Transmission Reduction Intervention Project
| Status: | Enrolling by invitation |
|---|---|
| Conditions: | HIV / AIDS |
| Therapuetic Areas: | Immunology / Infectious Diseases |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 4/21/2016 |
| Start Date: | April 2013 |
| End Date: | July 2017 |
Preventing HIV Transmission by Recently-Infected Drug Users
Half or more of HIV transmission events may occur within the period of high infectivity (and
often high risk behavior) that can last 11 months or more after a person is initially
infected. Unfortunately, neither test-and-treat intervention methods nor Acute HIV Infection
projects have found effective ways to intervene against transmission during this risky
"recent infection" period. The investigators seek to develop effective intervention
techniques against HIV transmission during the recent infection period using a combination
of injection-, sexual- and social-network-based contact tracing methods; community alerts in
the networks and venues of recent infectees; and the logic of going "up" and "down"
infection chains.
The investigators first Aim is to develop and evaluate ways to locate "seeds," defined as
drug users and other people who have recently been infected. The investigators second Aim
targets members of seeds' networks and people who attend their venues. The investigators
will test them for acute and for recent infection, and alert them to the probability that
their networks contain highly-infectious members so they should reduce their risk and
transmission behaviors for the next several months to minimize their chances of getting
infected. This may also reduce transmission by untested people with recent infection.
Community, network and venue education about the need and value of supporting those with
recent infection should reduce stigma. The investigators third Aim is to reduce HIV
transmission and to develop new ways to evaluate "prevention for positives" generally as
well as The investigators own success in reducing transmission.
The investigators will do this using a combination of follow-up interviews and testing,
including of viral loads; phylogenetic techniques; and discrete event simulation modeling to
assess The investigators effectiveness.
often high risk behavior) that can last 11 months or more after a person is initially
infected. Unfortunately, neither test-and-treat intervention methods nor Acute HIV Infection
projects have found effective ways to intervene against transmission during this risky
"recent infection" period. The investigators seek to develop effective intervention
techniques against HIV transmission during the recent infection period using a combination
of injection-, sexual- and social-network-based contact tracing methods; community alerts in
the networks and venues of recent infectees; and the logic of going "up" and "down"
infection chains.
The investigators first Aim is to develop and evaluate ways to locate "seeds," defined as
drug users and other people who have recently been infected. The investigators second Aim
targets members of seeds' networks and people who attend their venues. The investigators
will test them for acute and for recent infection, and alert them to the probability that
their networks contain highly-infectious members so they should reduce their risk and
transmission behaviors for the next several months to minimize their chances of getting
infected. This may also reduce transmission by untested people with recent infection.
Community, network and venue education about the need and value of supporting those with
recent infection should reduce stigma. The investigators third Aim is to reduce HIV
transmission and to develop new ways to evaluate "prevention for positives" generally as
well as The investigators own success in reducing transmission.
The investigators will do this using a combination of follow-up interviews and testing,
including of viral loads; phylogenetic techniques; and discrete event simulation modeling to
assess The investigators effectiveness.
TRIP Design This is an exploratory research project. It aims to develop the TRIP model in
preparation for a phase 3 clinical trial with random assignment of geographic areas to
intervention versus control conditions. Since TRIP itself is exploratory, design elements
may vary. And there are multiple outcomes..
TRIP has three arms: 1. The Recent infection network tracing (primary) arm; 2. the Contact
tracing of HIV+' who are not recently infected comparison arm; and 3. the HIV negative
comparison arm. Before the investigators start the main part of the intervention, and during
the intervention as well, the investigators will use all available means to educate at-risk
communities about the nature of acute and recent HIV infection and about the reasons not to
stigmatize those who have recently been infected.
1. The Recent infection network tracing (primary) arm This is the primary arm of the
intervention. It will include index subjects of two kinds: a. people who are tested and
screened who turn out to have recent HIV infection (LAg+). b. People who are referred
to us by clinicians as having recent or acute HIV infection. It will also include
network/venue members of these index subjects. These will consist of 1. People who are
in the social and/or risk networks of people who have recently become infected with
HIV; and 2. People who go to their "venues"—i.e., places where people who have recently
become infected with HIV say they sometimes go in order to engage in drug taking or
sexual risk behaviors or to meet people with whom to take risks. Network tracing will
recruit not only direct contacts of Index Cases but also the network/venue members of
these contacts. (The investigators may continue to the third network ring if this seems
warranted as part of the exploratory nature of the project).
Network/venue members will be tested for recent and acute HIV and perhaps for other
diseases. Each time a network/venue member is found to have recent or acute HIV
infection the investigators will then (for network/venue tracing purposes) treat them
as if they were an index case in the sense that the investigators will trace their
network/venue contacts.
