HIV & AIDS: Lecture Notes PDF

HUMAN IMMUNODEFICIENCY VIRUS (HIV) & AIDS  At the end of this Aetiology & lecture students epidemiology should be able to: replication,...

HUMAN IMMUNODEFICIENCY VIRUS (HIV) & AIDS  At the end of this Aetiology & lecture students epidemiology should be able to: replication, pathogenesis, & Describe the clinical manifestations laboratory diagnosis, treatment and prevention of HIV infection. LEARNING list of AIDS-defining OUTCOMES illnesses Describe AIDS other opportunistic infections in AIDS. Aetiology HIV is the causative agent for acquired immunodeficiency syndrome (AIDS) HIV infection is caused by HIV-1 or HIV-2, which are enveloped RNA retroviruses in the Retroviridae family & belongs to Lentivirus genus Each HIV -1 & HIV-2 is composed of multiple subtypes or clades Genetically, HIV-1 and HIV-2 are superficially similar, but each contains unique genes and its own distinct replication process HIV has long incubation periods (6 wks-6 months) HIV has high genetic variability, thus this serves as an obstacle to the treatment of HIV infection  HIV-1 & HIV-2 Found worldwide. The HIV-1 group M viruses predominate & responsible for the AIDS pandemic. Other groups are N & O. primarily in West Africa Group M (major) can be further subdivided into (A-H) groups clades /subtypes (A-K) based on genetic sequence data (env & gag genes). less virulent less transmissible some of the subtypes are known to be more progress more slowly to virulent or are resistant to different medications. AIDS HIV: Important Properties HIV genome is the most complex of the known retroviruses & contains 3 species- defining retroviral/structural genes & 6 regulatory genes HIV: Genes & Proteins  HIV: Replication Entry of HIV into the cell by binding of the virion Virion gp41 proteins gp120 to the CD4 mediate fusion of the protein on the cell viral envelope with In the cytoplasm, RT In the nucleus, the surface. the cell membrane transcribes the new viral RNA is The gp 120 interacts the virion core genome RNA into transcribed & with a second protein containing the DNA, which migrates formed from on the cell surface one nucleocapsid, RNA to nucleus, where it proviral DNA by of the chemokine genome, & RT enters integrates into host RNA polymerase of receptors the cytoplasm cell DNA. the host cell (CXCR4/CCR5)  HIV: Replication The new viral RNA translated into Maturation of the virus New viral RNA & (infectious virion) polyproteins in the proteins move to the occurs by protease cytoplasm & buds cell surface and releasing individual from the cell become immature HIV HIV proteins. membrane  HIV: Risk factors Unprotected sexual intercourse, especially receptive anal intercourse Mucosal contact with infected blood or sharp injuries Multiple promiscuity (Multiple sexual partners) Sharing of intravenous drug paraphernalia Prior or current sexually transmitted diseases (STDs) eg: Gonorrhea, Chlamydia infection, Syphilis & Herpes genitalis  HIV: Transmission HIV transmission occurs by: Sexual contact (primarily): oral, anal, or vaginal HIV NOT transmitted by: Transfusion / direct contact with infected Touching, hugging, kissing /contaminated blood Coughing, sneezing HIV-infected mothers to infants during pregnancy, delivery, or breastfeeding Sharing glasses, plates and other utensils  HIV: Immunity Once a person is infected with HIV, the individual considered to be infected for life as a result, of integration of viral DNA into the host DNA. HIV has several main mechanisms by which HIV evades the host immune system: The main immune response to HIV infection consists of Integration of viral DNA into host cytotoxic CD8-positive lymphocytes. cell DNA A high rate of mutation of the env gene These cells respond to the initial infection & control it for many years. HIV undergoes antigenic drift of gp120 The production of the Tat and Nef When CD4 helper T cells have died, cytotoxic T cells lose proteins that downregulate class 1 their effectiveness, thus supply of lymphokines required to MHC proteins required for cytotoxic activate the cytotoxic T cells is no longer sufficient. T cells to recognize & kill CD4 T cells Antibodies against various HIV proteins e.g p24, gp120, gp41 are produced, but they neutralize the virus poorly in vivo.  