Clinical Manifestations of HIV

1
Clinical Manifestations of HIV

• Ardis Ann Moe, M.D.
• Center for AIDS Research and Education

2
Summary

• Know Who to Test
• Know Early Warning Signs of HIV
• Absence of Risk Factors Does Not Mean Absence of
  Whoops Factors

3

• D.W., Diagnosed with AIDS 1993. CD4 count 110.
• Develops PCP, MAC, wasting disease, peripheral
  neuropathy
• Tried on multiple HIV regimens AZT, D4t3TC, and
  various protease inhibitor combinations beginning
  1996

4

• Now has MDR-HIV, CD4 count 8 in 2001.
• Begun on T-20, abacavir, 3TC, tenofovir,
  lopinavir/ritonavir and soft gel saquinavir
• (50,000/year treatment)

5

• CD4 count now 256, viral load undetectable. MAC
  resolves.
• Working part time, raises 2 children. Wife still
  HIV-
• Diabetes, cholesterol 356, triglycerides 780, Cr
  1.9, facial wasting.

6
Epidemiology

• 900,000 persons with HIV in US, 1/3 unaware
• Over half of new infections are among
  African-Americans, and 30 of new infections are
  in women
• MSM 42, IDU 25, heterosexuals 33

7
(No Transcript)
8

• Young MSM African-American men in New York rate
  of seroconversion 15/year
• Young MSM crystal meth users in Los Angeles rate
  of seroconversion 20/year
• Overall increase in number of new HIV and AIDS
  cases

9

• Seroconversion parties bug-chasers and gift
  givers
• Complacent attitude fostered by glowing
  advertisements of perfect health while on HIV
  medications
• Drug use drives much of this epidemic, directly
  or indirectly

10

• Death rate about 15,000/year
• 40,000 new HIV cases/year
• Liver failure and bacterial pneumonia now leading
  causes of death OI related deaths now less than
  1/3 of cases

11
Routes of Transmission

• Blood products (100)
• Pregnant mom to unborn child (40 if breast
  feeding)
• Receptive anal intercourse(1)
• Shared IDU(1)
• Needlesticks(1/300)
• Insertive anal intercourse(1/1,000)

12

• Male to female female to male (IF male is
  uncircumscised) (1/1000)
• Oral-genital sex (1/10,000)
• Shared razors
• Shared toothbrushes
• Exposure to open skin lesions

13
How to Prevent Transmission

• Counsel at-risk groups
• Offer HIV testing to all pregnant women
• PEP for needlesticks (within 1 hour)
• Treat infected persons with HIV meds
• Reduce drug use in community
• Treat STDs

14
When to Offer HIV Testing

• Shingles in person lt60
• Recurrent, unexplained vaginal yeast infections
  (3/year)
• All pregnant women
• Gay/bisexual men

15

• Unusually severe ear or sinus infections
• Failure to thrive in children
• Persistent diarrhea
• Unexplained weight loss
• Unexplained lymphadenopathy

16

• Person of African race with unexplained kidney
  failure
• FUO
• Bacterial pneumonia in healthy young person
• TB

17

• Primary pulmonary hypertension
• Idiopathic Thrombocytopenic Purpura
• Severe Seborrhea
• Unexplained persistent leukopenia

18

• Any history of any STD, including warts,
  hepatitis A, B, C, or GI parasites
• History of unexplained enteric infections,
  especially Shigella
• Thrush
• B cell lymphomas

19

• Jail
• Homeless
• Cocaine use
• Crystal meth or other substance abuse
• And anyone who asks for an HIV test!

20
(No Transcript)
21
(No Transcript)
22
(No Transcript)
23
(No Transcript)
24
(No Transcript)
25
(No Transcript)
26
(No Transcript)
27
(No Transcript)
28
(No Transcript)
29
(No Transcript)
30
(No Transcript)
31
Types of HIV Tests

• Elisa with Western blot or IFA
• Anonymous vs Confidential Testing
• Rapid HIV tests becoming more available
• Home HIV tests
• Urine and saliva HIV tests

32

• M.V. 65 yo male presents for routine heart valve
  surgery. Married, retired MD.
• Housestaff get HIV test without patients
  consent. Patient is HIV, CD4 count 420

33
Clinical Signs of HIV

• Onychomycosis
• Often seen in diabetics as well
• Indefinite treatment with itraconazole, lamisil,
  etc.

