Pediatric Case = Conundrums

Dr. Robert M. Lawrence

University of Florida, Gainesville

Saniyyah Mahmoudi, ARNP

Carol M. Fulton, ARNP

University of Florida, Jacksonville

Disclosure of Financial Relationships

The speakers have no significant financial relationships with commercial entities to disclose.

This slide set has been peer-reviewed to ensure that there areno conflicts of interest represented in the presentation.

Objectives

• Present in a case-based discussion format –unique scenarios which highlight interesting concepts in Pediatric HIV care

• Utilization of Post-exposure Prophylaxis (PEP)

• Acute HIV Infection in a teenager• Rheumatologic complications of HIV

disease

Case #1• A 10 year African-American female with perinatal

HIV infection• On Epivir, Stavudine and Lopinavir/r for three +

years.• Viral load has been <50 for 3 years• CD4 counts are stable @ 29-39% (765-1259)• CDC Classification B3 – recurrent bacterial

infections and CD4 % < 15% repeatedly @ 4 years of age

• History of peripheral neuropathy – improved on Vitamin B6 50mg daily

Case #1

• !0 yo AA female present to the ER with pain in her left foot and left buttocks / hip without fever, gait reported as normal

• Urinalysis shows + leukocyte esterase, 10 WBCs, 5 RBCs (subsequent culture + for Enterococcus >100,000 cfus)

• Positive Family History for “Rheumatoid Arthritis in the Paternal Grandmother

• Recent VL <50, CD4 28%, 966• Given Septra for UTI, and hydrocodone for hip

pain

What is the most likely diagnosis at this time?

1. HIV-associated arthralgia / myalgia

2. Reactive Arthritis

3. Septic arthritis / osteomyelitis

4. Systemic Lupus Erythematosis

Rheumatologic Manifestations of HIV Infection

Common Disorders• HIV assoc. arthralgia/myalgia• Reactive arthritis• Psoriatic arthritis• Vasculitis• Polymyositis• Pyomyositis• Septic arthritis/osteomyelitis

• Zidovudine myositis

Less Common Disorders• Avascular necrosis• Rhabdomyolysis• Diffuse infiltrative

lymphocytosis syndrome (DILS)

• Rheumatoid arthritis• Systemic lupus

erythematosis• Sarcoidosis

Reveille JD, Best Pract & Res Clin Rheumatology 20:1159-79, 2006Colmenga I, Curr Opinion Rheumatology 18:88-95, 2006

Case #1• This 10 year old AA female returns 6 weeks later complaining of

different joint pains, especially the left knee > right knee, no dysuria, no fevers, a 3 pound weight loss, and occasional loose stools

• She has a red, warm, swollen left knee > the simply swollen right knee and decreased ROM of wrists and ankles due to pain not weakness (no “arthritis”)

• Rapid Strept throat swab + culture, urinalysis and culture, stool cultures, Urine for GC/CZ, ASO, PCR for CMV, EBV, HBV, HCV, HTLV-I and Parvovirus, along with a Rheumatologic panel and routine HIV labs are sent

• Patient is given Naprosyn 375 mg PO BID, Prevacid for symptomatic treatment

Arthritis of Left Knee

What is the most likely diagnosis at this time?

1. Rheumatic Fever

2. Reactive Arthritis

3. HIV associated Arthritis

4. Rheumatoid Arthritis

5. Systemic Lupus Erythematosis

Case #1• All the “reactive arthritis” labs are negative.• Her VL is <50 and CD4 counts are stable.• The ANA is positive 1:1280. The RNP, SSA and SSB, Smith Ab, Anti-

phospholipid Ab and Histone Ab are all positive with normal C3 and C4 levels.

• The tentative diagnosis is drug mediated autoimmune antibody response (Kaletra). Pt. continues on Prevacid, Indocin, and ASA with symptomatic relief.

• Her ARVs are changed based on Genotype testing and she intermittently has VL < 50 due to poor compliance.

• She is followed by the Rheumatology and ID services.

