HIV Infections Clinical Trial
Official title:
Integrating Mobile Phone-Based Intervention With Test and Treat Strategy to Improve Clinic Attendance for Antiretroviral Pills Pick Up Among HIV Positive Individuals in Nepal: A Randomized Controlled Trial
Antiretroviral therapy (ART) has been a game changer in the context of HIV-epidemic. From 2005 to 2015, HIV-related deaths have fallen by 45% thanks to ART. However, ART's success heavily depends on HIV-positive individuals' high adherence to it. This includes clinic attendance for various purposes. It is necessary among HIV-positive individuals for their antiretroviral (ARV) pills pick up, monitoring of their treatment outcomes, and treatment of their opportunistic infections. Among them, ARV pills pick up is the major reason for the ART clinic attendance. Improving clinic attendance for pills pick up remains one of the key challenges to ART programs. The World Health Organization (WHO) recommends more than 90% on-time ARV pills pick up as per the early warning indicators of HIV-drug resistance. Among six Asian countries, none of the 1048 clinics under the study could meet the WHO target. Among HIV-positive individuals, clinic attendance for pills pick can be improved by using mobile phones. Those who receive mobile phone reminders are two times more likely to attend their clinics regularly than those who did not receive such reminders. Nepal belongs to a low-income country and is facing a similar problem, too. In 2015, approximately 39,000 people were estimated to be living with HIV and ART coverage was limited to only 31.5%. In the same year, only 32% of the HIV-positive individuals attended their clinics regularly for ARV pills pick up. Like other countries, one of the potential strategies is to use mobile phones effectively in Nepal. Mobile phones have been very widely used in Nepal. In 2016, Nepal had 27.9 million mobile phone users, against the population of 26.5 million. Under such a context, mobile phone reminders can be effective to improve clinic attendance among HIV-positive individuals. However, the effectiveness of such interventions barely remains examined by using a randomized controlled trial. This study evaluates the effectiveness of mobile phone reminder intervention on improving clinic attendance for ARV pills pick up and medication adherence among HIV-positive individuals on ART following the implementation of test and treat strategy in Nepal.
Background Antiretroviral therapy (ART) has been a game changer in the context of
HIV-epidemic. From 2005 to 2015, HIV-related deaths have fallen by 45% thanks to ART. In
addition, ART has produced a two-fold positive impact on the lives of HIV-positive
populations. First, it has increased the life expectancy and improved the quality of life of
HIV-positive individuals. Second, it has prevented new infections in the population.
However, ART's success heavily depends on HIV-positive individuals' high adherence to it.
This includes clinic attendance for various purposes. It is necessary among HIV-positive
individuals for their antiretroviral (ARV) pills pick up, monitoring of their treatment
outcomes, and treatment of their opportunistic infections. Among them, ARV pills pick up is
the major reason for the ART clinic attendance.
Three negative consequences may occur when HIV-positive individuals miss their clinic
attendances. First, it can directly impair their medication adherence. Second, HIV-drug
resistance and treatment failure could rise. Finally, mortality may increase among
HIV-positive individuals. In addition, missed clinic attendances increase economic burden to
the health system. However, both in high-and low-income countries, significant proportions of
HIV-positive individuals miss their scheduled clinic attendances for ARV pills pick up.
Improving clinic attendance for pills pick up remains one of the key challenges to ART
programs. The World Health Organization (WHO) recommends more than 90% on-time ARV pills pick
up as per the early warning indicators of HIV-drug resistance. However, in 2012, worldwide,
more than 30% of the ART clinics did not meet WHO target of timely ARV pills pick up.
Achieving WHO's pills pick up target is more challenging in low-income countries. For
instance, in the Sub-Saharan Africa, 59 to 83% of the ART clinics could not achieve the WHO
target of on-time pills pick up. Similarly, among six Asian countries, none of the 1048
clinics under the study could meet the WHO target.
Among HIV-positive individuals, clinic attendance for pills pick can be improved by using
mobile phones. Mobile phones are generally used in two ways. First, a voice call is used to
remind HIV-positive individuals about their scheduled clinical appointments. Second, a short
message is sent to HIV-positive individuals to remind them about their appointments. Those
who receive mobile phone reminders are two times more likely to attend their clinics
regularly than those who did not receive such reminders. Particularly, mobile phone reminders
have shown positive effects to improve clinic attendance for pills pick up in low-income
settings.
Nepal belongs to a low-income country and is facing a similar problem, too. In 2015,
approximately 39,000 people were estimated to be living with HIV, and ART coverage was
limited to only 31.5% of the total eligible people. In the same year, only 32% of the
HIV-positive individuals attended their clinics regularly for ARV pills pick up. They faced
barriers to regular clinic attendance such as a dearth of family support, long commuting
time, lack of ART knowledge, and non-participation in support programs.
To improve the HIV-positive individuals' health status, the Government of Nepal (GoN) has
made significant decisions at the national level. Free ART services were the primal ones. It
consists of free ARV drugs and care package including follow-up, tuberculosis screening,
isoniazid preventive therapy, community and home-based care. GoN initiated the free ART
service in 2004 from Sukra Raj Tropical and Infectious Disease Control Hospital, Teku,
Kathmandu. Since the first initiation, the ART services have been provided through more than
60 ART clinics located in non-governmental and government health facilities. From 2017, Nepal
has also started a test and treat strategy recommended by WHO to achieve 90-90-90 targets by
2020 and ending AIDS epidemic by 2030. However, limited efforts have been made to improve ARV
pills pick up. Therefore, effective strategies are urgently needed to improve on-time ARV
pills pick up.
