By: Eka Windari R., I Wayan Adi Pranata, Lois E. Bang, Melinda Setiyaningrum, Natalia Regina, Nur Latifa Hanum, Restu Amalia, Riza Danu Dewantara
The Indonesia InVITE study is currently undergoing random quality assurance (QA) by the local Data Management team. Once this process is completed, the Sites team will prepare for a site close-out visit (SCV). The Secretariat and Sites team are coordinating to ensure the completeness of study documents and the necessary supplies for SCV activities. Additionally, designated serum specimens will be shipped to the Central Laboratory in two batches scheduled for September and October 2024 using the World Courier service. The Secretariat team is in ongoing discussions with the US-NIAID team to finalize the shipment preparations.
This month, the Secretariat bids farewell to dr. Natalia Regina M. Kes, a bright and dedicated research assistant (RA) from Site 02 (TC Hillers Hospital, Maumere, East Nusa Tenggara). She will be departing from the InVITE study as her contract has come to an end. In this newsletter, dr. Natalia shares her experiences working as an RA at Site 02 for almost 2.5 years. Site 02 was initially selected for the InVITE study due to its endemic risk of malaria, which is one of the sub-groups of interest in the protocol for evaluating immunogenicity after COVID-19 vaccination.
Dr. Natalia was supervised by the Site Principal Investigator (PI) dr. Asep Purnama, Sp.PD, FINASIM, along with Co-PIs dr. Mario B. Nara, Sp.A, and dr. Dwi Kurniawan Nugroho, Sp.PK. She expresses gratitude for the enthusiastic and supportive nature of her supervisors. Dr. Asep, with extensive research experience in malaria, HIV, and rabies, was deeply interested in the InVITE study to gain insights into the immunological properties of the COVID-19 vaccination. Dr. Mario, Sp.A, was particularly helpful in networking with primary health care and enrolling pregnant women in the study. Dr. Dwi, Sp.PK, was always ready to resolve any laboratory issues that arose during the InVITE study.
Dr. Natalia shared the challenges she faced during the preparation for the InVITE study. Having prior experience as an RA in the Tanjungsari Cohort Study (2016-2018), she found her new role in the INA-RESPOND study both unique and exciting. With the national COVID-19 mass vaccination schedule set to begin in August 2021, dr. Natalia had to quickly prepare for the InVITE study. She underwent RA training, participated in enrollment mock sessions, and coordinated with laboratory technicians Daniel Fremidon Ndoa, Amd.K, Elisabeth Nona Stefani, S.ST, and study nurse Wahyuni, Amd. Keb. She also managed study logistics and soon initiated subject enrollment. The first enrollment period targeted TC Hillers Hospital health workers who received their second vaccination booster with Moderna. Her diligence and bravery impressed us, especially considering she was new to the hospital. The RA from the INA104-PROACTIVE study also assisted her in successfully recruiting 228 subjects in approximately four months. Dr. Natalia also faced challenges related to administration and bureaucracy. She and her team had to secure permission from The National Unity Politics and Community Protection Agency (Kesbangpol) to collaborate with primary healthcare, allowing for expanded subject recruitment in satellite locations. Thanks to their efforts, Site 02 achieved a high enrollment rate, contributing 32% of the total subjects for the InVITE study in Indonesia.
The subject recruitment process posed significant challenges, especially when potential participants were not health workers. Socioeconomic and educational limitations heavily influenced their willingness to participate. It was difficult to explain the study’s purpose to these individuals, particularly since they did not perceive any direct benefits from participating. Many subjects from rural areas were also apprehensive about repeated blood draws. Even those enthusiastic about participating faced logistical barriers such as the long distance between their homes and the healthcare facilities where follow-up visits were conducted. However, some subjects were motivated to join the study because they were interested in learning about their SARS-CoV-2 antibody levels over time. The varying education levels among the subjects provided dr. Natalia and the team with an opportunity to refine their communication skills, ensuring that all participants received clear and consistent information. Sample collection was also challenging due to the lack of a freezer for temporarily storing specimens at the blood draw location. The team addressed this by using a cool box with ice packs and taking turns to promptly transport the samples to the laboratory.
