RESEARCH AND PRACTICE

Integrated Behavioral Intervention to Improve HIV/AIDS

Treatment Adherence and Reduce HIV Transmission
Seth C. Kalichman, PhD, Chauncey Cherry, MPH, Moira O. Kalichman, MSW, Christina M. Amaral, BA, Denise White, MA, Howard Pope, BA,
Connie Swetzes, LPN, Lisa Eaton, PhD, Rene Macy, MA, and Demetria Cain, MPH

Antiretroviral therapy (ART) improves the

health and increases the longevity of people
infected with HIV.1 Growing evidence indicates
that ART can also reduce HIV infectiousness,
raising the possibility of using HIV treatment as
prevention.23 Mathematical models suggest
that HIV testing with immediate treatment may
have a substantial preventative effect in high HIV
prevalence populations.46 The potential preventative benefits of treating HIV infection are
shifting prevention policies. Most notably, the
Swiss Federal AIDS Commission has stated that
repeated undetectable HIV RNA (viral load) tests
can render individuals noninfectious.79 Although biologically and epidemiologically plausible,10,11 using HIV treatment as prevention will
fail when medication adherence is poor and
when there are co-occurring sexually transmitted
infections (STIs).
Most ART regimens demonstrate suppressive effects in the genital tract that are similar to
those in blood plasma,12 and the genital tract
suffers similar detrimental ramifications of ART
nonadherence.13 The most forgiving ART regimens require at least 85% adherence to suppress
HIV replication, avoid treatment-resistant variants of the virus, and reduce infectiousness.1416
Evidence also shows that individuals who experience difficulty adhering to ART engage in
higher-risk sexual behaviors.17 Even under optimal adherence, persons with undetectable peripheral blood viral loads will be highly infectious
in their genital secretions when they have cooccurring STIs.18
Co-occurring STIs are prevalent among
people living with HIV/AIDS19,20 and cause
HIV shedding in genital fluids.21 Individuals who
are coinfected with HIV and other STIs are
therefore far more infectious than their blood
plasma viral load indicates. The poor concordance between blood plasma and semen HIV
RNA is at least in part the result of inflammatory
processes caused by co-occurring STIs.22 The
interplay between treatment, viral load, and

Objectives. We conducted a randomized clinical trial to test an integrated

behavioral intervention designed to enhance using HIV treatment as prevention
by improving medication adherence, reducing risks for other sexually transmitted infections, and minimizing risk compensation beliefs.
Methods. Individuals living with HIV/AIDS (n = 436) participated in a randomized clinical trial testing an intensive behavioral intervention aimed at reducing
HIV transmission risks compared with an attention control condition. We used
unannounced pill counts to monitor antiretroviral therapy adherence and
computerized interviews to measure risk behaviors.
Results. The integrated transmission risk reduction intervention demonstrated
increased antiretroviral therapy adherence and less unprotected intercourse
with nonseroconcordant partners at 3- and 6-month follow-ups as well as fewer
new sexually transmitted infections diagnosed over the 9-month follow-up
period (adjusted odds ratio = 3.0; P < .05; 95% confidence interval = 1.01, 9.04).
The integrated intervention also reduced behavioral risk compensation beliefs.
Conclusions. A theory-based integrated behavioral intervention can improve
HIV treatment adherence and reduce HIV transmission risks. HIV treatment as
prevention should be bundled with behavioral interventions to maximize
effectiveness. (Am J Public Health. 2011;101:531538. doi:10.2105/AJPH.2010.
197608)

sexual transmission is further complicated by risk

compensation; individuals who believe they are
less infectious take fewer precautions against
infecting partners.2326
To succeed, the use of HIV treatment as
prevention, or so-called test and treat strategies, will require a comprehensive approach
that encompasses adherence support, sexual
risk reduction, and the amelioration of risk
compensation.27 HIV transmission risk reduction interventions for people infected with HIV
have thus far focused exclusively on reducing
unprotected sex with non-HIVpositive partners.28 Similarly, ART adherence interventions
have not directly addressed HIV transmission
risks. One example of an intervention that addressed treatment adherence and transmission risk reduction was the Healthy Living Project.2930 In a multisite trial, the Healthy Living
Project targeted mental health, treatment adherence, and risk behaviors in separate intervention modules delivered several weeks apart.
The investigators of the Healthy Living Project

March 2011, Vol 101, No. 3 | American Journal of Public Health

examined the 3 modules independently in

separate analyses. The Healthy Living Project
medication module demonstrated significant
increased treatment adherence,28 and the
prevention module resulted in significant reductions in HIV transmission risk behaviors.29 Unfortunately, the Healthy Living Project did
not test the synergistic effects of the adherence
and risk reduction modules. We are not aware
of any unified behavioral intervention that has
attempted to simultaneously reduce HIV
infectiousness by improving treatment adherence and reducing HIV exposures. We sought to
fill this gap by testing an integrated adherence
and risk-reduction intervention designed for use
in conjunction with HIV treatment as prevention.
The aim of this clinical trial was to test
the effects of a theory-based integrated behavioral intervention for reducing HIV transmission risks in individuals living with HIV/
AIDS. Our primary hypothesis was that an
integrated intervention approach would improve treatment adherence and reduce risk

Kalichman et al. | Peer Reviewed | Research and Practice | 531

RESEARCH AND PRACTICE

behaviors relative to a matched-contact control intervention. The secondary hypothesis

was that the integrated intervention would
reduce risk compensation beliefs concerning
undetectable HIV RNA.

