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/mm3 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 Didanosine Pancreatitis, peripheral neuropathy Stavudine Peripheral neuropathy. Tenofovir is a nucleotide analog. Zalcitabine Pancreatitis, peripheral neuropathy. 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

Ritonavir GI distress Nelfinavir GI distress

Non-nucleoside Reverse Transcriptase Inhibitors. These drugs are non competitive inhibitors of reverse transcriptase. Efavirenz Somnolence, confusion and psychiatric problems Nevirapine Rash, hepatotoxicity Delavirdine Rash

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.