Participants in the primary arm of the intervention who test HIV+ will all be referred
for medical evaluation and treatment.
People who have recent or acute infection will receive expedited scheduling of doctor
appointments and will receive direct assistance in getting to doctor's offices if they
need it. They will also get extra assistance in receiving social assistance.
Whenever the investigators find an acute or recent infection, with their assistance the
investigators will distribute oral and written "community alerts" that warn people in
their networks and venues to be super-careful in their behaviors for the next 6 months
because their social environment includes people who are highly infectious; that tells
them how to be safer; and that repeats the importance of assisting rather than
stigmatizing anyone they suspect has recently become infected.
2. Contact tracing of HIV+ people who are not recently infected comparison arm This
comparison arm will start with 50 subjects in each city who are HIV tested as part of
the screening process and who are antibody positive but LAg negative—and who report
that have just learned their HIV antibody status at this time. the investigators will
recruit their sexual and injection partners, and other risk environment contacts, for
two steps, as in Arm 1. If the investigators get a recent/acute in that set, the
investigators will follow another two steps. (In analysis, the investigators will also
study the subset of those the investigators would have recruited via more conventional
contact tracing—i.e., those who would have been recruited if the investigators had
stopped following the network whenever the investigators came to someone uninfected.)
In each case, one key comparison will be the numbers of recents & acutes found in
contact tracing vs. in the networks of recents. In addition, the investigators will
compare this comparison group of non-recent HIV+ and their network members with the
TRIP group of recently-infected people and their networks on behavior change and on
adverse/supporting events.
3. HIV negative comparison arm This comparison arm will consist of 150 uninfected people
in each city whom the investigators screen in the course of testing. The key
comparisons here are on two of the central variables: adverse/supportive events and
behavior change. This comparison arm will help mitigate social desirability effects
that can lead to inaccurate reporting and/or Hawthorne effects and related processes
that can lead to behavior changes simply based on the interview. Participants in this
arm will be matched on age (within five years), risk group, and gender with an Arm 1
member.
Assays by category of subject
Negative screenees (HIV-):
N=150 Baseline: They will have been tested for HIV antibodies by the Aristotle project
(HIV-).
Follow up: They will be tested for HIV antibodies by the TRIP project. If HIV-, no more
tests. If HIV+ confirmed by WB (seroconverters), they will also be tested using LAg and HIV
RNA by TRIP.
If HIV+ confirmed by WB (seroconverters), the investigators presume they are recently
infected (the investigators look for LAg and HIV RNA but this does not change how the
investigators treat them. That is, the investigators treat them as seeds for finding more
recents. However, analytically, it is possible that their first negative test was negative
in error, so the investigators analyze this later).
Long-term positive screenees (HIV+, LAg-):
N=50 Baseline: They will have been tested at baseline for HIV antibodies (HIV+) by the
Aristotle project and for LAg (they will be negatives-LAg-) by TRIP.
Follow-up: No test. HIV RNA data can be obtained by their clinical records, if available.
Contact tracing:
All traced contacts will be tested for HIV antibodies by TRIP. HIV positives (HIV+,
confirmed by WB): They will be tested for LAg by TRIP. HIV positives (HIV+, confirmed by WB)
who are also LAg positives (LAg+): They will be tested for HIV RNA by TRIP.
HIV positives (HIV+, confirmed by WB) who are LAg negatives (LAg-): No further test.
HIV negatives (HIV-): No further test (store in freezer for possible HIV RNA test in the
future).
Follow-up of network/venue members of long-term positive screenees:
Long-term positives at baseline (HIV+ confirmed by WB, LAg-): HIV RNA info collection by
clinical records.
Recently infected at baseline (HIV+ confirmed by WB, LAg+ and/or HIV RNA+): HIV RNA info
collection by clinical records.
Negatives at baseline (HIV-): HIV test. If they are HIV positive (HIV+ confirmed by WB),
then LAg test and HIV RNA by TRIP. If HIV-, the investigators stop.
If HIV+ confirmed by WB (seroconverters), the investigators presume they are recently
infected (the investigators look for LAg and HIV RNA but this does not change how the
investigators treat them. That is, the investigators treat them as seeds for finding more
recents. However, analytically, it is possible that their first negative test was negative
in error, so the investigators analyze this later).
Recently infected screenees (HIV+, LAg+):
N=unknown Baseline: They will have been tested at baseline for HIV antibodies by the
Aristotle project (HIV+), for LAg (they will be positives-LAg+); and once known to be LAG+,
they will be tested for HIV RNA (+) by TRIP.
