Antiretroviral Therapy in Prevention of HIV and TB: Update on Current Research Efforts.

2011·0.54 MB·English

by  Granich, Reuben

446 Current HIV Research, 2011, 9, 446-469
Antiretroviral Therapy in Prevention of HIV and TB: Update on Current

Research Efforts
Reuben Granich*,1, Somya Gupta1, Amitabh B. Suthar1, Caoimhe Smyth1, David Hoos2,
Marco Vitoria1, Mariangela Simao2, Catherine Hankins2, Bernard Schwartlander2,
Renee Ridzon3, Brigitte Bazin4, Brian Williams5, Ying-Ru Lo1, Craig McClure1, Julio Montaner6
and Gottfried Hirnschall1 on behalf of the ART in Prevention of HIV and TB Research Writing Group§
1World Health Organization, Geneva, Switzerland; 2UNAIDS, Geneva, Switzerland; 3Bill and Melinda Gates
Foundation, Seattle, United States of America; 4National Agency for Research on AIDS and Viral Hepatitis (ANRS),
Paris, France; 5South African Centre for Epidemiological Modelling and Analysis, Stellenbosch, South Africa; 6British
Columbia Centre for Excellence in HIV/AIDS, Vancouver, Canada
Abstract: There is considerable scientific evidence supporting the use of antiretroviral therapy (ART) in prevention of
human immunodeficiency virus (HIV) and tuberculosis (TB) infections. The complex nature of the HIV and TB
prevention responses, resource constraints, remaining questions about cost and feasibility, and the need to use a solid
evidence base to make policy decisions, and the implementation challenges to translating trial data to operational settings
require a well-organised and coordinated response to research in this area. To this end, we aimed to catalogue the ongoing
and planned research activities that evaluate the impact of ART plus other interventions on HIV- and/or TB-related
morbidity, mortality, risk behaviour, HIV incidence and transmission. Using a limited search methodology, 50 projects
were identified examining ART as prevention, representing 5 regions and 52 countries with a global distribution. There
are 24 randomised controlled clinical trials with at least 12 large randomised individual or community cluster trials in
resource-constrained settings that are in the planning or early implementation stages. There is considerable heterogeneity
between studies in terms of methodology, interventions and geographical location. While the identified studies will
undoubtedly advance our understanding of the efficacy and effectiveness of ART for prevention, some key questions may
remain unanswered or only partially answered. The large number and wide variety of research projects emphasise the
importance of this research issue and clearly demonstrate the potential for synergies, partnerships and coordination across
funding agencies.
Keywords: HAART, highly active antiretroviral therapy, HIV prevention, randomised controlled trials, research activities,
tuberculosis prevention.
INTRODUCTION receiving ART. Besides individual benefits, ART has
substantial potential to enhance prevention efforts because it
Antiretroviral therapy (ART) reduces mortality and suppresses HIV viral load, and therefore infectiousness, of
morbidity related to human immunodeficiency virus (HIV)
persons already infected with HIV [5,7,8]. As a result, there
infection. The need to provide expanded access to ART is
is increasing scientific evidence supporting the use of ART
now widely accepted, and there is a pressing demand for
in prevention of HIV and tuberculosis (TB) as part of
both increased investment and more efficient use of funding broader combination prevention efforts [5,6,8]. The HIV
in order to achieve and sustain universal access [1]. Prevention Trials Network (HPTN) 052 randomized
Furthermore, the World Health Organization (WHO) controlled trial assessing the effect of early ART initiation
estimates that less than 40% of people living with HIV know
on HIV incidence reduction in discordant couples announced
their status and there is a need for expanded access to HIV
their results early when the data and safety monitoring board
testing and counseling [2] both as a prevention measure itself
found a 96% reduction in HIV transmission in the arm that
and also as a gateway to other HIV services including care received ART immediately between 550-350 CD4 cells/
and treatment. Although ART has considerable potential to mm3 versus deferral of ART to < 250 cells/mm3 [9]. While
save lives while reducing HIV transmission [3-6], without a the results from HPTN 052 include a significant benefit for
reduction in HIV incidence it is unlikely that we will be able
earlier ART for reducing extrapulmonary TB, there was no
to meet and sustain Universal Access targets by 2015 [2].
benefit for pulmonary TB and the results have raised
Indeed, in 2010 an estimated 58% of those eligible were not
questions regarding the overall value of earlier ART for
prevention of TB. Observational studies suggest that ART
has been associated with up to a 92% reduction in the
*Address correspondence to this author at the Antiretroviral Treatment and
incidence of tuberculosis, benefiting both people living with
HIV Care, Department of HIV/AIDS, Building D, 1st Floor, Room 1005,
HIV and potentially reducing TB transmission to others
World Health Organization, Avenue Appia 20, CH-1211, Geneva 27,
Switzerland; Tel: [phone]; Fax: [phone]; [10,11]. Recognising these benefits, research is increasingly
E-mail: [email protected] focusing on answering open questions regarding feasibility

§Alphabetised by first name—see appendix for contact information.

