Clinicopathologic Conference Advanced Update in HIV Medicine and Clinical Research October 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

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

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

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

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

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

History of Present Illness Admission continued –CD 4 : 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

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

History of Present Illness 6 months after admission and ART/TB Treatment –Supraclavicular node resolved –TB treatment stopped (6 months completed) –CD 4 : 236 / 6% (↑ 9 / 1% at baseline) –VL: 3342 –Weight: 15 kg (~3%)

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

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

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

Lab Results 18 Months on ART –CD 4 : 146 / 6.1 % –VL: 4300 –Hb: 10.6 MCV 96 –LFTs: Normal

Follow-up 5 months after presentation to Sinikithemba –Mother reported good adherence No side effects –CD 4 : 471 / 17.9% –VL: 22,000 copies / ml –Weight: Kg (<5%) A diagnostic test was performed

Differential Diagnosis Dr. Tammy M. Meyers

Discussion of Management Dr. Tammy M. Meyers

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

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

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: Kg (5% - 10%) –CD4: 193 / 5.8% –VL: 150