Welcome to I-TECH HIV/AIDS Clinical Seminar Series

13 August, 2009

Mystery Cases

Shireesha Dhanireddy, MD

Opportunistic Infections

• 1981 - Reports of PCP in 5 gay men in Los Angeles

1

10

100

1,000

10,000

100,000

1,000,000

10,000,000

Pla

sma

HIV

RN

A

Plasma RNA Copies

CD4 Cells

4-8 Weeks Up to 12 Years 2-3 Years

CD

4 Cell C

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500

Intermediate Stage AIDS

Typical Course

OIs start here

Anti-HIVT-cell response

Sero-conversionAntibody response

From Harrington RD

HIV: Pathogenesis

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

• 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 continued

• Exam - thin, temporal wasting, +inguinal lymphadenopathy, erythematous ulceration on penis; left buttock indurated, erythematous area c/w abscess; neurologic exam normal

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 - penile lesion

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

• 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

• 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 1 - blood culture

Case 1

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

1. Mycobacterium avium complex

2. Salmonella nontyphi

3. Vibrio cholera

4. Staphylococcus aureus

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

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

CD

4 co

un

t

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

CMV, MAC, microsporidia, Isospora, KS

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

• 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 - continued

What about his other symptoms and other tests ?

Case 1 - additional testing

RPR +, VDRL + 1:16What is your next step?1. Treat with PCN IM x 1 for primary or early

latent syphilis2. Perform lumbar puncture and then treat

based on CSF results3. Treat with PCN IM x 3 for late latent

syphilis4. False positive result, do not treat

Syphilis & HIV

• Can enhance transmission of HIV

• Can have negative impact on immune status

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

• 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

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?

Differential diagnosis of genital ulcer disease:

HSV, chronic

Syphilis

H. ducreyi

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

• 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 2007Watson-Jones D et al. NEJM 2008Celum C et al. Lancet 2008

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

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

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

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

What is your diagnosis?

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 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 - pathology

Case 2 - pathology

Diffuse Large B Cell Lymphoma

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

• 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 - 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

Case 3 - continued

Sputum culture: 4+ afbUnderwent 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

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

retroviral therapy

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

• 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

• 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 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 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

Possibly sooner rather than later …

Improved survival for OI’s (including TB)

Worse possibly for cryptococcal meningitis

Zalopa. ACTG 5164, CROI 2008, Boston, Abst# 142Karim, SAPIT study, CROI 2009, Montreal, Abst# 36aMacadzange, CROI 2009, Montreal, Abst #38cLB

Good News

• With prevention and increased recognition/early treatment, decreased mortality

• Treatment at higher CD4 counts --> less OI’s

Thank you!Next session: 20 August, 2009

Listserv: itechdistlearning@u.washington.eduEmail: DLinfo@u.washington.edu

Welcome to I-TECH HIV/AIDS Clinical Seminar Series

Next session: 20 August, 2009

Judd Walson, MD

HIV and Tropical Diseases