HIV

Question 1

Origins of AIDS epidemic

Answer 1

• 1900 - HIV enterd human populations from chimpanzees in east central Africa
• 1981 - AIDS first described by CDC
• 1984 - HIV-1 first isolated
• 1987 - First antiretroviral approved by US FDA
• 1996 - Beginning of HAART era
• 2003 - Start of global rollout of antiretrovirals
• 2009 - Over 7000 new infections/day

Question 2

How HIV infection leads to AIDS

Answer 2

• CD4+ T lymphocyte is main host cell for HIV-1
  
  • HIV uses CD4 receptor and co-receptor (CCR5 or CXCR4) to enter cell
• CD4+ lymphocyte count correlates with disease progression
• Plasma HIV RNA level (viral load) is measure of extent of ongoing replication in lymphoid tissue
  
  • Correlates with progression of disease without treatment
• Infection leads to continual decline in immune function
• AIDS defined as CD4+ level < 200 cells/mL

Question 3

Primary HIV infection

Answer 3

• Primary HIV infection:
  
  • Acute febrile illness, similar to mono, 2-3 weeks after infection, with or without aseptic meningitis
  • Occurs in 50% of patients, and they may or may not realize it
  • Frequently missed by providers, especially in situations like ED
  • Manifestations due to virus itself

Question 4

Specific s/s of primary HIV infection

Answer 4

• Fever
• Fatigue
• Maculopapular rash
• Myalgia
• Headache
• Pharyngitis
• Cervical nodes
• Arthralgia
• Oral ulcers
• Odynophagia
• Weight loss
• Diarrhea
• Oral candidiasis = thrush
• Photophobia

Question 5

Chronic HIV infection

Answer 5

• Result of immune suppression, often leads to opportunistic infections
• Restoring CD4 count decreases frequency and intensity of infections, can even reverse them
• Opportunistic infections take advantage of weakened immune system, typically only occur when CD4+ count is low (< 200 cells/mm³)

Question 6

Opportunistic infections in chronic HIV

Answer 6

• Pneumocystis pneumonia
• Kaposi’s sarcoma
• Candida = thrush
• CMV retinitis
• CNS toxoplasmosis
• Extrapulmonary TB
• Cryptosporidium diarrhea

Question 7

Pneumocystis pneumonia

Answer 7

• One of earlier symptoms of infection
• Particularly prevalent in 80s before advanced therapies
• Characterized by diffuse pneumonia
  
  • As opposed to focal, lobar presentation of other bacteria
• Interstitial infiltrates

Question 8

Kaposi’s sarcoma

Answer 8

• HIV-induced cancer
• More prevalent in the 80s

Question 9

Candida

Answer 9

• AKA thrush
• Sign of immunodeficiency
• Flag for HIV in the clinic
  
  • But not exclusive to HIV

Question 10

CMV retinitis

Answer 10

• Pre-terminal sign of severe infection
• Common cause of HIV-related blindness

Question 11

CNS toxoplasmosis

Answer 11

• Live within cysts in muscles, brains
• Non-enhancing ring lesion on CT of brain

Question 12

Extra-pulmonary TB

Answer 12

• Cysts found in muscles, etc.
• Psoas abscess

Question 13

Use of antiretroviral drugs in HIV

Answer 13

• Success story in medicine over last 20-30 years
• Target specific steps of HIV life cycle
• Classes of drugs include:
  
  • Entry inhibitors
  • Fusion inhibitors
  • Reverse transcriptase inhibitors: NTRIs or NNTRIs
  • Integrase inhibitors
  • Protease inhibitors

Question 15

Virologic and immunologic effects of antiretroviral treatment

Answer 15

• Potent inhibition of viral replication
• Early HIV: prevents immunologic deterioration
• Advanced HIV: allows immunologic recovery

Question 17

Clinical effects of antiretroviral treatment

Answer 17

• Prevention of opportunistic infections
• Improvement in existing opportunistic infections
• Reduced hospitalization, long term care facility use, medications for opportunistic infections, and cost