34
(No Transcript)
35
Scabies

• Can be widespread over entire body, with heavy
  encrustations of organisms Norwegian
  scabes Looks like severe psoriasis
• Patients should be isolated

36

• Shingles
• Rare in young persons, but can occur in up to 10
  of HIV persons
• More likely to occur when HIV meds started
• Shingles of the face may cause blindness from
  corneal involvement
• Shingles may cause secondary skin infections from
  staph, Group A strep

37

• Warts
• HPV can be widespread
• Cause of cervical cancer, and now responsible for
  increasing number of cases of anal cancer in HIV
  men
• Tends to recur difficult to eradicate

38
(No Transcript)
39

• Peripheral neuropathy
• Can occur in up to 1/3 of HIV persons
• Many causes HIV, CMV, diabetes, INH, HIV meds,
  alcohol, etc

40

• Thrush, vaginal yeast infections
• Thrush usually occurs in the mouth a few months
  to a few weeks before PCP or other AIDS OI occurs
• Women have more severe and difficult yeast
  infections

41

• Primary pulmonary hypertension
• Most cases occur in women
• Reversible with HIV medications
• Unknown mechanism

42

• ITP
• Auto platelet antibodies from HIV stimulation of
  the immune system
• Best treated with HIV medications and gamma
  globulin possible splenectomy

43
Opportunistic Infections

• T.W. 25 yo woman presents with DOE and fevers in
  1997. CD4 count 45. Boyfriend died of PCP in
  1995.
• PCP has 50 mortality if diagnosed late 5
  mortality if diagnosed within 3 days of admission

44
(No Transcript)
45

• Can present as normal CXR, normal LDH, normal
  ABGs
• Most commonly presents as unusually severe DOE,
  cough and fever in previously healthy person. CD4
  count lt200

46

• Can cause pneumothorax
• May be unilateral, apical, or with a pleural
  effusion
• Usually dry sputum production, but bacterial
  pneumonia often co-pathogen

47
(No Transcript)
48

• T.W. now with CD4 count 850 on HIV meds,
  completed MBA, married, undetectable
• She did not face up to her AIDS until she got the
  same pneumonia that killed her boyfriend

49

• TB
• Tenfold risk of progressive TB infection if PPD
  positive (5 mm induration)
• More likely to have atypical presentation
• Spine TB, TB pericarditis, lower lobe infiltrates
• DOT therapy standard of care

50
(No Transcript)
51
(No Transcript)
52
(No Transcript)
53
(No Transcript)
54

• J.F. 31 yo male presents with paraplegia 1996
  CD4 count 11.
• TB of lower spine and skull
• Treated with 4 TB drugs and HIV medications
• Finally learns to walk again after 5 months.
• Working full time now

55
Bacterial pneumonias

• K.L., 37 yo married woman presents with lobar
  pneumona. Previously healthy.
• CD4 count 340, HIV
• Husband HIV-, no other sexual partners, no drug
  use, no transfusions, no needlestick injuries
  (UCLA care partner)

56

• Treated in Kenya for malaria with cholorquine
  injections
• Doctor gave her AIDS from a dirty needle
• She is classified as an IDU risk factor

57

• 1 of 7 deaths in AIDS still due to bacterial
  pneumonias unchanged since 1987.
• No effect of HIV meds seen
• Flu vaccines, pneumovaccines helpful
• HIV infected persons more likely to have PCN
  resistant strains

58

• Kaposis Sarcoma
• Caused by HHV8 and co infection with HIV (or
  other immune suppression)
• Usually presents on legs, arms, tips of ears.
• Can involve lymphatics and cause massive leg
  edema
• Deaths usually from lung involvement

59
(No Transcript)
60
(No Transcript)
61

• Treated with chemotherapy (IV and topical)
• Radiation therapy to face helpful
• HIV meds alone will treat 1/3 to ½ of cases
• Also a sexually transmitted disease

62

• R.S. presents with new KS of his legs in 1983
• Finally dies of bacterial pneumonia at age 61 in
  2003
• Worked full time until day before death

63

• Mycobacterium Avium Complex
• Blood, lymph nodes, liver, spleen most often
  infected
• Presents as fever, night sweats, anemia,
  hepatosplenomegaly in persons lt50 CD4 cells

64

• CMV
• Usually presents as a retinal infection with
  floaters in persons lt50 CD4 cells
• Can also involve brain, intestines, esophagus

65
(No Transcript)
66

• R.G.
• 41 yo male with CMV retinitis and CMV
  encephalitis in 1996. Comatose
• Sent to nursing home to die and started on
  triple-drug therapy as a trial

67

• 1 month later, becomes a major irritant to the
  nursing staff, who discharge him home

68

• Toxoplasmosis
• Parasite found in soil, cat feces, undercooked
  meat
• 15 of US population colonized
• Presents as seizures, focal neurologic signs and
  fever in persons lt100 CD4 cells

69
(No Transcript)
70
(No Transcript)
71

• Occasionally presents as pneumonia or retinal
  disease
• Treated with sulfadiazine and pyramethamine

72

• S.M. 32 yo male, CD4 10 1996
• Developed toxoplasmosis and has residual basal
  ganglia injury
• Parkinsons disease and permanent stutter

