case discussion: complications after art

Case Discussion:Complications after ART

Weerawat Manosuthi, MDDepartment of Medicine

Bamrasnaradura Infectious Diseases Institute, Ministry of Public Health, Thailand

Case: SW, 55 year-old male 1994 - First diagnosed with HIV and CD4

290ZDV+ddI

1994-2001 - ARV regimens had been changed due to virologic rebound without resistance test.- He reported fair adherence.- His last VL in 2001 was 4.1 logs.

ZDV+ddC+SQV 2 yrs d4T+ddI+IDV/r 3 yrsZDV+3TC+EFV 1 yr

2002-2006 - Lost to follow-up.

Case: SW, 55 year-old male 1994 - First diagnosed with HIV and CD4 290 ZDV+ddI


ZDV+ddC+SQV 2 yrsd4T+ddI+IDV/r 3 yrsZDV+3TC+EFV 1 yr


April 2007 - Presented with visual loss. - CD4 28 (3%), VL 5.3 log - HBs Ag - neg, anti-HCV - neg, A1C 9.3% - Cr 0.7 mg/dL, CrCl 101, urine protein 1+- HIV genotype: No evidence of resistance

TDF+3TC+LPV/r (on 7 May 2007)

Q1: Do you agree with this regimen “TDF+3TC+LPV/r” ?1. I do2. I do not

Case: SW, 55 year-old male 1994 - First diagnosed with HIV and CD4 290 ZDV+ddI


ZDV+ddC+SQVd4T+ddI+IDV/rtvZDV+3TC+EFV

2002-2006 - Lost to follow-up.April 2007 - Presented with visual loss.

- CD4 28 (3%), VL 5.3 log - HBs Ag - neg, anti-HCV - neg, A1C 9.3% - Cr 0.7 mg/dL, CrCl 101, urine protein 1+- HIV genotype: No evidence of resistance

TDF+3TC+LPV/rtv (on 7 May 2007)

30 May 2007

- Fever with intra-abdominal lymph node enlargement and necrosis.

I, E, Z, Quinolone(Rifabutin was not available)

Case: SW, 55 year-old male 1994 -First diagnosis with HIV and CD4 290 ZDV+ddI


ZDV+ddC+SQV 2 yrsd4T+ddI+IDV/rtv 3 yrsZDV+3TC+EFV 1 yr


April 2007 - Presented with visual loss. - CD4 28 (3%), VL 5.3 log, HBs Ag - neg, anti-HCV – neg, CrCL 101- Cr 0.7 mg/dL, A1C 9.3, urine protein 1+- HIV genotype: No evidence of resistance

TDF+3TC+LPV/rtv (on 7 May 2007)Metformin

30 May 2007 - Fever with intraabdominal lymph node enlargement and necrosis. I, E, Z, Quinolone

Aug 2007(Regular visit without symptoms)

- CD4 52 (11%), VL 68 (1.8 log), Cr 11.6 mg/dl, - Na 122 K 6 Cl 97 HCO3 11 CrCl 6 ml/min- Urine protein 1+, U/S of kidney: high normal size- Renal biopsy: diabetic nephropathy, interstitial nephritis and tubular epithelial damage.

Q2: What is the most likely cause of renal impairment?1. Tenofovir2. Lopinavir/rtv3. Anti-TB drugs4. Diabetes 5. Others

Rodrı ́guez-No ́voa S, et al. Clin Infect Dis 2009;48:e108-16.Kalyesubula R, et al. AIDS Research and Treatment 2011.

Nelson M, et al. AIDS 2008;22,1374-1376.Zimmermann AE, et al. Clin Infect Dis 2006;42,:283-290.

Rodrı ́guez-No ́voa S, et al. Expert Opinion 2012;9:545-559.

Older age Elevated baseline creatinine Low body weight Low CD4 nadir Other comorbidities: diabetes, HCV Concomitant use of nephrotoxic

drugs Combined therapy with PI

Inhibition of MRP4 by PI/r leads to increased intracellular tenofovir levels

Genetic factors, involving polymorphisms at cellular transporter gene

Risk Factors Associated with TDF-Induced Nephrotoxicity

Mitochondrial toxicity

Interfere tubular cell function

Case: SW, 55 year-old male 1994 -First diagnosis with HIV and CD4 290 ZDV+ddI








- CD4 52 (11%), VL 68 (1.8 log), Cr 11.6 mg/dl, Hb 9- Na 122 K 6 Cl 97 HCO3 11 CrCl 6 ml/min- Urine protein 1+, U/S of kidney: high normal size- Renal biopsy: diabetic nephropathy, interstitial nephritis and tubular epithelial damage.

