Sumarry Of Retroviral Disease
INTRODUCTION
HIV INFECTION AND AIDS
Acquired immune deficiency syndrome (AIDS) is the most advanced stage of infection with human immunodeficiency virus (HIV). Two subtypes of HIV have been identified. HIV-1 is more widespread than HIV-2, the latter mainly being found in west Africa. HIV-2 is less virulent and less transmissible than HIV-1. HIV weakens the immune system by causing a deficit in CD4 T lymphocytes.
Pathogenesis
HIV, in common with other retroviruses, possesses the enzyme reverse transcriptase and consists of a lipid bilayer membrane surrounding the capsid. Its surface glycoprotein molecule (gp120) has a strong affinity for the CD4 receptor protein found predominantly on the T-helper/inducer lymphocytes. Monocytes and macrophages may also possess CD4 receptors in low densities and can therefore also be infected. The process of HIV entry is more complex than originally thought, and in addition to CD4 attachment, subsequent binding to co-receptors such as CCR-5
or CXCR-4 and membrane fusion also occur. After penetrating the host cell, the virus sheds its outer coat and releases its genetic material. Using the reverse transcriptase enzyme, the viral RNA is converted to DNA using nucleosides. The viral DNA is then integrated into the host genome in the cell nucleus, where it undergoes transcription and translation, enabling the production of new viral proteins. New virus particles are then assembled and bud out of the host cell, finally maturing into infectious virions under the influence of the protease enzyme.
STAGES OF THE DISEASE
The World Health Organization (WHO) has proposed a clinical classification of HIV infection in 4 Stages of severity for adults and adolescents and for children.
◈ Primary infection or acute retroviral syndrome: 50 to 70% of newly infected individuals develop during seroconversion (from 15days to 3 months post exposure), a viral syndrome with fever, malaise and lymphadenopathy
◈ Asymptomatic HIV infection (after seroconversion): a period of clinical latency, but not viral latency. The time period for progression from HIV infection to the development of severe immune deficiency in western countries is approximately 10 years. This periods appears to be shorter in developing countries.
◈ Symptomatic HIV infection: with progressive destruction of the immune system, common and more severe diseases occur more frequently, and with higher mortality, in seropositive individuals.
◈ AIDS: this stage corresponds to the development of severe opportunistic infections (TB, Fungal infections) and neoplasms.
DIAGNOSIS OF HIV INFECTION
The diagnosis is made with serological (detection of antibodies against the virus) or Virological (especially in infacts) testing. The two main methods are
◈ CD4 Lymphocyte counts: CD4 cell depletion is a marker of the progression of immune depression. The level of the cd4 cell count is a predictor of the development of opportunistic infections or neoplasms and can be used to orient their diagnosis.
◈ Viral Load: this is the presence of viral cells in the blood.
TREATMENT OF HIV INFECTION
Antiretroviral (ARV) treatment
A multi-drug (at least 3) antiretroviral therapy is the reference treatment. It does not eradicate the virus, but slows the progression of the disease and improved the patients clinical state by reducing viral replication and consequently increasing the CD4 cell count to levels beyond the threshold of opportunistic infections.
THERAPEUTIC CLASSES
◈ NRTI (Nucleoside/Nucleotide reverse transcriptase inhibitors): Zidovudine (AZT), Lamivudine (3TC), Abacavir (ABC), Tenofovir (TDF), Emtricitabine (FTC).
◈ NNRTI (Non-Nucleoside reverse transcriptase inhibitors): Efavirenz (EFZ), Nevirapine (NVP)
◈ PI (Protease inhibitors): Ritonavir (RTV), Lopinavir (LPV)
◈ INI (Integrase inhibitors): Dolutegravir, Raltegravir.
PRINCIPLE OF (ARV) TREATMENT
Daily triple therapy must be taken for life to prevent the rapid development of resistance. It is important that the patient