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BOSTON UNIVERSITY SCHOOL OF PUBLIC HEALTH
DEPARTMENT OF GLOBAL HEALTH
CULMINATING EXPERIENCE COVER PAGE
Name: Lindsey Garrison, BA
CE Advisor: Nafisa Halim, PhD
Culminating Experience Paper or Project Title: Adherence to Antiretroviral Therapy
Among Adolescents in South Africa: A Situational Analysis and Needs Assessment for
Future Policies
Abstract: Adolescents represent 40% of new HIV infections worldwide. As with other
age groups, females are disproportionately affected by HIV/AIDS and they account for
82% of all new cases of HIV among adolescents in South Africa. Adolescent adherence
to antiretroviral therapy (ART) is under researched worldwide, but especially in low-
resource settings, such as South Africa. Much of the published literature indicates that
HIV-positive adolescents often have poor adherence to their medication regimens due to
a variety of factors, including a desire to fit in with their peers, an inconsistent daily
routine, and the adverse side effects of ART. These factors are further compounded by
the emotional, physical, and psychological changes that individuals go through during
adolescence. This policy brief analyzes ST-AMP, a program designed for the Baltimore-
Metropolitan area of the United States, to improve adherence to ART among adolescents
through the use of confidential text messages and modified directly observed therapy
(DOT), if necessary. While some aspects of ST-AMP, such as the confidential text
messages, are readily applicable to the South African context to improve adherence to
ART among adolescents, the reliance on psychologists and social workers, as well as the
constant communication with medical providers are not necessarily feasible. This paper
identifies the gaps in current research, and makes recommendations for further research
to collect baseline statistics on HIV incidence and prevalence among adolescents ages 10-
14, and examine ways to accumulate gender-stratified, infection-stratified (behaviorally
or perinatally), and risk-group specific statistics.
Key Words: HIV/AIDS, adherence, adolescents, antiretroviral therapy, South Africa
	
  
	
  
	
  
	
  
	
  
	
  
	
  
	
  
  	
   1
	
  
Table of Contents
Executive Summary.......................................................................................................... 2
Situation Analysis ............................................................................................................. 5
Adherence to ART Among Adolescents and Consequences.......................................... 5
Male-Female Disparities in ART Adherence ................................................................. 7
Determinants of Poor Adherence .................................................................................... 8
Individual-Level Determinants....................................................................................... 8
Systems-Level Determinants .......................................................................................... 9
Analysis of Best Practices to Improve Adolescents’ Adherence to ART................... 11
Program Analysis: ST-AMP in the United States........................................................ 13
Components of ST-AMP .............................................................................................. 13
Benefits of ST-AMP ..................................................................................................... 14
Characteristics of ST-AMP That Address Barriers to Adherence................................ 15
Limitations of ST-AMP................................................................................................ 16
Implementing ST-AMP in South Africa....................................................................... 17
Need for Further Research ............................................................................................ 18
Conclusion ....................................................................................................................... 20
	
  
	
  
	
  
	
  
	
  
	
  
	
  
	
  
	
  
	
  
  	
   2
	
  
Executive	
  Summary	
  
Adolescents are a critical population for HIV prevention and treatment strategies in South
Africa, as in other sub-Saharan African countries. At the end of 2012, the United Nations
International Children's Emergency Fund (UNICEF) estimated that 2.1 million
adolescents, defined as individuals ages 10 to 19, were living with HIV/AIDS worldwide
(1). Roughly 85% of infected adolescents are living in South Africa and other sub-
Saharan African countries (1). Additionally, HIV is a rapidly growing epidemic amongst
adolescents, as they represent approximately 40% of new HIV infections globally (2).
Surprisingly, girls account for approximately two thirds of all new adolescent
HIV infections worldwide. This rate is even higher in South Africa, where females
account for 82% of all new HIV cases among adolescents (1). By 2050, the adolescent
population in sub-Saharan Africa is expected to double, which is a predicament in a
region where HIV infections are high and adolescents account for almost one quarter of
the current HIV-positive population (1). The HIV epidemic among this age group could
mirror the population growth, and there is the potential for the incidence of HIV among
adolescents to double, resulting in massive costs on healthcare systems. Between 2005
and 2012, AIDS-related deaths among adolescents increased by approximately 50%
(from 71,000 in 2005 to 110,000 in 2012), yet all other age groups saw a 32% decrease in
AIDS-related deaths during this time period (1). HIV is the top contributor to adolescent
mortality in sub-Saharan Africa, and second contributor throughout the world (3).
A consultation was held in Geneva, Switzerland from December 3-5, 2014, to
specifically address the difficulties faced by adolescents infected with HIV/AIDS. The
Joint United Nations Programme on HIV/Acquired Immune Deficiency Syndrome
  	
   3
	
  
(UNAIDS) and UNICEF convened the meeting and developed the “All In For
Adolescents” agenda, which will be launched in February 2015 to improve programs and
services targeted to this population. These organizations recognized that adolescents are
often not addressed by HIV programs and the subsequent incidence rates reveal this (3).
Antiretrovirals (ARVs) have transformed HIV/AIDS to a manageable, chronic
disease and have extended survival time for infected individuals for at least another forty
years after the initiation of ART (based on current estimates) (4). Successful long-term
treatment of HIV/AIDS requires patients to be at least 95% adherent to prevent drug-
resistance and maintain viral load suppression (5). A decrease of just 10% in adherence
has been associated with a doubling of the HIV RNA level, indicating that even these
small differences in medication adherence can have a large impact on suppressing one’s
viral load (5). This is a critical statistic for organizations to focus on in order to prevent
further transmission and reduce mortality.
Notably, adolescence can be characterized by a lack of interaction with health
services and a desire to fit in with their peers in social situations, and these circumstances
will likely lead to a decrease in adherence to ART during adolescence (2). This is a time
period where individuals are developing emotionally, sexually, physically, and
psychologically, as well as becoming more mature (1). Poor adherence to ART increases
the risk of drug-resistance; limits the efficacy of the treatment, which can increase the
rate of disease progression; reduces other therapeutic options; and increases the risk of
transmission to others due to a high viral load (2). As adolescents are a unique
demographic group, which has different issues than other high-risk populations, policies
should be designed specifically for their needs, to achieve the best outcomes.
  	
   4
	
  
I will examine any potential differences in adherence to ART among male and
female adolescents in South Africa and make programmatic recommendations to public
sector HIV healthcare providers to improve adherence among this population. While
evidence throughout the world will be reviewed, my main intervention analysis will be
conducted on ST-AMP out of the United States, as this is one of the most effective
adherence interventions among adolescents to date (6). While there are many different
subpopulations within adolescents infected with HIV/AIDS, distinguishing between
behaviorally and perinatally infected adolescents, as well as those orphaned due to
HIV/AIDS, is beyond the scope of this policy brief.
In what follows, I list the ways this paper contributes to the literature on
adherence to antiretroviral therapy (ART) among adolescents—an area, which is under-
researched in low-income countries. First, I will propose ways to increase adherence to
ART, now that many HIV-positive adolescents are eligible for treatment under the new
guidelines in South Africa. In July of 2014, South Africa expanded its HIV/AIDS
treatment guidelines based on WHO recommendations, so that all patients with a CD4+
cell count of 500 cells/µl or less are eligible to receive ART (7)1
. Second, I will propose
ways by which efforts can be triangulated to promote optimal adherence to medication
regimens going forward, to prevent further transmission among adolescents, a vital
population for new infections in South Africa, as mentioned above. Finally, I will
critically evaluate the extent ST-AMP2
in the United States may address barriers to ART
	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  
1	
  While this change in treatment guidelines will not result in an immediate increase in the number of HIV-
positive individuals receiving antiretroviral therapy, it will greatly increase the number of patients who are
eligible and will allow them to receive treatment at a much earlier time period in their disease progression.	
  