Like other countries, one of the potential strategies is to use mobile phones effectively in
Nepal. Mobile phones have been very widely used since the beginning of 21st century, and its
coverage has exceeded 100% compared to the total population. In 2016, Nepal had 27.9 million
mobile phone users, against the population of 26.5 million. Under such a context, mobile
phone reminders can be effective to improve clinic attendance among HIV-positive individuals.
However, the effectiveness of such interventions barely remains examined by using a
randomized controlled trial. This study evaluates the effectiveness of mobile phone reminder
intervention on improving clinic attendance for ARV pills pick up and medication adherence
among HIV-positive individuals on ART after the implementation of test and treat strategy in
Nepal.
Methods Study design This study is a two-arm randomized controlled trial with an HIV-positive
person as the unit of randomization. The allocation ratio will be 1:1.
Sample and Setting In 2016, 63 ART clinics were functional in Nepal. Out of 63 clinics, 18
clinics have a CD4 cell testing facility. As of May 2017, about 12,000 HIV positive
individuals were accessing these services. This study will be conducted at public ART clinics
in Kathmandu, Rupandehi, Banke, Kailali, and Kanchanpur districts of Nepal.
All the study clinics are under the Nepalese Ministry of Health. According to the information
from all of these target ART clinics, about 7000 HIV-positive individuals were accessing ART
services by May 2017.
This study will be carried from November 2017 to May 2018. These HIV-positive individuals
will be followed up for six months.
Sample size Clinic attendance is the primary outcome variable in this study. Based on the
previous study, I assumed regular clinic attendance rate of 33%. If the intervention
increased the rate from 33% to 48% (approximately 15 percentage points), then about 370
HIV-positive individuals, 185 in the intervention and 185 in the control group, would be
required to reject the null hypothesis that no difference exists between intervention and the
control group at the end of the follow up period. To counter for lost to follow-up and
missing data, I will recruit 600 HIV-positive individuals in total (intervention: 300 and
control: 300). I also assumed 95% confidence interval and 80% power of the test.
Enrolment procedure At first, the eligibility criteria will be assessed based on the medical
records, and all the eligible HIV-positive individuals will be invited to participate in the
trial. Next, written consent will be sought from each HIV-positive individual and then they
will be enrolled in the study. Enrollment will take place at each ART clinic.
Randomization and allocation concealment ART numbers are known as patient identification
numbers for HIV-positive individuals and they will be used in this study to maintain
anonymity. Trial assistants will collect the ART numbers of HIV-positive individuals. In this
study, their ART numbers will be converted to unique trial identity numbers to maintain the
confidentiality in the trial. An independent researcher will randomize the trial identity
numbers after collecting the background information. HIV-positive individuals will be
randomized to either the intervention group or the control group using a computer random
number generator (1:1 randomization).
Blinding This study will be a double-blinded RCT. HIV-positive individuals will be blinded to
allocation group. Further, those who deliver the intervention will be blinded to the
allocation.
Intervention and control groups will receive similar intervention strategies. Only the
content of the interventions will be different. Therefore, it is difficult for HIV-positive
individuals to tell if they are receiving intervention or control. The outcome assessor will
be masked to the allocation of each HIV-positive individual by using trial identity numbers.
Only the principal researcher will have complete access to all the information.
Interventions
Intervention arm:
HIV-positive individuals will receive the standard HIV care following the national ART
guidelines. In addition, the intervention group will receive mobile phone calls. A mobile
phone reminder will be made two days prior to their scheduled appointment for pills pick up.
Trained research assistants will remind them of their scheduled clinic appointment of pills
pick up. If the first call is missed, the second call will be made within the same day, if
the second call is also missed, the final call will be made next day. The intervention will
be delivered over the period of six months. Outcome assessors will not be involved in the
phone calls.
Control arm:
Control group will also receive the standard HIV care following the national ART guidelines
and phone calls educating them on healthy living. Phone calls will be made once a month.
Withdrawal from study HIV-positive individuals will be given full right to withdraw from this
trial at any stage. However, reasons for their withdrawal will be sought from them and will
be appropriately recorded.
A mixed-method (cross-sectional study and in-depth interviews) study will be conducted prior
to the intervention.
Outcome assessment Outcome data will be obtained from the medical records of HIV-positive
individuals maintained at the ART clinics. ART medication adherence data will be collected by
telephone interview. I will measure the effect of a mobile phone reminder intervention on
clinic attendance and medication adherence using generalized estimating equation. An
interviewer-administered, pre-tested questionnaire would be used to collect the data.
Trained research assistants will assess and collect data related to outcome in the coded
form. These research assistants will not be involved in the intervention delivery. Collected
data will be entered in EpiData software version 3.1(EpiData Association Denmark).
I will conduct a training on data collection for research assistants. The training includes
ethical issues, data collection and communication with HIV-positive individuals.
Data analyses The background characteristics of HIV-positive individuals will be compared
between intervention and control group using the chi-squared test or Fisher's exact test.
These tests will be used to compare the proportions, and Student's t-test will be used to
compare means. Main data analyses will be conducted on intention-to-treat principle. A
relevant multiple imputation method will be applied for completely missing data related to
primary and secondary outcomes. HIV-positive individuals' retention in trial will be measured
by an instrumental variable method. I will perform all analysis with two-sided tests with a
5% level of significance. STATA software version 13.1(College Station, Texas, USA) will be
used for data analyses.
Ethical Consideration Ethical approval will be first sought from the Research Ethics
Committee of the University of Tokyo and Nepal Health Research Council, Nepal. In addition,
written approval will be obtained from each study hospital. Written informed consent will all
be sought from each HIV-positive individual.
HIV-positive individuals will be given full right to withdraw from this trial at any stage of
the intervention. However, reasons for their withdrawal will be sought from them and will be
appropriately recorded.
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