Case #1

• 18 months later this 12 yo female develops hematuria and proteinuria along with very low C3 and C4 levels and “re-elevation” of her autoimmune antibodies (ANA again 1:1280)

• A renal biopsy shows diffuse proliferative immune complex (IgG, IgM, C3 and C1q) glomerulonephritis, most consistent with lupus nephritis, Class IV-G.

Mialou V et al. Lupus Nephritis in a Child with AIDS. Am J Kid Dis 37:E27, 2001Palacios R et al. HIV infect and SLE. Lupus 11:60, 2002Chang BG et al. Renal Manifestations of Concurrent SLE and HIV. Am J Kid Dis 33:441,1999Haas M et al. HIV-associated IC glomerulonephritis with “lupus-like” Kidney Int 67:1381,2005Chalom EC et al. Pediatric Pt. with SLE and congenital AIDS. Ped Rheum 6:7, 2008Sacilooto NC et al. Juvenile SLE in a adolescent with AIDS Rev Bras Rheum 50:467, 2010

Case #1

• This patient is now almost 16 years old with reasonable control of her Lupus nephritis and arthritis with monthly infusions of corticosteroids and cytoxan.

• Her medical care has been complicated by the separation and divorce of her parents.

• Her HIV is poorly controlled due to non-compliance with her ARV regimen.

Lupus NephritisWHO Class IV-G

Case #1Take Home Points

• Musculoskeletal disease in association with HIV is more common.

• Rheumatologic disease is also more common.• Effective ARV therapy / control is an important

aspect of therapy for these patients.• Corticosteroids is the mainstay of therapy in

most rheumatologic disease with HIV• Cytotoxic agents can be used in refractory cases,

with CD4 counts > 200.

Case #2• 17 yo WM presents to the ER with fevers, decreased

energy and whole body aches for 2 weeks, diarrhea and 3 lb. weight loss in the last week, arthalgia in lower extremities, a new rash on hands and feet

• Patient reports unprotected receptive anal intercourse• The patient has a 1.5 cm “painless” ulcer on the corona

of his penis. Temperature is 38.8 C. Both knees are swollen , warm but not red. His tonsils are 2+ without exudate or other oral lesions noted. There are multiple, bilateral 1-2cm. anterior cervical nodes which are mildly tender and non-tender 1 cm. inguinal LNs. His palms and soles have multiple 0.5-1 cm. red macules.

• His neurological exam is entirely normal.

What is the most likely diagnosis?

1. Syphilis

2. Chancroid (H.ducreyi)

3. LGV ( C. trachomatis)

4. Syphilis and GC

5. Syphilis and HIV

Clinical Picture of Primary HIV Infection

• Fever 20• Lethargy

12• Myalgia 8• Headache 8• Sore throat

19• Inflammed throat

17• Coated tongue 10• Enlarged tonsils 9• Cervical LNs 19

• Axillary LNs

15• LNs at > 2 sites

11

• Rash 15• Genital ulcer 2• Anal ulcer 2• Vomiting 8• Nausea 7• Diarrhea 6• Weight loss > 5 kg 4• Total # patients

20• Incubation 11-28 days

Gaines et al. BMJ 297:1363, 1988.

Exposure Risk(average, per episode, involving HIV-infected source)

Exposure Risk

Percutaneous (blood) 0.3%

Mucocutaneous (blood) 0.09%

Receptive anal intercourse 1%

Insertive anal intercourse 0.06%

Receptive vaginal intercourse 0.1 – 0.2%

Insertive vaginal intercourse 0.03 – 0.14%

Receptive oral sex with a male

0.06%

Female – female orogenital contact

(only 4 case reports)

IDU – needle sharing 0.67%

Perinatal (no prophylaxis) 24%

Verghese B et al. STD 2002;29:38-43. European Study Group BMJ 1992;304:809.Macaluso JM et al. STD 1999;26:450-8.

Should you do an LP on this patient looking for Neurosyphilis?

1. Yes

2. No

3. Abstain

HIV and SyphilisIs the LP indicated?

