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13 August, 2009 Mystery Cases Shireesha Dhanireddy, MD. Opportunistic Infections. 1981 - Reports of PCP in 5 gay men in Los Angeles. HIV: Pathogenesis. Typical Course. Sero-conversion Antibody response. Anti-HIV T-cell response. Intermediate Stage. AIDS. CD4 Cell Count.

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13 august 2009 mystery cases shireesha dhanireddy md
13 August, 2009

Mystery Cases

Shireesha Dhanireddy, MD

opportunistic infections
Opportunistic Infections
  • 1981 - Reports of PCP in 5 gay men in Los Angeles
hiv pathogenesis
HIV: Pathogenesis

Typical Course

Sero-conversion

Antibody response

Anti-HIV

T-cell response

Intermediate Stage

AIDS

CD4 Cell Count

Plasma RNA Copies

OIs start here

500

CD4 Cells

4-8 Weeks

Up to 12 Years

2-3 Years

From Harrington RD

case 1
Case 1
  • 31 year old Mexican MSM presented with gluteal pain.
  • He also noted intermittent fevers and diarrhea as well. +weight loss 20 lbs over 5 months, + nightsweats, productive cough white sputum x 1 month
  • Painful penile lesion x 2months
case 1 continued
Case 1 continued
  • Social History - moved to US from Mexico 8 months ago; works in a restaurant; MSM h/o unprotected sex 5 months ago; Pets - 6 dogs, many chickens (in Mexico)
case 1 continued1
Case 1 continued
  • Exam - thin, temporal wasting, +inguinal lymphadenopathy, erythematous ulceration on penis; left buttock indurated, erythematous area c/w abscess; neurologic exam normal
case 1 continued2
Case 1 - continued
  • Seen by surgery and underwent incision and drainage of buttock abscess and was sent home
  • He returned a few days later with continued fevers and was admitted for further workup
  • Buttock abscess had resolved
case 1 continued3
Case 1 - continued

Based on his following symptoms what tests would you order at this point?

Symptoms:

Intermittent fevers, diarrhea, weight loss, nightsweats, cough, penile lesion

case 1 differential diagnosis
Case 1 - Differential Diagnosis
  • HIV
  • TB - sputa x 3 for afb
  • Diarrhea - stool studies - O&P, enteric pathogens screen, cryptosporidium, isospora
  • Disseminated MAC - blood culture for afb
  • Blood cultures - for bacteria and afb
case 1 data
Case 1 - Data
  • Labs - HIV + ; CD4 count 103 (17%); HIV RNA 1 million copies/mL
  • Sputum afb negative x 3
  • Blood culture positive for this organism within 2 days …
case 11
Case 1

Which organism is most likely based on blood culture and clinical presentation?

  • Mycobacterium avium complex
  • Salmonella nontyphi
  • Vibrio cholera
  • Staphylococcus aureus
salmonellosis
Salmonellosis
  • Nontyphoid Salmonella bacteremia 20 to 100-fold higher in HIV+ people
  • From ingestion of contaminated food/water
  • Possibly from sexual activity
  • Patients with lower CD4 counts --> increased mortality, increased risk of bacteremia

Hung CC et al. Clin Infect Dis 2007;45:e60-7

salmonellosis1
Salmonellosis
  • Relapses common
  • Recurrent Salmonella septicemia is an AIDS-defining condition
  • Treatment of choice - fluoroquinolone ie ciprofloxacin (alternatives TMP/SMX or ceftriaxone)
  • Length of therapy for CD4 count < 200 is 2-6 weeks
  • If recurrent disease, consider 6 months + of antibiotics (secondary prophylaxis)
approach to diarrhea in hiv us
Approach to Diarrhea in HIV: US

Bacterial enteric pathogens, viruses such as Norwalk, Cryptosporidium, Giardia, E. histolytica