HIV: Pathogenesis HIV enters the body and binds to CD4 T cells (1st receptor) on monocytes, macrophages & dendritic cells. Then secondary binding of HIV to chemokine receptors on host cells take place HIV: Effects HIV infects CD4- HIV causes lytic HIV causes positive cells & kills infection of CD4 T syncytia them, resulting in HIV infects cells cells and formation with suppression of CMI. of macrophage persistent low- cells expressing This predisposes host lineage leading to level productive large amount of to various OI & certain clinical latency. infection of CD4 antigen & cancers macrophage subsequent lysis lineage cells of the cells leading eg: Kaposi’s sarcoma & to lymphoma. HIV does resulting to immunodeficiency NOT directly cause these dysfunction / & /loss of B cell tumours because HIV dysregulation of control genes are NOT found in immune control/lymphadeno the cancer cells. functions. pathy/hypergamma globulinaemia, cutaneous infections  HIV Infection: Stages Source :Updated from CDC June 2021  HIV Infection: Clinical presentations STAGE CLINICAL PRESENTATION LAB FINDINGS Acute HIV Infection (1) Flu-like illness/mononucleosis-like fever, lethargy, sore throat, CD4 count: Normal generalized lymphadenopathy, gen.rashes HIV RNA: Detected HIV viral load: Increased Antibody to HIV typically appear 10-14days after infection Chronic HIV Infection (2) Asymptomatic CD4 count: Initially normal, then reduced but remain above 400/microlitre HIV RNA: Detected HIV viral load: Low/not detected due to large amt. of HIV produced remains in the lymph node AIDS(3) Eye: CMV retinitis CD4 count: Reduced, 200/microlitre and GIT: Oral & esophagitis candidiasis/thrush, Cryptosporidiosis below Skin: Kaposi sarcoma,Herpes zoster,Moluscum-like lesions HIV RNA: Detected caused by T.marneffei HIV viral load: High RESP: Pneumonia (MTB/MAC,S.entiritidis pneumococci,CMV,PJP) CNS: HSV encephalitis, Cryptococcal meningitis,toxoplasmosis GUI: Cervical Ca  Asymptomatic Patient asymptomatic,CD4 count considered normal, then reduced but still at 400 Primary/ Acute infection cells/mm3 or above with HIV Patients may develop viral load low as large mononucleosis-like fever, amounts of HIV remains generalised rashes, sequestered in the LN. generalised lymphadenopathy etc with normal CD4 count at the beginning, with increasing viral load noted at week 3-6th Opportunistic infection which coincide with (OI)/AIDS decreasing CD4 count. Patients may develop one or more OI as CD4 count was < 200 cells/mm3 (immunosuppression) and high viral load evidenced by > 103 copies of HIV RNA. HIV Infection: Lab investigations Source :CDC  HIV Infection: Screening test 2 A) Screening assay/test HIV-1/2Antigen/Antibody immunoassay/Combo  HIV: Supplementary/Secondary tests Detection of p24/p31 Qualitative HIV-1 Nucleic acid Rapid HIV assay/test HIV-1/2 Antibody antigen & test/RNA Eg:Alere Determine HIV-1/2 differentiation assay glycoproteins detects RNA from HIV-1 Ag/Ab Combo test (Orgenics, An assay that enable (gp120/160 and gp41) used mainly when HIV-1/HIV- Ltd), the differentiation of may detect a greater 2 differentiation assay first rapid test approved by HIV-1 and HIV-2 number of recent produces indeterminate FDA in human serum, plasma, antibody infections before results and venous or fingerstick may produce seroconversion also used to detect the whole blood specimens indeterminate results occurs presence of HIV in the The test does NOT distinguish whole blood and blood between antibodies to HIV-1 components, by permitting and HIV-2 earlier detection of HIV-RNA NOT intended to be used for screening of blood donors HIV Infection: Supplementary/Secondary tests Western Blot less likely to give a Proviral DNA PCR false-positive result Indirect fluorescent usually performed only in because it can more antibody (IFA) test newborns because conventional effectively distinguish High specificity serologic testing will still detect HIV antibodies from However, it is more maternal antibodies that may other antibodies persist for 9 months or longer expensive than a requires highly Western blot test. Two or more negative results technical skills. separated by at least one month is considered as negative. HIV Infection: Treatment monitoring test Quantitative HIV-1 Nucleic acid test/RNA (viral load) surrogate marker of viral replication rate. done at the commencement of HIV treatment & used during the treatment (monitoring) NOT diagnosis HIV Infection: Sequence of appearance of lab markers interval between the appearance of characterized by a detectable HIV fully developed RNA and the first HIV antibody detection of antibodies. interval after HIV infection when no laboratory markers are consistently detectable. interval between infection with HIV and the first detection of antibodies.  