METHODS
Participants were 310 men and 126 women
recruited from AIDS service providers in
Atlanta, Georgia. The study commenced March
2005, enrollment ended October 2008, and
follow-ups were completed November 2009.
Atlanta has among the fastest growing HIV
epidemics in the United States,31 with more than
23 000 reported cases of AIDS and an HIV/
AIDS rate of 23 per 100000 population, exceeding the average 15 per 100 000 population
in other major US cities. For recruitment, we
notified AIDS service providers and infectious
disease clinics about the study opportunity. Recruitment brochures were placed in providers
lobbies and waiting areas. Interested persons
telephoned the research site to schedule an
intake appointment.
The study entry criteria were (1) aged 18
years or older and (2) name-matching proof of
positive HIV status and photo identification.
We did not screen participants for dependant
variables (ART adherence and risk behavior) to
ensure ecological validity of the intervention
groups, because they would occur in community and clinical services.

Overview of Intervention Conditions

We implemented the 2 conditions in this
trial using the same operational procedures.
We conducted all intervention group sessions at the same community-based AIDS
service provider. We formatted both arms
to deliver a 45-minute one-on-one orientation and goal-setting session with 1 of the
group facilitators before five 120-minute
group sessions and a 60-minute postgroup
one-on-one counseling session. The same
interventionists delivered both conditions in
malefemale facilitator pairs. All facilitators
received 2 weeks of training, delivered their
first group sessions with an experienced
facilitator, and received weekly supervision.
We conducted group sessions with 810
participants of mixed gender and sexual
orientations.

Integrated Risk Reduction and

Adherence Intervention
We grounded the experimental condition in
conflict theory of decision making.32 Conflict
theory posits that weighing risks and benefits of
behavioral options leads to more personally
effective decisions. We therefore used a single
model of decision-making skills that afforded
a fully integrated and unified intervention for 2
targeted outcomes, both of which hinge on
effective decision making: improved medication
adherence and reduced sexual transmission risk
behavior.
We conducted the first individual counseling
session to set personal treatment and prevention goals for the upcoming group. The first
group session built cohesion and trust, and in
it we discussed how risk reduction and treatment goals are related. The session included
a team-building game designed to educate
participants about the basics of HIV transmission, treatment resistance, and viral load. We
covered myths and facts about infectiousness
in detail. The second group session focused on
understanding HIV treatment, including deciding when to start medications. We applied
decisional balance exercises to treatment decisions and sexual relationships in contexts of
detectable and undetectable HIV RNA. Group
session 3 focused entirely on sexual decision
making under various nuanced conditions of
moods, substance use, relationships, HIV status
disclosure, treatment status, and viral load.
Group session 4 aimed to build treatment and
safer sex decision skills in relation to substance
use. A core activity in this session had participants
wear vision-disorienting goggles to simulate intoxication while filling a pillbox with mints and
then apply a condom to a penis model. We then
trained participants in medication management
and safer sex strategies, including using male and
female condoms. Group session 5 emphasized
treatment adherence to improve health and reduce infectiousness. We also offered skill-building
activities for recognizing symptoms of STIs. The
final individual counseling session occurred
within 1 week of the last group session and
delivered a personalized plan for treatment decisions, adherence, and safer sex.

Attention Control Condition

The control arm was a contact-matched
noncontaminating support group for

532 | Research and Practice | Peer Reviewed | Kalichman et al.

individuals living with HIV/AIDS. Participants

received 1 individual orientation session. The
first group session focused on building group
cohesion and discussed how to access quality
health information. The remaining 4 group
sessions covered detecting early warning signs
of cancer, breast and testicular self-examination, nutrition decision making, healthy food
selection, planning exercise, and relaxation.
The final individual counseling session set
personalized health improvement goals.

Outcome Measures
We assessed demographics, health, and
behavior at baseline and 3-, 6-, and 9-month
follow-ups using audio computer-assisted
self-interviews.33 We asked participants their
age, ethnicity, years of education, income, HIV
symptoms, employment, and disability status.
Participants also indicated whether they had
drunk alcohol or used other drugs in the previous 3 months. We monitored HIV treatment
adherence using unannounced pill counts.
ART adherence and viral load. We monitored HIV treatment adherence with
monthly, unannounced telephone-based
pill counts. Unannounced pill counts are reliable and valid in assessing HIV treatment
adherence when conducted in participants
homes and on the telephone.34,35 We gave
participants a free cell phone that restricted
service to project contacts and emergency use
(e.g., 911). After office-based training in the
pill-counting procedure, participants were called
at unscheduled times by a telephone assessor.
We took pill counts over 21- to 35-day intervals
and conducted them for each antiretroviral
medication the participants were taking. We
also collected pharmacy information from pill
bottles to verify the number of pills dispensed
between calls. We calculated adherence as the
ratio of pills counted to pills prescribed, taking
into account the number of pills dispensed. Two
consecutive pill counts were necessary for computing adherence. Adherence data represents
the percentage of pills taken as prescribed
following the initial office-based assessment averaged across antiretroviral medications. Telephone assessors were blind to assigned treatment
condition. The first 3 pill counts occurred before
the baseline assessment, allowing us to calculate at least 1 preintervention adherence value.
As part of the monthly telephone assessment,