1873-4251/11 $58.00+.00 © 2011 Bentham Science Publishers
Current TasP Research Efforts Current HIV Research, 2011, Vol. 9, No. 6 447
and cost-related issues of integrating ART into combination research projects. To assist with strategic planning and future
prevention approaches. policy formulation, this article identifies and reviews selected
“ART in prevention of HIV and TB” research efforts.
The current scale of HIV prevention efforts may reduce
new infections but are unlikely to achieve sustained and
METHODS
widespread reduction in HIV incidence, and there have been
widespread calls for intensification of prevention efforts in both
We sought studies that evaluate the impact of ART plus
scale and scope [12]. Interest in and exploration of ART in
other interventions on the HIV- and/or TB-related morbidity
prevention has increased and there have been a number of
and mortality, risk behaviour, HIV incidence and
stakeholders who have contributed to building understanding
transmission. We conducted a search on the websites of the
and the scientific evidence base [5,6]. New public health
National Library of Medicine, PubMed, NIH, HIV
interventions frequently require convincing evidence and
Prevention Trial Network (HPTN) and Clinical Trials.gov
considerable time before they are implemented. For example,
website to identify ongoing/planned research work on HIV
research on male circumcision took approximately 20 years and
and ART. The search strategy included the keywords “HIV
culminated in three definitive randomised controlled trials
and ART”, with “treatment”, “prevention”, “research”,
(RCTs) showing consistent efficacy [13-15]. Still a number of
"campaign" and “tuberculosis” alone and in combination.
high HIV-burden countries have not adopted circumcision as
Out of nearly 500 studies, selected studies pertaining
part of HIV prevention policy [16]. Similarly, prevention of
to evaluating the impact of ART plus other interventions on
mother-to-child transmission of HIV took years of basic science
HIV- and/or TB-related morbidity and mortality, risk
and field research before RCTs supported the use of ART to
behaviour, HIV incidence and transmission were obtained.
prevent transmission [17-21]. Ongoing areas of prevention
Community-based studies, randomised controlled trials,
research have been recently reviewed and include behavioural
cohort studies and other types of studies were included.
and biomedical approaches including HIV testing and
Scientific experts in this area of research, including funding
counselling (including couples testing and counselling); ART;
agencies were contacted for information on current projects.
oral and topical microbicides; pre-exposure prophylaxis;
They were asked to review the list of research projects on
vaccines; and how best to package together these interventions
ART treatment in the prevention of HIV and TB to
for specific populations (“combination HIV prevention”) [22-
determine if the list was comprehensive and ensure all
26]. Additionally, medication-assisted therapy (MAT) for the
projects were relevant to the topic. The bibliographies of
treatment of co-morbid opioid and other drug and alcohol use
studies selected to be included in this article were again
disorders among HIV-infected persons is another form of
searched for additional references. We focused on explicit
prevention via preventing relapse to drug use thereby improving
ART for prevention research studies and excluded studies
adherence to ART and decreasing HIV RNA levels [27-30].
that focused on other aspects of expanding ART or TB
Although biomedical interventions are more amenable to
treatment (e.g. adherence, best regimens,) and published
individual observational and randomised controlled trials,
studies (e.g. HPTN 052). The following project details were
effective prevention strategies are rarely implemented in
extracted and summarized: focus of research, study design,
isolation and WHO recommends a combined approach [26, 31].
principal interventions, primary outcome assessed, region,
The complex nature of the HIV prevention response, resource
time period, agency and sponsors (if funded).
constraints, remaining questions about cost and feasibility, and
the need to use a solid evidence base to make policy decisions,
RESULTS
and the implementation challenges to translating trial data to
operational settings require a well-organised and coordinated Summary of Studies
response to research on ART in prevention of HIV and TB.
Our initial search yielded nearly 500 studies, of which 50
In November of 2009, WHO convened a meeting of
were taken forward for full review. Of the 50, 20 were from
stakeholders including researchers, HIV program managers,
North America, 22 from Africa, 4 from Asia, 1 from Europe
civil society representatives, people living with HIV, human
and 3 were multisite international studies. Of the 24
rights experts and ethicists, donors and bilateral agencies on the
randomised control trials (individual or community cluster),
topic of ART for prevention. The meeting included over 100
12 of the planned or ongoing studies were from resource-
experts who reviewed the evidence base for ART in prevention
constrained settings. (See Table 1 and Figs. 1, 2).
of HIV and TB, discussed ethical issues, and examined broad
issues around the concept of ART for HIV prevention,
Region: Africa
including feasibility and acceptability, human rights and ethical
implications, and research priorities [32]. In May 2011, the Scaling Up Treatment to Reduce Population Level
British Columbia Centre for Excellence in HIV/AIDS (BCCfE)
Incidence of HIV/AIDS is a four-year study designed by
with co-organizers WHO, the Joint United Nations Programme
investigators at the British Columbia Centre for Excellence
on HIV/AIDS (UNAIDS), the International AIDS Society, the
in HIV/AIDS in British Columbia, Canada along with the
United States (US) National Institutes of Health (NIH) and Joint Clinical Research Centre in Uganda. This study uses a
other stakeholders, hosted a meeting that focused on ART in randomised step-wedge design to examine the impact of
prevention research [33]. It focused on critically reviewing increased access to ART in Ugandan regions on incidence
research related to the secondary preventive benefit (as it relates
measured by home-based testing. Because of decreased
to HIV and TB transmission) of expanding ART coverage
scale-up of ART in the year 2011, this study is being re-
among people living with HIV, commonly referred as
evaluated. This study has received funding from the
“Treatment as Prevention” (TasP). Participants also discussed Canadian Institutes of Health Research.
research priorities including a number of ongoing and planned
448 Current HIV Research, 2011, Vol. 9, No. 6 Granich et al.
Table 1. List of Ongoing and Planned Research Projects on Antiretroviral Therapy (ART) in Prevention of HIV and Tuberculosis
(TB)