2	
  In 2009, STAR TRACK (Special Teens At-Risk Together Reaching, Accessing Care, and Knowledge)
developed ST-AMP (the STAR TRACK Adherence to Medication Program), a program designed to
  	
   5
	
  
adherence specific to adolescents, and make recommendations for implementation of this
program in a South African context. The key components of ST-AMP are personalized
text message reminders; modified directly observed therapy, if necessary; and case
finding if the adolescent loses touch with the healthcare system (6).
Situation	
  Analysis	
  
Adherence	
  to	
  ART	
  Among	
  Adolescents	
  and	
  Consequences	
  
Adolescents have poor adherence to their ART medication regimens. The
medication regimens require 95% adherence to work optimally within the body, so these
deviations play a critical role in determining viral load suppression and the ability to
transmit the virus to others. If adolescents are not adhering at the proper levels, not only
will they become sicker, there is also a much greater risk that they will transmit the virus,
maintaining or increasing the epidemic among this population.
A study conducted in Harare, Zimbabwe found that very few adolescents had
ideal adherence to their ART, and identified the most common reasons for missing doses
as forgetting, inconvenience due to travel, concealing their illness and medication from
others, and a lack of funds for transportation to the clinic to collect their medication (8).
Of the study population, 21% of adolescents reported missing a dose of ART once a day
(50% adherence), 6% missed a dose once a week (96% adherence) and 12% of
adolescents missed a dose once a month (98% adherence) (8). These rates of adherence
vary greatly and can have a large effect on the clinical progression of HIV, as well as
transmission to others.
	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  
improved adherence to ART among adolescents in the Baltimore-Metropolitan area of the United States
(6). 	
  
  	
   6
	
  
A retrospective analysis of data from seven HIV clinics across urban Guateng and
rural Mpumalanga, South Africa compared HIV-positive ART-naïve young adolescents
(10-14 years), older adolescents (15-19), and young adults (20-24 years) and their
respective adherence to ART (11). In this study, young adolescents had the highest rate of
virological failure (6.3/100 person-years), defined as “two or more consecutive HIV-
RNA viral loads ≥ 400 copies/mL following suppression below this level (<400
copies/mL)” (11). Virological failure indicates that individuals are not adhering to their
medication regimens, because when individuals are properly adhering, the viral load level
should be fully suppressed (<400 copies/mL). This age group should receive targeted
programs to improve these behaviors.
One consequence of poor adherence is the failure to suppress the viral load, which
makes transmission more likely and generally decreases an individual’s CD4+3
count,
causing them to become sicker. This can be especially problematic during the adolescent
time period when individuals start to experiment sexually, as condom use is often low.
Treatment outcomes were analyzed at a community-based ART clinic in South Africa
and the adolescents involved in this study were less likely to achieve viral load
suppression, and therefore saw higher rates of virological failure than young adults in the
study (17).
	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  	
  
3	
  A CD4+ count is analyzed through lab tests that measure the number of CD4+ cells in a person’s blood.
CD4+ cells are a type of white blood cell that help protect your body from infection and indicate how well
your immune system is functioning. If you have a higher CD4+ count, you are better equipped to fight HIV
and other infections. A low CD4+ count with a positive HIV diagnosis often indicates that the virus is
progressing and the patient is becoming sicker (27).	
  
  	
   7
	
  
Male-­‐Female	
  Disparities	
  in	
  ART	
  Adherence	
  
	
  
Women are more biologically vulnerable to HIV and therefore face a
disproportionate burden of infection. Men typically have higher mortality rates from
HIV/AIDS, as they are less likely to seek care and when they do access health care, their
illness has generally progressed further (9). Once males are receiving care, they tend to
be less adherent than their female colleagues.
A cross-sectional study in Gaborone, Botswana observed that 75.6% of
adolescents in the study had excellent (>95%) pill count of their ART regimens, and all
but five participants had viral load suppression to <400 copies/mL. However, male
adolescents were significantly more likely to be non-adherent with their ART regimen,
and made up 65% of the non-adherent group, indicating that only 35% of females were
non-adherent (10). Throughout the univariate analysis, male sex was significantly
associated with poor ART adherence (odds ratio 3.38, p=0.02). This finding is supported
by previous studies that also found males to be less adherent to their medication regimens
(10). In the future, a qualitative component of this study should be conducted in order to
determine the rationale behind the differences in adherence among males and females.
Poor adherence can lead to drug resistance, and second- and third-line regimens are
typically not as effective, while also being much more costly.
This finding is consistent with an observational cohort study conducted in
Uganda, where the evidence suggests that male patients typically initiate ART later when
they have more advanced illness, and subsequently, have worse outcomes (12). These
findings emphasize the discrepancies between males and females in regards to
HIV/AIDS. The prevalence among females is much higher, yet they tend to adhere to
  	
   8
	
  
their medications better and die less frequently than males. The clinical relevance of these
outcomes is profoundly important as it explicitly highlights the need for more data on
adherence variances between male and female adolescents ages 10-14. Until this data
exists, interventions will not reach peak efficacy.
The previously described studies indicate that male adolescents tend to have
worse adherence than females. When designing interventions to improve adherence
among adolescents, programmatic components should be conceived independently for
both sexes to increase the potential for improved outcomes. This is not the current status
quo, but is a very important detail to focus on for the future. While there is a lack of
evidence regarding the efficacy of any adherence programming among this population,
there is a clear difference between male and female behaviors surrounding their
medication regimens and this needs to be recognized when designing interventions.
Determinants	
  of	
  Poor	
  Adherence	
  
Individual-­‐Level	
  Determinants	
  	
  
	
  
Adolescents have been identified as a high-risk group for poor adherence to ART
or even defaulting from their medication regimen altogether. This is due to a variety of
factors, including:
• Denial
• An inconsistent daily routine
• Forgetting to take their medication
• Fear of disclosing their status to their friends by having to take medication in
routine social settings
• The adverse side effects of the various medications
• Not understanding that they still need to take the medication even if they feel well
• The complexity of the drug regimen
• Lack of social support (11,13)
  	
   9
	
  
For those adolescents with a more recent HIV diagnosis, accepting the fact that they have
a chronic disease and will face a lifetime of treatment comes at a very inopportune
moment. The continued physical, mental, and emotional development taking place during
this time in one’s life, significantly affects the understanding and acceptance of having
HIV/AIDS and treating it appropriately, which greatly impacts adherence to their
medication regimen.
Adolescents in South Africa may be at an increased risk for behavioral and
emotional problems, as well as poverty and familial disruption, due to continuing
ramifications from the end of apartheid and the potential loss of one or both biological
parents due to the large burden of HIV/AIDS in the country (14). In South Africa, some
specialized adolescent health clinics have been developed to exclusively handle the needs
of HIV-positive adolescents (11). These clinics offer services such as counseling, testing,
and treatment targeted to one specific population; however, they have not been expanded
throughout the country.
Systems-­‐Level	
  Determinants	
  	
  
	
  
Due to vast improvements in ARVs in the past years, there is now a need to
transition adolescents infected with HIV to an adult healthcare facility (13). Healthcare
transition is defined as the planned and purposeful shift of children with HIV/AIDS from
a pediatric care facility to an adult-centered healthcare center. Often times, the pediatric
facilities offer a much more all-encompassing range of services including psychiatric as
well as clinical care, and they will work to include family members and build a support
system (13). Adolescents have often been treated at the same facility for the entire
duration of their illness, and leaving the support and familiarity of the pediatric health
  	