American Journal of Public Health | March 2011, Vol 101, No. 3

RESEARCH AND PRACTICE

TABLE 1Demographic Characteristics and Baseline Behaviors for Integrated and Comparison Interventions: Integrated
HIV Intervention Trial, Atlanta, GA, March 2005November 2009
Characteristics

Integrated Intervention (n = 217), No. (%) or Mean (SD)

Comparison Intervention (n = 219), No. (%) or Mean (SD)

161 (74)

149 (68)

c2 or t

Gender
Men
Women

56 (29)

70 (32)

2.00

Transgender (men)

13 (6)

17 (8)

0.50

Race
African American

199 (92)

198 (90)

White

12 (6)

14 (6)

Latino

4 (2)

3 (1)

Other

2 (1)

4 (2)

2.20

Unemployed

77 (35)

78 (35)

1.60

Disabled

113 (52)

118 (54)

1.60

Income < $10 000

152 (71)

155 (71)

0.20

Education 12 y
Substance use in past 3 mo

129 (59)

144 (66)

1.80

Alcohol
Marijuana
Other drugs
Sexually active

114 (48)

96 (56)

3.30

54 (25)

43 (20)

1.70

49 (22)

47 (21)

0.10

141 (65)

145 (66)

0.01

HIV nonseroconcordant
Sexual partner
STI in the past 3 mo
Taking ART

64 (30)

66 (30)

0.10

6 (3)
152 (70)

13 (6)
157 (72)

2.60
3.20

90% adherent to ART

62 (44)

51 (33)

3.70

Undetectable viral load

94 (44)

104 (48)

0.80

Age

44.2 (7.0)

44.7 (6.9)

0.8

Years since testing HIV+

13.1 (6.7)

12.4 (5.9)

1.1

0.9 (1.0)

1.0 (1.1)

0.7

1.3 (2.9)
0.6 (1.8)

1.3 (3.3)
0.7 (3.1)

1.4
0.2

Risk compensation beliefs

Sex behaviors for entire sample
No. of sexual partners
No. of nonpositive sexual partners
Unprotected intercourse with nonpositive partners

0.5 (2.9)

0.8 (5.6)

0.8

Condom-protected intercourse with nonpositive partners

1.6 (7.9)

0.9 (2.9)

1.2

Sex behaviors for sexually active only

No. of sexual partners

2.0 (3.4)

2.1 (3.9)

0.9

No. of nonpositive sexual partners

1.0 (2.1)

1.0 (3.7)

0.8

Unprotected intercourse with nonpositive partners

0.8 (3.6)

1.3 (6.8)

0.4

Condom-protected intercourse with nonpositive partners

Unannounced pill count adherence

2.5 (9.7)

1.4 (3.5)

1.3

ART adherence entire sample

85.7 (27.9)

90.7 (22.5)

1.7

ART adherence for 90% adherent

63.5 (25.5)

68.8 (23.6)

1.1

Note. ART = antiretroviral therapy; STI = sexually transmitted infection. All comparisons were nonsignificant.

participants also reported their CD4 cell count

and HIV viral load.
Sexual risk behaviors and STIs. Participants
responded to questions assessing their number
of male and female sexual partners and

frequency of unprotected and protected sexual

behaviors (anal and vaginal intercourse) with
seroconcordant (same HIV status) and nonseroconcordant (HIV negative and unknown
HIV status) partners in the previous 3

March 2011, Vol 101, No. 3 | American Journal of Public Health

months.36,37 Outcome analyses focused on testing the primary hypothesis regarding HIV
transmission risks, specifically reducing unprotected sexual behaviors with non-HIV-positive
partners. Participants also reported whether

Kalichman et al. | Peer Reviewed | Research and Practice | 533

RESEARCH AND PRACTICE

The mean risk compensation score was internally consistent (a =0.84).

Sample Size, Randomization, and

Blinding
We used a moderate effect size (d = 0.35) to
calculate statistical power for both projected
outcomes.28,42 We assumed 80% retention and
estimated a sample of 110 for each primary
outcome to achieve a 90% chance of detecting
differences between groups.
After 3 unannounced pill counts and the
baseline audio computer-assisted self-interview
assessment, we randomly assigned participants
to conditions. The project director performed
the allocation, manually drawing equal numbers of condition-coded markers without replacement. We did not breach randomization
throughout the trial.
Recruitment, screening, office-based assessment, and telephone assessment staff remained
blinded to condition throughout the study,
and interventionists never conducted assessments.

Statistical Analyses

Note. ACASI = audio computer-assisted self-interview.