CD4 count

CMV, MAC, microsporidia, Isospora, KS

approach to diarrhea in hiv us1
Approach to Diarrhea in HIV: US
  • Based on acuity of symptoms and whether bloody workup may include:
    • Stool culture for bacteria
    • O&P
    • Stool for afb & trichrome stain (for Cyclospora, Isospora, Cryptosporidium, microsporidia
    • C. difficile toxin assay
    • Giardia stool antigen
    • Blood cultures for MAC and Salmonella
    • Colonoscopy for CMV, KS
approach to diarrhea in hiv world
Approach to Diarrhea in HIV: World
  • Acute diarrhea <14 days - usually bacterial
    • No bloody in stool - manage symptomatically or metronidazole if severe
    • Blood in stool - fluoroquinolone x 5 days + metronidazole (for concern of amebic colitis)
  • Persistent diarrhea >14 days - usually Cryptosporidium, Isospora, microsporidia
    • WHO recommendations
      • If no blood in stool --> cotrimoxazole + metronidazole
      • If no response --> refer or albendazole/mebendazole
case 1 continued4
Case 1 - continued

What about his other symptoms and other tests ?

case 1 additional testing
Case 1 - additional testing

RPR +, VDRL + 1:16

What is your next step?

  • Treat with PCN IM x 1 for primary or early latent syphilis
  • Perform lumbar puncture and then treat based on CSF results
  • Treat with PCN IM x 3 for late latent syphilis
  • False positive result, do not treat
syphilis hiv
Syphilis & HIV
  • Can enhance transmission of HIV
  • Can have negative impact on immune status
syphilis
Syphilis
  • Primary - painless chancre (ulcer) 2-3 weeks after exposure
  • Secondary - typically 3-6 weeks after primary; but overlap between 1º and 2º more common with HIV
  • Tertiary - gumma, cardiovascular changes, neurosyphilis
neurosyphilis
Neurosyphilis
  • Can occur anytime
  • Risk factors - low CD4 count (<350), high titer, male gender
  • CSF evaluation for HIV + patients
    • with neurologic signs/symptoms
    • with late latent or syphilis of unknown duration, regardless of symptoms
  • Abnormal CSF protein or cell count or reactive CSF VDRL can be diagnostic
latent syphilis
Latent Syphilis

Definition - positive test in the absence of symptoms

Early latent - acquired within past year (documented negative test within a year

Late latent or unknown duration

what about the painful penile lesion
What about the painful penile lesion?

Differential diagnosis of genital ulcer disease:

HSV, chronic

Syphilis

H. ducreyi

chronic hsv
Chronic HSV
  • AIDS-defining illness
  • Non-healing lesions (x >1 month) usually in pts with low CD4 counts (< 100)
  • More commonly acyclovir resistant
  • Treat until lesions have healed completely
hiv hsv
HIV & HSV
  • HSV thought to facilitate transmission / acquisition of HIV
  • HSV suppressive therapy reduces HIV RNA levels
  • Use of acyclovir does not reduce HIV incidence
  • HSV suppression does not reduce HIV acquisition

Nagot N et al. NEJM 2007

Watson-Jones D et al. NEJM 2008

Celum C et al. Lancet 2008

case 2
Case 2

32 year old male presents with rectal bleeding x 2 weeks, more frequent stools

HIV - stage 3 (CD4 nadir 43 now 138 on ARVs, diagnosed 2001, intermittently on therapy due to adverse effects and depression

MSM

case 2 exam
Case 2 - Exam

Rectal exam - no masses, no hemorrhoids. Anoscopy - clotted blood seen, no masses

case 2 next steps
Case 2 - Next Steps
  • Stool Tests
    • C. difficile negative
    • Giardia negative
    • Stool enteric pathogen screen negative
    • O&P negative
    • Cyclospora, isopora, cryptosporidium negative
  • What would you do next?
case 2 colonoscopy
Case 2 - Colonoscopy

5 cm rectal mass seen (5cm from anal verge)

What is your diagnosis?

anal cancer
Anal Cancer
  • HIV-positive men 60x more likely than HIV-negative men
  • Overall incidence still low
  • HPV-associated cancer
  • Oncogenic HPV types implicated in disease
  • HPV vaccine not approved in men
anal cancer screening
Anal Cancer: Screening?
  • Anal Pap smears
    • 30-60% of HIV-positive persons will have anal cytologic abnormalities
    • If Pap smear abnormal --> high-resolution anoscopy
    • Systematic review in 2006 - not enough evidence to recommend routinely
  • Digital rectal exam recommended for MSM and women who have anal sex