   10
	
  
center can be very difficult for individuals. These environments typically encourage
optimal adherence due to provider and familial support, as well as increased comfort
within the healthcare system in which the individual is being treated.
Studies conducted in the United States indicate that HIV-positive adolescents and
young adults who receive treatment in adult-oriented HIV clinics are less likely to start
and stay on treatment, and often do not achieve viral suppression (11). Most of the
literature that has studied this transition has been conducted in the United States, and the
further implications for low-resource settings with a disproportionately high burden of
HIV/AIDS have not been analyzed. It is an assumption, but it is likely, that this is further
exacerbated by the disjointed health care system in South Africa that remains after
apartheid.
Within South Africa, a growing number of adolescents are seeking treatment in
public sector HIV clinics; yet these facilities are not equipped with criteria or guidelines
in how to treat and assist adolescents as a special population in these settings (11). Poor
rates of clinic attendance have been documented among adolescents attending public-
sector HIV clinics throughout Guateng and Mpumalanga, South Africa, and this creates
barriers to effectively treating the illness. Unlike many pediatric HIV patients,
adolescents may no longer have caregiver involvement in their disease management.
This is a potential contributing factor to the increased rates of loss-to-follow-up and
defaulting from the ARV regimen seen among adolescents and young adults (11).
A systematic review of ART adherence and intervention studies among
adolescents found that the most effective approaches to improve treatment adherence
tend to be multicomponent strategies, which is consistent with the evidence on adult
  	
   11
	
  
adherence interventions (15). These often include programs that incorporate peer support,
self-monitoring, caregiver and patient education, and follow-up via mobile phone.
However, it is difficult to measure adherence, as it is a dynamic measurement that cannot
truly be predicted at one specific point in time (16).
Analysis	
  of	
  Best	
  Practices	
  to	
  Improve	
  Adolescents’	
  Adherence	
  to	
  
ART	
  
	
  
A best practice to promote optimal adherence is working within a community to
reduce the stigma around HIV infection. This in turn enables individuals to be more
comfortable in their communities when dealing with topics such as disclosure and
treatment. This has shown to improve adherence. A study focusing on pediatric
adherence to ART in rural Zimbabwe found that a supportive social structure was a
critical predictor of treatment success. They defined an “AIDS competent community” as
a specific social setting, where people were likely to work collectively to augment
HIV/AIDS prevention and treatment strategies (18). It is these communities that can play
one of the largest roles in ensuring adherence, because they often possess lower levels of
stigma and increased willingness to help those who are infected with HIV/AIDS.
A small case study in the United States found that another best practice is to
utilize clinical social workers to increase adolescent comfort within the medical settings,
and therefore improve adherence to ART (19). If adolescents are less familiar with
clinical settings, social workers can help them adjust by introducing them to their
providers, giving tours of the clinic, and working to develop a medication schedule that
fits within the individual’s lifestyle. They can also work to support the patient and their
family throughout the disclosure process, if that is a concern. While working with a
  	
   12
	
  
licensed clinical social worker, home visits and a reward system for improved lab results
were implemented. If a patient saw improvements in their lab results, defined as an
increase in their CD4+ count or decrease in their viral load, they would receive a $25 gift
card every three months (19). If their viral load became undetectable, indicating
consistent adherence to their ART, they were eligible for a larger reward. However,
generalizability may be limited with this study since only 15 of the 37 patients were
identified as at risk for poor adherence, and significant financial resources were allocated
to support the intervention (19). Furthermore, an incentive program such as this is likely
beyond the financial means of the public healthcare system in South Africa.
A study conducted in Nyanza Province, Kenya, among adult HIV patients at
Chulaimbo Rural Health Center, found that an ideal intervention for their population was
to utilize mobile health reminders to increase adherence to ART. The study population
consisted of patients over 18 years who had initiated ART less than three months ago,
and did not restrict enrollment to patients who already owned a cell phone. At the
initiation of the study, 45% of participant households owned cell phones, and 97% of
participant households lived within cell phone network coverage (20). This study directly
analyzed the effect that short message service (SMS) reminders had on ART adherence.
The messages were all less than 160 characters, did not explicitly mention HIV or ART,
and were sent as “one-way” messages so that respondents could not reply (20). To
prevent treatment fatigue, messages were sent once daily at 12 pm. Interestingly, in the
longer text message reminders, additional phrases of encouragement were not more
effective than the short reminders or no reminders at all. The study also found that
weekly reminders improved overall adherence to ART, yet daily reminders did not,
  	
   13
	
  
which is likely due to habituation of the intervention (20). While this study did not
directly involve adolescents, it took place in a low-resource setting and shows promise
for similar studies among different populations.
While there were relatively few studies that specifically analyzed adolescent
adherence to ART, the effective programs contained elements that incorporated social
support systems, comfort within the healthcare system, incentives, and mobile health
(mHealth) campaigns that utilized text messages to remind patients to take their
medication. In a low-resource setting such as South Africa, the most practical
components include social support systems, increasing interaction and therefore comfort
with the health care system, and mHealth reminders.
Program	
  Analysis:	
  ST-­‐AMP	
  in	
  the	
  United	
  States	
  
Components	
  of	
  ST-­‐AMP	
  
	
  
ST-AMP utilizes mobile, video, and various web-based technologies in order to
improve adolescent adherence to ART (6). The initial phase of ST-AMP consisted of
general text messages sent as a reminder to take their antiretrovirals. These messages did
not explicitly mention HIV or ART and were designed with patient input. After the
adolescents took their medication, they replied to the staff with another previously
determined message. If patients were not responsive to this first stage, or laboratory tests
of viral load indicated that they were not accurately self-reporting (defined as maintaining
80% adherence to their ART), they were then enrolled in the second phase of the
program. This involved a modified version of DOT by sending a video message to clinic
staff of the adolescents taking the medication. If the adolescent did not respond to the two
  	
   14
	
  
initial texts, the case finder was notified to get in touch with the patient. These two
distinct phases were designed to prevent loss-to-follow-up and maintain contact with
adolescents who are at risk for poor adherence.
There were individual clinical sessions with each patient during this program,
where the social barriers to ART adherence were discussed, as well as basic education
and information about ART and living with HIV. The staff worked with each patient to
address the specific issues they were facing, and adolescents were given options to
change their medication schedules (e.g. taking their doses at night) in order to promote
adherence (6). If an adolescent expressed emotional distress or seemed to be depressed
during the clinical visits, they received counseling from the on-site psychologist. This
illustrates the absolute comprehensiveness of the program, as it combines the clinical
guidance necessary to begin an ART regimen, the psychological expertise, and problem
solving to ensure that the individual is set up for success before leaving the clinic.
Benefits	
  of	
  ST-­‐AMP	
  
	
  
ST-AMP allowed patients to directly communicate with medical providers 24
hours a day, obtain reliable health information instantaneously, and receive reminders
about upcoming appointments. Another benefit of ST-AMP, is that patients were able to
text clinic staff prior to running into any issues with their medication, such as difficulty
getting to the pharmacy on time for their refill, or to indicate when they were low on
medication before completely running out (6).
Prior to engaging in ST-AMP, the adolescents reported their adherence to be
roughly 40-50%; yet within 24 months of enrollment in the program, this increased to
approximately 80%. This translates to improvements in adherence between 30 and 40%
  	
   15
	
  
among the majority of participants (6). This program may be difficult to scale up on a
national level in South Africa; however, there are very few interventions that specifically
target adherence to ART among adolescents.
Characteristics	
  of	
  ST-­‐AMP	
  That	
  Address	
  Barriers	
  to	
  Adherence	
  
There were several barriers to adolescent adherence identified in the literature
(see pages 8-11), yet the characteristics of ST-AMP address the majority of these barriers
(see Figure 1 on page 16). The confidential text messages aim to prevent adolescents
from forgetting to take their ART, and also help with the desire to fit in with their peers,
as HIV and ART are not explicitly mentioned in the messages. By coordinating the
treatment plan with the clinic staff, medical professionals can address an inconsistent
daily routine as well as the complexity of the drug regimen, by ensuring that the
individual understands why the different medications are necessary and that the dose
timing is convenient to prevent missed doses. Meetings with the psychologists and
improved relationships with clinic staff can help patients conceptualize the importance of
strict adherence to the regimen, which should moderate side effects. This psychiatric
assistance can also help the adolescents address any other issues they are facing during
this period of development. The direct communication with medical providers hopes to
promote patient comfort within the healthcare system, and avoid preventable problems,
such as medication refills by maintaining open lines of communication at all times.
  	