CDC Guidelines• Neurologic or ophthalmic signs

or symptoms• Evidence of active tertiary

syphilis (aortitis, gumma or iritis)• Treatment failure• HIV infection with late latent

syphilis or syphilis of unknown duration

• CDCP 2002 MMWR 51: 18-30

Other Criteria?• 65 patients with neuorsyphilis

and had LP• 50/65 co-infected with HIV• Plasma RPR >/=1:32 -- ~6x

increased risk of neurosyphilis

• CD4+ count </= 350 cells -- 3x increased risk

• Both parameters ~ 18x risk• Marra CM 2004 JID 189:369

Case #2

Additional evaluation:

• No fluid in knees• No other joints involved• No penile discharge or “milkable

discharge”• No petechiae• No epididymitis, proctitis or anal

lesions• No iritis or uveitis• No known drug allergies

Preliminary labs:• BMP – WNL• LFTs – WNL, except Tot. protein =

8.2g/dL• WBC 6400 (69P/19L/7M/5E)• Hgb =12.4 and Hct = 35.9• Platelets 268,000• Monospot negative• Rapid Strep Test negative• Rapid HIV1/2, Ab + Ag positive

Empiric STI Treatment with what?

1. Rochephin and Azithromycin

2. Wait for test results

3. Rochephin and Doxycycline

4. Rochephin, Azithromycin and Penicillin

Case #2 – One Week LaterSigns and Symptoms

• Fevers, poor appetite• Thin and pale• Knees and ankle pain with

early morning stiffness• Weight loss 6 kg in 1 week• No vomiting or diarrhea• Penile lesion – flat

hypopigmentation• Rash – only peeling of palms

and soles• Diffuse lymphadenopathy

Follow-up labs

• RPR 1:64, TPHA +• HIV WB positive• HIV RNA PCR = 240,000• GC cultures of urethra, rectum

and throat all negative• Urine GC / CZ NA are negative• HIV Genotype pending• No lymphocyte subsets

What would you like to do now?

1. Lumbar puncture and repeat Penicillin

2. Repeat Penicillin, discuss HIV

3. Recommend ARV Therapy

4. Refer to GI

Case #2 Ongoing Care - 8 weeks

Treatment• Completed three weekly

IM injections of Benzathine PCN 2.4 million units

• Omperazole daily• Naprosyn 500mg PO

BID• Nu-iron 150 mg PO BID• MVI one tab PO BID

Response• No fevers, rashes• 5 kg weight gain• Only occasional joint

pain or morning stiffness / no arthritis

• HLA B 27 positive• RPR 1:16• Hgb 11.2 / Hct 33.8

Case #2Time CD4 Total

(%)Viral Load Other

0 -- 240,000 HIV Ag +, WB +

6 weeks 359 (17%) 395,430 ARV naive

13 weeks 221 (14%) 193,887 Genotype - pansensitive

18 weeks 249 (16%) 104,000

30 weeks 191 (18%) 123,000 Atripla started

44 weeks 396 (22%) 66

Aggarwal M. Acute HIV Syndrome in an Adolescent. Peds 2003; 112:e323.

Bell SK. Case 11-2009: Case Records of MGH. NEJM 2009; 360:1540.

Case no. 3

• 17 yo male with perinatal HIV infection• Past history significant for BOM with

effusion• No recent hospitalizations• Immunizations UTD• Lives with dad who is the primary caregiver• h/o non compliance

Date Medications CD4 (absolute)

Viral load

1/25/94-10/31/95 Zidovudine

10/31/95-3/18/97 Zidovudine, Didanosine

3/18/97-7/15/97 Zidovudine, Lamivudine,Ritonavir (ACTG 338)

1/1/98-8/18/98 Nelfinavir,Zidovudine, Epivir

490,641

8/18/98-1/5/99 Zidovudine, Epivir,Amprenavir (GSK 141study)

1/5/99-12/28/99 Stavudine,Didanosine,Amprenavir (GSK 141study)

12/28/99-2/25/03 Stavudine, Epivir, Efavirenz 174-401 2,439-10,965

2/25/03-6/24/03 Didanosine, Stavudine, Lopinavir/r

401-357 10,965-5,578

6/24/03-2/28/06 Abacavir + Didanosine + Stavudine + Lopinavir/r

357-316 (132)

5,578 - <400 (117,000)

