs (ARVs) helps to prevent the HIV virus from developing resistance. This multi-drug approach targets the virus at different stages of its lifecycle, making it more effective in reducing the viral load in the body. ### HAART is lifelong - why: - HAART is a lifelong treatment because HIV is a chronic infection that cannot be cured with current medical technology. Continuous treatment is necessary to keep the viral load suppressed, maintain immune function, and prevent the progression to AIDS. ### Adherence is most important - why: - Adherence to HAART is crucial because missing doses can lead to the development of drug-resistant strains of HIV. Consistent medication intake ensures the viral load remains low, which helps in maintaining health and reducing the risk of transmission to others. ### Also includes: - Prevention/treatment of opportunistic infections and cancer. - Prevention of HIV transmission - Specific antiviral treatment - Immune boosters - Psychological support → adherence counselling - Prevention/treatment of nutritional deficiencies ### Results: - Quantitative ↑ in CD4 + CD8 T cells - Qualitative improvement in CD4, CD8, monocyte function. - ↓ immune activation - **IRD = Immune Restoration Disease** - When the immune system is restored by HAART, an ongoing opportunistic infection might still remain untreated, leading to systemic inflammation. ### Goals of HAART: - Impossible to fully eradicate HIV → 2nd best is controlling the virus for a very long time → decrease individual related morbidity and mortality. - Decrease viral load to lower than detectable limit (LDL). - Partial recovery of immune system, by increasing CD4 cell count. - Improve quality of life - Increase survival and duration of infection-free life - Limit HIV transmission - There is still a small chance of transmission via body fluids! - Smaller viral load = smaller risk of transmission - Before the introduction of HAART, 85% of patients diagnosed with AIDS would die within three years. Now, with HAART, 85% of patients are still alive three years after an AIDS diagnosis, with even better outcomes for those who start treatment before reaching the AIDS stage. ### Largest Public Service Program: - South Africa has the largest public antiretroviral (ARV) treatment program globally, with over 510,000 people on ARVs. ### Who is Treated? - Individuals with a CD4 count < 350. - Patients in stages 3 or 4 of HIV, even if their CD4 count is > 350. - HIV-positive pregnant women. ### Regimen: - **First Line:** 1 NNRTI (Non-Nucleoside Reverse Transcriptase Inhibitor) + 2 NRTIs (Nucleoside Reverse Transcriptase Inhibitors). - **Second Line:** 2 NRTIs + PI (Protease Inhibitor). ### Regimen Changes: - If there are signs of intolerance to one of the drugs, switch to another first-line drug or one from the second line. - In cases of virological failure, switch to the second regimen. ## WHO staging - **World Health Organization** - Stages patients according to severity of disease progression - You don't have to study each and every opportunistic, note however that many of them are fungal, protozoa, or bacterial infections that do not normally infect people unless their immune system is significantly weakened. These infections take advantage of the weakened immune defences in people with advanced HIV/AIDS. | WHO Stage | Clinical Conditions | |---|---| | Stage 1 | Asymptomatic, Persistent generalized lymphadenopathy (PGL), Acute retroviral infection (seroconversion illness) | | Stage 2 | Moderate unexplained weight loss (<10% of body weight), Recurrent respiratory tract infections (RTIs: sinusitis, bronchitis, pharyngitis), Herpes zoster, Angular cheilitis, Recurrent oral ulcerations, Papular pruritic eruptions, Seborrhoeic dermatitis, Fungal nail infections (of fingers) | | Stage 3 | Severe weight loss (>10% of body weight), Unexplained chronic diarrhoea (longer than one month), Unexplained persistent fever (longer than one month), Oral candidiasis, Oral hairy leukoplakia, Pulmonary tuberculosis (diagnosed in last two years), Severe presumed bacterial infections (e.g., pneumonia, empyema, pyomyositis, bone/joint infection, meningitis), Acute ulcerative stomatitis, gingivitis, or periodontitis, Unexplained anaemia, neutropenia, or thrombocytopenia (for more than one month) | | Stage 4 | HIV wasting syndrome, Pneumocystis pneumonia, Recurrent severe or radiological bacterial pneumonia, Chronic herpes simplex infection (orolabial, genital, or anorectal >1 month), Oesophageal candidiasis, Extrapulmonary tuberculosis, Kaposi's sarcoma, CNS toxoplasmosis, HIV encephalopathy, Extrapulmonary cryptococcosis (including meningitis), Disseminated