Principal
Project Study Type Focus Outcomes Region Institution Time Period
Interventions
AFRICA
Scaling Up
HIV and TB
Treatment to Step-wedge Impact of ART University of British
Increased access to incidence, HIV-
Reduce Population community level scale-up on HIV Uganda Columbia, Joint Clinical 2011-2015
ART and TB-related
Level Incidence of randomised trial incidence Research Centre
mortality
HIV/AIDS
Discordant Couples Impact of ART on Risk of HIV University of British
ART for HIV Central-eastern
(DISCO) Cohort Cohort study partner acquisition acquisition in HIV Columbia, The AIDS 2009-2012
positive partner Uganda
Team of HIV negative partner Support Organization
Opt-out HIV
Implementation of
testing, ART for
effective
An HIV Prevention high viral load, Harvard University
Population-based behavioural and HIV incidence, Mochudi,
Program for behaviour School of Public Health, 2009-2013
observational study biomedical HIV transmission Botswana
Mochudi, Botswana modification USA
preventive
education and male
interventions
circumcision
Preventive effects London School of
(Population South Africa Funded
Randomized of universal testing ART irrespective Population-level Hygiene and Tropical
Effects of ART) (Western Cape) (Planning
controlled trial and treatment of CD4 cell count HIV incidence Medicine, Imperial
Trial (HPTN071) and Zambia Phase)
(UTT) intervention College London, UK
Africa Centre for Health
Effectiveness of
and Population Studies,
treatment-as- Widespread HIV
Cluster- University of KwaZulu-
TasP (Treatment as prevention in testing and ART Population-level Rural KwaZulu-
randomised Natal; Université 2011 onwards
Prevention) reducing HIV irrespective of HIV incidence Natal, South Africa
controlled trial Bordeaux, Hopitaux
incidence in a CD4 count
Universitaires de
general population
Geneve; ANRS sponsor
ART at CD4 count HIV and TB
Feasibility and
< 500 cells/mm3, incidence, HIV-
TasP (Treatment as Prospective cohort acceptability test, KwaZulu-Natal, Medecins Sans
male circumcision, and TB-related 2011 onwards
Prevention) study link, treat and South Africa Frontieres (MSF)
and test, link, treat morbidity and
retain strategy
and retain strategy mortality
Health, economic
HIV incidence; University of California,
and education
TB, malaria, San Francisco, USA,
Sustainable East outcomes of Annual HIV
Community maternal, HIV and International
Africa Research for community health testing, ART for all Uganda, Kenya,
cluster- all-cause mortality; Development Research 2010 onwards
Community Health campaign CD4 cell count, Tanzania
randomised trial education and Centre (IDRC), Kenya
(SEARCH) providing HIV streamlined care
economic Medical Research
testing and
outcomes Institute (KEMRI)
treatment services
STOP AIDS NOW!,
Clinton Health Access
Initiative (CHAI)
MaxART Swaziland, Ministry
Universal ART ART access for
Maximizing ART Population-based of Health, Nercha,
following concept 90% of people HIV incidence, TB
for Better Health observational study Swaziland Swannepha, 2011-2014
of Treatment 2.0 with HIV eligible incidence
and Zero New (entire country) SafAIDS, GNP+,
within 3 years for treatment
Infections University of
Amsterdam,
SACEMA and Dutch
Postcode Lottery
Early Antiretroviral Death (all-cause),
Treatment and/or AIDS-defining
Early Isoniazid Benefits and risks Early ART before disease, non- Université Bordeaux,
Prophylaxis against Randomised of early ART in CD4 count reaches AIDS-defining Abidjan, Cote France, Treichville
TB in HIV-infected controlled trial HIV-infected 350 cells/mm3 and malignancy, or d'Ivoire Université hôpital, 2008-2012
Adults people 6 months of non-AIDS- Abidjan, Côte d’Ivoire,
isoniazid ANRS Sponsor
(TEMPRANO defining invasive
Trial) bacterial disease
Relationship
between early
Immunology and
responses to ART
Outcomes after Risk of death in
and risk of death ART in advanced Gaborone, University of
HAART in Cohort study first 6 months after 2009-2014
among individuals HIV infection Botswana Pennsylvania, USA
HIV/TB Co- ART initiation
with advanced
infection
HIV disease and
active TB
Current TasP Research Efforts Current HIV Research, 2011, Vol. 9, No. 6 449

