Pharmacotherapy of HIV/AIDS – PST06106 Basic Pharmacotherapy
NTA Level 6 • Semester 1 • PST06106 Pharmacotherapy of HIV/AIDS Basic Pharmacotherapy • Source Session/Topic 4 Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability. PST 06106 Basic Pharmacotherapy Session 4: Pharmacotherapy of HIV/AIDS Learning Objective By the end of this session students are expected to be able to: Define HIV/AIDS Explain pathophysiology of HIV/AIDS Explain the clinical presentation of HIV/AIDS Outline diagnosis of HIV/AIDS Describe pharmacological treatment of HIV/AIDS Describe the monitoring of HIV/AIDS Therapy Activity: Buzzing What is HIV/AIDS? INTRODUCTION AIDs is a set of symptoms (or syndrome) caused by Human Immunodeficiency Virus (HIV). The clinical features may be due to HIV per se or as a result of immune system destruction. It has the following features: Fever, diarrhoea, weight loss, skin rashes, sores, generalized pruritis , altered mental status, persistent severe headache, oral thrush or Kaposi’s sarcoma may be found in patients with advanced disease Most patients, however, present with symptoms due to opportunistic infections such as tuberculosis, candidiasis and pyogenic infections Human immunodeficiency virus Pathophysiology of HIV/AIDS The virus through its envelope proteins attaches to the CD4 receptor and co-receptors found on the surface of T lymphocytes and macrophage to gain entry to the host cells. Following entry of the HIV into a susceptible host cell using the enzyme reverse transcriptase, the viral genome copies itself from RNA to DNA genetic material. The viral DNA copy enters the nucleus of the host cell and becomes intimately incorporated into the host cell’s own DNA using the enzyme integrase. Pathophysiology of HIV/AIDS CONT… The virus thus becomes a permanent part of an infected person’s nuclear proteins. There follows a latent period during which the provirus in the infected nucleus waits for an external stimulus to start reproducing. CD4+ T lymphocytes, when stimulated by new HIV, other infections and infestations which would normally result in the CD4+ T lymphocyte reproducing itself, now responds to these stimuli by manufacturing HIV. As more and more viruses are produced and leave the host cell, the cell membrane weakens leading eventually to the death of the infected CD4+ T lymphocytes 37 Pathophysiology of HIV/AIDS CONT … The multiple steps in replication of HIV provide multiple opportunities for intervention. Therapeutic regimens may be directed at one or several of the following stages essential for viral replication: Attachment of HIV to the host cell; Reverse transcription of viral RNA to DNA; Integration of the pro-viral DNA into the host cells’ DNA; or Expression of the viral gene after it has been integrated into host cell DNA, including the transcription of more viral RNA and the translation of viral proteins . Clinical Presentation Of HIV/AIDS In the absence of ART, disease progression goes through the following clinical stages Primary Infection or becoming HIV Infected Most primary infection, i.e. new infection with HIV, usually is not immediately noticed. It presents with short illnesses and flu-like symptoms such as fever, malaise, enlarged lymph nodes, sore throat, skin rash, and/or joint pain soon after being infected. It may last for a few weeks. This acute febrile illness is accompanied by widespread dissemination of the virus to different tissues, especially the lymphoid system. This is called sero -conversion illness. Clinical Presentation Of HIV/AIDS Cont …. Clinically Asymptomatic Stage This stage is free of symptoms, except for the possibility of swollen glands: persistent generalized lymphadenopathy – Persistent Generalized Lymphadenopathy (PGL). However, this is the stage where there is ongoing extensive immunologic fighting/changes and rapid viral replication begins. This may last for an average of eight to ten years. However, disease progression in children and elderly is faster due to high set point. This is WHO Stage1 Clinical Presentation Of HIV/AIDS Cont … Symptomatic HIV Over time, the immune system loses the struggle to contain HIV, resulting in extensive destruction of CD4 cells This is characterised by the occurrence of opportunistic infections (OIs), which is when) symptoms develop The most common symptoms include fever, respiratory infections, cough, TB tuberculosis, weight loss, skin diseases, viral infections, oral thrush, pain, and lymphadenopathy This is WHO Stage 2 or 3, depending on the particular OI seen Clinical Presentation Of HIV/AIDS Cont … Acquired Immune Deficiency Syndrome (AIDS) AIDS is defined as a point when a person with HIV develops severe immunosuppression, OIs, or malignancies/cancers. Such conditions are: severe weight loss, Kaposi’s sarcoma, Cryptococcus meningitis, PCP, toxoplasmosis, CMV (Cytomegalovirus) retinitis, etc. This is WHO Stage 4 Diagnosis of HIV/AIDS ELISA Test — ELISA, which stands for enzyme-linked immunosorbent assay, is used to detect HIV infection (detects antibodies against HIV-1)and is both highly sensitive and specific If an ELISA test is positive, the Western blot test is usually administered to confirm the diagnosis. If an ELISA test is negative, but you think you may have HIV, you should be tested again in one to three months ELISA is quite sensitive in chronic HIV infection, but because antibodies aren't produced immediately upon infection, you may test negative during a window of a few weeks to a few months after being infected. Viral Load Test — This test measures the amount of HIV in your blood. It quantifies viremia by measuring the amount of viral RNA. Generally, it's used to monitor treatment progress or detect early HIV infection. Three technologies measure HIV viral load in the blood: reverse transcription polymerase chain reaction (RT-PCR), branched DNA ( bDNA ) and nucleic acid sequence-based amplification assay (NASBA). The basic principles of these tests are similar. HIV is detected using DNA sequences that bind specifically to those in the virus Western Blot — This is a very sensitive blood test used to confirm a positive ELISA test result Activity: Small Group Discussion •What explanations can you give on monitoring therapy for HIV/AIDS? Pharmacological treatment of HIV/AIDS Early initiation of combination treatment (ART) is associated with health benefits in terms of reduced morbidity and mortality in all age groups. In addition, ART is