HIV and Acquired Immunodeficiency syndrome (AIDS) Learning Objectives • The student should know. – Classification of HIV infection – Correlation between CD4 count and HIV associated diseases. – Importance of Viral load monitoring – Antiretroviral therapy and its side effects. • HIV is a single stranded RNA retrovirus from Lentivirus family. • After mucosal exposure, HIV is transported to lymph nodes via. dendritic, CD4 lymphocytes or Langerhan cells where infection becomes established. • Free or cell associated virus is then disseminated widely through the blood with seeding of ‘sanctuary’ sites like CNS and latent CD4 cell reservoirs. Classification of HIV • Primary infection – It is symptomatic in 70 – 80 % of cases and usually occurs 2-6 weeks after exposure. – Major clinical manifestations are • Fever with rash • Pharyngitis with cervical lymphadenopathy • Myalgia / Arthralgia • Headache • Mucosal ulceration – High plasma HIV-RNA levels and a fall in CD count up to 400 cells/mm 3 • Asymptomatic infection – Category A disease in the Centers for Disease Control (CDC) classification. – Follows and lasts for a variable period, during which the infected individual remains well with no evidence of disease except for possible presence of persistent generalized lymphadenopathy. – There is persistent viremia with decline in CD4 cells around 50 to 150 cells per year. • Mildly symptomatic disease – CDC classification category B disease. – Develops in many indicating some impairment of cellular immunity but which is not AIDS defining. – Clinical manifestations • Oral hairy leukoplakia • Recurrent oropharyngeal candidiasis. • Recurrent vaginal candidiasis • Severe pelvic inflammatory disease • Bacillary angiomatosis • Cervical dysplasia • Idiopathic thrombocytopenic purpura • Weight loss • Chronic diarrhea • Herpes zoster • Acquired Immunodeficiency Syndrome – CDC category C disease is defined by the development of specified opportunistic infections and tumors (AIDS defining lesions). – AIDS defining diseases • Esophgeal candidiasis • Cryptococcal meningitis • Chronic cryptosporidial diarrhea • Cerebral toxoplasmosis • CMV retinitis or colitis • Pneumocystis jirovecii pneumonia • Disseminated Mycobacterium avium intracellulare • Kaposi sarcoma • Non-Hodgkin lymphoma • Primary cerebral lymphoma • HIV associated dementia • HIV associated wasting Correlation between CD4 count and HIV associated diseases • >500 cells/mm3 • Acute primary infection • Recurrent vaginal candidiasis • Persistent generalized lymphadenopathy • <500 cells/mm3 • Pulmonary tuberculosis • Pneumococcal pneumonia • Herpes zoster • Oropharyngeal candidiasis • Oral hairy leukoplakia • ITP • <200 cells/mm3 • Pneumocystis jirovecii pneumonia • Cryptosporidium • Microsporidium • Esophageal candidiasis • HIV associated wasting • <100 cells/mm3 • Cerebral toxoplasmosis • Cryptococcal meningitis • Non-Hodgkin lymphoma • HIV associated dementia • <50 cells/mm3 • CMV retinitis / colitis • Primary CNS lymphoma • Disseminated MAI • CD4 count is also used for determining. • When to start prophylactic medication. • When to initiate antiretroviral medication. Viral Load Monitoring • Monitoring of viral load is the best method to monitor adequate response to therapy when patient is on anti retroviral medications. • High viral load indicates a greater risk of complications of the disease. • Viral sensitivity is done to determine which antiretroviral medications will be effective in an individual patient. Antiretroviral Therapy • Currently available agents and their side effects. – Nucleoside Reverse Transcriptase Inhibitors • Zidovudine Leukopenia, anemia, GI distress • • • Tenofovir is a nucleotide analog. • – Protease Inhibitors • Hyperlipidemia, hyperglycemia and elevated LFTs, abnormal fat loss from face and extremities and redistribution in neck and back. These side effects are seen with all. • Indinavir Nephrolithiasis, hyperbilirubenemia • • – Non-nucleoside Reverse Transcriptase Inhibitors. • These drugs are non competitive inhibitors of reverse transcriptase. • Efavirenz Somnolence, confusion and psychiatric problems • • When to start therapy • Guidelines for starting are – CD4 < 350/microliter – Viral load (by PCR-RNA) >55000 What to start • Use two nucleosides combined with a protease inhibitor OR • Use two nucleosides combined with efavirenz OR • Use two nucleosides combined with two protease inhibitors.
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