ARV Resistance Surveillance

1
????????????????????????????????????? (ARV
Resistance Surveillance )

• ??.????? ?????????
• ???????????????????????????????
• 18 ????????? 2551

2
Highly Active Antiretroviral Therapy (HAART)

• ??????????????? HAART ????????????????????????????
  ??????
• ????????????????????????????? ?????????????????
• ????????????????? HAART ??????????????????????????
  ???????????????????????????????????????? ???...

3
?????????????????????

• ?????????????????????????????????????
• 2535 AZT mono-therapy
• 2538 Dual therapy AZTddI, AZTddC
• 2540 Triple therapy ?????????????????
• 2543 Access to Care (ATC1-2)
• 2547 National Access to Antiretroviral Program
  for PHA (NAPHA)
• 2549 National AIDS Program

4
ARV Resistance

• ???????????????????????????????????????
• ?????????????????????????????????????????(????????
  ????????????? 1/1000???? 10??????????????
  ???????????????????)
• ??????????????????????????????????????????????????
  ?
• ???????? (poor Adherence)
• ???????????????? (Absorption)
• ?????????????????????????? (Lack of potency of
  the regimen)
• ???????????????????????????????????????????????
  ((Drug interaction)

5
HIV DR ?????????????

• ????????????????????
• ?????????????????????????????
• ???????????????????????????????????

6
???????????????????????????????????????

• ????????????????????????????????
• ???????????????????
• ???????????? ??? Adherence
• ??????????????????????? HIVDR

7
HIV Drug Resistance
Prevention

• Primary resistance
• ??????????????????????????
• ?????????????????????
• Secondary resistance
• ?????????????????????????????
• ???????????????????

???????????????
Adherence
8
Secondary versus Primary (Transmitted) Drug
Resistance
Failing Therapy
Secondary DR
Rx
Rx
HIV person not on treatment
Primary DR
WT
Wild Type Virus
Drug Resistant Virus
9
ARV resistance among ARV-naïve persons with
recent HIV infection in Thailand

• Evaluate ARV-DR 2003-2006
• 7/305 (2) had baseline ARV-DR
• Contract tracing all sexual partners prior ARV
  Rx failure and low (lt75) ARV adherence

Apisarnthanarak A. et al HIV Medicine
vol9.no5,May 2008 pp.322-325
10
Primary HIV Drug Resistance

• ???????????? 24.1
• ??????? 11.2
• ?????? 8.1
• ?????? 6.2
• ????????? 2.4

11
Primary HIV Drug Resistance

• ?????????
• ??????????
• ???????????????????

12
????????????????

• Genotypic drug resistant testing
• -??????????????????????????? peptide
  ????????????????
• -????????????????????????????????????????????????
  ??????????????????????????????
• -????????????????????????????????????????????????
  ??????

13
ARV resistance network
TUC SL3
Global Fund SL3-GF
Pilot I (2006-2009)
6 hospitals in 4 northern provinces n 304

• 38 hospitals
• in 5 regions
• n 1,000

Laboratory network
8 hospitals in 5 regions n 362
5 Service laboratories 2 being setting Total are
7 laboratories
14

• ??????????????????????????????????????????????????
  ???????????????????
• (ARV Resistance Surveillance among Patients under
  the National ART Program)
• ????????????? ??????????????????????????
• ???????????????????????????????
• ??????????????
• ??????????????
• ?????????????????? ????????????????
• ??????????????? ????????????????
• ??????????????? ???????????????
• ??????????????? ???????????????
• ??????? Global AIDS Program ???????????????????-??
  ????????????????

15
Methodology

• Study Design Cohort Study 2 years
• Study Populations
• ??????? HIV/AIDS ???????????????????????????????
• ???? gt 18 ??
• ???????????????????????? 2 ??
• ??????????????????????????? PMTCT

16

• Data every 6 months
• Clinical monitoring ARV, Drug, OI, ADR,
  Adherence
• Laboratory record CD4, VL
• If VLgt1,000 copies/ml, performing DR testing
• Behavior factors relate DR

Mo. 0
Mo. 6
Mo.12
Mo.18
Mo.24

• Demographic data
• VL DR (Base line) Last CD4
• OI prophylaxis
• Clinical history TB, PEP, PMTCT

• Summary off study

17
CD4 count during ART
of patients
FU month
Data is not complete in the period of the
follow up, its 50 patient on period of
monitoring
18
???????????
19
Median CD4cell change from baseline
Cell / ul
20
Viral load during ART
of patients
72.37
FU month
Data is not complete in the period of the
follow up
21
Adverse Drug Event
(N 304)
22
OI Occurrence
(N 304)
1 old TB case
23
Baseline Genotypic Mutations VS Clinical Response
Total 304 naive persons with ART 14 of 304
with major genotypic mutations at baseline
24
Clinical history among patient with NNRTI
resistance at baseline
25
Occurrence of Major Genotypic Mutations after ART
Total 304 naive persons with ART290 of 304
without major genotypic mutations at baseline
26
NNRTI mutation gene along the treatment
Prevalence of mutation ()
(N311)
(N5)
(N7)
(N7)
(N4)
(N5)
27
PR mutation gene along the treatment
Prevalence of mutation ()
(N311)
(N5)
(N7)
(N7)
(N4)
(N5)
28
Summary of Outcomes at End Point FU Period
Exclude referred patients Include
referred patients
29
Summary of Program Failure Rate
Baseline n 304
Exclude referred patients and non-AIDS related
deaths
30
???????????

• Primary resistance ??? NNRTI 1.6
• ????????????? genotype mutation ??? TrueGene
• 4/5 ???????????? (VL lt 50 copies/ml2)
  ?????????????? 72 ???????
• 9 ?????????? PI ????????????????? PI ??????
  (???????????????????? PI ???????????
• Secondary resistance lt5

31
?????

• ?????????????????????? (VL lt 50 copies/ml2)?
• ????????????????????????????????????????????????
• ??????????????????????????????????? subtype
  B??????????????????? subtype AE????????
• ?????????????????????? ?

32
????

• ??????????????????????????????????????????????????
  ?????? subtype B strain ??????????????????????????
  ??????????? subtype AE ???????????????????????????
  ????????????
• ???????????????? Sequence ???????????????????????
• ???????? in-house software ??????????????????????
  ???? subtype AE

33
????

• 4. ??????? Drug resistance ???????????????????????
  ????????????????????????? (lt5)
• 5. ???????????????????????????????????????????????
  ????????????
• 6. ???????????????????????????????????????????????
  ????? ??????? ????????????????????????????????????
  ???????????????????? ? ????????????

34
??????????????????

• Adherence
• Prevention

35
Thank you