(Table 1) contd…..
Principal
Project Study Type Focus Outcomes Region Institution Time Period
Interventions
Effects of
enhanced Risk of HIV
Enhance Early ART,
Randomised prevention acquisition in ICAP, Columbia
Prevention in counselling, male Lesotho 2009-2013
controlled trial package for HIV- negative University, USA
Couples (EPIC) circumcision
serodiscordant partner
couples
Effects of
Multi-component,
evidence-based ART, male
Targeted HIV
Randomised behavioural and circumcision, Population-level Eastern and University of
Prevention for Sub- 2010-2011
controlled trial biomedical behavioural HIV transmission Southern Africa Washington, USA
Saharan Africa:
preventive interventions
PreventionRx
interventions
Enhanced HIV
Effectiveness of testing,
Interventions to
home-based behavioural Community viral
Decrease HIV
Community voluntary interventions, load and Uganda, South University of
Infectiousness in 2010-2013
randomised trial counselling and effective linkages transmission Africa Washington, USA
Uganda and South
testing (VCT) to ART and potential
Africa
platform treatment of co-
infections
Impact of ART on
HIV/HAART and decisions Contraceptive use,
Community-based John Hopkins
Pregnancy/Contrac regarding HIV fertility outcomes,
observational ART Rakai, Uganda University, Baltimore, 2009-2012
eption in Rakai, prevention, HIV risk
study USA
Uganda contraceptive use behaviour
and pregnancy
Impact of HIV,
ART and TB Impact of ART on
Mortality in MDR
Genotype on survival in MDR Albert Einstein College
Cohort study ART TB/HIV co- South Africa 2010-2015
Survival in Multi- TB/HIV co- of Medicine, USA
infected people
drug resistant infection
(MDR) TB
Early access to
Campaign HIV testing, HIV prevalence,
Integrated
population-based Campaign-based counselling, feasibility of rapid
Prevention Vestergaard Frandsen,
observational approach to testing distribution of mass multi- Lurambi, Kenya 2008-ongoing
Demonstration Switzerland
study (province- and referral to care disease prevention disease prevention
Campaign (IPD)
wide) commodities and campaign
referral to care
Gender-specific New York University,
Effectiveness of Prevention
Combination HIV USA and University of
gender-specific Gender-specific method uptake,
Prevention for Nairobi, Impact
Cohort study youth HIV interventions - adherence, risk Western Kenya 2011-2015
Youth in High- Research and
prevention MP3-Youth compensation
Burden Settings Development
package behaviour
(MP3-Youth) Organisation, Kenya
Needle exchange
Implementation
programme, rapid New York University,
Test and Linkage Step-wedge research on seek, Efficacy of seek,
HIV testing and USA, Kenyan National Planning
to Care (TLC-IDU) cluster- test, treat and test, treat and Kenya
point of care CD4 AIDS and STI Control Phase
Kenya randomised trial retain paradigm retain strategy
testing, peer Programme
with IDUs
treatment
Scale-up of Impact of large- Botswana,
Increased ART
Antiretroviral scale testing and Malawi,
coverage and early Community-level
Therapy and early ART Mozambique,
Cohort study ART (according HIV viral load; IeDEA Southern Africa 2011 onwards
Transmission of strategy, and role South Africa,
to WHO HIV incidence
HIV in Southern of routine viral Zambia,
guidelines)
Africa load monitoring Zimbabwe
Swaziland Ministry of
Swaziland HIV Impact of HIV Health, PEPFAR,
Male HIV incidence,
Incidence Population-based prevention, care CDC, ICAP,
circumcision, sexual risk Swaziland 2011-2014
Measurement study and treatment Columbia University,
ART scale-up behaviours
Survey (SHIMS) activities University of
Washington
450 Current HIV Research, 2011, Vol. 9, No. 6 Granich et al.

(Table 1) contd…..
Principal
Project Study Type Focus Outcomes Region Institution Time Period
Interventions
Ability of ART
Sites to Implement
2010 Adult HIV Early ART for
Treatment HIV-infected ART irrespective
Recommendation adults in of CD4 cell count
New HIV Chongwe and National Antiretroviral
to Treat HIV+ Cohort study discordant for HIV-infected 2011-2012
infections Mumbwa, Zambia Programme, Zambia
Adults in relationship as a partner in
Discordant preventive discordant couple
Relationships and strategy
Determine Patient
Outcomes
Enhanced testing, Home-based HIV Feasibility of
HPTN 070:
treatment and testing, home- enhanced HIV and
International HIV
Feasibility study linkage to care based TB TB testing,
Testing and Multi-site study in Planning
for a community strategy versus screening, linkage treatment and NIH, NIAID, HPTN
Linkage to Care Africa Phase
randomised trial standard of care in to care, ART for linkage to care
and Treatment
resource-limited people with high strategy, HIV
(iTLCT) Study
settings viral load transmission
ASIA
Seek, Test, Treat HIV testing in
Effectiveness of
Strategies for drug treatment ART uptake, ART
seek, test, treat John Hopkins
Vietnamese Drug Randomised centers, referral to adherence,
model for Hanoi, Vietnam University, Baltimore, 2010-2015
Users: A controlled trial care and retention treatment
injection drug USA
Randomized of people on ART outcomes
users
Controlled Trial in treatment
National Center for
AIDS/STD Control and
HIV Testing as ART for Prevention (NCAIDS),
Population-based Prevention effects HIV incidence
Prevention Strategy serodiscordant China Center for
observational of ART in among
and ART couples China Disease Control and 2011 onwards
study (selected serodiscordant serodiscordant
Treatment as irrespective of Prevention (CDC),
cities) couples couples
Prevention Strategy CD4 count British Columbia
Centre for Excellence
in HIV/AIDS, Canada
Cost and cost-
Cost and cost- effectiveness of
Population-based effectiveness of Rapid HIV Treatment 2.0
Wuhan City and
Treatment 2.0 observational community-based testing, expanded project, cost and NCAIDS and AIDS
Xiangfang City, 2011 onwards
Project in China study (selected HIV testing and access to quality cost-effectiveness Care, China
Hubei, China
cities) treatment ART of ART for
strategies serodiscordant
couples
HIV incidence,
Optimal time for TB incidence,
Population-based
ART initiation and Early ART, AIDS-related Ministry of Health,
Treatment 2.0 observational Planning
effects of alternate simple service mortality, cost and Vietnam WHO, other
Project in Vietnam study (selected Phase
service delivery delivery system cost-effectiveness stakeholders
provinces)
systems of simple service
delivery system
EUROPE
Risk of HIV
Partners of People Copenhagen HIV
transmission in
on ART: a New Programme (CHIP),
Observational serodiscordant HIV transmission 14 European
Evaluation of the ART, condom use Denmark Royal Free 2011 onwards
study couples on ART risk countries
Risks (PARTNER University College
who do not use
Study) Medical School, UK
condoms
NORTH