Follow-up: HIV RNA by TRIP or collect info by clinical records. Then the investigators stop.
Network/venue members:
All will be tested for HIV antibodies by TRIP. HIV positives (HIV+ confirmed by WB): They
will be tested for LAg by TRIP. HIV positives (HIV+ confirmed by WB) and LAg positives
(LAg+): They will be tested for HIV RNA by TRIP.
HIV positives (HIV+ confirmed by WB) and LAg negatives (LAg-): No further test. HIV
negatives (HIV-): They will be tested in pools using HIV RNA (batch testing) by TRIP.
Follow-up of network/venue members:
Long-term positives at baseline (HIV+ confirmed by WB, LAg-): HIV RNA info collection by
clinical records.
Recently infected at baseline (HIV+ confirmed by WB, LAg+ and/or HIV RNA+): HIV RNA info
collection by clinical records.
Negatives at baseline (HIV-, LAg-, HIV RNA-): HIV test. If they are HIV positive at
follow-up (HIV+ confirmed by WB), then LAg test and HIV RNA by TRIP. If HIV-, the
investigators stop.
If HIV+ confirmed by WB (seroconverters), the investigators presume they are recently
infected (the investigators look for LAg and HIV RNA but this does not change how the
investigators treat them. That is, the investigators treat them as seeds for finding more
recents. However, analytically, it is possible that their first negative test was negative
in error, so the investigators analyze this later).
preparation for a phase 3 clinical trial with random assignment of geographic areas to
intervention versus control conditions. Since TRIP itself is exploratory, design elements
may vary. And there are multiple outcomes..
TRIP has three arms: 1. The Recent infection network tracing (primary) arm; 2. the Contact
tracing of HIV+' who are not recently infected comparison arm; and 3. the HIV negative
comparison arm. Before the investigators start the main part of the intervention, and during
the intervention as well, the investigators will use all available means to educate at-risk
communities about the nature of acute and recent HIV infection and about the reasons not to
stigmatize those who have recently been infected.
1. The Recent infection network tracing (primary) arm This is the primary arm of the
intervention. It will include index subjects of two kinds: a. people who are tested and
screened who turn out to have recent HIV infection (LAg+). b. People who are referred
to us by clinicians as having recent or acute HIV infection. It will also include
network/venue members of these index subjects. These will consist of 1. People who are
in the social and/or risk networks of people who have recently become infected with
HIV; and 2. People who go to their "venues"—i.e., places where people who have recently
become infected with HIV say they sometimes go in order to engage in drug taking or
sexual risk behaviors or to meet people with whom to take risks. Network tracing will
recruit not only direct contacts of Index Cases but also the network/venue members of
these contacts. (The investigators may continue to the third network ring if this seems
warranted as part of the exploratory nature of the project).
Network/venue members will be tested for recent and acute HIV and perhaps for other
diseases. Each time a network/venue member is found to have recent or acute HIV
infection the investigators will then (for network/venue tracing purposes) treat them
as if they were an index case in the sense that the investigators will trace their
network/venue contacts.
Participants in the primary arm of the intervention who test HIV+ will all be referred
for medical evaluation and treatment.
People who have recent or acute infection will receive expedited scheduling of doctor
appointments and will receive direct assistance in getting to doctor's offices if they
need it. They will also get extra assistance in receiving social assistance.
Whenever the investigators find an acute or recent infection, with their assistance the
investigators will distribute oral and written "community alerts" that warn people in
their networks and venues to be super-careful in their behaviors for the next 6 months
because their social environment includes people who are highly infectious; that tells
them how to be safer; and that repeats the importance of assisting rather than
stigmatizing anyone they suspect has recently become infected.
2. Contact tracing of HIV+ people who are not recently infected comparison arm This
comparison arm will start with 50 subjects in each city who are HIV tested as part of
the screening process and who are antibody positive but LAg negative—and who report
that have just learned their HIV antibody status at this time. the investigators will
recruit their sexual and injection partners, and other risk environment contacts, for
two steps, as in Arm 1. If the investigators get a recent/acute in that set, the
investigators will follow another two steps. (In analysis, the investigators will also
study the subset of those the investigators would have recruited via more conventional
contact tracing—i.e., those who would have been recruited if the investigators had
stopped following the network whenever the investigators came to someone uninfected.)
In each case, one key comparison will be the numbers of recents & acutes found in
contact tracing vs. in the networks of recents. In addition, the investigators will
compare this comparison group of non-recent HIV+ and their network members with the
TRIP group of recently-infected people and their networks on behavior change and on
adverse/supporting events.
