Transcript Directly Administered Antiretroviral Therapy (DAART): A

Directly Administered
Antiretroviral Therapy (DAART):
A Literature Review
Brian McPhee, BA
AIDS Institute
New York State Dept. of Health
History of DAART
Directly Administered Antiretroviral
Therapy (DAART)- TB Public Health
initiatives from India, Hong Kong and the
US.
TB treatment- 5-9 month regimen w/
perfect adherence.
Purpose- Eradicate organism, prevent
resistant TB, prevent transmission.
TB DOT
TB prevention- Must ensure adherence to
TB antibiotics.
State agencies given authority to ensure
mandatory compliance.
Called Directly Observed Therapy (DOT).
Specifics of TB DOT
A patient with TB takes medication 2 or 3
times per week for 5-9 months.
A health care worker observes the patient
taking medication.
DOT can occur in a clinic setting or in the
community.
Development of DAART
HIV and TB- Different challenges to public and
individual health, yet both require diligent
adherence.
Researchers began to explore similar programs
for Highly Active Antiretroviral Therapy (HAART).
Models in which patients go to providers or
providers go to patients have been developed.
Types of Recent Research
There are various types of studies that
have investigated the effectiveness of
DAART among a variety of populations.
----------------------------------------------------------1) Descriptive papers
2) Preliminary studies
3) Prospective Observational studies
4) Non-random Comparison studies
5) Randomized Clinical Trials
Summary of Major Studies
Year
Investigator
Study Type
Substance
users
Effective
2004
Conway:
Vancouver
Prospective
Yes
Yes
2005
Mitty: Brown
Prospective
Yes
Yes
2006
Lucas: Johns
Hopkins
Non-random
comparison
Yes
Yes
2004
Altice: Yale
RCT
Yes
Yes
2006
Wohl: LA
RCT
No
No
Descriptive Papers
Differences between TB DOT and
DAART1: no cure for HIV, dosing
frequency, duration of treatment, biology of
HIV.
Suggest DAART may have greatest
impact on cocaine and methamphetamine
substance users.2
12002:
Lucas, Flaxner, Moore. “DAART in treatment of HIV infection. AIDS Patient Care.
16(11)
22004:
Kresina, Normand, Khalsa et al. Addressing the need for treatment paradigms for
drug-abusing patients. Clinical Infectious Diseases. 38(Sup 5)
Qualitative Interest Study
Researchers1 interviewed 47 HIV-positive
subjects to determine interest in DAART.
Only 17% choose DAART.
Significant proportion found DAART
invasive, impractical, burdensomeInvolves meeting with a provider daily.
1Santos,
Adeyemi, Tenorio. “Attitudes toward DAART among HIV-positive inpatients in an
inner city public hospital.” AIDS Care. Oct 06; 18(7)
Preliminary Pilot Study
Small pilot1: Once-day DAART home
delivery in rural Haiti (n=100) and Boston
(n>100).
Haiti: 98% retention and decrease in OIs,
but no lab data (1999-2004).
Boston: 87% retention, 35.7 mean CD4
count increase, 73% of patients
undetectable viral load after 1 year.
12004: Behforouz, Farmer, Mukherjee. “From DOT to Accompagnateurs.” Clinical Infectious
Diseases 38(Sup 5)
Preliminary Pilot Study: Brown
Studied1 community based DAART. n=25.
Subjects- used substances and history of
failed adherence.
Doses were delivered to the patient daily
or less frequently, depending on need.
12004:
Macalino, Mitty, Bazerman et al. “MDOT for the treatment of HIVseropositive substance users.” Clinical Infectious Diseases 38(Sup 5)
Preliminary Pilot Study: Brown
After 1 yr, viral load net decrease 1.9 log
copies/mL. CD4 cell percentage
increased from 2.6% to 6.8%.
However, very few subjects could maintain
DAART 7 days a week: moved, took
meds on their own, or discontinued
treatment under medical advice.