AMERICA
Association of
Highly Active
Antiretroviral
Therapy Coverage, Relation between
Population Viral Population-based ART coverage, ART coverage, British Columbia
New HIV British Columbia,
Load, and Yearly observational HIV-1 viral load viral load, CD4 Centre for Excellence 2009-ongoing
diagnoses per year Canada
New HIV study and HIV count in HIV/AIDS, Canada
Diagnoses in British transmission
Columbia, Canada:
a Population-based
Study
Current TasP Research Efforts Current HIV Research, 2011, Vol. 9, No. 6 451

(Table 1) contd…..
Principal
Project Study Type Focus Outcomes Region Institution Time Period
Interventions
Survival benefits ART at CD4
Effect of Early
of early ART count >350 British Columbia
Versus Deferred Observational initiation for cells/mm3 and Relative risk of United States and Centre for Excellence 2009-ongoing
ART for HIV on Study death Canada
asymptomatic CD4 count >500 in HIV/AIDS, Canada
Survival patients cells/mm3
HAART
Effects of
Optimism, Drug
expanded
Use and Risky HIV risk
Population-based universal and free-
Sexual Behaviour Universal and free behaviour among British Columbia, Simon Fraser
observational of-cost ART as a 2011-2016
among men who ART access men who have sex Canada University, Canada
study preventive
have sex with men with men
measure for high-
(MSM) in British
risk population
Columbia
Effect of HAART
Expansion on
Effects of
Community Levels HIV risk
Population-based expanded access Vancouver,
of HIV Viral Load Universal and free behaviour among Simon Fraser
observational to ART on HIV British Columbia, 2010-2013
and HIV Risk ART access MSM, HIV viral University, Canada
study risk behaviour and Canada
Behaviours among load
viral load
MSM in British
Columbia
Decreases in
Community Viral
Relation between Increased HIV
Load are Population-based Annual number of San Francisco
community viral testing, ART San Francisco,
Accompanied by observational newly diagnosed Department of Public 2004-ongoing
load and new HIV coverage and California, USA
Reductions in New study HIV cases Health, USA
infections effectiveness
HIV Infections in
San Francisco
Viral suppression,
reducing all-cause
Project HOPE 1) an active mortality,
Compare two
(NIH CTN 0049) -- patient navigator increasing linkage
approaches to
Hospital Visit as component, 2) a to and retention in Planning
improving University of Miami
Opportunity for Randomised passive HIV primary care, enrollment (12
outcomes among Multi-site, USA Miller School of
Prevention and controlled trial incentives/conting increasing linkage month study,
hospitalised Medicine
Engagement for ency management to and retention in 800 patients)
substance-using
HIV-infected Drug component, 3) drug abuse
HIV patients
Users treatment as usual treatment, and
reducing
hospitalisations
Expanded HIV
TLC+ (HPTN testing, linkage to
065): A Study to HIV care and viral
Evaluate the suppression, a
Feasibility of an Feasibility of test, computer- Viral suppression, Washington DC,
Community-based Columbia University
Enhanced Test, link-to-care and delivered expanded testing, the Bronx, New 2010-2014
study and CDC, USA
Link to Care, Plus treat strategy prevention for linkage to care York, USA
Treat Approach for positives
HIV Prevention in intervention, and
the United States surveys of patients
and clinicians
A Randomized Efficacy of test HIV testing,
Providence, Friends Research
Controlled Trial Randomised and link-to-care On-site rapid HIV retention in care,
Rhode Island and Institute and The
and Cohort Study controlled trial and strategy at testing and 1-year ART initiation, 2010-2015
Baltimore, Miriam Hospital-
of HIV Testing and cohort study community Project Bridge HIV plasma viral
Maryland in USA Lifespan, USA
Linkage to Care correction load
Individually
Barriers to HIV
Effectiveness of Peer-based delivered peer-
care, linkage and
Peer Navigation to navigation versus based learning University of
Randomised retention in care, Los Angeles,
Link Released usual care for approach to California, Los 2010-2015
controlled trial ART adherence, USA
HIV+ Jail Inmates HIV+ released address barriers to Angeles, USA
viral load
to HIV Care inmates and facilitators of
suppression
HIV care retention
Design, Individual,
implement and community,
Improving Linkage Monitoring Miriam Hospital,
test monitoring institutional and
to HIV Care Observational strategy for Brown University,
strategy for HIV+ political factors USA 2010-2015
Following Release study follow-up HIV Providence Rhode
ex-inmates to influencing
from Incarceration medical care Island, USA
improve linkage to linkage to care and
care ART outcomes
452 Current HIV Research, 2011, Vol. 9, No. 6 Granich et al.