HIV INFECTION: WINDOW PERIOD Antibody tests can usually detect HIV 23 to 90 days after exposure. Most rapid tests and self-tests are antibody tests. A rapid antigen/antibody test done with blood from a finger stick can usually detect HIV 18 to 90 days after exposure. An antigen/antibody lab test using blood from a vein can usually detect HIV 18 to 45 days after exposure. A nucleic acid test (NAT) can usually detect HIV 10 to 33 days after exposure. HIV Infection: Relevant test CD4+ T-cell Count the CD4 T-cell count is a reliable indicator of the current risk of OI. serial counts are generally a better measurement of any significant changes. The reference range for CD4 counts is 500- 2000 cells/μL After seroconversion, CD4 counts tend to decrease (around 700/μL on average) and continue to decline over time. a CD4 count under 200/μL is considered AIDS-defining owing to the increased risk of OI at this level. HIV: The initial workup of a patient with newly diagnosed HIV infection CMV:The presence of anti-CMV IgG Toxoplasmosis by indicates doing anti- previous Toxoplasma Gonococcal & exposure to antibody test: to chlamydial CMV. Syphilis: RPR determine whether infection: rapid can be used patients have had Ophthalmologic amplification initially, but testing toxoplasmosis, and TB: Purified examination is thus are at risk for protein used to more specific Hep A, B & C testing should infection by reactivation of derivative evaluate for infection. (PPD) skin CMV retinitis. be used for performing testing follow-up, as serology test. RPR can yield false-positive results.  HIV Infection: Treatment The aims of treatment are: The treatment depends on: to prevent the immune system from stage of the disease deteriorating to the point that OI & certain malignancies become more presence of concomitant OI likely. CD4 counts to reduce viral load. viral load In general, initial antiretroviral therapy Co - infection with HBV/HCV (ART) consists of one to two regimens, each one of which consists of 3 drugs resistance pattern of the HIV 1st regimen: 2NRTI + 1PI Pregnant vs non pregnant 2nd regimen: 2NRTI + NNRTI These combinations are known as ‘Highly active antiretroviral therapy’ (HAART)  HIV & AIDS Acquired Immunodeficiency Syndrome (AIDS) A = Acquired, not inherited I = Weakens the Immune system D = Creates a Deficiency of CD4+ cells in the immune system S = Syndrome, or a group of illnesses taking place at the same time  HIV & AIDS The CDC definition of AIDS includes: < 200 CD4+ T cell /μL OR One of more of the illnesses listed: Candidiasis of bronchi, esophagus, trachea or lungs Cervical cancer that is invasive Coccidioidomycosis that has spread Cryptococcosis that is affecting the body outside the lungs Cryptosporidiosis affecting the intestines and lasting more than a month CMV disease outside of the liver, spleen or lymph nodes CMV retinitis that occurs with vision loss Encephalopathy that is HIV-related NB: refer to following table AIDS DEFINING ILLNESS: CDC  Extrapulmonary TB Non -tuberculous Mycobacterium (NTM) that has spread/disseminate Penicilliosis by P.marneffei AIDS: Opportunistic infections (OI) Disseminated Sporotrichosis by S.schenkii POP QUIZ 1. HIV enter the cell by binding to gp120 to the CD4 protein. 2.HIV is transmitted to the newborn via breastfeeding of HIV infected mother. 3.Flu-like illness is one of the presentations in stage 3. 4.OI develops when CD4 count less than 200 cells/mm3. 5.Qualitative HIV-1 test detects RNA from HIV-1. 6.HIV 1/2 antigen/antibody assay produces high rate of false positive result. 7.Window period is characterized by fully developed antibody. Today is your opportunity to build the tomorrow you want