FIGURE 1Flow of participants through the randomized trial: Integrated HIV Intervention
Trial, Atlanta, GA, March 2005November 2009.

they had been diagnosed with a non-HIV sexually transmitted infection (gonorrhea, chlamydia,
syphilis, and nongonococcal urethritis) during
each 3-month retrospective period.
Adherence and prevention strategies and risk
compensation beliefs. To assess adherence
strategies, we asked participants to indicate
whether they had used 15 common strategies
for improving medication adherence by
responding on 5-point scales in which 0 =
never and 4 = always (a = 0.70).38,39 To
determine their use of prevention strategies, we

asked participants to report how often they had

used 9 common behavioral strategies for sexual
risk reduction in the previous 3 months. We
summed these items to create an index of safer
sex strategies.40 We adapted risk compensation
beliefs from previous research41 and included
7 items (e.g., People with HIV who take HIV
medications are less likely to infect their sexual
partners during unsafe sex and It is safe to have
sex without a condom when my viral load is
undetectable) on 6-point scales in which
1= strongly disagree and 6 = strongly agree.

534 | Research and Practice | Peer Reviewed | Kalichman et al.

In our outcome analyses, we used an intentto-treat approach, in which we included all

available follow-up data from participants in
the analyses regardless of their exposure to the
intervention sessions. Preliminary analyses involved procedures suggested by Jurs and
Glass43 to test baseline equivalence between
conditions and effects of attrition on dependent
measures.
In primary and secondary outcome analyses,
we used generalized estimating equations
with unstructured working correlation matrixes. We used Poisson distribution for count
data and normal distribution for scaled data.
All outcome analyses controlled for baseline
scores, gender, and date of study enrollment.
We entered condition, time of assessment,
and condition time interactions as model
effects. We used planned contrasts with a least
significant difference adjustment to test for
simple effects. We tested sexual risk reduction
outcomes, including safer sex strategies, for all
sexually active participants and continuous
adherence values for all participants receiving
ART with < 90% baseline adherence. We analyzed adherence strategies for all participants
taking HIV treatment and analyzed risk

American Journal of Public Health | March 2011, Vol 101, No. 3

RESEARCH AND PRACTICE

compensation beliefs for the entire sample. We

employed logistic regression analysis to analyze the dichotomous STI outcome for all
sexually active participants, controlling for potentially confounding HIV physical symptoms.
We used SPSS version 18 (SPPS, Inc, Chicago,
IL) for all primary outcome analyses.
We tested the simultaneous effect of the
intervention on multiple outcomes using structural equation modeling with AMOS version 18
(AMOS Development Corp, Crawfordville, FL).
Specifically, we tested the intervention condition
as a predictor of 6-month follow-up nonseroconcordant unprotected intercourse, medication
adherence, and subsequent infectiousness beliefs. We entered STI diagnoses over the 9month follow-ups as the dependant variable and
unprotected intercourse and infectiousness beliefs as predictor variables. In addition, we included adherence as a predictor of viral load. We
report model coefficients for paths and goodness
of fit indexes.

RESULTS
The majority (91%) of participants were
African American, 55% of men reported current male sexual partners, and the mean age
was 44.1 years (SD = 6.8). Seventy-one percent
of participants were receiving ART that included nonnucleoside reverse transcriptase inhibitors (n = 54; 24%), protease inhibitors
(n = 31; 14%), or protease inhibitors boosted by
a pharmacokinetic enhancer (n =132; 58%).
Nine (4%) were using other regimens. No
differences were found between conditions on
any baseline measures (Table 1).
As shown in Figure 1, the trial retained more
than 90% of participants randomized to conditions for audio computer-assisted self-interviews and 84% for monthly telephone assessments. Six participants were known to have
died during the trial, 5 withdrew, and 3 moved
out of state. Attrition was proportional for the 2
conditions at the 3- and 6-month follow-ups.
However, significantly more participants in the
integrated intervention were lost at the 9month follow-up (c2(1490) = 8.3; P < .01); 89%
of experimental and 95% of control participants were retained more than 9 months.
Overall retention was higher than the 80%
initially expected, with > 90% of participants
retained. In the planned attrition analyses

suggested by Jurs and Glass,43 we did not find

differences between retention and attrition by
condition for participant characteristics or outcome variables.
Intervention attendance was also proportional across conditions. Participants in both
conditions attended the same average of 3.5
(SD = 2.1) group sessions and 1.6 (SD = 0.1)
individual sessions; 196 of 217 (90%) participants in the integrated intervention attended at
least 1 group session as did 196 of 219 (89%) in
the comparison group. Similarly, 135 of 217
(62%) integrated participants and 138 of 219
(63%) comparison participants attended the
final individual goal-setting session.

Treatment Adherence Outcomes

Figure 2 shows adjusted estimated means
(SEs) for unannounced pill count adherence by
condition over the 12-month observation period. Results indicated a significant intervention
condition effect (Wald c2 = 4.1; P < .05); integrated intervention participants demonstrated
significantly greater adherence over the followup period than did the comparison group.
The time effect (Wald c2 = 6.4) and the condition time interaction (Wald c2 = 9.6) were
not significant.