Vancouver MMTP Prospective
Study
Examined once and twice daily DAART among
substance users at a methadone clinic1.
Enrolled 54 HIV and HCV co-infected subjects
for 24 months, no control group.
17 out 29 achieved viral suppression in once
daily DAART, and 18 of 25 achieved viral
suppression with twice daily DAART.
12004:
Conway, Prasad, Reynolds et al. “Directly observed therapy for the management of HIV-infected
patients in a methadone program.” Clinical Infectious Diseases. 38(Suppl 5).
Vancouver MMTP Prospective
Study
Some subjects had ongoing cocaine and heroin
use, indicating utility of DAART among active
users.
The provision of methadone on-site facilitated
DAART encounters with on-site providers.
Results indicate that DAART can be effective
among co-infected patients with substance use
problems, especially in an MMTP.
Prospective Study: Brown
n = 69 in a community-based DAART program.1
Subjects- documented adherence issues.
Outreach workers delivered medications once
daily and tapered visits as needed.
96% had substance use history, 71% were
incarcerated at some point, and 93% were
treatment experienced.
12005:
Mitty, Macalino, Bazerman et al. “The use of community-based MDOT for the treatment of HIVinfected persons. JAIDS. 39(5).
Prospective Study: Brown
At 6 months, less than half were still receiving
visits. Reasons for not receiving visitsmedication holidays, hospitalization,
incarceration, lost to program and death.
Of those still in the program, mean viral load
decreased 2.7 log, from mean baseline 4.8 log.
Paper suggests that DAART is useful among
treatment experienced substance users.
Non-randomized Comparative
Study: Johns Hopkins
82 substance users in DAART at a JHU MMTP1.
Enrolled if starting ARVs or were switching due
to failure.
Subjects in DAART were observed taking doses
on clinic days and self-administered evening and
methadone “take home” days.
Subjects were compared to data from other
groups in Johns Hopkins HIV Cohort.
12006
Lucas, Mullen, Weidle et al. DAART in methadone clinics is associated with improved HIV
treatment outcomes. Clinical Infectious Diseases. 42(1 June).
Non-randomized Comparative
Study: Johns Hopkins
Year End Results
CD4 Increase
DAART
% Viral Load
<400
56%
IDU-methadone
32%
21 cells
IDU nonmethadone
Non-IDU
33%
33 cells
44%
84 cells
74 cells
Non-randomized Comparative
Study: Johns Hopkins
DAART participants significantly more
likely to achieve viral suppression than
each of the 3 comparison groups.
Substance using DAART participants CD4
increase comparable to non-IDU control.
The First Randomized Controlled
Trial: Connecticut IDUs
Yale1- The first RCT for DAART
72 HIV-infected IDUs in New Haven, CT
Randomly assigned to DAART + arm
(DAART plus ancillary medical services) or
a self-administered HAART arm.
12004:
Altice, Mezger, Hodges et al. “Developing a DAART intervention for HIVinfected drug users: Implications for program replication. Clinical Infectious
Diseases. 38(Sup 5).
Randomized Controlled Trial:
Connecticut IDUs
DAART subjects met counselors once a
day during week on a mobile health van.
MEMS caps monitored adherence for both
arms.
Counselors addressed other substance,
mental and medical issues, referring as
needed to ancillary services.
Randomized Controlled Trial:
Connecticut IDUs
85% were antiretroviral experienced.
76.2% of supervised doses taken.
49.9% of unsupervised doses taken.
Baseline- 50% of doses taken.
No reported virologic or immunologic
outcomes.
Randomized Controlled Trial:
Connecticut IDUs Lessons Learned
Once daily observed regimens most effective,
but DAART target pop is treatment experienced,
limiting once daily options.
Explored the use of DAART+, which included
on-site HIV specialist, drug treatment
coordinator, case manager and bilingual
outreach workers.
DAART works to ensure adherence among
substance users.
