1. Pediatric Case = Conundrums
Dr. Robert M. Lawrence
University of Florida, Gainesville
Saniyyah Mahmoudi, ARNP
Carol M. Fulton, ARNP
University of Florida, Jacksonville

2. 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 are no conflicts of interest represented in the presentation.

3. 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

4. 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 29-39% ( )
CDC Classification B3 – recurrent bacterial infections and CD4 % < 15% 4 years of age
History of peripheral neuropathy – improved on Vitamin B6 50mg daily

5. 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

6. What is the most likely diagnosis at this time?
HIV-associated arthralgia / myalgia
Reactive Arthritis
Septic arthritis / osteomyelitis
Systemic Lupus Erythematosis

7. Rheumatologic Manifestations of HIV Infection
Less Common Disorders
Common Disorders
Avascular necrosis
Rhabdomyolysis
Diffuse infiltrative lymphocytosis syndrome (DILS)
Rheumatoid arthritis
Systemic lupus erythematosis
Sarcoidosis
HIV assoc. arthralgia/myalgia
Reactive arthritis
Psoriatic arthritis
Vasculitis
Polymyositis
Pyomyositis
Septic arthritis/osteomyelitis
Zidovudine myositis
Reveille JD, Best Pract & Res Clin Rheumatology 20: , 2006
Colmenga I, Curr Opinion Rheumatology 18:88-95, 2006

8. 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

9. Arthritis of Left Knee

10. What is the most likely diagnosis at this time?
Rheumatic Fever
Reactive Arthritis
HIV associated Arthritis
Rheumatoid Arthritis
Systemic Lupus Erythematosis

11. 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.

12. 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, 2001
Palacios R et al. HIV infect and SLE. Lupus 11:60, 2002
Chang BG et al. Renal Manifestations of Concurrent SLE and HIV. Am J Kid Dis 33:441,1999
Haas M et al. HIV-associated IC glomerulonephritis with “lupus-like” Kidney Int 67:1381,2005
Chalom EC et al. Pediatric Pt. with SLE and congenital AIDS. Ped Rheum 6:7, 2008
Sacilooto NC et al. Juvenile SLE in a adolescent with AIDS Rev Bras Rheum 50:467, 2010

13. 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.

14. Lupus Nephritis WHO Class IV-G

15. Case #1 Take 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.

16. 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 cm. red macules.
His neurological exam is entirely normal.

17. What is the most likely diagnosis?
Syphilis
Chancroid (H.ducreyi)
LGV ( C. trachomatis)
Syphilis and GC
Syphilis and HIV

18. 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 days
Gaines et al. BMJ 297:1363, 1988.

19. Exposure Risk (average, per episode, involving HIV-infected source)
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
Female – female orogenital contact
(only 4 case reports)
IDU – needle sharing
0.67%
Perinatal (no prophylaxis)
24%
Verghese B et al. STD 2002;29: European Study Group BMJ 1992;304:809.
Macaluso JM et al. STD 1999;26:450-8.

20. Should you do an LP on this patient looking for Neurosyphilis?
Yes No
Abstain

21. HIV and Syphilis Is the LP indicated?
CDC Guidelines
Other Criteria?
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
65 patients with neuorsyphilis and had LP
50/65 co-infected with HIV
Plasma RPR >/=1: ~6x increased risk of neurosyphilis
CD4+ count </= 350 cells -- 3x increased risk
Both parameters ~ 18x risk
Marra CM 2004 JID 189:369

22. Case #2 Additional evaluation: 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
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

23. Empiric STI Treatment with what?
Rochephin and Azithromycin
Wait for test results
Rochephin and Doxycycline
Rochephin, Azithromycin and Penicillin

24. Case #2 – One Week Later Follow-up labs Signs 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
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

25. What would you like to do now?
Lumbar puncture and repeat Penicillin
Repeat Penicillin, discuss HIV
Recommend ARV Therapy
Refer to GI

26. Case #2 Ongoing Care - 8 weeks
Treatment
Response
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
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

27. Case #2 Time CD4 Total (%) Viral Load Other -- 240,000 HIV Ag +, WB +--
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 : Case Records of MGH. NEJM 2009; 360:1540.

28. 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

29. 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,
12/28/99-2/25/03
Stavudine, Epivir, Efavirenz
2,439-10,965
2/25/03-6/24/03
Didanosine, Stavudine, Lopinavir/r
10,965-5,578
6/24/03-2/28/06
Abacavir + Didanosine + Stavudine + Lopinavir/r
(132)
5,578 - <400
(117,000)
3/14/06-6/4/08
Epzicom + Lopinavir/r + Stavudine
12,400-1,580
8/1/08-9/27/10
Truvada + Norvir + Atazanavir
141-29

30. HIV GenoSURE 07/11/2006 Epzicom, Stavudine, Lopinavir/r

31. TRUGENE HIV-1
7/11/2007
Epzicom, Stavudine,
Lopinavir/r

32. Phenotype 6/7/09 Truvada, Atazanavir/r

33. TRUGENE HIV-1 5/4/2009 Truvada, Atazanavir/r

34. TRU GENE HIV-1 7/26/10 Truvada, Atazanavir/r

35. Mutations RT mutations- 184V, T215Y/D, A62V
PI mutations: L10I, M36I/V, I54M, D60E, L63, A71T, V77I, L90M

36. Mutation Interpretation
PI Major Resistance Mutations: I54M, L90M PI
Minor Resistance Mutations: L10I, A71T Other Mutations: M36IV, D60E, L63P, V77I

37. Mutation Interpretation
NRTI Resistance Mutations: A62DV, M184V, T215DY
NNRTI Resistance Mutations: None
Other Mutations: None

38. 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.

39. What is the next best step
What is the next best step? He wants to take medications but is tired of taking so many pills
Take him off all HAART and start OI prophylaxis
Take him off all HAART, start OI prophylaxis, start 3TC
Start new regimen
Adherence counseling

40. 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

41. 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

42. 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

43. 12/
pt was on atazanavir/r, raltegravir , emtricitabine/ tenofovir

44. 1/2009-10 pt was on atazanavir/r, raltegravir, emtricitabine/ tenofovir

45. Date
Medications
CD4 (absolute)
Viral load
Mutations
Mid 1999
70R, 67N, 98G 103N ,219Q yo
Zidovudine, Lamivudine, Abacavir, Nelfinavir
184V yo
Didanosine, tenofovir, lopinavir/ritonavir yo
315 (20%)
308,000 yo
189 (15%)
>750,000
11/ yo
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 to
10/2010
48 (7%)
6 (1%)
72,700
325,000
M36I
HAART stop
3/2011
8 (1%)
>100,000

46. What would you do next?
Take off HAART and continue OI prophylaxis only
Stress adherence and continue current HAART
Construct a new regimen
Take off HAART and start Epivir + OI prophylaxis