non-tuberculous mycobacterial infection, Progressive multifocal leukoencephalopathy (PML), Candida of trachea, bronchi, or lungs, Cryptosporidiosis, Isosporiasis, Visceral herpes simplex infection, Cytomegalovirus (CMV) infection (retinitis or organ other than liver, spleen, lymph nodes), Any disseminated mycosis (e.g., histoplasmosis, coccidiomycosis, penicilliosis), Recurrent non-typhoidal salmonella septicaemia, Lymphoma (cerebral or B-cell non-Hodgkin), Invasive cervical carcinoma, Visceral leishmaniasis | ## Diagnosis ### Why would we want to test for HIV? - **Clinical Suspicion:** - **Clinical History:** Includes sexual history and history of infections - **Clinical Signs:** Look for signs of infection, opportunistic infections, and wasting. ### How would we test? - **Appropriate Laboratory Testing:** - **Non-Specific Tests:** Determine if there is any infection, such as an increased white cell count. - **Specific Tests:** Provide proof of specific infections. ### Tools: - Clinical picture and history (history of opportunistic infections or contact with HIV). - Microscope - Light/Electron microscopy. - Culture assays - Anti-bodies = used to indirectly assess immune response to infection ### Choosing the most appropriate testing method? - **What are we looking for?** - The virus or antibodies? - Time course of infection - Different targets for testing can either be present or not depending on the course of infection. - Mother-to-child transmission (MTCT) of infections like HIV illustrates how different testing targets are relevant at different stages: - **Early Infection:** Direct virus detection (e.g., PCR) is crucial because maternal antibodies can interfere with antibody tests. - **Later Stages:** Antibody tests become more relevant as the infant's immune system responds, but maternal antibodies can still complicate results. ### Testing for HIV antibodies - **Antibody Development:** When a person is infected with HIV, their immune system produces antibodies against HIV antigens. - **Seroconversion:** This process, where antibodies become detectable, is called seroconversion. It can be delayed for up to 3 months after infection. - **Persistence:** Once developed, these antibodies persist for life. - **Detection:** HIV antibodies are readily detectable through various testing methods. ### Screening vs confirmatory tests? - **Screening Tests:** - **Highly Sensitive:** These tests should detect the virus even at very low viral loads, ensuring that a positive result indicates the presence of the virus. - **Clinical Usefulness:** Most useful when a negative result confidently indicates the absence of HIV. - **Confirmatory Tests:** - **Highly Specific:** These tests should only return a positive result if the specific strain of HIV being investigated is present, minimizing false positives - **Clinical Usefulness:** Most useful when a positive result confirms the presence of HIV, distinguishing it from other conditions ### Examples of tests used for antibodies: - **ELISA (Enzyme-linked immunosorbent assay)** - **Function:** Uses HIV antigen to capture HIV antibodies in blood. - **Purpose:** Primarily for diagnostic screening. - **Detection:** Both HIV-1 and HIV-2. - **Accuracy:** 99.99% sensitivity and specificity. - **Usage:** Most widely used serological technique. - **Rapid test** - **Ease:** Easy to perform, no training needed, and cost-effective. - **Type:** Immuno-chromatographic. - **Validation:** Control used to validate results. - **Purpose:** Used for screening and can be confirmatory. - **Accuracy:** High sensitivity and specificity. - **Western Blot** - **Advantages:** Western Blotting can distinguish between different antibodies and possesses high sensitivity and specificity. - **Current Use:** It is no longer used for confirmation in HIV testing, largely replaced by faster and more sensitive methods like 4th gen immunoassays. ### Testing for the virus (HIV): - **Detection:** Viral nucleic acid (DNA or RNA) is detected. - **Advantages:** - **Early Detection**: The virus can be detected from the primary infection stage. - **Accuracy:** There is a lower chance of false negatives compared to antibody tests. ### Examples of tests used for virus: - **P24Antigen** - **Protein:** P24 is a core protein of HIV. - **Detection:** During high viral replication periods (primary infection and AIDS). - **Limitations:** Not highly detectable during the asymptomatic phase. - **Purpose:** Confirmatory test, not a replacement for antibody tests. - **Accuracy:** Poor sensitivity, good specificity. - **PCR (Polymerase Chain Reaction)** - **Primers:** Target specific portions of the HIV genome. - **Process:** Exponential