3. HIV negative comparison arm This comparison arm will consist of 150 uninfected people
in each city whom the investigators screen in the course of testing. The key
comparisons here are on two of the central variables: adverse/supportive events and
behavior change. This comparison arm will help mitigate social desirability effects
that can lead to inaccurate reporting and/or Hawthorne effects and related processes
that can lead to behavior changes simply based on the interview. Participants in this
arm will be matched on age (within five years), risk group, and gender with an Arm 1
member.
Assays by category of subject
Negative screenees (HIV-):
N=150 Baseline: They will have been tested for HIV antibodies by the Aristotle project
(HIV-).
Follow up: They will be tested for HIV antibodies by the TRIP project. If HIV-, no more
tests. If HIV+ confirmed by WB (seroconverters), they will also be tested using LAg and HIV
RNA by TRIP.
If HIV+ confirmed by WB (seroconverters), the investigators presume they are recently
infected (the investigators look for LAg and HIV RNA but this does not change how the
investigators treat them. That is, the investigators treat them as seeds for finding more
recents. However, analytically, it is possible that their first negative test was negative
in error, so the investigators analyze this later).
Long-term positive screenees (HIV+, LAg-):
N=50 Baseline: They will have been tested at baseline for HIV antibodies (HIV+) by the
Aristotle project and for LAg (they will be negatives-LAg-) by TRIP.
Follow-up: No test. HIV RNA data can be obtained by their clinical records, if available.
Contact tracing:
All traced contacts will be tested for HIV antibodies by TRIP. HIV positives (HIV+,
confirmed by WB): They will be tested for LAg by TRIP. HIV positives (HIV+, confirmed by WB)
who are also LAg positives (LAg+): They will be tested for HIV RNA by TRIP.
HIV positives (HIV+, confirmed by WB) who are LAg negatives (LAg-): No further test.
HIV negatives (HIV-): No further test (store in freezer for possible HIV RNA test in the
future).
Follow-up of network/venue members of long-term positive screenees:
Long-term positives at baseline (HIV+ confirmed by WB, LAg-): HIV RNA info collection by
clinical records.
Recently infected at baseline (HIV+ confirmed by WB, LAg+ and/or HIV RNA+): HIV RNA info
collection by clinical records.
Negatives at baseline (HIV-): HIV test. If they are HIV positive (HIV+ confirmed by WB),
then LAg test and HIV RNA by TRIP. If HIV-, the investigators stop.
If HIV+ confirmed by WB (seroconverters), the investigators presume they are recently
infected (the investigators look for LAg and HIV RNA but this does not change how the
investigators treat them. That is, the investigators treat them as seeds for finding more
recents. However, analytically, it is possible that their first negative test was negative
in error, so the investigators analyze this later).
Recently infected screenees (HIV+, LAg+):
N=unknown Baseline: They will have been tested at baseline for HIV antibodies by the
Aristotle project (HIV+), for LAg (they will be positives-LAg+); and once known to be LAG+,
they will be tested for HIV RNA (+) by TRIP.
Follow-up: HIV RNA by TRIP or collect info by clinical records. Then the investigators stop.
Network/venue members:
All will be tested for HIV antibodies by TRIP. HIV positives (HIV+ confirmed by WB): They
will be tested for LAg by TRIP. HIV positives (HIV+ confirmed by WB) and LAg positives
(LAg+): They will be tested for HIV RNA by TRIP.
HIV positives (HIV+ confirmed by WB) and LAg negatives (LAg-): No further test. HIV
negatives (HIV-): They will be tested in pools using HIV RNA (batch testing) by TRIP.
Follow-up of network/venue members:
Long-term positives at baseline (HIV+ confirmed by WB, LAg-): HIV RNA info collection by
clinical records.
Recently infected at baseline (HIV+ confirmed by WB, LAg+ and/or HIV RNA+): HIV RNA info
collection by clinical records.
Negatives at baseline (HIV-, LAg-, HIV RNA-): HIV test. If they are HIV positive at
follow-up (HIV+ confirmed by WB), then LAg test and HIV RNA by TRIP. If HIV-, the
investigators stop.
If HIV+ confirmed by WB (seroconverters), the investigators presume they are recently
infected (the investigators look for LAg and HIV RNA but this does not change how the
investigators treat them. That is, the investigators treat them as seeds for finding more
recents. However, analytically, it is possible that their first negative test was negative
in error, so the investigators analyze this later).
Inclusion Criteria:
- Must be able to answer questionnaire and qualify for one of the Arms
Exclusion Criteria:
- Inability to answer questionnaire
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