Analyses of monthly reports of viral load did

not indicate significant differences between
conditions. Between 45% and 55% of participants in both conditions reported undetectable
HIV RNA throughout the study.

Sexual Transmission Risk Reduction

Outcomes
Results indicated significant differences between conditions for HIV exposure risks to
uninfected sexual partners. There was a significant intervention time interaction for
unprotected intercourse; the integrated intervention engaged in significantly less nonseroconcordant unprotected intercourse at the
3- and 6-month follow-ups (Table 2). The
integrated intervention group reported 121
nonseroconcordant unprotected intercourse
acts between the baseline and the 6-month
follow-up compared with 356 nonseroconcordant unprotected sex acts reported by the
comparison group. The difference between
conditions was no longer significant at the 9month follow-up. Inspection of disaggregated
anal and vaginal intercourse indicated a nonsignificant trend for a condition effect on
nonseroconcordant unprotected anal intercourse and a significant condition effect for

Note. ART = antiretroviral therapy.

FIGURE 2Estimated means (SE) for ART adherence outcomes over 12 months of
observation: Integrated HIV Intervention Trial, Atlanta, GA, March 2005November 2009.

March 2011, Vol 101, No. 3 | American Journal of Public Health

Kalichman et al. | Peer Reviewed | Research and Practice | 535

RESEARCH AND PRACTICE

TABLE 2Nonseroconcordant Sexual Behavior Outcomes, Skills, and Strategies and Risk Compensation Beliefs for Integrated
and Comparison Interventions: Integrated HIV Intervention Trial, Atlanta, GA, March 2005November 2009
Measures

Integrated Intervention, Mean (SD)

Comparison Intervention, Mean (SD)

3 mo

0.5 (1.4)

0.6 (1.3)

6 mo

0.6 (1.1)

0.9 (5.1)

9 mo

0.04 (0.6)

0.4 (0.6)

Condition, c2

Time, c2

Condition Time, c2

No. of nonpositive partners

Unprotected intercourse
3 mo

0.9 (5.3)

2.3 (15.0)

6 mo

0.2 (1.0)

1.0 (3.8)

9 mo

1.1 (4.5)

0.9 (4.3)

3 mo

0.2 (1.4)

0.4 (2.4)

6 mo

0.1 (0.7)

0.6 (2.9)

9 mo

0.4 (1.7)

0.6 (3.7)

0.7

4.5

0.1

0.8

10.3***

8.1***

2.7*

6.5***

3.2

4.6**

13.4***

3.6

Unprotected anal intercourse

Unprotected vaginal intercourse

3 mo

0.1 (1.1)

0.3 (2.0)

6 mo

0.1 (0.3)

0.1 (0.2)

9 mo

0.1 (0.5)

0.1 (0.2)

3 mo

0.8 (4.9)

2.0 (14.0)

6 mo

0.2 (0.9)

0.8 (3.5)

9 mo

1.0 (4.2)

0.8 (4.0)

Condom-protected intercourse

Safer sex strategies

3 mo

47.4 (104.2)

31.8 (59.3)

6 mo

29.4 (38.7)

31.3 (37.5)

9 mo

43.5 (89.3)

25.9 (44.9)

3 mo

16.4 (13.4)

15.2 (10.3)

6 mo

16.2 (11.7)

16.2 (13.6)

9 mo

15.5 (13.4)

13.8 (10.8)

0.5

0.1

3.9

4.9**

7.2

4.4

4.0**

7.9**

1.0

4.8**

1.6

1.7

Adherence strategies

Risk compensation beliefs

3 mo

0.9 (1.0)

1.1 (1.1)

6 mo

1.0 (1.0)

1.1 (1.2)

9 mo

0.9 (1.0)

1.1 (1.1)

Note. All analyses control for baseline scores, gender, and date of study enrollment
*P < .10; **P < .05; ***P < .01.

nonseroconcordant unprotected vaginal intercourse; integrated intervention participants

reported lower rates of both behaviors. We
found no significant differences between
groups in number of sexual partners and
condom-protected intercourse.
Analyses for acquiring a new bacterial STI
aggregated over the 9-month postintervention
showed a significant difference between conditions; fewer participants in the integrated
intervention (5 of 143 sexually active; 3.5%)
reported new STIs than did those in the

comparison intervention (13 of 150 sexually

active; 8.6%; adjusted odds ratio = 3.0; P < .05;
95% confidence interval [CI] =1.01, 9.04).

did the comparison condition. The condition

time interactions were not significant.

Behavioral Strategies and Beliefs

Structural Model of Integrated

Intervention Outcomes

The integrated intervention participants

reported greater use of safer sex risk reduction
and medication adherence strategies (Table 3).
A significant time effect also showed that
adherence strategies increased across groups.
The integrated intervention demonstrated less
endorsement of risk compensation beliefs than

Structural equation modeling simultaneously tested intervention outcomes and their

association to intervention endpoints (Figure 3;
all baseline scores controlled not shown). Results demonstrated a good fit of the data to
the model (c2 = 38.4; P > .05; root mean
square error of approximation = 0.031; 95%

536 | Research and Practice | Peer Reviewed | Kalichman et al.

