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