The follow-up period for InVITE study subjects was extended by one year from the original timeline, increasing the number of follow-up visits to eight. Every two weeks, dr. Natalia would contact subjects to inquire about COVID-19 symptoms and remind them of their scheduled follow-up visits. However, economic circumstances made it difficult to reach all subjects as some did not have cell phones. To address this challenge, dr. Natalia and the study nurse began visiting the subjects’ homes directly, which not only facilitat-ed communication but also helped them build a good rapport with the subjects and adapt to the local community’s customs. During the study, rumors circulated in Maumere that hospitals or healthcare workers were diagnosing patients with COVID-19 for financial gain. This created an additional challenge as some subjects hesitated to disclose their symptoms. The discrepancy between subjective data obtained from interviews and objective data from antibody-level results provided the research team with valuable insights on how to analyze and interpret the collected data accurately.
Research activities are always closely tied to data documentation. In remote areas, supportive tools such as printers, scanners, and reliable internet connections are critical to ensure smooth document uploads. We recall several instances where dr. Natalia had to go to the hospital in the evening to upload documents because the internet connection was sometimes unreliable during the day. Additionally, the availability of spare parts for laboratory equipment and technicians’ readiness also posed challenges during the study at Site 02. Another significant obstacle at Site 02 was related to specimen delivery to the INA-RESPOND Reference Laboratory. The lack of air lines willing to ship specimens with dry ice, the absence of direct flights from Maumere to Tangerang, the infrequent flight schedules, and the long travel time combined with strict temperature monitoring requirements complicated the specimen shipping process. However, these challenges were overcome through coordination and teamwork, with one effective solution being the use of Crēdo Cube, a reusable cold chain shipper, for specimen shipping.
Dr. Natalia and the team gained extensive experience from the InVITE study, including systemically organizing documentation, participating in a well-designed study, and coordinating with various parties from different backgrounds. Their unexpected challenges brought the team closer together as they worked hard to cover any gaps. The strict division of tasks between dr. Natalia and the laboratory technicians gradually disappeared, and they all collaborated happily. Follow-up visit days became something they looked forward to, as it was a chance to meet, work together, and share laughs.
Dr. Natalia and the team successfully completed the study activities at Site 02 according to the timeline, thanks to the excellent collaboration of all parties involved and the support of the PI and co-PIs from start to finish. They are now preparing for the SCV, including organizing the shipment of documents from Site 02 to the INA-RESPOND Secretariat and inventorying INA-RESPOND-owned equipment at the site.
The InVITE study at Site 02 was a success, and the INA-RESPOND Secretariat gained invaluable insights from the experience. We extend our deepest gratitude and appreciation to the Site 02 team for their cooperation. Words of thanks and apologies might not be enough to express our gratitude for the Site 02 research team’s patience, flexibility, and hard work during the study. We’re excited to work with TC Hillers Hospital on more INA-RESPOND projects in the future and wish the entire Site 02 research team continued success. A special thanks to dr. Natalia — we are truly grateful for your dedication and responsiveness throughout the InVITE journey, even beyond office hours. Our hectic moments and communication ups and downs will indeed become fond memories. We wish you happiness and success in your next endeavor, and we hope our paths will cross again.
Epang gawang! (“thank you” in Sikka language).
The INA-PROACTIVE investigators, Secretariat, and partners are currently working on both primary and additional manuscripts. The first manuscript, titled “A Prospective Observational Cohort Study of HIV Infection in Indonesia: Baseline Characteristics and One-Year Mortality,” was submitted to BMC Infectious Diseases, and the team is now awaiting feedback following its submission on August 7, 2024. Meanwhile, the Scientific, Data, and Site teams are engaging in extensive discussions to finalize the subsequent manuscripts.