American Journal of Public Health | March 2011, Vol 101, No. 3

RESEARCH AND PRACTICE

Note. ART = antiretroviral therapy.

*P < .05; **P < .01

FIGURE 3Structural equation model for intervention effects on primary outcomes and
association of primary outcomes to health-related endpoints: Integrated HIV Intervention
Trial, Atlanta, GA, March 2005November 2009.

CI = 0.000, 0.051). The intervention condition

demonstrated significant effects on nonseroconcordant unprotected intercourse and ART
adherence. The intervention also significantly
affected subsequent risk compensation beliefs.
As expected, adherence and risk reduction
behavioral outcomes predicted their respective
endpoints.

DISCUSSION
The current trial demonstrated significant
improvement in ART adherence and reductions in HIV transmission risks resulting from
an integrated behavioral intervention designed
to improve adherence and to prevent HIV
transmission. The magnitude of effects parallel
those reported by an intervention that aimed to
reduce risks and increase adherence in separate modules.2930 To our knowledge, this trial
is the first test of an intervention designed to
simultaneously and synergistically reduce HIV
transmission risks by improving adherence, reducing unprotected intercourse, and minimizing
risk compensation. The pattern of results for the
primary and secondary outcomes suggests that
an integrated behavioral intervention has the
potential to bolster the use of HIV treatments
to avert new HIV infections.
Although adherence improvements were
relatively stable over the 9 months of followup, the sexual risk reduction outcomes were
shorter lived, dissipating before 9 months after
the intervention. The durability of behavioral
outcomes may prove more optimistic when
the intervention is delivered in clinical care

given the opportunities for ongoing support.

Another limitation of this trial was its reliance
on self-reported measures for sexual risk and
biological outcomes. Although the consistency
of findings supports the studys internal validity, further testing of this intervention should
be undertaken with biological endpoints. We
emphasized ecological validity in designing the
intervention, focusing on simple and lowcost strategies for reducing risk and improving
adherence.44 Although we strived to maintain
implementation simplicity, the intervention included 2 individual and 5 group sessions. Operations research is needed to examine whether the
intervention can be shortened and whether it can
be infused within existing clinical services, such
as support groups, medication adherence groups,
and case management.
Risk compensation beliefs conceptually link
adherence and HIV transmission risk behaviors. We have previously proposed that some
individuals who believe that they are not infectious after learning they have undetectable
HIV RNA will adjust their sexual practices by
using condoms less and engaging in higher
rates of unprotected sex, therefore exposing
themselves to co-occurring STIs and greater
infectivity. In the integrated intervention tested
in this trial, we used a uniform decision-making
model to simultaneously affect adherence, risk
behaviors, and risk compensation beliefs.
These findings confirm the conceptual basis
for the intervention and suggest that other
integrated intervention models may be effective in addressing multiple related health behaviors.

March 2011, Vol 101, No. 3 | American Journal of Public Health

HIV treatment used for prevention offers

great hope for extending the benefits of ART to
avert new HIV infections. Behavioral interventions can be bundled with HIV treatments
used for prevention and offered as a unified
prevention package. Failure to directly address
factors such as ART adherence, risk behaviors,
co-occurring STIs, and risk compensation will
undermine the promise of using HIV treatment
for prevention. It is incumbent on test and
treat programs, as well as other approaches
that use HIV treatment for prevention, to provide adequate resources for integrating behavioral interventions to sustain adherence,
risk reduction, and STI control. j

About the Authors

Seth C. Kalichman, Chauncey Cherry, Moira O. Kalichman,
Christina M. Amaral, Denise White, Howard Pope, Connie
Swetzes, Lisa Eaton, Rene Macy, and Demetria Cain are
with the Department of Psychology at the University of
Connecticut, Storrs.
Correspondence should be sent to Seth C. Kalichman,
Department of Psychology, 406 Babbidge Road, University
of Connecticut, Storrs, CT 06269 (e-mail: seth.k@uconn.
edu) or Moira Kalichman, Department of Psychology, 406
Babbidge Road, University of Connecticut, Storrs, CT
06269 (e-mail: aidsandbehavior@yahoo.com). Reprints
can be ordered at http://www.ajph.org by clicking the
Reprints/Eprints link.
This article was accepted June 4, 2010.

Contributors
S. C. Kalichman conceptualized and designed the trial,
data analyses, and paper. C. Cherry, C. M. Amaral, D.
White, H. Pope, and C. Swetzes contributed to the
conceptualization, design, and execution of the trial.
M. O. Kalichman contributed to intervention development and trial design, execution, and management. L.
Eaton contributed to analyses and interpretation. R.
Macy and D. Cain managed and ensured data quality.

Acknowledgments
The National Institute of Mental Health (grant R01MH71164) supported this study.
Cynthia Grossman was the program officer.
The authors wish to thank Jeff Parsons, Dan Dunable,
Juanita Williams, Richard Anderson, George Burgess,
and the AIDS Survival Project of Atlanta for their
contributions.
S. C. Kalichman had full access to all the data in the
study and takes responsibility for the integrity of the data
and the accuracy of the data analysis.