   16
	
  
Figure 1: Logic Model Linking ST-AMP Program Components to Adolescent
Adherence to ART
Limitations	
  of	
  ST-­‐AMP	
  
	
  
While ST-AMP has seen impressive success in improving adherence among HIV-
positive adolescents in the Baltimore-Metropolitan area, there are some concerns about
expanding this program on a larger scale, especially within the context of South Africa.
ST-AMP only analyzed 87 patients, 17 female and 70 male between the ages of 15 and
24, which is older than the young adolescent (ages 10 to 14) age group this policy brief is
focusing on. Of these 87 patients, 90% were African American, 7% were Caucasian, 2%
were Hispanic, and 1% identified as another race. Additionally, all patients who were
enrolled in ST-AMP had their own cell phones prior to their enrollment in the program
  	
   17
	
  
(6). One issue that came up for some patients was an aspect of confidentiality if they
were sharing their cellular phone with another member of their family or a friend.
Implementing	
  ST-­‐AMP	
  in	
  South	
  Africa	
  
Some elements of ST-AMP could be implemented in the South African context,
such as the confidential text messages and the coordination among clinic staff to adjust
medication regimens based on what is most convenient and tolerable for the adolescent.
However, the extensive effort put forth by psychiatrists and social workers in ST-AMP is
not likely transferrable to South Africa.
In 2013, the World Bank reported that there were 147 mobile phone subscriptions
per 100 people in South Africa, indicating that mHealth technology is a viable tool to
improve adherence to ART (21). Assuming that adolescent mobile phone use is similar in
South Africa as it is in other countries of comparable resources, the confidential text
messages that ST-AMP utilized may provide parallel success. The study out of Nyanza
Province, Kenya signifies that improvements in adherence to ART are possible among
adults in low-resource settings through weekly SMS reminders. It is reasonable to assume
that similar improvements may also be seen among adolescents if this approach is
employed (20). If implemented, further research is necessary to determine gaps in cellular
subscriptions in rural regions of South Africa, to assess network failures, literacy rates,
and the acceptability of the intervention among adolescents. Also, the second phase of
ST-AMP, which employs video messages, as a modified form of directly observed
therapy, may not be applicable, depending on the types of mobile phones that adolescents
have. All of these factors may negatively affect implementation of ST-AMP.
  	
   18
	
  
As of 2013, South Africa had 0.78 trained physicians per 1,000 people and 4.0
nursing and midwife personal per 1,000 people (22). This shortage does not allow
healthcare workers the opportunity to provide assistance 24 hours a day like ST-AMP is
able to. Despite the shortage, it is more conceivable for physicians or nurses to discuss
the treatment regimen with the adolescent while in the facility and address any concerns
they have about the side effects or an inconvenience to their daily schedule.
A major component of ST-AMP is the dedicated psychiatrists and social workers.
As it is, South Africa is already facing a social worker shortage. In 2013, the South
African Council for Social Services Professions reported that there were currently 16,164
social workers registered with the council, yet estimates indicated the country was in
need of 68,498, to fully execute all of its planned programs and social work activities
(23). This disparity in human resources would negatively impact the effect that ST-AMP
could have in South Africa.
Need	
  for	
  Further	
  Research	
  
	
  
While analyzing adolescent adherence to ART is becoming more prominent in the
academic literature, there is still a need for further studies executed on a large scale with
statistical rigor. The Centers for Disease Control and Prevention (CDC), UNICEF, and
the World Health Organization (WHO) have different definitions of what constitutes an
adolescent. The CDC and UNICEF frame adolescence as the time period between 10 and
19 years old, while the WHO defines it as ages 10 to 24 years old (24). This makes it
difficult to draw concrete conclusions across multiple datasets due to the differing
parameters. Beyond the varying definitions, this is a very large age frame, in which the
  	
   19
	
  
adolescents will undergo various physical, mental, and emotional changes that may not
be comparable among the total age bracket. While there is information on ART
adherence among pediatric patients and older adolescents (typically ages 15 to 24),
adolescents ages 10 to 14 are often excluded from research. Reasons for this include a
lack of questions that are appropriate for their age and maturity level, and difficulty
obtaining parental consent (1).
There is also a need for gender-stratified research, analyzing a potential difference
in adherence behaviors among male and female adolescents. World Bank data indicates
that the prevalence of HIV/AIDS disproportionately affects women ages 15-24 when
compared to men in South Africa, at 13.1% and 4.0% respectively (25,26). However,
men seek care less frequently and therefore have higher mortality rates, despite the large
difference in prevalence (9). Men’s HIV/AIDS is typically further progressed before
seeking treatment, leading to worse outcomes. While this data on care seeking behavior
and retention in care does not seem to exist for adolescents in South Africa, it is
necessary to develop appropriate programs to improve adherence. After all, it is difficult
to improve adherence if individuals are not connected to care and receiving
antiretrovirals. Furthermore, 82% of new HIV infections among adolescents in South
Africa occur in females, and while biological susceptibility does increase the risk of
transmission among females, additional studies have not explored why this rate is so
much higher in female adolescents (1).
Within this population, there are many distinct subpopulations that should be
reviewed to promote optimum adherence. These include differentiating between
adolescents who were perinatally or behaviorally infected, those who are orphans due to
  	
   20
	
  
the HIV/AIDS epidemic, and adolescents whom engage in other high-risk behaviors such
as injection drug use (IDU) or commercial sex work (CSW). These trends should be
taken into account when designing programs.
Prior to implementing ST-AMP in South Africa, an economic evaluation of the
program is necessary. Considerable financial resources would be necessary for proper
implementation. There is also a lack of essential human and institutional resources. ST-
AMP is extremely holistic in terms of care, yet the burden of HIV/AIDS in South Africa
may be too much for the program to overcome.
Conclusion	
  
	
  
Adolescent adherence to ART is a severely understudied topic among the
published literature. While most health organizations define adolescence as a very broad
time frame (CDC and UNICEF: 10-19 years, WHO: 10-24), there are clear physical and
neurocognitive differences throughout these age groups. These need to be taken into
account when designing and evaluating potential interventions (24). In order to design the
most effective interventions for this population, there is extensive research that still needs
to be conducted. Without baseline data on general indicators such as incidence and
prevalence among adolescents ages 10-14, interventions are at a standstill.
Adolescents are one of the few populations where the number of new HIV
infections is continuously increasing, and while interventions should be implemented to
reduce the incidence; they also need to focus on creating good habits among those
already infected. South Africa faces a large burden of HIV/AIDS and the public
healthcare system is struggling to support it. The new guidelines for ART eligibility are
  	
   21
	
  
only going to exacerbate this, as more of the infected population is eligible for ART. If
optimum adherence is promoted at a young age, mortality rates due to HIV/AIDS could
decrease and the public health system could potentially reduce AIDS-related
expenditures.
  	
