Transcript STDs and HIV

Modified Directly Observed
Therapy for First Virologic
Failure: ACTG A5234
PI Dr A Chisada
Presenter: Dr W Samaneka
MBChB, MSc
UZ-UCSF ARD
17 April 2015
Background
• Sustained and consistent adherence is
a key factor for durable ART success
• 2nd line therapy is typically more
complex and expensive than 1st line
• Conventional DOT is logistically
challenging
• Enhanced partner support may benefit
patients with prior treatment failure.
Main Objective
 To test whether a partner-based
modified DOT (mDOT) intervention
would result in higher rates of virologic
suppression compared with standard of
care after first-line treatment failure
Methods
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Study duration: Apr 2009 – Sep 2011
Confirmed virologic failure on 1st line
Identifiable mDOT partner (family, friend, etc.)
1:1 allocation to mDOT and standard of care
2nd line: lopinavir/r (400 mg/100 mg) BID +
TDF/FTC (300 mg/200 mg) qD
Brazil, Botswana, Haiti, Peru, SA, Uganda, Zambia, Zimbabwe
End Points
Primary efficacy endpoint
• Confirmed Virologic Failure HIV RNA>400
cpm by week 48
Secondary endpoints
• Confirmed virologic failure HIV RNA>400
cpm by week 24
• Adherence measured using electronic
monitors[MEMS] summarized quarterly as %
of doses taken
mDOT Intervention Design
• Single training session of mDOT partner (1.5
hrs)
 Drug regimen
 Adherence &handling missed doses
 Side effects
 Examples of +ve and –ve social support
 Documentation of observed doses
 How and when to contact site for help
 Provision of airtime (buddie)

Duration of active phase: 24 weeks (total follow
up 52 wks)
Participant Flow Diagram
RESULTS
Baseline Characteristics
Characteristic
mDOT
SOC
n =129
N=128
Median age (IQR)
38 y (34,44)
37 y (33, 45)
Female sex
62 (48%)
65 (51%)
Black race
101 (78%)
103 (80%)
Hispanic ethnicity
27 (21%)
25 (20%)
Prior rx duration
153 wks
144 wks
(IQR)
(82, 230)
(89, 245)
Entry CD4 (median)
164 c/mm3
201 c/mm3
(IQR)
(91, 250)
(97, 292)
Nadir CD4 (median)
122 c/mm3
109 c/mm3
(IQR)
(37, 187)
(45, 202)
HIV RNA (median)
4.2 log cpm
4.2 log cpm
(IQR)
(3.8, 4.9)
(3.8, 4.9)
Endpoints by Study Arm
mDOT
SOC
Endpoint
n =129
N = 128
VF wk 48
34 (26%)
23 (18%)
0.13
VF wk 24
24 (19%)
17 (13%)
0.31
Adherence Q1
95%
96%
0.38
Adherence Q2
91%
94%
0.30
Adherence Q3
90%
93%
0.17
Adherence Q4
90%
93%
0.36
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P-value
Fishers Exact Points for VF,Wicoxon Rank Sum test for Adherence Endpoints
Virologic suppression ≤ 400
• At all time points after week 12
undetectable VL was higher in SOC,
however not significant
• Week 48, 75% (CI 67-83) in mDOT and
82% in SOC (CI 74-89) had VL ≤ 400,
(p=0.37)
• No sig diff between groups at week 24;
p=0.18
Virologic Suppression (HIV-RNA
≤ 400 cpm)over time
Conclusion
• mDOT had no significant impact on
virologic failure
High rate of suppression in both arms
• mDOT had no significant impact on
adherence
 High rate of adherence in both arms
• Other interventions still need to be
tested in this setting
• Although mDOT intervention not
successful findings are encouraging >
high rates of virologic success on
second line therapy in RLS
Acknowledgements
• Sponsors – NIAID
- Abbott Laboratories
- Gilead Sciences
• Study participants + partners
• CAB
• CRS Leader- Prof JG Hakim
• ACTG site staff
• UZ-UCSF