FOR 25 YEARS, IT WAS AXIOMATIC IN THE HIV

PREVENTION FIELD TO STATE THAT RISK REDUCTION

BEHAVIOR CHANGE WAS THE ONLY AVAILABLE

MEANS TO PREVENT THE DISEASE

From the late-1980s forward, public health efforts to prevent the transmission of

HIV infection rested almost fully on helping persons make and sustain changes in

their sexual and drug use risk practices.

This gave rise to a large body of research that developed and evaluated the

effectiveness of behavioral, social, and structural interventions designed to r educe

the prevalence and frequency of high-risk behavior practices at various levels:

• Individual level

• Small group level

• Social setting level

• Social network level

• Community level

• Structural levels

• Societal and macro levels

BEHAVORIAL, SOCIAL, AND STRUCTURAL

INTERVENTIONS HAVE BEEN CONVINCINGLY SHOWN

TO REDUCE LEVELS OF BEHAVIOR RESPONSIBLE FOR

TRANSMITTING AND CONTRACTING HIV INFECTION

Collectively, decades of research has established that theoretically-based, contextually-

tailored, sufficiently intensive interventions that motivate behavior change help people

develop skills for behavior change, and reinforce behavior change efforts can reduce sexual

and substance use risk practices even in populations where risk is longstanding and high.

Effect sizes have often been moderate to high, reflecting risk behavior declines by one-third

in many intervention outcome trials.

Evidence of effects of these interventions on HIV incidence outcomes in behavioral trials

has been more elusive:

• Unlike large biomedical trials, behavioral intervention studies have rarely been

powered with samples large enough to detect effects on HIV incidence.

• Interventions have rarely been compared to inert placebo controls.

• Behavior change effects are not always well-maintained.

MANY IN THE PUBLIC HEALTH FIELD

HAVE PERSUASIVELY ARGUED THAT INTERVENTIONS

TO PROMOTE RISK REDUCTION HAVE AVERTED

A MUCH WORSE HIV EPIDEMIC

Holtgrave and others have modeled what would have been the HIV

epidemic picture in the United States and the world without the

development and deployment of effective HIV prevention behavior change

interventions, and the picture would have been far worse.

HIV incidence and prevalence has declined in many populations from

earlier levels, including drug users and MSM in the United States, with

the exception of African American MSM.

Yet, annual HIV incidence in the US has remained at a 50,000 plateau for

many years.

The HIV prevention intervention field became, in my opinion, fatigued

and uncertain of where to go next by the early 2000s.

BEGINNING IN THE LATE-2000S, SEVERAL SETS

OF LARGE TRIALS ESTABLISHED THE EFFICACY

OF BIOMEDICAL INTERVENTIONS TO PREVENT

AND PROTECT AGAINST HIV TRANSMISSION

• Male circumcision in the context of generalized heterosexual epidemics

• Treatment-as-prevention (viral suppression among PLH as a result ofantiretroviral treatment), HPTN-052

• Pre-exposure prophylaxis (ART regimens as a protection againstcontrac-ting HIV among high-risk uninfected persons, PrEP) (iPREX)

• Mixed picture to date for vaginal and anal microbicides

Although biomedical in nature, these developments have also reinvigoratedthe HIV behavioral, social, and structural intervention fields.

ALTHOUGH THERE IS UNEQUIVOCAL EVIDENCE OF

THE EFFICACY OF TREATMENT-AS-PREVENTION AND

PREP IN CLINICAL TRIALS, THESE NEW

PARADIGMS CAN ACHIEVE PUBLIC HEALTH IMPACT

ONLY IN THE CONTEXT OF ACCOMPANYING

BEHAVIORAL INTERVENTIONS

In the case of PrEP, protective outcomes were strongly dependent on levels of

consistent medication-taking adherence among high-risk uninfected persons

In at least some microbicide trials, lack of effect appears due to poor

adherence as well as product and formulation limitations

In the case of treatment-as-prevention (perhaps the most promising and

feasible biomedical prevention model), public health deployment and public

health effectiveness of biomedical HIV prevention depends on better behavioral

interventions employed at multiple junctures and with multiple aims.