increase in detectable DNA through DNA polymerase. - **Detection:** Can detect a single copy of HIV DNA/RNA in a blood sample. - **Accuracy:** Very high sensitivity and specificity. - **Tissue Culture** - **Growth:** HIV can be grown in cell culture. - **Usage:** Rarely used in clinical settings, mostly for research. - **Process:** Incubation with fresh peripheral blood mononuclear cells and IL-2. - **Detection:** Visible microscopically, detection of p24 antigen or reverse transcriptase activity. - **Accuracy:** High sensitivity and specificity. ### Other Tests for HIV: - **Saliva, Vaginal Fluid, and Urine** - Saliva and Vaginal Fluid: These can be used for HIV testing, though they are less common than blood tests. - Urine: Viral load is typically low in urine, making it less effective for diagnostic purposes. - **Usage:** - **Surveillance Studies:** These tests are more useful in surveillance studies rather than for diagnostic purposes. | Test Type | Test Name | Function/Process | Purpose | Detection | Accuracy | Usage | |---|---|---|---|---|---|---| | **Antibody Tests** | ELISA | Uses HIV antigen to capture HIV antibodies in blood | Diagnostic screening | Both HIV-1 and HIV-2 | 99.99% sensitivity and specificity | Most widely used serological technique | | | Rapid Test | immuno-chromatographic easy to perform, no training needed, cost-effective | Screening and confirmatory | HIV antibodies | High sensitivity and specificity | Widely used for quick results | | | Western Blot | Distinguishes between different antibodies, high sensitivity and specificity | Previously used for confirmation | HIV antibodies | High sensitivity and specificity| Largely replaced by faster methods like 4th gen immunoassays | | **HIV Virus Tests** | P24 Antigen | Detects P24 core protein of HIV during high viral replication periods | Confirmatory test| HIV during primary infection and AIDS | Poor sensitivity, good specificity | Not highly detectable during asymptomatic phase | | | PCR (Polymerase Chain Reaction) | Targets specific portions of the HIV genome, exponential increase in detectable DNA | Detects single copy of HIV DNA/RNA | HIV DNA/RNA | Very high sensitivity and specificity | Highly accurate, used for early detection | | | Tissue Culture | Grows HIV in cell culture, incubation with fresh peripheral blood mononuclear cells and IL-2 | Research | HIV | High sensitivity and specificity | Rarely used in clinical settings, mostly for research | ## Understanding HIV Test Results: - **a. Positive Result:** - Indicates the presence of HIV antibodies or viral components, confirming HIV infection. - **b. Negative Result:** - Indicates the absence of detectable HIV antibodies or viral components. However, it may not rule out recent infection if within the window period. - **c. Confirmatory (Second) Test:** - Should be done if the initial test is positive to confirm the result. - Also recommended if there is a high-risk exposure or symptoms suggestive of HIV despite a negative initial test. - **d. Trusting the Results:** - Generally, HIV tests are highly accurate, but confirmatory tests are essential to rule out false positives or negatives. ### False Positive Results: - **Frequency:** 0.0004% - 0.0007%. - **Common Causes:** Vaccinations (e.g., influenza) due to protein similarities. - **Action:** Repeat test if no other evidence of infection. ### False Negative Results: - **Common Causes:** Technical errors, testing during the window period. - **Window Period:** Can take up to 6 months to detect antibodies in some people (average 3-6 weeks). ### Testing in Newborns: - Infants born to HIV+ mothers can test positive for up to 18 months due to maternal antibodies. - Most effective test: PCR. - Risk Factors: High maternal viral load and lack of ARV therapy. # Infectious diseases SARS-CoV-2 ## Disclaimer These study notes on infectious diseases are based on my own research and understanding. Where information was omitted or unclear, Al assistance was used to fill in the gaps. While every effort has been made to ensure accuracy, these notes do not guarantee a pass or success in any examination or assessment. Always refer to official textbooks, peer-reviewed articles, and guidelines for comprehensive and authoritative information. ## Corona viruses: - **What?** - Large & diverse group of respiratory viruses that infect a multitude of species - **Targets:** - Bats, camels, cats & humans - **Examples:** - Middle East Respiratory Syndrome - Severe Acute Respiratory Syndrome - SARS-CoV-2 | Feature | SARS (2002) | MERS (2012) | SARS-CoV-2 (COVID-19, 2019) | |---|---|---|---| | First Reported | 2002 in China | 201