1. Rare Cases of Hypokalemia Associated With Tenofovir Use Slideset on: Cirino CM, Kan VL. Hypokalemia in HIV patients on tenofovir. AIDS. 2006;20:1671- 1673.

2. clinicaloptions.com/hiv Rare Cases of Hypokalemia Associated With Tenofovir Use Cirino CM, Kan VL. AIDS. 2006;20:1671-1673.  More than 12,000 patients administered tenofovir through clinical trials and expanded access programs –Overall rates of adverse events low  Rarely, renal insufficiency and failure historically associated with tenofovir use –Fanconi syndrome –Proximal tubulopathy –Proteinuria –Nephritis –Diabetes insipidus  Current study a case review analyzing risk factors associated with tenofovir use, hypokalemia, and other nephrotoxicities Background and Rationale

3. clinicaloptions.com/hiv Rare Cases of Hypokalemia Associated With Tenofovir Use Cirino CM, Kan VL. AIDS. 2006;20:1671-1673.  Query resulted in 39 individual safety reports plus 1 patient who presented with hypokalemia at investigator’s clinic  Grade 3 hypokalemia: n = 2 –Serum potassium levels: 2.0-2.4 mmol/L –Median serum potassium levels: 2.7 mmol/L (range: 1.3-3.7)  Nephrotoxicity at presentation: 76%  Required hospitalization: 65%  Median serum creatinine levels: 258.3 mmol/L (range: 52.8-994.4)  Median creatinine clearance: 35.7 mL/minute (range: 5.2-122.2)  Fanconi syndrome: n = 10  Patients with reported outcomes: n = 32 –Resolved: n = 15 –Symptoms improved: n = 6 –Unresolved: n= 7 –Died: n = 4 Main Findings

4. clinicaloptions.com/hiv Rare Cases of Hypokalemia Associated With Tenofovir Use Cirino CM, Kan VL. AIDS. 2006;20:1671-1673.  Antiretroviral regimen containing ritonavir: 84% –Regimen also contained didanosine: 38%  Concomitant medications known to cause hypokalemia and nephrotoxicity: n = 3 –Amphotericin B: n = 2 –Cidofovir: n = 1  Median time on tenofovir-containing HAART before onset of hypokalemia: 50 weeks (range: 1.3-137) Other Outcomes

5. clinicaloptions.com/hiv Rare Cases of Hypokalemia Associated With Tenofovir Use Cirino CM, Kan VL. AIDS. 2006;20:1671-1673. Risk Factors for Tenofovir- Associated Renal Insufficiency  Tenofovir postmarketing safety database indicates the rate of serious renal adverse events 43.3/100,000 person-years  Risk factors for tenofovir-associated renal insufficiency or failure –Baseline renal insufficiency –Low body weight –Concomitant use of ritonavir or didanosine  Tenofovir excretory pathway mediated by multidrug resistance protein 4

6. clinicaloptions.com/hiv Rare Cases of Hypokalemia Associated With Tenofovir Use Cirino CM, Kan VL. AIDS. 2006;20:1671-1673.  Tenofovir-associated serious adverse events are generally rare –40 cases of tenofovir-associated hypokalemia reported since 2001 –65% of the cases required hospitalization –66% recovered or improved after tenofovir discontinuation –4 patients died  Risk factors associated with renal insufficiency and tenofovir use included –Baseline renal insufficiency –Low body weight –Concomitant use of ritonavir and didanosine Key Conclusions