Human Participant Protection

The University of Connecticut institutional review board
approved all study protocols.

References
1. Lima VD, Harrigan R, Bangsberg DR, et al. The
combined effect of modern highly active antiretroviral

Kalichman et al. | Peer Reviewed | Research and Practice | 537

RESEARCH AND PRACTICE

therapy regimens and adherence on mortality over time.

J Acquir Immune Defic Syndr. 2009;50(5):529536.

decreased sexual risk behavior in HIV clinic patients.

J Acquir Immune Defic Syndr. 2005;39(2):211218.

2. Dieffenbach CW, Fauci AS. Universal voluntary

testing and treatment for prevention of HIV transmission.
JAMA. 2009;301(22):23802382.

18. Ping LH, Cohen MS, Hoffman I, et al. Effects of

genital tract inflammation on human immunodeficiency
virus type 1 V3 populations in blood and semen. J Virol.
2000;74(19):89468952.

3. Donnell D, Baeten JM, Kiarie J, et al. Heterosexual

HIV-1 transmission after initiation of antiretroviral therapy: a prospective cohort analysis. Lancet. 2010;375
(9731):20922098.
4. Granich RM, Gilks CF, Dye C, De Cock KM, Williams
BG. Universal voluntary HIV testing with immediate
antiretroviral therapy as a strategy for elimination of HIV
transmission: a mathematical model. Lancet. 2009;
373(9657):4857.

19. Brewer TH, Metsch LR, Zenilman JM. Use of a public

sexually transmitted disease clinic by known HIV-positive
adults: decreased self-reported risk behavior and increased disease incidence. J Acquir Immune Defic Syndr.
2002;29(3):289294.
20. Kalichman SC, Rompa D, Cage M. Sexually transmitted infections among HIV seropositive men and
women. Sex Transm Infect. 2000;76(5):350354.

5. Blower SM, Gershengorn HB, Grant RM. A tale of

two futures: HIV and antiretroviral therapy in San
Francisco. Science. 2000;287(5453):650654.

21. Pilcher CD, Chuan Tien H, Eron JJ, et al. Brief but
efficient: acute HIV infection and the sexual transmission
of HIV. J Infect Dis. 2004;189(10):17851792.

6. Wilson DP, Law MG, Grulich AE. Relation between

HIV viral load and infectiousness: a model-based analysis. Lancet. 2008;372(9635):314320.

22. Kalichman SC, DiBerto G, Eaton L. Human immunodeficiency virus viral load in blood plasma and semen:
review and implications of empirical findings. Sex Transm
Dis. 2008;35(1):5560.

7. Vernazza P, Hirschel B, Bernasconi E, Flepp M. HIV

transmission under highly active antiretroviral therapy.
Lancet. 2008;372(9652):18061807; author reply
1807.
8. Vernazza PL, Troiani L, Flepp MJ, et al. Potent
antiretroviral treatment of HIV infection results in suppression of the seminal shedding of HIV. AIDS. 2000;
14(2):117121.
9. Vernazza P, Hirschel B, Bernasconi E, Flepp M. HIVpositive individuals without additional sexually transmitted diseases (STD) and on effective anti-retroviral
therapy are sexually non-infectious. Schweiz Arzteztg.
2008;89(5):165169.
10. Quinn TC, Wawer MJ, Sewankambo N, et al. Viral
load and heterosexual transmission of human immunodeficiency virus type 1. Rakai Project Study Group. N
Engl J Med. 2000;342(13):921929.
11. Wawer MJ, Gray RH, Sewankarnbo NK, et al. Rates
of HIV-1 transmission per coital act, by stage of HIV-1
infection, in Rakai, Uganda. J Infect Dis. 2005;191(9):
14031409.
12. Kashuba AD, Dyer JR, Kramer LM, Raasch RH, Eron
JJ, Cohen MS. Antiretroviral-drug concentrations in semen: implications for sexual transmission of human
immunodeficiency virus type 1. Antimicrob Agents Chemother. 1999;43(8):18171826.
13. Vernazza PL, Gilliam BL, Dyer J, Fiscus SA, Eron JJ,
Cohen F. Quantification of HIV in semen: correlation
with antiviral treatment and immune status. AIDS.
1997;11(8):987993.