The second manuscript, expected to be finalized in the coming months, will focus on the trends and characteristics of late presenters (LP) in the INA-PROACTIVE cohort. LP is defined as a person living with HIV who presents for care with a CD4 count below 350 cells/μμL or with an AIDS-defining event, regardless of their CD4 count. The INA-PROACTIVE study collected demographic and clinical data from patients at the time of their first positive HIV test across 19 sites in Indonesia. This allows the team to analyze changes over time in the proportion of LP and identify associated factors. Addressing LP is crucial due to its association with high morbidity and mortality, as well as the potential delays in anti-retroviral therapy (ART) initiation that could hinder the achievement of the UNAIDS 95-95-95 targets.
The INA-PROACTIVE team also highlights the opportunity to focus on a vulnerable population in the study: children living with HIV (CLWH). In 2022, an estimated 18,000 CLWH were in Indonesia, yet only 29% received ART, a rate lower than that of adults. This population deserves equal access to appropriate programs and services. In collaboration with INA-RESPOND Warm-Based Research Assistants (RAs), the Secretariat conducted a scoping review of CLWH research in Indonesia, covering all fields since the first HIV case was reported in 1987. The team aims to provide scientific summaries for this age group and promote HIV control efforts in Indonesia. This scoping review will also support the preparation of a PROACTIVE manuscript focused on pediatric subjects.
The scoping review followed the Arksey and O’Malley approach, which consists of five stages: (1) formulating research questions, (2) identifying relevant studies, (3) selecting eligible studies, (4) charting the data, and (5) collating, summarizing, and reporting the results. The team developed two key research questions: “What CLWH research is available in Indonesia?” and “What are the research gaps regarding CLWH in Indonesia?” They established eligibility criteria for articles and conducted a comprehensive search in online electronic databases using keywords found throughout the text of potentially relevant publications. The search terms included: “(HIV OR AIDS) AND INDONESIA AND (NEONATE OR INFANT OR CHILD OR CHILDREN OR PEDIATRIC OR ADOLESCENT OR YOUNG).” The search included original papers written in English and published from 1987, when the first HIV case was reported in Indonesia, to February 2024. Multinational studies involving CLWH in Indonesia were also included. Duplicate journal titles were removed from the search results.
Several articles were excluded due to having less than 10% of participants aged 18 years or younger, lacking age-specific stratification, or not providing separate analyses or discussion for children (Figure 1). The Secretariat team conducted further searches to identify research specifically related to CLWH. Lead authors were available for consultation during the finalization of records. Following the final assessment, the selected articles were categorized into ten categories: epidemiology, opportunistic infections, non-opportunistic infections, non-infectious diseases, social/behavioral/attitude/education, virological outcomes, immunological outcomes, clinical outcomes, laboratory, and other categories.
The full text of categorized articles was re-viewed independently by assigned groups consisting of six groups with two authors in each. To ensure accuracy, the articles were then swapped between two groups for a second review. Any discrepancies were discussed with the lead authors, who made the final decision when consensus could not be reached. In line with scoping review guidelines, the team did not appraise the methodological quality or risk of bias of the included articles.
A data charting form in Microsoft Excel was used to capture the details of the selected studies. The team then developed a table and narrative synthesis to map and summarize the existing knowledge on research about CLWH in Indonesia. This was an exciting part of the scoping review process. Authors were required to provide a summary of the research, noting similarities and differences among articles within the same category, highlighting key findings, and presenting any unique results.
As the team was still learning together, they held small, active, and productive discussions within each pair of groups. Following these discussions, the next step is to finalize the review report draft and discuss it with the entire team. The scoping review draft will also be consulted with US-NIAID partners, pediatricians, HIV experts, and members of the Health Policy Agency of the Ministry of Health. The team hopes to complete the scoping review draft soon.