GARDNER’S HIV TREATMENT CASCADE TO VIRAL

SUPPRESSION HAS BEEN WIDELY ADOPTED

TO CONCEPTUALIZE STEPS TO ACHIEVE

TREATMENT-AS-PREVENTION OUTCOMES

Positive Serostatus Knowledge

Linkage to Care

Retention in Care

ART and Viral Suppression

Undetectable Viral Load

THE CASCADE IS ALSO A USEFUL HEURISTIC FOR IDENTIFYING

KEY POINTS FOR BEHAVIORAL INTERVENTION

Cascade Point Interventions

Postitive Serostatus Knowledge • Interventions to increase routine testing

policy adoption

• Interventions to increase frequent and

regular testing

• Interventions to detect acute infection

Linkage to Care • Interventions to improve care linkage

• Systems-level interventions

Retention to Care • Early intervention when care appointments

are missed

• Community interventions that can reach

out-of-care PLH

ART and Viral Suppression • Adherence interventions

• Interventions to sustain adherence

Undetectable Viral Load • Life course interventions

FOR TREATMENT-AS-PREVENTION TO WORK

ON A PUBLIC HEALTH SCALE, BETTER BEHAVIORAL

AND SOCIAL SCIENCE-BASED INTERVENTIONS ARE NEEDED

AT EACH JUNCTURE

At this stage in the HIV prevention field, biomedical approaches hold great

promise but this potential can only be realized if health actions among PLH

become recognized as behavior and if behavioral intervention research is directed

towards these health actions.

“Implementation science” has been used to describe what is needed. This needs to

squarely address not just the implementation process but also the development of

interventions based on sound behavioral and social science.

Some junctures on the cascade are receiving substantial attention:

• Encouragement of testing

• Treatment adherence (at least short-term)

• Linkage-to-care

Other critical junctures and issues remain understudied.

KNOWLEDGE OF ONE’S HIV+ SEROSTATUS IS

FUNDAMENTAL TO ENTERING TREATMENT,

BUT THERE IS STILL A LONG WAY TO GO

TO ACHIEVE EARLY DETECTION

Campaigns to promote testing are one of the oldest HIV prevention

strategies, but about 20% of Americans with HIV still do not know it.

Most gay men (and many injection drug users) have been tested at some

point, and most people testing positive previously had a negative test.

Testing may too often be viewed as a one-time or occasional need, and

regularity of testing—frequent testing—needs to become an explicit goal

for MSM, substance users, those with STD histories, and others at

continuing high risk.

Interventions that emphasize frequent, regular testing are needed at levels

of social networks, community campaigns, and among service pr oviders.

STRIDES ARE BEING MADE IN DEVELOPING STRATEGIES

TO LINK NEWLY-DIAGNOSED PLH TO CARE, BUT A NEGLECTED

POPULATION IS THE MUCH LARGER NUMBER OF PLH

IN THE COMMUNITY WHO HAVE LONG BEEN OUT OF CARE

Many of the 50,000 Americans newly-diagnosed with HIV will benefit from new care linkage

initiatives.

However, CDC data show that almost half of persons in the US awar e that they are HIV+ have

not received any medical care for their disease in the past 6 months or longer, some never.

These 500,000 Americans will not be in linkage programs, will not benefit from care, and will

greatly limit the public health impact of treatment-as-prevention models until they are

engaged or re-engaged into care systems.

Big behavioral and social science research questions:

• Who are in this very large pool of out-of-care PLH in the community?

• Why are they not in care?

• How can they be reached in the community?

• How can they be engaged to enter care?

Community and social network intervention methods seem well-suited for interventions

designed to reach out-of-care PLH in the community.

ANOTHER EARLY DETECTION/LINKAGE QUESTION

THAT HAS RECEIVED VERY LITTLE ATTENTION

INVOLVES GETTING PERSONS WITH ACUTE INFECTION

QUICKLY INTO CARE

During the first weeks following seroconversion, persons with newly acquired

(acute) HIV infection (AHI) have very high viral load and are very likely to transmit

the disease to others. A greatly disproportionate number of infections are

transmitted by newly-infected persons during their brief AHI phase, in the US and

abroad.

Persons with AHI are critical but elusive given the brevity of their superinfectious

window. However, influenza-like symptoms usually accompany and can signal AHI.