(Table 1) contd…..
Principal
Project Study Type Focus Outcomes Region Institution Time Period
Interventions
Plasma HIV
Randomized Mandatory or opt-
RNA, HIV
Controlled Trial of Multi-component out HIV testing,
transmission risk
an Augmented intervention universal ART
Randomised behaviour, North Carolina University of North
Test, Treat, Link, programme for access, 2010-2015
controlled trial incident sexually and Texas, USA Carolina, USA
& Retain Model for prisoners pre- and personalised
transmitted
North Carolina and post-release linkage to care and
infections (STIs),
Texas Prisoners support services
adherence to ART
Opt-out HIV
testing in jails,
Effectiveness of
transition case
seek, test, treat
Seek, Test, Treat: management,
Community-based model (STT) that
An Integrated Jail- university-based Community-level University of Illinois,
observational begins in jail and Illinois, USA 2010-2015
Prison-Community telemedicine, HIV viral load Chicago, USA
study extends into
Model for Illinois incentives for
community post-
retention in care
release
and social
networking
HIV testing for
high risk
population, re-link
Cost and cost-
Seek, test, treat to low- or no-cost
effectiveness of
Seek, Test, and model (STT) for treatment services, Medical College of
Community-based entire STT model USA 2010-2015
Treat Strategies correctional HIV testing Wisconsin, USA
and its individual
populations referral for high-
components
risk negative
individuals and
their networks
HIV viral
Use of Miriam
CARE Corrections: suppression, HIV
information and Hospital/Brown
Technology for Jail transmission Rhode Island and
Randomised communication CARE and University, New York
HIV/HCV Testing, behaviours and Washington DC, 2010-2015
controlled trial tools (ICT) with CARE+ University, George
Linkage, and Care cost-effectiveness USA
discharge planning Washington University,
(TLC) of CARE and
for jail detainees USA
CARE+
Proportion of
Finding, Testing Community-based
Expanded HIV eligible
and Treating High- seek, test, treat Research Triangle
Randomised testing and individuals Oakland,
risk Probationers model for drug Institute, North 2010-2015
controlled trial counselling, recruited, tested California, USA
and Parolees with users on probation Carolina, USA
Project Bridge and HIV risk
HIV or parole
behaviour
HIV reentry
Proportion of
Efficacy of program for
inmates receiving
comprehensive incarcerated
START Together: HIV testing and
intervention populations, National Development
HIV Testing and Randomised proportion of New York City,
package START computer and Research Institutes, 2010-2015
Treatment in and controlled trial individuals with USA
Together in assessment and New York City, USA
after Jail undetectable HIV
criminal justice risk-reduction
viral load post-
system education, peer
release
health navigators
Effect of depot- HIV-1 RNA level,
naltrexone for CD4 count,
Alcohol
alcohol- Medication retention in care,
Pharmacotherapies Randomised
dependent HIV- assisted therapy - alcohol treatment Connecticut, USA Yale University, USA 2010-2015
among Released controlled trial
positive prisoners Depot-naltrexone outcome, HIV risk
HIV+ Prisoners
transitioning to the behaviour, adverse
community side effects
Naltrexone for Effect of depot- HIV-1 RNA level,
Opioid Dependent naltrexone for CD4 count,
Released Human opioid- dependent Medication retention in care, Connecticut and
Randomised
Immunodeficiency HIV- positive assisted therapy - opiate treatment Massachusetts, Yale University, USA 2010-2015
controlled trial
Virus Positive prisoners Depot-naltrexone outcome, HIV risk USA
(HIV+) Criminal transitioning to the behaviour, rate of
Justice Populations community reincarceration
Peer-driven
Interventions to Peer-driven
Seek, Test and interventions to Peer-driven HIV Efficacy of multi-
New York City, New York University, Planning
Treat To be determined overcome barriers testing and level peer-driven
USA USA Phase
Heterosexuals at to seek, test, treat treatment interventions
High Risk for HIV HHR
(HHR)
Current TasP Research Efforts Current HIV Research, 2011, Vol. 9, No. 6 453