73

• Multiple ring enhancing lesions on CT with
  contrast
• Can occur with other CNS diseases cryptococcus,
  CMV, lymphoma

74

• HIV encephalitis
• Progressive loss of brain cells and
  encephalopathy due to cytokine poisoning
• Partially reversible with HIV medications
• Limited number of HIV meds penetrate blood-brain
  barrier

75

• Cryptococcal meningitis
• Presents as fever, AMS, neurologic deficits,
  seizures in persons CD4 lt70
• A.H., 41 yo male, HIV x 8 years. Refuses meds
• Brought in by wife in coma. cryptococcal
  meningitis

76

• Requires repeated lumbar taps to decrease brain
  pressure
• Treated with 2 weeks of ampho B and 5 FC
• Recovers and back working full time

77
(No Transcript)
78

• Progressive Multifocal Leukoencephalopathy
• Caused by JC virus, CD4 lt50
• Rapid loss of functionstroke-like events
• Residual personality changes, blindness
• Survival 50 at 1 year even with HIV meds

79
(No Transcript)
80

• If HIV untreated, survival 4 months
• G.I., 55 yo woman. In Hospital 9 months for
  unexplained weight loss and leucopenia
• Finally gets HIV test and diagnosed with PML.
• Fed through G-tube x 3 months

81

• After HIV meds and treatment with cidofovir and
  steroids, learns to feed herself and walk after 6
  months.
• Takes dancing lessons and moves to Rome because
  the shopping is better
• Still mad at me for taking away her driving
  license

82

• Lymphoma
• Hodgkins and non-Hodgkins lymphomas
• Usually B-cell
• CNS lymphoma almost always associated with AIDS
• Rapid progression to death unless AIDS and
  lymphoma can be aggressively treated

83

• L.M., 33 yo male with AIDS and MDR-HIV
• Presents with vertigo July 22, 2003. MRI normal
• Presents with diplopia August 1. New mass on MRI
• Dead from lymphoma August 19.

84

• Cryptosporidium
• Intestinal parasite, travelers diarrhea
• Cholera-like secretory diarrhea
• Up to 17 liters of diarrhea/day
• Only known treatment HIV medications to improve
  immune system
• CD4 count lt150

85

• L.O. 47 yo male
• Presents with cryptosporidium diarrhea in 1994
• Treated with TPN. Multiple line infections
• Dead in 6 months

86

• Wasting disease
• Progressive loss of muscle mass
• Usually associated with chronic diarrhea
• Multifactorial causes food issues, dysphagia,
  OIs, HIV virus, low serum testosterone in men.

87
HIV Treatment Related Problems

• Lipodystrophy
• Fat accumulation
• Lipoatrophy
• Diabetes
• Elevated cholesterol and triglycerides

88

• 75 of all patients on protease inhibitors will
  have some problem with fat accumulation or fat
  wasting after 2years of protease inhibitor
  therapy.
• Some contribution from stavudine

89

• Fat accumulation syndromes may be due to
  interference between HIV protease inhibitors and
  natural proteases that digest fat molecules
• Fat atrophy syndromes may be due to mitochondrial
  toxicity

90

• 55 of persons on protease inhibitors will
  develop insulin resistance within 4 weeks of
  treatment
• 16 develop elevated fasting glucose
• 7 develop frank diabetes
• Partially reversible by stopping proteases

91

• Family history, gender, race, obesity all factors
  as well
• HIV virus itself
• HIV persons have elevated triglycerides, low HDL
  cholesterol and more facial wasting than HIV-
  persons, regardless of treatment

92

• White males over 40 more likely to develop facial
  wasting
• Obese African American women most likely to
  develop fat accumulation and diabetes (neck
  collar fat, breast enlargement)

93

• Avascular necrosis
• Usually presents as sudden hip pain in men
• Risk factors use of prednisone, weight lifting
• ?megace, androgens
• Seen before protease inhibitors

94

• Only treatment is with hip replacement or other
  hip surgery

95

• Lactic acidosis
• Caused by all nucleoside-based HIV medications
• Most commonly seen with D4T, DDI, and DDC
• Can cause death within 48 hours
• Indistinguishable from sepsis

96

• Treated with removal of HIV medications and IV
  thiamine, riboflavin and L-carnitine
• Low level lactic acidosis may be causing
  osteopenia in long-term HIV survivors

97

• Overall, survival of persons with AIDS
  dramatically improved
• 6 month survival in 1985 to 17 years
• 1 cause of death in young adults in US in 1995
  to 14 cause of death 18 months later

98

• Key factor is to test persons who are at risk for
  any reason, and refer for evaluation
• Treatment now delayed until CD4 count lt350, or
  symptomatic from HIV, or pregnant
• Studies on treatment interruptions ongoing.