3/14/06-6/4/08 Epzicom + Lopinavir/r + Stavudine

183-329 12,400-1,580

8/1/08-9/27/10 Truvada + Norvir + Atazanavir 141-29 5520-9730

HIV GenoSURE07/11/2006Epzicom,

Stavudine, Lopinavir/r

TRUGENE HIV-17/11/2007Epzicom, Stavudine,Lopinavir/r

Phenotype 6/7/09

Truvada, Atazanavir/r

TRUGENE HIV-1

5/4/2009

Truvada, Atazanavir/r

TRU GENE HIV-1

7/26/10

Truvada, Atazanavir/r

Mutations

• RT mutations- 184V, T215Y/D, A62V

• PI mutations: L10I, M36I/V, I54M, D60E, L63, A71T, V77I, L90M

Mutation Interpretation

• PI Major Resistance Mutations: I54M, L90M PI

• Minor Resistance Mutations: L10I, A71T Other Mutations: M36IV, D60E, L63P, V77I

Mutation Interpretation

• NRTI Resistance Mutations: A62DV, M184V, T215DY

• NNRTI Resistance Mutations: None • Other Mutations: None

Mutation Interpretation

• M184V/I cause high-level in vitro resistance to 3TC and FTC and low-level in vitro resistance to ddI and ABC. M184V/I increases susceptibility to AZT, TDF, and d4T.

• T215Y causes AZT and D4T resistance and reduces susceptibility to ABC, ddI, and TDF particularly when it occurs in combination with M41L and L210W.

• T215S/C/D/E/I/V are transitions between wild type and the mutations Y and F.

• Other A62V is associated with multinucleoside resistance caused by Q151M; its effect in the absence of Q151M is not known.

What is the next best step? He wants to take medications but is tired of taking so many

pills

1. Take him off all HAART and start OI prophylaxis

2. Take him off all HAART, start OI prophylaxis, start 3TC

3. Start new regimen

4. Adherence counseling

What regimen options would you choose?

1. Atripla® (efavirenz/tenofovir/ emtricitabine) + Raltegravir

2. Darunavir/r + Truvada® (emtricitabine/tenofovir) + etravirine or raltegravir

3. Tipranavir/r + Truvada ® (emtricitabine/tenofovir) + etravirine or raltegravir

4. Send tropism assay for maraviroc

Current regimen

• Atripla® (efavirenz/tenofovir/emtricitabine), raltegravir (CD4 at start-29)

• Continued dapsone/azithromycin• One month and 3 months later: CD4 29 to

95 (10%), VL remains undetectable

Case # 4• 20 yo with perinatal HIV infection• Highly treatment experienced• Currently on darunavir/r, raltegravir,

emtricitabine/tenofovir, azithromycin, fluconazole, dapsone

• Remains noncompliant last VL >100,000,

CD4 8 (1%) March of 2011• Ongoing issues: wasting (wt down to 94 lbs),

diarrhea, candida esophagitis, pneumonia

12/2009-11 pt was on atazanavir/r, raltegravir , emtricitabine/ tenofovir

1/2009-10 pt was on atazanavir/r, raltegravir, emtricitabine/ tenofovir

Date Medications CD4 (absolute)

Viral load Mutations

Mid 1999 70R, 67N, 98G 103N ,219Q

2001 11yo Zidovudine, Lamivudine, Abacavir, Nelfinavir

184V

2003 13 yo Didanosine, tenofovir, lopinavir/ritonavir

2006 16yo 315 (20%) 308,000

2007 17yo 189 (15%) >750,000

11/2008 19yo Atazanavir/ritonavir, emtricitabine/tenofovir, raltegravir

22 (3%) 461,000

2/2009 95 (8%) 570

4/2009 44 (5%) 1,690,000 R41K, 164V

6/2010 to10/2010

48 (7%)6 (1%)

72,700325,000

M36I HAART stop

3/2011 8 (1%) >100,000

What would you do next?

1. Take off HAART and continue OI prophylaxis only

2. Stress adherence and continue current HAART

3. Construct a new regimen

4. Take off HAART and start Epivir + OI prophylaxis