Yale Group Expands on DAART+
Same data (n=72) but virologic outcomes
correlated with ancillary service use:
medical, case management and
substance use services.1
Virologic success = log decrease or <400.
Virologic success at 6 mos correlated with
high case management and medical
service use.
Smith-Rohrberg, Mezger, Walton et al. “Impact of enhanced services on virologic outcomes in a
DAART trial for HIV-infected drug users.” JAIDS. 43(Sup 1)
12006:
Yale Group Expands on DAART+
DAART fully effective among substance users
when ancillary services offered on site.
Utilization of on-site medical and case
management services independently associated
with improved virologic outcomes.
Proximity to services likely contributed to
outcomes but not proven.
A Second RCT: Los Angeles
RCT in LA county1, comparing DAART,
intensive adherence case management
and standard care control group.
Enrolled 250 subjects from public clinics in
LA who were treatment naïve or failed only
one regimen.
12006:
Wohl, Garland, Valencia. A Randomized trial of DAART and adherence
RCT Los Angeles
DAART doses were delivered once daily, 5 days
a week, for 6 months.
Majority were male, Latino, and earned less than
$10,000 a year.
At baseline, similar proportions of each group
had viral suppression.
At 6 months, each group had similar viral
suppression and CD4 cell increases.
RCT LA: Results
Viral Suppression by group: DAART 71%,
Adherence counseling 80%, Control 74%
No statistical differences in 6 month CD4
cell count changes or self-reported
adherence.
The study gave no conclusive evidence
that DAART is effective.
Yale Group Responds to LA
Yale- “LA study did not enroll subjects with
known problems with adherence.”1
“LA study should have also looked at viral
load reduction, not just number of virally
suppressed subjects.”
12006:Smith-Rohrberg,
Altice. Letters to editor. Correspondence. Clinical
Infectious Diseases. 43(1 Nov).
LA responds to Yale
LA- Chose viral suppression: expected outcome
in naïve and second-line patients1
Subjects: high rates of mental illness, unstable
housing, limited social support and missed visits.
Studied effectiveness of DAART in general clinic
population w/o prior adherence problems.
DAART mostly effective among patients with
known adherence problems, but not in the
general population.
12006:
Wohl, Witt et al. Letters to editor. Correspondence. Clinical Infectious Diseases. 43(1 Nov).
Yale and LA Studies
Although LA study found DAART
ineffective in general pop, useful among
substance users.
LA group looks forward to further
publication of DAART research.
Summary of Major Studies
Year
Investigator
Study Type
Substance
users
Effective
2004
Conway:
Vancouver
Prospective
Yes
Yes
2005
Mitty: Brown
Prospective
Yes
Yes
2006
Lucas: Johns
Hopkins
Non-random
comparison
Yes
Yes
2004
Altice: Yale
RCT
Yes
Yes
2006
Wohl: LA
RCT
No
No
DAART- Is it effective?
Narrative papers, preliminary studies, and
observational cohort studies: DAART a
useful intervention, esp. among substance
users.
Yale RCT study: DAART most effective
among substance users when combined
with ancillary services.
DAART- Is it effective?
LA RCT: DAART no more effective than
standard care among patients without prior
adherence problems or substance use.
DAART most effective among substance
users.
More research should explore the use of
DAART among non-substance users with
prior adherence problems.
Next Questions
Should DAART be a standard practice?
DAART effective only for substance users?
DAART effective for those with prior adherence
problems but not substance users?
How long should DAART programs last?
Mode- delivered, mobile or in clinic?
Further Research
Case management aids DAART
effectiveness, but more research needed
to explore how.
Proximity to medical care may aid DAART
effectiveness, but more research needed
to verify and quantify relationship.
Conclusions
DAART: Effective among substance users,
especially when combined with other
medical, case management and
substance use services.
DAART: May be effective among nonsubstance users with prior adherence
problems, but more RCTs are required to
completely evaluate DAART.
Thank You
Brian McPhee
AIDS Institute
NYS Dept. of Health