Chiao EY et al. Clin Infect Dis 2006;43:223-33

case 2 pathology1
Case 2 - pathology

Diffuse Large B Cell Lymphoma

case 3
Case 3
  • 34 year old male with low grade fevers, intermittent abdominal pain, and weight loss (20 lb) x 3 months
  • HIV +
  • Presents to outside MD, CD4 count 6, VL >1,000,000
  • Started on lopinavir/ritonavir/emtricitabine/tenofovir
case 3 continued
Case 3 - continued
  • 3 days into therapy -- diarrhea, nausea, vomiting
  • 4 days later, presents to our hospital with worsening symptoms and altered mental status
  • Admitted to Neurology
  • Diagnostic tests?
case 3 continued1
Case 3 - continued

LP - normal OP; glu 49; TP 19; WBC 0; RBC 0; PCRs negative, CSF cx negative

MRI brain: unremarkable

Blood cultures sent

CXR: diffuse patchy interstitial opacities

Chest CT: ground glass opacities, hilar/mediastinal LAD

Sputum culture: 4+ afb

case 3 continued2
Case 3 - continued

Sputum culture: 4+ afb

Underwent bronchoscopy: 4+ afb, PCP neg

  • Blood culture for afb +
  • He developed hypotension and was transferred to unit briefly
  • Discharged on treatment for MAC

What explains his clinical deterioration?

How could it have been avoided?

immune reconstitution syndrome
Immune Reconstitution Syndrome

Worsening of signs/symptoms due to infections that results from improvement in immune function after the initiation of anti-retroviral therapy

immune reconstitution syndrome1
Immune Reconstitution Syndrome
  • Occur in 10 to 40% of patients on HAART
  • Mycobacterial infections involved in 1/3 of cases
  • Onset is typically within 8 weeks of HAART (range 1 week to 7 months)
irs treatment options
IRS - Treatment Options
  • Interrupt HAART (try to avoid this)
  • NSAIDs
  • Steroids - improved symptoms but no effect on survival
  • IVIG?
  • Thalidomide?

Meintjes, CROI-2009, Montreal, Abst#34

case 3 back to patient
Case 3 - back to patient
  • ARVs stopped for 3 weeks and then restarted
  • Symptoms improved and then worsened again 10 days after reinitiation of ARVs
  • Started on prednisone and NSAIDs, ARVs continued
  • When would you start taper?
case 3 back to patient1
Case 3 - back to patient
  • Taper started after 3 weeks
  • Fevers, abdominal pain recurred 2 weeks into taper
  • Steroids continued and tapered more slowly over the course of months
  • Intially improved but then developed worsening abdominal pain - multiple CTs showed mesenteric LAD
case 32
Case 3
  • Then 1 year after his diagnosis --
    • Acutely worsening abdominal pain, low blood pressure --> unresponsive --> cardiac arrest
    • Found to have Gram negative sepsis (GI source)
    • Imaging showed diffuse bowel edema and necrotic enlarged LN
    • Made comfort care and died
ideal time to start arvs
Ideal time to start ARVs

Possibly sooner rather than later …

Improved survival for OI’s (including TB)

Worse possibly for cryptococcal meningitis

Zalopa. ACTG 5164, CROI 2008, Boston, Abst# 142

Karim, SAPIT study, CROI 2009, Montreal, Abst# 36a

Macadzange, CROI 2009, Montreal, Abst #38cLB

good news
Good News
  • With prevention and increased recognition/early treatment, decreased mortality
  • Treatment at higher CD4 counts --> less OI’s
slide53
Next session: 20 August, 2009

Listserv: itechdistlearning@u.washington.edu

Email: DLinfo@u.washington.edu

next session 20 august 2009 judd walson md hiv and tropical diseases
Next session: 20 August, 2009

Judd Walson, MD

HIV and Tropical Diseases