Clinicopathologic Conference Advanced Update in HIV Medicine and Clinical Research October 1, 2009

1. Clinicopathologic ConferenceAdvanced Update in HIV Medicine and Clinical ResearchOctober 1, 2009 Tammy M. Meyers, BA, MBBCh (WITS), FCPaed (SA), Mmed, DTM&H University of the Witwatersrand Thumbi Ndung'u, DVM, PhD. Nelson R. Mandela School of Medicine

2. “A 7-year-old boy with elevated HIV ribonucleic acid levels despite antiretroviral medications” Presentation of Case Brian C. Zanoni, M.D.

3. History of Present Illness • 7 year old HIV positive child on ART transferred care to Sinikithemba Clinic

4. Past Medical History • Birth history • Full term normal spontaneous vaginal delivery • 3.4 Kg • Mother with prenatal care but no HIV testing • Breastfed for 3 months • Received all routine immunizations • Including BCG

5. History of Present Illness • At age 3 hospitalized for pneumonia • Clinically diagnosed with pulmonary TB • Completed 6 months of RIF, INH, PZA

6. History of Present Illness • 5 years 10 months old admitted for respiratory distress • Mantoux negative • HIV positive • Treated with ceftriaxone, clarithromycin, trimethoprim-sulfamethoxazole (TMP/SMX), albuterol (salbutamol), and hydrocortisone • No improvement

7. History of Present Illness • Admission continued • CD4: 9 / 1% • VL: 2.2 million copies / ml • Weight: 14 Kg (<5%) • After 5 days of no improvement started on RIF, INH, PZA for presumptive TB • Began HAART with AZT, 3TC, Ritonavir • Discharged on day 11 • Continued TMP/SMX, TB treatment, and ART

8. History of Present Illness • 4 months later • Developed a supraclavicular abscess • No response to antibiotics • I and D • Culture: No growth (bacterial or mycobacterial) • Pathology: Caseating granulomas with necrosis • Consistent with TB

9. History of Present Illness • 6 months after admission and ART/TB Treatment • Supraclavicular node resolved • TB treatment stopped (6 months completed) • CD4: 236 / 6% (↑ 9 / 1% at baseline) • VL: 3342 • Weight: 15 kg (~3%)

10. History of Present Illness • After 18 months on ART • Unable to continue with private physician for financial reasons • Transferred to McCord Hospital Sinikithemba Clinic • Mother reported good adherence with ART and TMP/SMX • Patient was unaware of his HIV status

11. Social/Family History • Father died of unknown illness when patient was an infant • Mother tested HIV positive after diagnosis of patient • Siblings tested HIV negative • No known TB contacts

12. Presentation to Sinikithemba • Physical exam • Weight < 5% • Axillary adenopathy • Otherwise normal • Preliminary management • AZT dose increased • 3TC dose increased • Ritonavir changed to lopinavir/ritonavir • TMP/SMX continued

13. Lab Results • 18 Months on ART • CD4: 146 / 6.1 % • VL: 4300 • Hb: 10.6 MCV 96 • LFTs: Normal

14. Follow-up • 5 months after presentation to Sinikithemba • Mother reported good adherence • No side effects • CD4: 471 / 17.9% • VL: 22,000 copies / ml • Weight: 17.39 Kg (<5%) • A diagnostic test was performed

15. Differential Diagnosis Dr. Tammy M. Meyers

16. Discussion of Management Dr. Tammy M. Meyers

17. Follow-up Brian C. Zanoni, M.D.

18. Follow-up • CD4 nadir 59 / 6% • Darunavir – Obtained on a compassionate basis from company • Drug registered with Medicine Counsel • Regimen changed: • Darunavir 375 mg twice daily • Ritonavir 100 mg twice daily • EFV 300 mg daily

19. Follow-up • 2 weeks later • Developed fever, cough, and new right middle lobe infiltrate • Diagnosed with pneumonia • Responded to oral antibiotics • 8 weeks after change of regimen • Clinically well • Weight: 21.43 Kg (5% - 10%) • CD4: 193 / 5.8% • VL: 150