Health and testing providers are in a position to diagnose AHI early and to avert

many onward transmissions, but behavioral interventions with pr oviders, in gay

communities, and in substance user communities to bring persons with AHI to

testing and care:

• Community-level interventions to heighten awareness of AHI symptoms

• Interventions with providers to heighten awareness of possible AHI

RETENTION IN CARE IS AS CRITICAL

AS LINKAGE BUT HAS RECEIVED MUCH LESS

INTERVENTION ATTENTION

Systems-level interventions coupled with close care management and

accessible, low-threshold care have shown promise for improving the linkage

of newly-diagnosed PLH into care. However, cascade analyses at national and

state levels show that long-term treatment retention over time becomes much

lower. If persons leave care, by definition they will not benefit from care.

Factors that predict poor care retention consistently include substance abuse,

life chaos, housing instability, and mental health disorders.

The field urgently needs interventions focused on maintaining care retention.

These interventions either must address drop out risk factors or be robust

enough to work even against the backdrop of these barriers.

ADHERENCE FOR THE LONG HAUL

Medication nonadherence has been the factor limiting efficacy in almost all trials of

ART regimens used for treatment, prevention, and protection.

Trials such as HPTN-052, iPREX, and others did not ignor e adherence. All of the

trials counsel patients at the start of treatment and points of contact later. Still, a high

proportion do not adhere sufficiently to derive maximum benefit.

Medication non-adherence is not a new problem nor is it limited to ART for HIV.

However, even modest nonadherence poses greater threat than in many other health

areas.

Increased attention to new paradigms for improving sustained adherence is critical if

the potential of ART for treatment, prevention, and protection is to be realized.

Promising paradigms include:

• Technology linked to real-time medication taking

• Sustained interventions for sustained effects

• Mobilizing social and normative supports for adherence

• Addressing concurrent life issues that jeopardize adherence

LIFE COURSE PERSPECTIVES

IN CARE AND PREVENTION

Due to treatment advances, HIV infection is no longer primarily a disease of

youth, and life course perspectives for treatment and adherence are needed.

HIV prevention and adherence research has taken very short-term

perspectives to intervention and effect assessment.

We still know very little about how to intervene to produce long-term change

whether in risk reduction, treatment engagement, and ART adherence. Very

long-term effects are rarely measured.

Although HIV infection produces neuropsychological impairment greater

than the normal effects of aging, interventions to promote adherence in older

adults living with HIV remain understudied.

Greater attention to life course HIV social and behavioral issues is needed.

IN AN ERA OF NEW APPROACHES TO HIV PREVENTION

BUT LIMITED FUNDING, RESEARCH TO GUIDE

RESOURCE ALLOCATION DECISIONS IS ESSENTIAL

Cost-effectiveness research has always sought to determine the public health

benefits that would accrue through the adoption of various HIV prevention

interventions.

Especially with the prospect of decreased public health funding but also the

emergence of promising new prevention strategies, a new set of researchable

questions has emerged. Examples include:

• If prevention resources were directed toward treatment rather than

traditional risk reduction prevention, what would be the effect on HIV

incidence (assuming various realistic scenarios of treatment coverage

and adherence)?

• At what points on the HIV treatment cascade will expansion of

resources have the greatest effect on future incidence?

THE LEVELS OF INTERVENTION MODELS

PREVIOUSLY USED ONLY FOR HIV RISK REDUCTION

CAN GUIDE THE FIELD’S THINKING ABOUT

INTERVENTIONS NEEDED TO IMPLEMENT NEW

BIOMEDICAL HIV PREVENTION APPROACHES

Although the behavior change targets of cascade-related goals are

different than those of risk reduction interventions, revisiting

conceptions of levels of intervention may prove useful for guiding

research into new challenges related to biomedical prevention.

• Individual level

• Small group level

• Social setting level

• Social network level

• Community level

• Structural levels

• Societal and macro levels

ALTHOUGH THERE ARE IMPORTANT NEW OPPORTUNITIES

FOR BEHAVIORAL SCIENCE INTERVENTION RESEARCH

RELATED TO BIOMEDICAL ADVANCES, BALANCE

MUST BE MAINTAINED BETWEEN ESTABLISHED

APPROACHES AND NEW OPPORTUNITIES.

As the field pursues new agendas to move biomedical advances to scalable

and effective applied prevention strategies, it is important to continue to

refine interventions to reduce high-risk behavior.

HIV prevention needs will not be met by biomedical prevention alone.

Coverage and adherence will always be imperfect, and risk behavior

reduction will always remain a critical objective.

Failure to also pursue risk behavior reduction interventions targeting those

populations with highest incidence will result in more infections, not fewer.

Combination behavioral, social, and biomedical prevention represents the

most promising strategy for high-impact outcomes.