Dr. Chureeratana Bowon

Chonburi Hospital Thailand

1 Oct., 2016

30 min.

Case Discussion

Date BW CD4(%) ART

May 05 49 106(7%) d4T, 3Tc, EFV

Nov 05 61 “” “’

Jun 06

(mon13)

57 203(15%)

VL <50

“” “”

Lactate 0.8 mm/ml

M 23 y-o NBW 65kg. OI: TB Lymph node

Hx : loss of appetite, afebrile, no cough

PE : no abnormalities detected

Q 1. Will you replace d4T with other NRTIs?

A. Yes B. No

Case I: Loosing BW in suppressed VL man

Date BW CD4(%) ART

May 05 49 106(7%) d4T, 3Tc, EFV

Nov 05 61

Jun 06 57 203(15%)

VL <50

Lactate 0.8

Sep 06 55 AZT, 3Tc, EFV

Apr. 07 50 301(18%)

VL <50

Lactate 0.9

61 to 50 kg.

CBC Hct 15.4, Hct 45.2 PMN 6,270 PMN 57.9 Lc 32.1 Plt 206K

UA: WNL CXR neg.

ESR 6 mm./hr

LFT DB 0.1, TB 0.5 OT 18 PT 12 AP 83

FBS 86 mg%

US: Upper abdomen neg.

Lactate < 1 x 2 times

Cho 132 TG 38 HDL 45 LDL 79.4

FT4 1.4 TSH 0.673

BW from 61 kg to 50 kg.

With permission

Work up ‘ weight loss ’

Date BW CD4(%) ART

May 05 49 106(7%) d4T, 3Tc, EFV

Nov. 05 61

Jun. 06 57 203(15%)

VL <50

Lactate 0.8

Sep. 06 55 AZT, 3Tc, EFV

Apr. 07 50 301(18%)

VL <50

Lactate 0.9

Nov. 07 49 3Tc, TDF, EFV

May.08 41.5 377(19%) “” “”

61 to 41.5 kg.

With permission

Q 2 Will you change TDF, 3Tc, EFV to other regimens?

Yes

No

Panel Discussion

“ What regimen?”

Regimen after mark weight loss from 3Tc,TDF, EFV?

TDF Package inserted

Unexplained weight

Loss from TDF

Date BW CD4(%) ART

May 05 49 106(7%) d4T, 3Tc, EFV

Nov. 05 61

Sep. 06 55 AZT, 3Tc, EFV

Apr. 07 50 301(18%)

VL <50

Lactate 0.9

Nov.07 49 3Tc, TDF, EFV

May 08 41.5 377(19%) 3Tc, LPVr

Jul. 08 47 344(18%)

VL <50

“” “’

Nov. 08 52 “” “’

Date BW CD4(%) ART

Nov.07 49 3Tc, TDF, EFV

May. 08 41.5 377(19%) 3Tc, LPVr

Jul. 08 47 344(18%)

VL <50

“” “’

Nov. 08 52 “” “’

Mar. 09 59 “” “’

Nov. 09 61 521 (24%) “” “”

Jul. 16 70 666 ( 28%)

VL <50

“” “”

May 08, 41 kg. 3Tc, TDF, EFV Nov. 08, 52 kg. 3Tc, LPVr

With permission

Mar. 09, 59 kg. 3Tc, LPVr Nov. 09, 61 kg. 3Tc, LPVr

A. Since he is happy, I will continue 3Tc, LPVr

B. No, I do add him one more ARV to

strengthen the regimen

Q 3. Below is your plan for him?

Study design Result

GARDEL[1] Naïve. N=426

3Tc+LPVr vs 2NRTI+LPVr

At 48 w Non inferior

: VL<50 cpm

: CD4 gain

OLE [2] Suppressed N= 239

3Tc+LPVr vs 2NRTI+LPVr

At 48 w Non inferior

: VL<50 cpm

SALT [3] Suppressed N=325

3Tc+ATVr vs 2NRTI+ATVr

At 48 w Non inferior

: VL<50 cpm

SALT:: Simplification to ATV/r + lamivudine as maintenance therapy

GARDEL: Global AntiRetroviral Design Encompassing LPVr, 3Tc vs LPVr, 2NRTI

1. Cahn P, et al. Lancet Infect Dis. 2014;14:572-580.

2. Gatell J, et al. AIDS 2014. Abstract LBPE17.

3. Perez-Molina JA, et al. IAC 2014. Abstract LBPE18.

2 Drugs Regimens

Anup Bastola

MCTM Thesis, Tropical med. Faculty, Mahidol Univ, 2015

14

Jan 2008-2014 N=94 Duration 12- 90 mon

Inclusion : Intolerated NNRTI, No Previous Virological failure

HBsAg neg.

Month Virological Failure (%) Low VL (copies/ml)

12 2/94 (2.1%) 334, 100

24 1/69 (1.4%) 986

Outcome of LPVr +3Tc as a maintenance Rx among HIV-1 infected Thai pts

“ Caution in patients with ARV resistance mutations

After simplification, monitor in 2-6 wks

(laboratory and clinical) ”

How to select Nuke-Sparing Regimen?