(Table 1) contd…..
Principal
Project Study Type Focus Outcomes Region Institution Time Period
Interventions
Efficacy of
buprenorphine in
HIV, improving ART
Medication ART adherence,
Buprenorphine, Randomised outcomes for Washington DC,
assisted therapy - retention in care, Yale University, USA 2010-2015
and the Criminal controlled trial opiate-addicted USA
Buprenorphine HIV transmission
Justice System prisoners
transitioning to the
community
GLOBAL
Chances of
developing AIDS
START - Strategic and other
ART initiation at University of
Timing of Randomised Effects of early illnesses, and drug
CD4 count >500 37 countries Minnesota, Minnesota, 2009-2015
Antiretroviral controlled trial ART initiation cells/mm3 resistance, quality USA
Treatment of life, health care
utilisation and cost
of care
HIV transmission
Population-based Implementation at population
Test and Treat to Large-scale testing Multi-site (3 or TTEA, Lundy
observational research on test level, long-term 2011 onwards
End AIDS (TTEA) and early ART more countries) Foundation, USA
study and treat strategy costs and
mortality
AIDS progression; All of the 18
virologic and international
The Reducing CD4+ cell ACTG sites are
Early Mortality and response; HIV and eligible to
Early Morbidity by TB drug participate. (Haiti,
Empiric Impact of ART Empiric TB resistance; safety Peru, Brazil, 2011-2014 (96
Tuberculosis Randomised and empiric treatment or local and tolerability of South Africa, Multiple, to be weeks+ 9
Treatment controlled trial treatment for TB standard of care and adherence to Zimbabwe, determined months)
Regimens TB treatment HIV and TB Zambia, Tanzania,
(REMEMBER) drugs; cost- Kenya, Uganda,
study (ACTG effectiveness of Botswana,
5274) the two strategies Malawi, India and
Thailand).
Discordant Couples (DISCO) Cohort Team is a four-year program. HIV incidence and molecular methods to elucidate
cohort study of discordant couples in central-eastern Uganda. transmission pathways will be used to evaluate the impact of
It is a partnership between researchers at the BC Centre for the trial which will last for five years (2009-2013).
Excellence in HIV/AIDS in British Columbia, Canada and
The Population Effects of Anti-Retroviral Therapy
The AIDS Support Organisation (TASO) in Uganda [34].
(PopART/HPTN-071) study is a cluster randomised trial
The study follows 550 HIV-uninfected individuals who are
developed by scientists based at the London School of
co-habiting partners of HIV-infected individuals (i.e.
Hygiene and Tropical Medicine and Imperial College
serodiscordant). In 260 of the couples, the HIV-infected
London in the United Kingdom, with partners in South
partner will be receiving ART, this therefore being the Africa (Western Cape) and Zambia [36]. The purpose of the
variable being manipulated. The control is 290 couples where
study is to evaluate the impact of a Universal Testing and
the HIV-infected partner has not yet initiated ART (CD4 cell
Treatment (UTT) intervention on population-level HIV
count > 250 cells/mm3, WHO stage I or II). This study has
incidence compared to enhanced standard of care in sub-
received funding from the Canadian Institutes of Health
Saharan Africa. The UTT intervention will be delivered as
Research.
part of a comprehensive combination prevention package
An HIV Prevention Program for Mochudi in Botswana, and will offer immediate treatment to all those who test
led by Harvard School of Public Health AIDS Initiative, will positive for HIV irrespective of CD4 cell count. NIH funding
determine the feasibility and acceptability of a has recently been confirmed.
comprehensive program of interventions, including male
Following a pilot study in 2010, the Africa Centre for Health
circumcision, with a test-and-treat strategy [35]. HIV-
and Population Studies at the University of KwaZulu-Natal
positive people with a CD4 cell count above 250 cells/mm3
(Africa Centre) [37] is starting the first phase of a cluster-
will be offered three-drug ART if they have acute infections
randomised controlled trial, Treatment-as-prevention (TasP), in
and/or their viral load is greater than 50,000 RNA
rural KwaZulu-Natal, South Africa, as part of its overall
copies/mL, while those with a CD4 cell count below 250
research objective to test the effectiveness of interventions in
cells/mm3 will be referred for ART through the public
reducing HIV incidence in one of the HIV-hyperendemic rural
454 Current HIV Research, 2011, Vol. 9, No. 6 Granich et al.

Ability of ART sites to implement ART recommendation in Zam bia

Ending New Infections in Swaziland4, SHIMS13, REMEMBER23
Scaling up treatment to reduce population level incidence of HIV/AIDS, MP3-Youth12
ART optimism among MSM16
ART scale-up and HIV transmission in Southern Africa, PARTNER14, ANRS TasP2, MSF TasP2, Testing and treatment as prevention
strategy and Treatment 2.0 projects in China, TTEA22

PreventionRx7
ART expansion among MSM17, HIV preventive
interventions in Africa8

TLC+19
ART for MDR TB10, 13 NIH funded studies on
HIV prevention, testing and treatment in jails20
SEARCH3

