Ongoing Studies – INA-RESPOND

InVITE Study

By: Eka Windari R., Nur Latifah Hanum, Restu Amalia Mukti

InVITE specimens from main visits 1, 2, and 3, as well as symptomatic visits, are currently being analyzed at the Central Laboratory. RNA extracted from mid-turbinate swabs collected in Universal Transfer Media (UTM) during symptomatic visits has been processed and will be shipped along with serum specimens from extension visits 4 and 5. These specimens are scheduled for shipment in June 2025. The INA-RESPOND team is preparing to submit new Material Transfer Agreement (MTA) documents for this shipment to the MTA Committee.

Figure 1. SCV Wrap-Up Meeting

Additionally, the InVITE global database is still in the process of being locked, while the Indonesia data has already undergone a soft lock. Consequently, the InVITE Global Study Team approved conducting the Site Closeout Visit (SCV) for Indonesia ahead of the full database lock for all countries. This decision was also approved by the Ethics Committee of RSUD Kabupaten Tangerang, which prioritizes the Indonesian data. The online SCV Wrap-Up was held on February 19, 2025, attended by site teams, the INA-RESPOND Secretariat, the INA-RESPOND Reference Laboratory team, and the NIAID team, represented by Aaron Neal.

The SCV Wrap-Up discussion began with an overview of Global General Information (presented by CRSS), highlighting that all seven countries (Guinea, Liberia, Mexico, Mongolia, Mali, Indonesia, and Congo/DRC) had completed subject visits. A total of 5,401 subjects were enrolled globally, with the highest number enrolled by the DRC team, at 1,100 subjects, while Indonesia successfully enrolled 700 subjects.

The discussion then moved on to Indonesia General Information, which covered the timeline of study activities and the target completion of post-SCV activities, coordinated by the INA-RESPOND Secretariat team. The drafting of the Final Report is currently in progress and will be submitted to the Institutional Review Board (IRB) and the hospital directors no later than May 2025.

The status of subjects in Indonesia was also presented, detailing the number of enrolled subjects who completed up to visit 5 (extension visit). Information on the number of subjects who completed the study and the reasons for early termination, whether decided by the subjects or the site team, was also discussed.

The INA-RESPOND Data Management team provided updates on reports related to SDW/CRF completion across all sites and a random quality assurance (QA) report summary, which included error rates for each site. This QA activity ensured data quality before proceeding with the local database lock.

Figure 2. Dynamics of SARS-CoV-2 anti-S-RBD IgG antibody levels during the study in participants without SARS-CoV-2 infection or additional vaccination post-Visit 2.

Preliminary data results were presented, including baseline characteristics and local serology testing results during the study using the CLIA (chemiluminescence immunoassay) platform at the INA-RESPOND Reference Laboratory (Figure 2). Additionally, the Scientific Team shared updates on manuscripts that have already been published, and publication plans that are still under discussion. Hopefully, Indonesia’s results will be included in upcoming publications, and if possible, a dedicated Indonesia-specific publication will be developed based on the local findings.

All site research documents will be archived at Indo Arsip (an archiving vendor). The CRA also provided information on protocol deviations and adverse events (AEs) that occurred during the study, the number and types of specimens collected, the results of the QA specimen inventory activities, and details regarding the disposition of Government Furnished Equipment (GFE) for Site 02- TC Hillers Hospital and Site 03- Ansari Saleh Hospital, which are not core sites of INA-RESPOND.

The SCV Wrap-Up marks the conclusion of the InVITE study activities in Indonesia. We extend our sincere gratitude to all Site PIs, Co-PIs, RAs, and the entire site team for their excellent collaboration and efforts throughout the study. We hope to maintain strong professional relationships and look forward to the opportunity to collaborate again in the future.

PROACTIVE Study

By: Eka Windari R., Nur Latifah Hanum, Restu Amalia Mukti

Reporting of COVID-19 Incidents during the PROACTIVE Study

The INA-104 study is now in its final stage, with the study team preparing the final report for submission to the Ethics Committee of FKUI. A critical component of this report is the documentation of adverse events (AEs) and serious adverse events (SAEs) that occurred during the study. As an observational study with no investigational drug interventions, the only study procedure involved was blood sampling for specimen collection. Consequently, any AE recorded in this study refers to undesirable or harmful medical occurrences in participants within 48 hours of blood draw, which may or may not be related to the procedure. Similarly, SAEs are defined as events directly related to blood collection occurring within the same 48-hour period. By the end of the study, three AEs were reported: bruising, hematoma, and presyncope and were appropriately managed by the study team and fully resolved without further complications. Notably, no serious adverse events (SAEs) related to blood draws were recorded.