23. Crepaz N, Hart TA, Marks G. Highly active antiretroviral therapy and sexual behavior: a meta-analytic
review. JAMA. 2004;292(2):224236.
24. Kalichman SC, Rompa D. HIV treatment adherence
and unprotected sex practices in people receiving antiretroviral therapy. Sex Transm Infect. 2003;79(1):59
61.
25. Kalichman SC, Rompa D, Austin J, Luke W, DiFonzo
K. Viral load, perceived infectivity, and unprotected
intercourse. J Acquir Immune Defic Syndr. 2001;28(3):
303305.
26. Eaton LA, Kalichman S. Risk compensation in HIV
prevention: implications for vaccines, microbicides, and
other biomedical HIV prevention technologies. Curr
HIV/AIDS Rep. 2007;4(4):165172.
27. Kalichman SC. Co-occurrence of treatment nonadherence and continued HIV transmission risk behaviors: implications for positive prevention interventions.
Psychosom Med. 2008;70(5):593597.
28. Crepaz N, Lyles CM, Wolitski RJ, et al. Do prevention
interventions reduce HIV risk behaviours among people
living with HIV? A meta-analytic review of controlled
trials. AIDS. 2006;20(2):143157.
29. Johnson MO, Charlebois E, Morin SF, Remien RH,
Chesney MA. Effects of a behavioral intervention on
antiretroviral medication adherence among people living
with HIV: the Healthy Living Project Randomized Controlled Study. J Acquir Immune Defic Syndr. 2007;46(5):
574580.

14. Parienti JJ, Das-Douglas M, Massari V, et al. Not all

missed doses are the same: sustained NNRTI treatment
interruptions predict HIV rebound at low-to-moderate
adherence levels. PLoS ONE. 2008;3(7):e2783.

30. Healthy Living Project Team. Effects of a behavioral

intervention to reduce risk of transmission among people
living with HIV/AIDS: the Healthy Living Project Randomized Controlled Study. J Acquir Immune Defic Syndr.
2007;44(2):213221.

15. Bangsberg DR, Kroetz DL, Deeks SG. Adherenceresistance relationships to combination HIV antiretroviral therapy. Curr HIV/AIDS Rep. 2007;4(2):6572.

31. El-Sadr WM, Mayer KH, Hodder SL. AIDS in

Americaforgotten but not gone. N Engl J Med. 2010;
362(11):967970.

16. Parienti JJ, Ragland K, Lucht F, et al. Average

adherence to boosted protease inhibitor therapy, rather
than the pattern of missed doses, as a predictor of HIV
RNA replication. Clin Infect Dis. 2010;50(8):1192
1197.

32. Janis IL, Mann L. Decision-Making: A Psychological

Analysis of Conflict, Choice, and Commitment. New York:
Free Press; 1977.

17. Diamond C, Richardson JL, Milan J, et al. Use of and

adherence to antiretroviral therapy is associated with

34. Bangsberg DR, Hecht FM, Charlebois ED, Chesney

M, Moss A. Comparing objective measures of adherence
to HIV antiretroviral therapy: electronic medication
monitors and unannounced pill counts. AIDS Behav.
2001;5(3):275281.
35. Kalichman SC, Amaral CM, Cherry C, et al. Monitoring antiretroviral adherence by unannounced pill
counts conducted by telephone: reliability and criterionrelated validity. HIV Clin Trials. 2008;9(5):298308.
36. Napper L, Fisher DG, Reynolds GL, Johnson ME.
HIV risk behavior self-report reliability at different recall
periods. AIDS Behav. 2010;35(4):350354.
37. Schroder KE, Carey MP, Vanable P. Methodological
challenges in research on sexual risk behavior: I. Item
content, scaling, and data analytic options. Ann Behav
Med. 2003;26(2):76103.
38. Catz SL, Kelly JA, Bogart LM, Benotsch EG,
McAuliffe TL. Patterns, correlates, and barriers to medication adherence among persons prescribed new treatments for HIV disease. Health Psychol. 2000;19(2):124
133.
39. Kalichman SC, Cain D, Cherry C, Kalichman M, Pope
H. Pillboxes and antiretroviral adherence: prevalence of
use, perceived benefits, and implications for electronic
medication monitoring devices. AIDS Patient Care STDS.
2005;19(12):833839.
40. Kalichman SC, Cain D, Weinhardt L, et al. Experimental components analysis of brief theory-based HIVAIDS risk reduction counseling for sexually transmitted
infection patients. Health Psychol. 2005;24(2):198208.
41. Kalichman SC, Eaton L, Cain D, et al. Changes in
HIV treatment beliefs and sexual risk behaviors among
gay and bisexual men, 19972002. Health Psychol.
2007;26(5):650656.
42. Amico KR, Harman JJ, Johnson BT. Efficacy of
antiretroviral therapy adherence interventions: a research synthesis of trials, 1996 to 2004. J Acquir Immune
Defic Syndr. 2006;41(3):285297.
43. Jurs SG, Glass GV. The effect of experimental
mortality on the internal and external validity of the
randomized comparative experiment. J Exp Educ. 1971;
40(1):6266.
44. Mills EJ, Cooper C. Simple, effective interventions
are key to improving adherence in marginalized populations. Clin Infect Dis. 2007;45(7):916917.

33. Gribble JN, Miller HG, Cooley PC, Catania JA,

Pollack L, Turner CF. The impact of T-ACASI interviewing on reported drug use among men who have sex
with men. Subst Use Misuse. 2000;35(68):869890.

538 | Research and Practice | Peer Reviewed | Kalichman et al.

American Journal of Public Health | March 2011, Vol 101, No. 3

Copyright of American Journal of Public Health is the property of American Public Health Association and its
content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's
express written permission. However, users may print, download, or email articles for individual use.