DISCO1, ART in pregnancy9

HIV Prevention Program Mochudi, EPIC6
ART in HIV/TB co-infection5

START21

BCCfE studies on ART 15a, 15b

Early ART &/or IPT for TB in HIV+

IPD Campaign11
San Francisco community-based study18

2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016

Fig. (1). Timeline of projects on antiretroviral therapy (ART) in prevention of HIV and tuberculosis (TB).
Note: Figure includes studies with an available timeline—others not listed.
1. DISCO - Discordant Couples Cohort Team
2. TasP – Treatment as Prevention
3. SEARCH - Sustainable East Africa Research for Community Health
4. MaxART Maximizing ART for Better Health and Zero New Infections
5. Immunology and Outcomes after HAART in HIV/TB co-infection
6. EPIC – Enhance Prevention in Couples
7. Multi-component, Targeted HIV Prevention for Sub-Saharan Africa: PreventionRx
8. Interventions to Decrease HIV Infectiousness in Uganda and South Africa
9. HIV/HAART and Pregnancy/Contraception in Rakai, Uganda
10. Impact of HIV, ART and TB Genotype on Survival in MDR TB
11. IPD Campaign – Integrated Prevention Demonstration Campaign
12. MP3-Youth - Gender-specific Combination HIV Prevention for Youth in High-Burden Settings
13. SHIMS - Swaziland HIV Incidence Measurement Survey
14. PARTNER - Partners of people on ART: a New Evaluation of the Risks
15. BCCfE – British Columbia Centre for excellence in HIV/AIDS, British Columbia, Canada
a. Effect of early versus deferred ART for HIV on survival.
b. Association of highly active antiretroviral therapy coverage, population viral load, and yearly new HIV diagnoses in British Columbia,
Canada: a population-based study
16. HAART Optimism, Drug Use and Risky Sexual Behaviour among MSM in British Columbia
17. Effect of HAART Expansion on Community Levels of HIV Viral Load and HIV Risk Behaviours among MSM in British Columbia
18. Decreases in Community Viral Load Are Accompanied by Reductions in New HIV Infections in San Francisco
19. HPTN-065, TLC+: A Study to Evaluate the Feasibility of an Enhanced Test, Link to Care, Plus Treat Approach for HIV Prevention in the United
States
20. 13 NIH (National Institutes of Health, USA) funded studies on HIV prevention, testing and treatment in jails
• A Randomized Controlled Trial and Cohort Study of HIV Testing and Linkage to Care
• Effectiveness of Peer Navigation to Link Released HIV+ Jail Inmates to HIV Care
• Improving Linkage to HIV Care Following Release from Incarceration
• Randomized Control Trial of an augmented test, treat, link, & retain model for North Carolina and Texas Prisoners
• Seek, Test, Treat: An Integrated Jail-Prison-Community Model for Illinois
• Seek, Test, and Treat Strategies
• CARE Corrections: Technology for Jail HIV/HCV Testing, Linkage, and Care (TLC)
• Finding, Testing and Treating High-risk Probationers and Parolees with HIV
• START Together: HIV Testing and Treatment in and after Jail
• Seek, Test, Treat Strategies for Vietnamese Drug Users: A Random Controlled Trial
• Alcohol Pharmacotherapies among Released HIV+ Prisoners
• Naltrexone for Opioid Dependent Released Human Immunodeficiency Virus Positive (HIV+) Criminal Justice Populations
• HIV, Buprenorphine, and the Criminal Justice System
21. START - Strategic Timing of Antiretroviral Treatment
22. TTEA - Test and Treat to End AIDS
23. REMEMBER - The Reducing Early Mortality and Early Morbidity by Empiric Tuberculosis Treatment Regimens study
Current TasP Research Efforts Current HIV Research, 2011, Vol. 9, No. 6 455

Fig. (2). Map representing countries planning or implementing antiretroviral therapy (ART) in prevention of HIV and/or tuberculosis (TB)
research. Dark blue represents countries that are conducting ART in prevention of HIV and/or TB research, light blue represents country-
wide efforts (United States, Swaziland), and the red dots represent selected study sites within countries conducting research (some countries
had too many sites to represent on this graphic).
communities in Southern Africa [38]. The trial is funded by the The Sustainable East Africa Research for Community
French National Agency for Research on AIDS and Viral Health (SEARCH) collaboration and University of
Hepatitis (Agence Nationale de Recherche sur le SIDA et les California, San Francisco are performing pilot studies and
hepatitis virales [ANRS]) and is conducted in collaboration with community mapping, funded by NIH and the World Bank, in
the University of Bordeaux, the Hôpitaux Universitaires de preparation for a community cluster-randomised study of 40
Genève, and the University of the Mediterranean Aix-Marseille communities to evaluate health (HIV, TB, malaria, maternal
II. The cluster-randomised trial will start in 2011 in four out of mortality), economic and education outcomes of offering
the total 32 clusters randomly assigned to either universal ART treatment to all HIV-infected persons in three East African
or standard of care. The primary outcome of the controlled trial countries—Uganda, Kenya and Tanzania. Intervention
is longitudinally-measured HIV incidence; secondary outcomes communities will receive annual HIV testing during a
include the acceptability and feasibility of treatment as community health campaign, and ART will be offered to all
prevention, as well as the economic and social consequences. HIV-infected children and adults through streamlined care
delivery systems. Resource mobilisation in underway for a
Doctors Without Borders/Médecins Sans Frontières
target start date of November 2012 [39].
(MSF) is planning a pilot community-based Treatment as
Prevention (TasP) project in KwaZulu-Natal, South Africa, STOP AIDS NOW! and Clinton Health Access Initiative
in collaboration with the Department of Health, beginning in (CHAI) have been granted Euro 8.8 million for a Treatment
2011. The program will aim to reduce HIV and TB Centered Prevention (TCP) project in Swaziland from 2011-
incidence, in addition to reducing HIV- and TB-related 2014 [40]. Titled MaxART Maximizing ART for Better
morbidity and mortality, and to demonstrate the feasibility Health and Zero New Infections, the project will ensure that
and acceptability of different approaches to enhanced testing, at least 90% of those in need of treatment under current
linkage to care, ART, and retention in care. Pending ethics guidelines are on treatment by the end of 2014. The impact
approval, the project will offer ART for all patients with of universal access to treatment based on clinical and
CD4 counts below 500 cells/mm3 and those with CD4 counts immunologic criteria on HIV incidence will be evaluated.
above 500 cells/mm3 if their viral load is greater than The study will determine whether a 50% reduction in the
100,000 RNA copies/mL. Combination prevention, number of new HIV infections in Swaziland is possible by
including medical male circumcision, will be offered and 2020.
substantial efforts will be made to reduce “leakage” across
Early Antiretroviral Treatment and/or Early Isoniazid
the test, link, treat, and retain cascade. HIV incidence will be
Prophylaxis against Tuberculosis in HIV-infected Adults
measured by synthetic cohort prevalence surveys at baseline
(ANRS 12136, TEMPRANO) study is being conducted by
and every 2-3 years.
Université de Bordeaux [41]. This randomised trial will