Beyond AEs and SAEs, the study also documented “Reportable Events” (REs) for serious incidents outside the AE definition. The EC was made aware of this classification through a memo on December 11, 2018. REs, which are not related to the study procedure, include serious medical incidents such as those leading to death, life-threatening conditions, hospitalization or prolonged hospitalization, permanent disability, congenital abnormalities, or any event deemed a significant health risk based on medical judgment (Important Medical Events (IMEs)).

As explained in the previous edition, the INA-104 study, which began in 2018 and concluded in 2024, spanned the COVID-19 pandemic, requiring adaptive operational strategies to maintain study continuity. The global impact of COVID-19 has been immense, particularly on those living with HIV, who face a higher risk of severe complications. Therefore, the Protocol Team determined that COVID-19 cases in participants should be documented as IMEs. Throughout the study, 821 REs were recorded, of which 140 (17%) were classified as IMEs. Among these, 138 events were COVID-19 cases, and 10 participants died due to COVID-19-related complications. In this edition, we will explore publications discussing the impact of the COVID-19 pandemic on people living with HIV (PLWH).

Evaluating the impact of COVID-19 on people living with HIV

The COVID-19 pandemic has increasingly impacted both HIV research and management. A systematic review, “COVID-19 outcomes in HIV patients” (https://doi.org/10.1016/j.amsu.2022.103768), explores the impact of the COVID-19 pandemic on PLWH. HIV and SARS-CoV-2 are very different viruses; HIV is transmitted through bodily fluids, while COVID-19 spreads through respiratory droplets and direct contact. The symptoms of COVID-19 experienced by PLWH are generally similar to those observed in the general population. However, studies show that people with HIV/AIDS—especially those with low CD4 counts—are more likely to contract COVID-19 compared to the general population. This suggests that individuals with weakened immune systems may be at a higher risk of infection, making prevention and early treatment especially critical.

One of the biggest questions has been whether HIV increases the risk of dying from COVID-19, and the findings have been mixed. Some studies suggest that HIV-positive individuals face a higher mortality risk, with a large meta-analysis showing they are about 1.4 times more likely to die from COVID-19 (https://doi.org/10.1007/s10238-022-00840-1). However, other research indicates little to no difference in death rates once factors like age and comorbidities are considered (https://doi.org/10.1016/j.jiph.2022.05.006). Overall, the latest evidence suggests that well-controlled HIV does not significantly worsen COVID-19 outcomes, but untreated or advanced HIV can increase the risk of severe illness and death.

Beyond the direct health impact, COVID-19 has also disrupted HIV care worldwide. Many healthcare professionals who previously focused on HIV treatment were reassigned to handle COVID-19 cases, leaving gaps in services for PLWH. This shift made it harder for HIV patients to access routine check-ups and refill their antiretroviral therapy (ART), increasing the risk of treatment interruptions. The pandemic has also worsened existing inequalities, particularly for marginalized populations who are disproportionately affected by both HIV and COVID-19. Racial minorities, low-income groups, sex workers, transgender individuals, and the homeless often face significant barriers to healthcare access. Lockdowns, economic instability, and overwhelmed health services have made it harder for these communities to receive the care they need. This widening gap in healthcare access highlights the urgent need for policies prioritizing vulnerable populations.

Mental health has been another major concern during the pandemic, and PLWH have felt its impact deeply. Social isolation, fear of infection, financial hardship, and disruptions in HIV care have led to increased levels of anxiety, depression, and stress. PLWH also faced double stigma—not only the stigma associated with HIV but also discrimination related to COVID-19. These combined pressures have affected overall well-being and, in some cases, led to poor adherence to HIV treatment. Addressing the mental health needs of PLWH is essential to ensuring their overall health and quality of life.

As the world moves forward, healthcare systems must adapt to protect and support PLWH. Ensuring uninterrupted access to ART, integrating mental health services into HIV care, and addressing healthcare inequalities are critical steps in minimizing the impact of future health crises. Following the report findings from our INA-PROACTIVE study to the EC, these issues will be further explored in the upcoming manuscript on the three-year findings. We hope this research will enrich our understanding of the impact of COVID-19 on PLWH and contribute to improving healthcare strategies for this population.