Vertical transmission

AIDS on ART x 5 yrs.

Failure first line NNRTI based regimens

OI: Pulmonary Tuberculosis, chronic bronchiectasis

Case II: Body build disfiguring in 13 yo. girl

27 Jun 2008 : Start 2nd. line ART - 3Tc, TDF, LPVr

With permission

June 2008: 3Tc, TDF, LPVr Dec 2008: 3Tc, TDF, LPVr

: VL < 20

With permission

Nov. 2009: 3Tc, TDF, LPVr

CD4 632 (28%), VL <40

May 2009: 3Tc, TDF, LPVr

: VL < 20, CD4

31 Aug, 2012

CD4 632 (28%), VL <40

31 Aug, 20122009

A. Lipodystrophy from PI, change LPVr to RAL

B. No idea, consult other experts

With permission

Q. 1 What will be your plan?

Panel Discussion

“ What will be your plan?”

Body disfiguring while on 3Tc, TDF, LPVr?

With permission

LPVr and Fluticasone

FTS and RTV

100 mg. bid

Fluticazone AUC

350 x

C. Max 25-fold

Adrenal insufficiency, Cushing’s

syndrome. Do not coadminister

FTSRTV

CYP450–3A4

potent inhibitor

Important Drug Interaction: RTV & Fluticasone (FTS)

RTV : a potent inhibitor of CYP450–3A4,

Fluticasone (FTS) : extensively metabolized by CYP450–3A4

RTV increased FTS level and lead to systemic complications

31 Aug, 2012

Fluticasone (FTS) inhaled

Cortisol level 0.19 mg/dl (6.2-19.4 mg/dl)

With permission

HIV Medicine

Volume 4, Issue 2,

pages 149–150, April 2003

4 cases of Cushing's syndrome induced

by the association of fluticasone/RTV

Steroid preparations should be given with caution with

boosted PIs, regardless of administration route

Coadministration can result in adrenal insufficiency, including Cushing’s

syndrome

Cushing’s syndrome in a patient treated by LPVr and inhaled FTS

31 Aug, 2012

With permission

28 Sep, 2012 22 Feb, 2013

Aug, 20122009

2015

ART Events

1. d4T, 3Tc, NVP Rash Day 7

F 44 y-o, current CD4 314 (11%)

Case III: Super rash in middle age lady

Q 1: Do you think ‘ it is NVP rash’ ?

Yes, sure

No

Case III: Super rash in middle age lady

Q 2: What will be next regimen?

NNRTI based with EFV or RPV

Non NNRTI based eg. PI or ISTI containing regimen

Panel Discussion

“ What regimen?”

Super rash from d4T, 3T, NVP

ART Events

1. d4T, 3Tc, NVP Rash Day 7

2. 3Tc, TDF, RPV Rash Day 4

F 44 y-o Current CD4 314 (11%)

Case III: Super rash in middle age lady

Q: Do you think is it RPV rash ?

Yes, likely

No

ART Events

1. d4T, 3Tc, NVP Rash Day 7

2. 3Tc, TDF, RPV Rash Day 4

3. 3Tc, LPVr Rash Day3

F 44 y-o current CD4 314 (11%)

Case III: Super rash in middle age lady

“ She is allergy to 3Tc !!! ”

Indian J Pharmacol. 2013 May-Jun; 45(3): 298–300.

Dolanchampa Modak and Subhasish Kamal Guha

1. F, 30

CD4 174

1. AZT, 3Tc, NVP Rash Day 8

Off All drugs

2. AZT, 3Tc, LPVr Rash after frist dose

3. AZT, ddI, LPvr ; OK

2. F 32,

CD4 25

1.AZT, 3Tc, NVP : rash Day 10

2.AZT, 3Tc, LPVr : Severe rash

3.AZT, TDF, LPVr : OK

3. M 32 YO

CD4 223

1.AZT, 3Tc, NVP Rash, mucosa D 7

2. AZT, 3Tc, LPVr: Severe rash

3. AZT, TDF, LPVr

4. F 36 yo

CD4 34

1.AZT, 3Tc, NVP Day 10

2. AZT, 3Tc, EFV Rash after first dose

3. AZT, TDF, EFV

Severe skin rash with lamivudine in HIV infected patients

• N=23 (0.7%), out of 3,213

• ART : AZT [TDF] + 3TC +NVP/EFV during the study period of 5 years [Feb

2009–Dec 2013]

• The mean age 37.5 ± 12.8 (17-60) years.

• 3Tc rash : F>M (19:4)

Severe skin rash with lamivudine in HIV infected patients

Indian J Pharmacol. 2013 May-Jun; 45(3): 298–300.

Dolanchampa Modak and Subhasish Kamal Guha

Conclusion : Comorbidities case Discussion

1. All NRTI could create AE

d4T> AZT> TDF

Nuk sparing regimen may play role in some specific cases

2. Drug interactions with ART are emerging.

Don’t miss it (eg. LPVr vs Fluticasone)

3. The safest drugs does not mean safe to all patients

eg. 3Tc Rash

35

So much evidence,So little time

36

HIV Clinicians

37Thank you very much for your attention

Kusinara, India 2015