Q3: Which of the following is the best next regimen?1. PI/r + integrase inhibitor + 3TC2. PI/r + etravirine + 3TC3. PI/r + integrase inhibitor + Etravirine 4. Others

Case: SW, 55 year-old male

Q4: Which of the following is a next regimen if he is in the resource-limited setting (3 classes available) ?1. PI/r + 3TC2. PI/r + AZT + 3TC3. Others

1994 -First diagnosis with HIV and CD4 290 ZDV+ddI








- CD4 52 (11%), VL 68 (1.8 log), Cr 11.6 mg/dl, Hb 9- Na 122 K 6 Cl 97 HCO3 11 CrCL 6 ml/min- Urine protein 1+, U/S of kidney: high normal size- Renal biopsy: diabetic nephropathy, interstitial nephritis and tubular epithelial damage.

Case: SW, 55 year-old male Aug 2007(Regular visit without symptoms)

- CD4 52 (11%), VL 68 (1.8 log), Cr 11.6 mg/dl, - Na 122 K 6 Cl 97 HCO3 11 CrCl 6 ml/min- Urine protein 1+, U/S of kidney: high normal size- Renal biopsy: diabetic nephropathy, interstitial nephritis and tubular epithelial damage.

- 3TC+LPV/rtv- Modified dose of anti-TB drugs- Hemodialysis

Nov 2007 - CD4 23 (8%), VL <50, Cr 7-10 mg/dl

Feb 2008 - CD4 109 (8%) and VL <50, Cr 3-4 mg/dl- Markedly decreased size of intraabdominal LN

Aug 2008 CD4 103 (10%), VL <50 Off anti-TB drugs


- CD4 52 (11%), VL 68 (1.8 log), Cr 11.6 mg/dl, - Na 122 K 6 Cl 97 HCO3 11- Urine protein 1+, U/S of kidney: high normal size- Renal biopsy: diabetic nephropathy, interstitial nephritis and tubular epithelial damage.


Nov 2007 - CD4 23 (8%), VL <50, Cr 7-10 mg/dl


Aug 2008 - CD4 103 (10%), VL <50 - Off anti-TB drugsMay 2009 - CD4 104 (7%), VL <40

- Chest x-ray as - Sputum AFB +ve, PCR TB +ve, DST: pending

Q5: What would you manage this episode of TB?


- CD4 52 (11%), VL 68 (1.8 log), Cr 11.6 mg/dl, - Na 122 K 6 Cl 97 HCO3 11 CrCL 6 ml/mim- Urine protein 1+, U/S of kidney: high normal size- Renal biopsy: diabetic nephropathy, interstitial nephritis and tubular epithelial damage.


Nov 2007 - CD4 23 (8%), VL <50, Cr 7-10 mg/dl


Aug 2008 - CD4 103 (10%), VL <50 - Off anti-TB drugs

May 2009 - CD4 104 (7%), VL <40- Chest x-ray - Sputum AFB +ve and PCR TB +ve

- 3TC+LPV/rtv- I, E, Z, Quinolone

Aug 2009 - CD4 93 (13%), VL <40- Sputum culture grew M. TB. - Sense: R, Resist: I, E, S

Levoflox, amikacin, cycloserine, PAS, ethionamide

Aug 2011 - CD4 102 (13%), VL 200, infiltrations cleared - Off anti-TB drugs




Nov 2007 - CD4 23 (8%), VL <50, Cr 7-10 mg/dl



May 2009 - CD4 104 (7%), VL <40- Chest x-ray, Sputum AFB +ve and PCR TB +ve

Aug 2009 - CD4 93 (13%), VL <40- Sputum culture grew M. TB. Sense: R, Resist: I, E, S

- Levoflox, amikacin, cycloserine, PAS, ethionamide

Aug 2011 - CD4 102 (13%), VL 200, resolved infiltration - Off anti-TB drugs

Nov 2011 - Lost to follow-upJan 2012 - CD4 135 (15%), VL 61,000 co/ml, Cr 2.6 mg/dl

- Genotypic report: M184V, no major PRAM

Q6: Which of the following is the best next regimen?1. PI/r + integrase inhibitor + Etravirine 2. PI/r + integrase inhibitor + 3TC3. PI/r + 3TC4. Others




Nov 2007 - CD4 23 (8%), VL <50, Cr 7-10 mg/dl



May 2009 - CD4 104 (7%), VL <40- Chest x-ray, Sputum AFB +ve and PCR TB +ve

Aug 2009 - CD4 93 (13%), VL <40- Sputum culture grew M. TB. Sense: R, Resist: I, E, S

- Levoflox, amikacin, cycloserine, PAS, ethionamide

Aug 2011 - CD4 102 (13%), VL 200, resolved infiltration - Off anti-TB drugs

Nov 2011 - Lost to follow-upJan 2012 - CD4 135 (15%), VL 61,000 co/ml, Cr 2.6 mg/dl

- Genotypic report: M184V, no major PRAM- 3TC+LPV/rtv

Apr 2012 - CD4 132 (16%), VL <40 - 3TC+LPV/rtvMar 2013 - CD4 162 (16%), VL <40 - 3TC+LPV/rtv

THANK YOU

case discussion: complications after art

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