   22
	
  
References
1. Idele P, Gillespie A, Porth T, Suzuki C, Mahy M, Kasedde S, et al. Epidemiology
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adolescents living with HIV: systematic review and meta-analysis. AIDS
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men-gender-health-and-hiv-and-aids-in-south-africa-1/file
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11. Evans D, Menezes C, Mahomed K, Macdonald P, Untiedt S, Levin L, et al.
Treatment outcomes of HIV-infected adolescents attending public-sector HIV
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Survival of HIV-infected adolescents on antiretroviral therapy in Uganda: findings
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[cited 2014 Oct 8];6(4):e19261. Available from:
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13. Dowshen N, Kuhns LM, Johnson A, Holoyda BJ, Garofalo R. Improving
adherence to antiretroviral therapy for youth living with HIV/AIDS: a pilot study
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14. Petersen AB, Myeza N, Alicea S, John S, Holst H, McKay M, et al. Psychosocial
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adolescents in South Africa. A qualitative investigation. AIDS Care.
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15. Reisner SL, Mimiaga MJ, Skeer M, Perkovich B, Johnson C V, Safren SA. A
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Infected Youth. Top HIV Med. 2009;17(1):14–25.
16. Biadgilign S, Deribew A, Amberbir A, Deribe K. Barriers and facilitators to
antiretroviral medication adherence among HIV-infected pediatric patients in
Ethiopia - A qualitative study. J Soc Asp HIV/AIDS. 2009;6(4):148–54.
  	
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17. Nglazi MD, Kranzer K, Holele P, Kaplan R, Mark D, Jaspan H, et al. Treatment
outcomes in HIV-infected adolescents attending a community-based antiretroviral
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trez&rendertype=abstract
18. Campbell C, Skovdal M, Mupambireyi Z, Madanhire C, Nyamukapa C, Gregson
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[Internet]. Elsevier; 2012 Mar [cited 2014 Oct 24];18(2):123–31. Available from:
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Adolescents With HIV: A Case Study of Social Work Interventions. J HIV AIDS
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2014 [cited 2014 Dec 4]. Available from:
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LindseyGarrison_CE

