HIV (Human Immunodeficiency Virus) - Important Information PDF

‫بسم الله الرحمن‬ ‫الرحيم‬ Human Immunodeficiency Virus (HIV) Human Immunodeficiency Virus (HIV) was first recognized in 1981 and is caused by a retrovirus of 2 types: HIV-1 and 2. Pathophysiology  HIV isa Lentivirus, a subgroup of retroviruses.  This family of viruses is known for...

‫بسم الله الرحمن‬ ‫الرحيم‬ Human Immunodeficiency Virus (HIV) Human Immunodeficiency Virus (HIV) was first recognized in 1981 and is caused by a retrovirus of 2 types: HIV-1 and 2. Pathophysiology  HIV isa Lentivirus, a subgroup of retroviruses.  This family of viruses is known for latency, persistent viremia, infection of the nervous system, and weak host immune responses. - HIV has high affinity for CD4 T lymphocytes and monocytes. The virus replicates itself by generating a DNA copy by reverse transcriptase.  Pathophysiology  Viral DNA becomes integrated into the host DNA, enabling further replication.  - Replication of HIV contributes to early death of T cells, depletion of CD4 cells, and immunocompromise, resulting in increased risk for opportunistic infections and development of AIDS. - Progression from HIV infection to AIDS occurs at a median of 11 years after acute infection. Modes of Transmission: 1- Sexual transmission: HIV is transmitted primarily through heterosexual and homosexual contact (over 70%); 2- Parenteral transmission: Transfusion of blood and blood products Use of contaminated needles and syringes e.g. in intravenous drug users (IVDU) (risk of transmission through needle sticks is 0.3%) ° Occupational exposure especially in dentists and surgeons. 3- Vertical / perinatal (mother to child) transmission. Clinical Picture HIV stages according to CDC 4 count: ◦Stage I CD4 500 cells/uL Acute HIV infection ◦Stage II CD4 500 cells/uLAsymptomatic HIV ◦Stage III CD4 350 cells/uL Early Symptomatic HIV ◦ Stage IV CD4 200 cells/uL Late Symptomatic HIV (progression to AIDS) Clinical Picture Stage 1- Acute virus infection (Acute retroviral syndrome) - This stage starts two to four weeks after getting HIV and lasts for one or two weeks. - Symptoms: flu-like illness, fever, pharyngitis, rash, arthralgia, myalgia, headache, nausea, vomiting and generalized lymphadenopathy - In acute stage: The immune system begins to respond to the virus by producing HIV antibodies (seroconversion). Clinical Picture Stage 2 – Asymptomatic Stage ◦Lasts for an average of ten years – ◦No major symptoms ◦- HIV viral load drops to lower levels ◦- Antibody tests will show a positive result. ◦- Virus remains active during this stage. Clinical Picture Stage 3 - symptomatic HIV Disease - Immune system damaged by HIV - Lymph nodes and tissues become non functioning - Body fails to keep up with the loss of T helper cells - The immune system fails and various symptoms develop (unexplained diarrhea lasting more than one month, unexplained fever, weight loss). Clinical Picture Stage 4-— AIDS - AIDS diagnosis is confirmed if a person with HIV develops one or more of the AIDS-defining illnesses and CD4 < 200 cells/uL - AIDS diagnosis NEVER goes away even when the patient’s condition improves AIDS-defining illnesses Bacterial infections: multiple or recurrent, Staph. Aureus, Salmonella septicemia, recurrent  Mycobactertum avium complex (MAC) or Mycobacterium Kansasii, disseminated or extrapulmonary  Mycobacterium tuberculosis of any site, pulmonary, disseminated, or extrapulmonary  Fungal infections: disseminated Candidiasis, Coccidioidomycosis, Cryptococcosis, Cryptosporidiosis, Histoplasmosis, Pneumocystis jiroveci pneumonia (PJP)  Cervical cancer, invasive AIDS-defining illnesses Viral infections: Cytomegalovirus, herpes simplex (Chronic ulcers or bronchitis, pneumonitis, or esophagitis)  Encephalopathy, HIV related Isosporiasis, chronic intestinal  Lymphoma, Kaposi sarcoma Progressive multifocal leukoencephalopathy Toxoplasmosis of the brain  Wasting syndrome attributed to HIV DIAGNOSIS Physical examination: may reveal signs of opportunistic infections and malignancies: Head, eyes, ears, nose, and throat - Oral candidiasis, oral hairy leukoplakia - Retinal toxoplasmosis (choroidoretinitis) Neck - Persistent generalized lymphadenopathy - Meningismus (frequently absent in cryptococcal meningitis) Pulmonary - Findings suggestive of consolidation, pleural effusion Abdomen - Tenderness (e.g., pancreatitis, biliary tract disease) - Hepatosplenomegaly DIAGNOSIS Neurologic: confusion, dementia, focal deficits Skin: - Maculopapular rash (primary HIV infection) - Syphilis - Staph. aureus skin infections (folliculitis, ecthyma, impetigo, furuncles and carbuncles) - Eosinophilic folliculitis - Mucocutaneous candidiasis - Seborrheic dermatitis - Genital warts (HPV), chronic herpes simplex - Kaposi sarcoma - Nutritional deficiencies - Vasculitis (palpable purpuric eruptions) Investigations: Laboratory: - HIV Testing  With the recent implementation of the fourth-generation HIV test ‘HIV-1/2 antigen/antibody combination immunoassay”. This test combines an immunoassay for HIV antibody with a test for HIV p24 antigen. Western blot testing is no longer recommended. Investigations: - Confirmation of diagnosis: A positive result on HIV-1/2 antigen/antibody combination assay is followed by testing of the sample with the HIV-1/HIV-2 antibody differentiation immunoassay. Samples negative on the antibody differentiation immunoassay are tested with an HIV-1 nucleic acid amplification test (NAAT); if the NAAT result is positive with a negative antibody, then acute HIV infection is diagnosed. Specimens positive on the initial antigen/antibody combination immunoassay but negative on the antibody differentiation immunoassay and NAAT represent false- positive results. PROGNOSTIC TESTS The following may be useful as prognostic tests and in monitoring the response to antiretroviral therapy: measured at baseline than serially. 1. HIV viral load. HIV viral load in serum may be measured by assays which detect HIV-RNA e.g. RT-PCR 2. CD4 counts — The CD 4 count decreases with disease progression, reflecting the stage of the disease. Measurement of CD4 has an important value in monitoring disease progression and response to antiretroviral therapy. According to the clinical presentation: Laboratory Tests e.g.: CBC (eg, anemia of chronic disease, cytopenias), liver and kidney functions ----- Blood , suptum , urine cultures Viral hepatitis markers, CMV, EBV---- Tests for TB, syphilis, toxoplasma Rapid Plasma Reagin (RPR) or VDRL screening test for Syphilis Monitoring of drug toxicities Bone marrow aspiration and biopsy lumbar puncture with cerebrospinal fluid analysis According to the clinical presentation: Imaging Studies: Chest radiograph, x ray and CT scan may show: - Pneumonia / bronchopneumonia, tuberculosis, P jirovecii pneumonia, - Tuberculosis (Interstitial infiltrations, consolidation, cavitation, hilar adenopathy , pleural effusions) CT scan and MRI brain: indicated in headache or focal neurologic deficit - Toxoplasmosis: multiple, hypodense, and ring-enhancing lesions - Primary CNS lymphoma PREVENTION Prevention of HIV transmission: includes: - Sexual transmission: sex education, safe sex practices. - Parenteral transmission: proper selection of donors, screening of donated blood. - VACCINATION PREVENTION TREATMENT - Antiretroviral Therapy (ART) - Symptomatic and supportive therapy e.g. Prophylaxis and treatment of opportunistic infections. TREATMENT Antiretroviral drugs used to treat HIV aiming to: - Reduce the amount of HIV RNA (viral load) in the blood to an undetectable amount - Restore the CD4 count to a normal level - Several classes of antiretroviral drugs are used together to treat HIV infection. - These drugs block HIV from entering human cells or block the activity of one of the enzymes HIV needs to replicate inside human cells and/or integrate its genetic material into human DNA. The drugs are grouped into classes based on how they act against HIV: 1. Reverse transcriptase inhibitors: prevent HIV reverse transcriptase from converting HIV RNA into DNA. There are three types of these drugs: nucleoside (Tenofovir, Lamivudine), nucleotide, and non-nucleoside (Efavirenz,,Nevirapine) 2. Protease inhibitors: prevent protease from activating certain proteins inside newly produced viruses, e.g. Atazanavir. 3. Entry (fusion) inhibitors prevent HIV from entering cellse.g. Maraviroc. 4. Post-attachment inhibitors These are used mainly for HIV infection that is resistant to several other drugs 5. Integrase inhibitors prevent HIV DNA from being integrated into human DNA. 6. Attachment inhibitors prevent HIV from attaching to host T cells Recommendations for initial HIV treatment include use of: Tenofovir and emtricitabine or abacavir and lamivudine as the dual nucleoside reverse transcriptase inhibitor "backbone." Options for a third agent to complete the regimen include the ritonavir-boosted protease inhibitor darunavir or the integrase inhibitors raltegravir, dolutegravir, or cobicistat-boosted elvitegravir. These regimens are effective and are associated with low toxicity.