CTN 328: COVID-19 Vaccine in HIV

About The Study

CTN 328 has established a cross-Canada cohort of people living with HIV who have received one or more doses of a COVID-19 vaccine. The study is assessing how people’s immune systems respond to the vaccine, how long immunity might last, and the safety and tolerability of the vaccine. CTN 328 is also looking at how the most vulnerable groups, such as older people or those with low CD4 counts, respond to the vaccine and whether vaccination is effective against COVID-19 variants.

About The Disease

People living with HIV are vulnerable to the development of other health concerns, including some chronic conditions and infectious diseases. At this time, it is unclear whether people living with HIV are more likely to have worse outcomes from COVID-19 than people without HIV due to the effect of HIV on their immune system or due to potential comorbidities. Because of changes to their immune systems, people living with HIV tend to have less robust immune responses to vaccines, such as the influenza, hepatitis A and B, and human papillomavirus (HPV) vaccines. Past research also suggests that when people living with HIV are vaccinated, their immune responses don’t last as long as for others. Previous COVID-19 vaccine studies were relatively short and enrolled only a small number of people living with HIV, therefore they don’t provide definitive information for this community. All of these factors combined mean that we have a lot to learn about COVID-19 vaccines in people with HIV, and how best to protect people during and after the pandemic.

Study Approach

This study enrolled 376 people living with HIV from four sites across Canada: Montreal, Ottawa, Toronto, and Vancouver. Depending on whether or not participants have received one or two doses of vaccine, they provided blood samples and questionnaire responses at either three, four or five time points over the study period. Participants who choose to receive a third COVID-19 dose during the study also attended an additional study visit at 1 month following the third vaccine dose. Each visit takes approximately 20 minutes to one hour. Blood samples are tested for COVID-19 antibodies before and after vaccination as well as for other markers of immune function. Researchers are analyzing how these markers may change over the study period. The team is also investigating how well a third dose increases the vaccine’s effectiveness by comparing the immune response in people who receive two versus three doses. Participants that receive a fourth dose while enrolled in the study are being asked to attend a final study visit four weeks after the fourth dose. Participants’ data is also being compared to data from a group of people not living with HIV who are enrolled in a separate study. Study participants who test positive for COVID-19 infection after vaccination provided saliva samples via Canada Post and be asked to record their signs and symptoms until they are recovered.

Affiliated Studies

In parallel to the main CTN 328 study, CTN Investigator Dr. Zabrina Brumme is focusing specifically on the BC cohort and using additional timepoints, lab measurements, and BC-based control participants without HIV. In doing so, Dr. Brumme is asking related and complementary questions about how COVID-19 vaccines interact with the immune system in people living with HIV. Additionally, CTN Investigators Drs. Ann Burchell and Hasina Samji are investigating how effective COVID-19 vaccines are at preventing hospitalizations and death in people living with HIV. This involves using provincial-level vaccination and health data in BC (led by Dr. Samji) and Ontario (led by Dr. Burchell) to understand how vaccination affects rates of SARS-CoV-2 infection (both symptomatic and asymptomatic), and COVID-19–related hospitalization or death in people living with HIV compared to those not living with HIV.

Results

Published in November, 2022, the first results from CTN 328 showed that the immune response to COVID-19 vaccination was similar between people living with and not living with HIV. However, the results suggest that immunity may wane slightly faster in some people living with HIV, highlighting the importance of booster doses. COVID-19 vaccines were also found to be safe and well tolerated in people living with HIV. A publication from Dr. Brumme’s lab showed that a history of low CD4 count was not associated with a lower response to vaccination, but that older age and a higher number of co-morbidities negatively affected vaccine responses in all participants, regardless of HIV status. Dr. Brumme’s lab also showed that immune responses after a third dose in people living with HIV were comparable to, or in some cases even higher, than people not living with HIV, and that immunity lasted for a similar period of time.

Looking at data prior to the Omicron variant, Drs. Burchell and Samji found that two doses of COVID-19 vaccine were effective at preventing symptomatic illness and serious outcomes in people living with HIV in BC and Ontario. The BC analysis suggests that, in people living with HIV, it may take longer for the vaccines to reach peak effectiveness compared with people not living with HIV, and effectiveness may wane somewhat quicker. While the lab-based antibody findings suggest that immune response is similar regardless of HIV status, this real-world effectiveness result suggests that there may be a shorter window of peak effectiveness in people living with HIV. The reason behind this discrepancy is yet to be determined.

Overall, the results from this study show that COVID-19 vaccines elicit a strong immune response and are safe and effective in people living with HIV. The results also highlight the importance of timely booster doses, as well as prioritization of older people, those with comorbidities, and people who have an uncontrolled viral load or low CD4 count.