  • 1. BOSTON UNIVERSITY SCHOOL OF PUBLIC HEALTH DEPARTMENT OF GLOBAL HEALTH CULMINATING EXPERIENCE COVER PAGE Name: Lindsey Garrison, BA CE Advisor: Nafisa Halim, PhD Culminating Experience Paper or Project Title: Adherence to Antiretroviral Therapy Among Adolescents in South Africa: A Situational Analysis and Needs Assessment for Future Policies Abstract: Adolescents represent 40% of new HIV infections worldwide. As with other age groups, females are disproportionately affected by HIV/AIDS and they account for 82% of all new cases of HIV among adolescents in South Africa. Adolescent adherence to antiretroviral therapy (ART) is under researched worldwide, but especially in low- resource settings, such as South Africa. Much of the published literature indicates that HIV-positive adolescents often have poor adherence to their medication regimens due to a variety of factors, including a desire to fit in with their peers, an inconsistent daily routine, and the adverse side effects of ART. These factors are further compounded by the emotional, physical, and psychological changes that individuals go through during adolescence. This policy brief analyzes ST-AMP, a program designed for the Baltimore- Metropolitan area of the United States, to improve adherence to ART among adolescents through the use of confidential text messages and modified directly observed therapy (DOT), if necessary. While some aspects of ST-AMP, such as the confidential text messages, are readily applicable to the South African context to improve adherence to ART among adolescents, the reliance on psychologists and social workers, as well as the constant communication with medical providers are not necessarily feasible. This paper identifies the gaps in current research, and makes recommendations for further research to collect baseline statistics on HIV incidence and prevalence among adolescents ages 10- 14, and examine ways to accumulate gender-stratified, infection-stratified (behaviorally or perinatally), and risk-group specific statistics. Key Words: HIV/AIDS, adherence, adolescents, antiretroviral therapy, South Africa                
  • 2.     1   Table of Contents Executive Summary.......................................................................................................... 2 Situation Analysis ............................................................................................................. 5 Adherence to ART Among Adolescents and Consequences.......................................... 5 Male-Female Disparities in ART Adherence ................................................................. 7 Determinants of Poor Adherence .................................................................................... 8 Individual-Level Determinants....................................................................................... 8 Systems-Level Determinants .......................................................................................... 9 Analysis of Best Practices to Improve Adolescents’ Adherence to ART................... 11 Program Analysis: ST-AMP in the United States........................................................ 13 Components of ST-AMP .............................................................................................. 13 Benefits of ST-AMP ..................................................................................................... 14 Characteristics of ST-AMP That Address Barriers to Adherence................................ 15 Limitations of ST-AMP................................................................................................ 16 Implementing ST-AMP in South Africa....................................................................... 17 Need for Further Research ............................................................................................ 18 Conclusion ....................................................................................................................... 20                    
  • 3.     2   Executive  Summary   Adolescents are a critical population for HIV prevention and treatment strategies in South Africa, as in other sub-Saharan African countries. At the end of 2012, the United Nations International Children's Emergency Fund (UNICEF) estimated that 2.1 million adolescents, defined as individuals ages 10 to 19, were living with HIV/AIDS worldwide (1). Roughly 85% of infected adolescents are living in South Africa and other sub- Saharan African countries (1). Additionally, HIV is a rapidly growing epidemic amongst adolescents, as they represent approximately 40% of new HIV infections globally (2). Surprisingly, girls account for approximately two thirds of all new adolescent HIV infections worldwide. This rate is even higher in South Africa, where females account for 82% of all new HIV cases among adolescents (1). By 2050, the adolescent population in sub-Saharan Africa is expected to double, which is a predicament in a region where HIV infections are high and adolescents account for almost one quarter of the current HIV-positive population (1). The HIV epidemic among this age group could mirror the population growth, and there is the potential for the incidence of HIV among adolescents to double, resulting in massive costs on healthcare systems. Between 2005 and 2012, AIDS-related deaths among adolescents increased by approximately 50% (from 71,000 in 2005 to 110,000 in 2012), yet all other age groups saw a 32% decrease in AIDS-related deaths during this time period (1). HIV is the top contributor to adolescent mortality in sub-Saharan Africa, and second contributor throughout the world (3). A consultation was held in Geneva, Switzerland from December 3-5, 2014, to specifically address the difficulties faced by adolescents infected with HIV/AIDS. The Joint United Nations Programme on HIV/Acquired Immune Deficiency Syndrome
  • 4.     3   (UNAIDS) and UNICEF convened the meeting and developed the “All In For Adolescents” agenda, which will be launched in February 2015 to improve programs and services targeted to this population. These organizations recognized that adolescents are often not addressed by HIV programs and the subsequent incidence rates reveal this (3). Antiretrovirals (ARVs) have transformed HIV/AIDS to a manageable, chronic disease and have extended survival time for infected individuals for at least another forty years after the initiation of ART (based on current estimates) (4). Successful long-term treatment of HIV/AIDS requires patients to be at least 95% adherent to prevent drug- resistance and maintain viral load suppression (5). A decrease of just 10% in adherence has been associated with a doubling of the HIV RNA level, indicating that even these small differences in medication adherence can have a large impact on suppressing one’s viral load (5). This is a critical statistic for organizations to focus on in order to prevent further transmission and reduce mortality. Notably, adolescence can be characterized by a lack of interaction with health services and a desire to fit in with their peers in social situations, and these circumstances will likely lead to a decrease in adherence to ART during adolescence (2). This is a time period where individuals are developing emotionally, sexually, physically, and psychologically, as well as becoming more mature (1). Poor adherence to ART increases the risk of drug-resistance; limits the efficacy of the treatment, which can increase the rate of disease progression; reduces other therapeutic options; and increases the risk of transmission to others due to a high viral load (2). As adolescents are a unique demographic group, which has different issues than other high-risk populations, policies should be designed specifically for their needs, to achieve the best outcomes.
  • 5.     4   I will examine any potential differences in adherence to ART among male and female adolescents in South Africa and make programmatic recommendations to public sector HIV healthcare providers to improve adherence among this population. While evidence throughout the world will be reviewed, my main intervention analysis will be conducted on ST-AMP out of the United States, as this is one of the most effective adherence interventions among adolescents to date (6). While there are many different subpopulations within adolescents infected with HIV/AIDS, distinguishing between behaviorally and perinatally infected adolescents, as well as those orphaned due to HIV/AIDS, is beyond the scope of this policy brief. In what follows, I list the ways this paper contributes to the literature on adherence to antiretroviral therapy (ART) among adolescents—an area, which is under- researched in low-income countries. First, I will propose ways to increase adherence to ART, now that many HIV-positive adolescents are eligible for treatment under the new guidelines in South Africa. In July of 2014, South Africa expanded its HIV/AIDS treatment guidelines based on WHO recommendations, so that all patients with a CD4+ cell count of 500 cells/µl or less are eligible to receive ART (7)1 . Second, I will propose ways by which efforts can be triangulated to promote optimal adherence to medication regimens going forward, to prevent further transmission among adolescents, a vital population for new infections in South Africa, as mentioned above. Finally, I will critically evaluate the extent ST-AMP2 in the United States may address barriers to ART                                                                                                                 1  While this change in treatment guidelines will not result in an immediate increase in the number of HIV- positive individuals receiving antiretroviral therapy, it will greatly increase the number of patients who are eligible and will allow them to receive treatment at a much earlier time period in their disease progression.   2  In 2009, STAR TRACK (Special Teens At-Risk Together Reaching, Accessing Care, and Knowledge) developed ST-AMP (the STAR TRACK Adherence to Medication Program), a program designed to
  • 6.     5   adherence specific to adolescents, and make recommendations for implementation of this program in a South African context. The key components of ST-AMP are personalized text message reminders; modified directly observed therapy, if necessary; and case finding if the adolescent loses touch with the healthcare system (6). Situation  Analysis   Adherence  to  ART  Among  Adolescents  and  Consequences   Adolescents have poor adherence to their ART medication regimens. The medication regimens require 95% adherence to work optimally within the body, so these deviations play a critical role in determining viral load suppression and the ability to transmit the virus to others. If adolescents are not adhering at the proper levels, not only will they become sicker, there is also a much greater risk that they will transmit the virus, maintaining or increasing the epidemic among this population. A study conducted in Harare, Zimbabwe found that very few adolescents had ideal adherence to their ART, and identified the most common reasons for missing doses as forgetting, inconvenience due to travel, concealing their illness and medication from others, and a lack of funds for transportation to the clinic to collect their medication (8). Of the study population, 21% of adolescents reported missing a dose of ART once a day (50% adherence), 6% missed a dose once a week (96% adherence) and 12% of adolescents missed a dose once a month (98% adherence) (8). These rates of adherence vary greatly and can have a large effect on the clinical progression of HIV, as well as transmission to others.                                                                                                                                                                                                                                                                                                                                           improved adherence to ART among adolescents in the Baltimore-Metropolitan area of the United States (6).  
