Transcript Related Journal Club Presentation

Journal Club
Alcohol, Other Drugs, and Health: Current Evidence
July–August 2013
Featured Article
Antiretroviral prophylaxis for HIV
infection in injecting drug users in
Bangkok, Thailand (the Bangkok
Tenofovir Study):
a randomised, double-blind, placebocontrolled phase 3 trial
Choopanya K, et al. Lancet. 2013;381(9883):2083–2090.
Study Objective
• To assess whether daily oral use of
tenofovir disoproxil fumarate
(tenofovir), an antiretroviral, can
reduce HIV transmission (acquisition)
in people with injection drug use.
www.aodhealth.org
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Study Design
• Randomized, double-blind, placebo-controlled trial.
• Population was 2413 volunteers from 17 drug-treatment clinics
in Bangkok, Thailand who were eligible if they were aged 20–60
years, were HIV-negative, and reported injecting drugs during
the previous year.
• Participants were assigned to either tenofovir (N=1204) or
placebo (N=1209). They were enrolled between 2005 and 2010.
• Subjects chose either daily directly observed treatment or
monthly visits and could switch at monthly visits.
• All subjects received monthly HIV testing, individualized riskreduction and adherence counseling, blood “safety assessments”
every 3 months, and were offered condoms and methadone
treatment (if indicated).
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Assessing Validity of an Article
about Therapy
• Are the results valid?
• What are the results?
• How can I apply the results to patient
care?
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Are the Results Valid?
• Were patients randomized?
• Was randomization concealed?
• Were patients analyzed in the groups to
which they were randomized?
• Were patients in the treatment and control
groups similar with respect to known
prognostic variables?
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Are the Results Valid? (cont‘d)
• Were patients aware of group allocation?
• Were clinicians aware of group allocation?
• Were outcome assessors aware of group
allocation?
• Was follow-up complete?
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Were patients randomized?
• Yes.
– Participants were randomized in blocks of 4
to either tenofovir or placebo.
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Was randomization concealed?
• Yes.
– Subjects were randomized using a
computer-generated randomization
sequence.
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Were patients analyzed in the groups
to which they were randomized?
• Yes (intention-to-treat analysis).
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Were the patients in the treatment
and control groups similar?
• No.
– Baseline characteristics differed on sexual
intercourse with a casual partner in the past 12
weeks and men having sex with men in the past 12
weeks, both of which were more common in the
placebo group (40% versus 36% and 6% versus
4%, respectively).
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Were patients aware of group
allocation?
• No.
– Participants were masked to treatment
group assignment.
– Tenofovir and placebo tablets were
similar in shape, color, and taste.
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Were clinicians aware of group
allocation?
• No.
– Study staff were masked to treatment group
assignment.
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Were outcome assessors aware of
group allocation?
• No.
– Two researchers were unmasked after the
data were locked.
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Was follow-up complete?
• No.
– The authors followed-up participants for 9665
person-years. There were no differences in followup time, withdrawal, or loss to follow-up between
treatment groups.
– Of the tenofovir group, 409 of 1204 participants
did not provide complete follow-up.
– Of the placebo group, 410 of 1209 participants did
not provide complete follow-up.
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What Are the Results?
• How large was the treatment effect?
• How precise was the estimate of the
treatment effect?
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How large was the treatment effect?
The authors confirmed HIV infection in 52 participants
total:
• 17 (33%) in the tenofovir group.
• 35 (67%) in the placebo group.
• There was a 48.9% reduction in HIV incidence in
the tenofovir group compared with the placebo
group in the intention-to-treat analysis (an
incidence of 0.35 per 100 person-years versus
0.68 per 100 person-years).
The cumulative probability of HIV infection in the two
groups separated consistently after 36 months.
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How Can I Apply the Results to
Patient Care?
• Were the study patients similar to the
patients in my practice?
• Were all clinically important outcomes
considered?
• Are the likely treatment benefits worth
the potential harm and costs?
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Were the study patients similar to
those in my practice?
• The study took place in Bangkok, Thailand.
• Demographics included:
– % Male: 80
– Education level of primary school or less: mean 48%
– Largest age group represented: 20–29 (mean 43%)
• Clinical characteristics
– 63% of subjects injected drugs in the 12 weeks prior
to study enrollment
– Largest percentage of subjects reported injecting less
frequently than every week (mean 32%)
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Were all clinically important
outcomes considered?
• Yes.
- The trial was not powered to assess efficacy
by subgroup, but tenofovir showed
statistically significant reductions in HIV
incidence among women (79%,P=0.03) and
participants aged ≥40 years (89%, P=0.01).
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Are the likely treatment benefits
worth the potential harm and costs?
• Yes.
– This study is the first to show that daily oral preexposure prophylaxis with tenofovir, used in
combination with other HIV prevention strategies,
reduces the risk of HIV infection among people with
injection drug use.
– Prevalence of nausea and/or vomiting was slightly
higher in tenofovir group over placebo (8% versus
5%).
– Costs were not reported.
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