  • 7.     6   A retrospective analysis of data from seven HIV clinics across urban Guateng and rural Mpumalanga, South Africa compared HIV-positive ART-naïve young adolescents (10-14 years), older adolescents (15-19), and young adults (20-24 years) and their respective adherence to ART (11). In this study, young adolescents had the highest rate of virological failure (6.3/100 person-years), defined as “two or more consecutive HIV- RNA viral loads ≥ 400 copies/mL following suppression below this level (<400 copies/mL)” (11). Virological failure indicates that individuals are not adhering to their medication regimens, because when individuals are properly adhering, the viral load level should be fully suppressed (<400 copies/mL). This age group should receive targeted programs to improve these behaviors. One consequence of poor adherence is the failure to suppress the viral load, which makes transmission more likely and generally decreases an individual’s CD4+3 count, causing them to become sicker. This can be especially problematic during the adolescent time period when individuals start to experiment sexually, as condom use is often low. Treatment outcomes were analyzed at a community-based ART clinic in South Africa and the adolescents involved in this study were less likely to achieve viral load suppression, and therefore saw higher rates of virological failure than young adults in the study (17).                                                                                                                 3  A CD4+ count is analyzed through lab tests that measure the number of CD4+ cells in a person’s blood. CD4+ cells are a type of white blood cell that help protect your body from infection and indicate how well your immune system is functioning. If you have a higher CD4+ count, you are better equipped to fight HIV and other infections. A low CD4+ count with a positive HIV diagnosis often indicates that the virus is progressing and the patient is becoming sicker (27).  
  • 8.     7   Male-­‐Female  Disparities  in  ART  Adherence     Women are more biologically vulnerable to HIV and therefore face a disproportionate burden of infection. Men typically have higher mortality rates from HIV/AIDS, as they are less likely to seek care and when they do access health care, their illness has generally progressed further (9). Once males are receiving care, they tend to be less adherent than their female colleagues. A cross-sectional study in Gaborone, Botswana observed that 75.6% of adolescents in the study had excellent (>95%) pill count of their ART regimens, and all but five participants had viral load suppression to <400 copies/mL. However, male adolescents were significantly more likely to be non-adherent with their ART regimen, and made up 65% of the non-adherent group, indicating that only 35% of females were non-adherent (10). Throughout the univariate analysis, male sex was significantly associated with poor ART adherence (odds ratio 3.38, p=0.02). This finding is supported by previous studies that also found males to be less adherent to their medication regimens (10). In the future, a qualitative component of this study should be conducted in order to determine the rationale behind the differences in adherence among males and females. Poor adherence can lead to drug resistance, and second- and third-line regimens are typically not as effective, while also being much more costly. This finding is consistent with an observational cohort study conducted in Uganda, where the evidence suggests that male patients typically initiate ART later when they have more advanced illness, and subsequently, have worse outcomes (12). These findings emphasize the discrepancies between males and females in regards to HIV/AIDS. The prevalence among females is much higher, yet they tend to adhere to
  • 9.     8   their medications better and die less frequently than males. The clinical relevance of these outcomes is profoundly important as it explicitly highlights the need for more data on adherence variances between male and female adolescents ages 10-14. Until this data exists, interventions will not reach peak efficacy. The previously described studies indicate that male adolescents tend to have worse adherence than females. When designing interventions to improve adherence among adolescents, programmatic components should be conceived independently for both sexes to increase the potential for improved outcomes. This is not the current status quo, but is a very important detail to focus on for the future. While there is a lack of evidence regarding the efficacy of any adherence programming among this population, there is a clear difference between male and female behaviors surrounding their medication regimens and this needs to be recognized when designing interventions. Determinants  of  Poor  Adherence   Individual-­‐Level  Determinants       Adolescents have been identified as a high-risk group for poor adherence to ART or even defaulting from their medication regimen altogether. This is due to a variety of factors, including: • Denial • An inconsistent daily routine • Forgetting to take their medication • Fear of disclosing their status to their friends by having to take medication in routine social settings • The adverse side effects of the various medications • Not understanding that they still need to take the medication even if they feel well • The complexity of the drug regimen • Lack of social support (11,13)
  • 10.     9   For those adolescents with a more recent HIV diagnosis, accepting the fact that they have a chronic disease and will face a lifetime of treatment comes at a very inopportune moment. The continued physical, mental, and emotional development taking place during this time in one’s life, significantly affects the understanding and acceptance of having HIV/AIDS and treating it appropriately, which greatly impacts adherence to their medication regimen. Adolescents in South Africa may be at an increased risk for behavioral and emotional problems, as well as poverty and familial disruption, due to continuing ramifications from the end of apartheid and the potential loss of one or both biological parents due to the large burden of HIV/AIDS in the country (14). In South Africa, some specialized adolescent health clinics have been developed to exclusively handle the needs of HIV-positive adolescents (11). These clinics offer services such as counseling, testing, and treatment targeted to one specific population; however, they have not been expanded throughout the country. Systems-­‐Level  Determinants       Due to vast improvements in ARVs in the past years, there is now a need to transition adolescents infected with HIV to an adult healthcare facility (13). Healthcare transition is defined as the planned and purposeful shift of children with HIV/AIDS from a pediatric care facility to an adult-centered healthcare center. Often times, the pediatric facilities offer a much more all-encompassing range of services including psychiatric as well as clinical care, and they will work to include family members and build a support system (13). Adolescents have often been treated at the same facility for the entire duration of their illness, and leaving the support and familiarity of the pediatric health
  • 11.     10   center can be very difficult for individuals. These environments typically encourage optimal adherence due to provider and familial support, as well as increased comfort within the healthcare system in which the individual is being treated. Studies conducted in the United States indicate that HIV-positive adolescents and young adults who receive treatment in adult-oriented HIV clinics are less likely to start and stay on treatment, and often do not achieve viral suppression (11). Most of the literature that has studied this transition has been conducted in the United States, and the further implications for low-resource settings with a disproportionately high burden of HIV/AIDS have not been analyzed. It is an assumption, but it is likely, that this is further exacerbated by the disjointed health care system in South Africa that remains after apartheid. Within South Africa, a growing number of adolescents are seeking treatment in public sector HIV clinics; yet these facilities are not equipped with criteria or guidelines in how to treat and assist adolescents as a special population in these settings (11). Poor rates of clinic attendance have been documented among adolescents attending public- sector HIV clinics throughout Guateng and Mpumalanga, South Africa, and this creates barriers to effectively treating the illness. Unlike many pediatric HIV patients, adolescents may no longer have caregiver involvement in their disease management. This is a potential contributing factor to the increased rates of loss-to-follow-up and defaulting from the ARV regimen seen among adolescents and young adults (11). A systematic review of ART adherence and intervention studies among adolescents found that the most effective approaches to improve treatment adherence tend to be multicomponent strategies, which is consistent with the evidence on adult
  • 12.     11   adherence interventions (15). These often include programs that incorporate peer support, self-monitoring, caregiver and patient education, and follow-up via mobile phone. However, it is difficult to measure adherence, as it is a dynamic measurement that cannot truly be predicted at one specific point in time (16). Analysis  of  Best  Practices  to  Improve  Adolescents’  Adherence  to   ART     A best practice to promote optimal adherence is working within a community to reduce the stigma around HIV infection. This in turn enables individuals to be more comfortable in their communities when dealing with topics such as disclosure and treatment. This has shown to improve adherence. A study focusing on pediatric adherence to ART in rural Zimbabwe found that a supportive social structure was a critical predictor of treatment success. They defined an “AIDS competent community” as a specific social setting, where people were likely to work collectively to augment HIV/AIDS prevention and treatment strategies (18). It is these communities that can play one of the largest roles in ensuring adherence, because they often possess lower levels of stigma and increased willingness to help those who are infected with HIV/AIDS. A small case study in the United States found that another best practice is to utilize clinical social workers to increase adolescent comfort within the medical settings, and therefore improve adherence to ART (19). If adolescents are less familiar with clinical settings, social workers can help them adjust by introducing them to their providers, giving tours of the clinic, and working to develop a medication schedule that fits within the individual’s lifestyle. They can also work to support the patient and their family throughout the disclosure process, if that is a concern. While working with a
  • 13.     12   licensed clinical social worker, home visits and a reward system for improved lab results were implemented. If a patient saw improvements in their lab results, defined as an increase in their CD4+ count or decrease in their viral load, they would receive a $25 gift card every three months (19). If their viral load became undetectable, indicating consistent adherence to their ART, they were eligible for a larger reward. However, generalizability may be limited with this study since only 15 of the 37 patients were identified as at risk for poor adherence, and significant financial resources were allocated to support the intervention (19). Furthermore, an incentive program such as this is likely beyond the financial means of the public healthcare system in South Africa. A study conducted in Nyanza Province, Kenya, among adult HIV patients at Chulaimbo Rural Health Center, found that an ideal intervention for their population was to utilize mobile health reminders to increase adherence to ART. The study population consisted of patients over 18 years who had initiated ART less than three months ago, and did not restrict enrollment to patients who already owned a cell phone. At the initiation of the study, 45% of participant households owned cell phones, and 97% of participant households lived within cell phone network coverage (20). This study directly analyzed the effect that short message service (SMS) reminders had on ART adherence. The messages were all less than 160 characters, did not explicitly mention HIV or ART, and were sent as “one-way” messages so that respondents could not reply (20). To prevent treatment fatigue, messages were sent once daily at 12 pm. Interestingly, in the longer text message reminders, additional phrases of encouragement were not more effective than the short reminders or no reminders at all. The study also found that weekly reminders improved overall adherence to ART, yet daily reminders did not,
  • 14.     13   which is likely due to habituation of the intervention (20). While this study did not directly involve adolescents, it took place in a low-resource setting and shows promise for similar studies among different populations. While there were relatively few studies that specifically analyzed adolescent adherence to ART, the effective programs contained elements that incorporated social support systems, comfort within the healthcare system, incentives, and mobile health (mHealth) campaigns that utilized text messages to remind patients to take their medication. In a low-resource setting such as South Africa, the most practical components include social support systems, increasing interaction and therefore comfort with the health care system, and mHealth reminders. Program  Analysis:  ST-­‐AMP  in  the  United  States   Components  of  ST-­‐AMP     ST-AMP utilizes mobile, video, and various web-based technologies in order to improve adolescent adherence to ART (6). The initial phase of ST-AMP consisted of general text messages sent as a reminder to take their antiretrovirals. These messages did not explicitly mention HIV or ART and were designed with patient input. After the adolescents took their medication, they replied to the staff with another previously determined message. If patients were not responsive to this first stage, or laboratory tests of viral load indicated that they were not accurately self-reporting (defined as maintaining 80% adherence to their ART), they were then enrolled in the second phase of the program. This involved a modified version of DOT by sending a video message to clinic staff of the adolescents taking the medication. If the adolescent did not respond to the two
  • 15.     14   initial texts, the case finder was notified to get in touch with the patient. These two distinct phases were designed to prevent loss-to-follow-up and maintain contact with adolescents who are at risk for poor adherence. There were individual clinical sessions with each patient during this program, where the social barriers to ART adherence were discussed, as well as basic education and information about ART and living with HIV. The staff worked with each patient to address the specific issues they were facing, and adolescents were given options to change their medication schedules (e.g. taking their doses at night) in order to promote adherence (6). If an adolescent expressed emotional distress or seemed to be depressed during the clinical visits, they received counseling from the on-site psychologist. This illustrates the absolute comprehensiveness of the program, as it combines the clinical guidance necessary to begin an ART regimen, the psychological expertise, and problem solving to ensure that the individual is set up for success before leaving the clinic. Benefits  of  ST-­‐AMP     ST-AMP allowed patients to directly communicate with medical providers 24 hours a day, obtain reliable health information instantaneously, and receive reminders about upcoming appointments. Another benefit of ST-AMP, is that patients were able to text clinic staff prior to running into any issues with their medication, such as difficulty getting to the pharmacy on time for their refill, or to indicate when they were low on medication before completely running out (6). Prior to engaging in ST-AMP, the adolescents reported their adherence to be roughly 40-50%; yet within 24 months of enrollment in the program, this increased to approximately 80%. This translates to improvements in adherence between 30 and 40%
  • 16.     15   among the majority of participants (6). This program may be difficult to scale up on a national level in South Africa; however, there are very few interventions that specifically target adherence to ART among adolescents. Characteristics  of  ST-­‐AMP  That  Address  Barriers  to  Adherence   There were several barriers to adolescent adherence identified in the literature (see pages 8-11), yet the characteristics of ST-AMP address the majority of these barriers (see Figure 1 on page 16). The confidential text messages aim to prevent adolescents from forgetting to take their ART, and also help with the desire to fit in with their peers, as HIV and ART are not explicitly mentioned in the messages. By coordinating the treatment plan with the clinic staff, medical professionals can address an inconsistent daily routine as well as the complexity of the drug regimen, by ensuring that the individual understands why the different medications are necessary and that the dose timing is convenient to prevent missed doses. Meetings with the psychologists and improved relationships with clinic staff can help patients conceptualize the importance of strict adherence to the regimen, which should moderate side effects. This psychiatric assistance can also help the adolescents address any other issues they are facing during this period of development. The direct communication with medical providers hopes to promote patient comfort within the healthcare system, and avoid preventable problems, such as medication refills by maintaining open lines of communication at all times.
  • 17.     16   Figure 1: Logic Model Linking ST-AMP Program Components to Adolescent Adherence to ART Limitations  of  ST-­‐AMP     While ST-AMP has seen impressive success in improving adherence among HIV- positive adolescents in the Baltimore-Metropolitan area, there are some concerns about expanding this program on a larger scale, especially within the context of South Africa. ST-AMP only analyzed 87 patients, 17 female and 70 male between the ages of 15 and 24, which is older than the young adolescent (ages 10 to 14) age group this policy brief is focusing on. Of these 87 patients, 90% were African American, 7% were Caucasian, 2% were Hispanic, and 1% identified as another race. Additionally, all patients who were enrolled in ST-AMP had their own cell phones prior to their enrollment in the program
  • 18.     17   (6). One issue that came up for some patients was an aspect of confidentiality if they were sharing their cellular phone with another member of their family or a friend. Implementing  ST-­‐AMP  in  South  Africa   Some elements of ST-AMP could be implemented in the South African context, such as the confidential text messages and the coordination among clinic staff to adjust medication regimens based on what is most convenient and tolerable for the adolescent. However, the extensive effort put forth by psychiatrists and social workers in ST-AMP is not likely transferrable to South Africa. In 2013, the World Bank reported that there were 147 mobile phone subscriptions per 100 people in South Africa, indicating that mHealth technology is a viable tool to improve adherence to ART (21). Assuming that adolescent mobile phone use is similar in South Africa as it is in other countries of comparable resources, the confidential text messages that ST-AMP utilized may provide parallel success. The study out of Nyanza Province, Kenya signifies that improvements in adherence to ART are possible among adults in low-resource settings through weekly SMS reminders. It is reasonable to assume that similar improvements may also be seen among adolescents if this approach is employed (20). If implemented, further research is necessary to determine gaps in cellular subscriptions in rural regions of South Africa, to assess network failures, literacy rates, and the acceptability of the intervention among adolescents. Also, the second phase of ST-AMP, which employs video messages, as a modified form of directly observed therapy, may not be applicable, depending on the types of mobile phones that adolescents have. All of these factors may negatively affect implementation of ST-AMP.
  • 19.     18   As of 2013, South Africa had 0.78 trained physicians per 1,000 people and 4.0 nursing and midwife personal per 1,000 people (22). This shortage does not allow healthcare workers the opportunity to provide assistance 24 hours a day like ST-AMP is able to. Despite the shortage, it is more conceivable for physicians or nurses to discuss the treatment regimen with the adolescent while in the facility and address any concerns they have about the side effects or an inconvenience to their daily schedule. A major component of ST-AMP is the dedicated psychiatrists and social workers. As it is, South Africa is already facing a social worker shortage. In 2013, the South African Council for Social Services Professions reported that there were currently 16,164 social workers registered with the council, yet estimates indicated the country was in need of 68,498, to fully execute all of its planned programs and social work activities (23). This disparity in human resources would negatively impact the effect that ST-AMP could have in South Africa. Need  for  Further  Research     While analyzing adolescent adherence to ART is becoming more prominent in the academic literature, there is still a need for further studies executed on a large scale with statistical rigor. The Centers for Disease Control and Prevention (CDC), UNICEF, and the World Health Organization (WHO) have different definitions of what constitutes an adolescent. The CDC and UNICEF frame adolescence as the time period between 10 and 19 years old, while the WHO defines it as ages 10 to 24 years old (24). This makes it difficult to draw concrete conclusions across multiple datasets due to the differing parameters. Beyond the varying definitions, this is a very large age frame, in which the
  • 20.     19   adolescents will undergo various physical, mental, and emotional changes that may not be comparable among the total age bracket. While there is information on ART adherence among pediatric patients and older adolescents (typically ages 15 to 24), adolescents ages 10 to 14 are often excluded from research. Reasons for this include a lack of questions that are appropriate for their age and maturity level, and difficulty obtaining parental consent (1). There is also a need for gender-stratified research, analyzing a potential difference in adherence behaviors among male and female adolescents. World Bank data indicates that the prevalence of HIV/AIDS disproportionately affects women ages 15-24 when compared to men in South Africa, at 13.1% and 4.0% respectively (25,26). However, men seek care less frequently and therefore have higher mortality rates, despite the large difference in prevalence (9). Men’s HIV/AIDS is typically further progressed before seeking treatment, leading to worse outcomes. While this data on care seeking behavior and retention in care does not seem to exist for adolescents in South Africa, it is necessary to develop appropriate programs to improve adherence. After all, it is difficult to improve adherence if individuals are not connected to care and receiving antiretrovirals. Furthermore, 82% of new HIV infections among adolescents in South Africa occur in females, and while biological susceptibility does increase the risk of transmission among females, additional studies have not explored why this rate is so much higher in female adolescents (1). Within this population, there are many distinct subpopulations that should be reviewed to promote optimum adherence. These include differentiating between adolescents who were perinatally or behaviorally infected, those who are orphans due to
  • 21.     20   the HIV/AIDS epidemic, and adolescents whom engage in other high-risk behaviors such as injection drug use (IDU) or commercial sex work (CSW). These trends should be taken into account when designing programs. Prior to implementing ST-AMP in South Africa, an economic evaluation of the program is necessary. Considerable financial resources would be necessary for proper implementation. There is also a lack of essential human and institutional resources. ST- AMP is extremely holistic in terms of care, yet the burden of HIV/AIDS in South Africa may be too much for the program to overcome. Conclusion     Adolescent adherence to ART is a severely understudied topic among the published literature. While most health organizations define adolescence as a very broad time frame (CDC and UNICEF: 10-19 years, WHO: 10-24), there are clear physical and neurocognitive differences throughout these age groups. These need to be taken into account when designing and evaluating potential interventions (24). In order to design the most effective interventions for this population, there is extensive research that still needs to be conducted. Without baseline data on general indicators such as incidence and prevalence among adolescents ages 10-14, interventions are at a standstill. Adolescents are one of the few populations where the number of new HIV infections is continuously increasing, and while interventions should be implemented to reduce the incidence; they also need to focus on creating good habits among those already infected. South Africa faces a large burden of HIV/AIDS and the public healthcare system is struggling to support it. The new guidelines for ART eligibility are
  • 22.     21   only going to exacerbate this, as more of the infected population is eligible for ART. If optimum adherence is promoted at a young age, mortality rates due to HIV/AIDS could decrease and the public health system could potentially reduce AIDS-related expenditures.
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