HepB-CpG vs HepB-Alum Vaccine in People With HIV and Prior Vaccine Nonresponse
Authors: Kristen M. Marks, Minhee Kang, Triin Umbleja, Andrea Cox, Karen J. Vigil, Ngan T. Ta, Ayotunde Omoz-Oarhe, Hugo Perazzo, Josphat Kosgei, Timothy Hatlen, Jennifer Price, Leolin Katsidzira, Khuanchai Supparatpinyo, Kevin Knowles, Beverly L. Alston-Smith, Parita Rathod, Kenneth E. Sherman, Oladapo Alli, Ceora Beijer, Stephanie Caruso, Shawn Chiambah, Lillian Collins, Kim Epperson, Francoise Giguel, Jan Kosmyna, Michael Leonard, Terence Mohammed, Leonard Sowah, Christina Vernon, Sara Zabih, Katrina Shea, Matthew Planchon, Paul Sax, Cheryl Keenan, Joyce Jones, Alex Hessel, Aleen Khodabakhshian, Lisa Mark, Eric S. Daar, Ruben Lopez, Rosemarie Ramirez, Dawn Rosenblum, Dennis Dentoni-Lasofsky, Cecilia Rivas Alfaro, Madhu Choudhary, Jen Sullivano, Rachel Bender Ignacio, Eli Burnham, Teresa Spitz, Raghd Alyatim, Susan Koletar, Robyn Cicarella, Carl J. Fichtenbaum, Michelle Saemann, Leila Hojat, Brenda Brown, Vivek Paul, Claudia Hawkins, Jaclyn Leone, Jonathan Oakes, Cornelius Van Dam, Kelly Phillips, Tracey Watkins, Ericka R. Patrick, Clifford Gunthel, Joslyn Axinn, Nicola Haakonsen, William Short, Pablo Tebas, Keisha Ballentine-Cargill, Nadi Islam, Daniel Finn, Catherine Jerry, Sharlaa Badal-Faesen, Iveshni Govender, Penelope Madlala, Rosie Mngqibisa, Nathalia Soliva, Tania Brum, Breno Riegel Santos, Rita de Cassia Alves Lira, Lerato Mohapi, Nadia Marengo, Sandra Rwambuya, Francis Ntengereze Ssali, Josphat Kosgei, Geoffrey Koskei, Ditlamelo Mareme, Boitshepho Seme, Mulinda Nyirenda, Maxwell Yohane, Michael Yin, Anyelina Cantos, Karen J. Vigil, Mariano J. Lodigiani, Patcharaphan Sugandhavesa, Daralak Tavornprasit, Shobha Swaminathan, Christie Lyn Costanza, Sonal S. Munsiff, Susan E. Hulse, Sonya L. Heath, E. Turner Overton, Megan Dieterich, Carrington Koebele, Anchalee Avihingsanon, Hay Mar Su Lwin, Maria Tarcela Gler, Melchor Frias, Ngan Ta Thi Dieu, Dat Quoc Vu
Journal: JAMA (2024)

Importance Nonresponse to hepatitis B vaccine is common among people with HIV, resulting in vulnerability to infection with hepatitis B virus (HBV). Objective To compare the seroprotection response achieved with a 2-dose (noninferiority, 10% margin) and a 3-dose hepatitis B vaccine with a cytosine phosphoguanine adjuvant (HepB-CpG vaccine) vs a conventional 3-dose hepatitis B vaccine with an aluminum hydroxide adjuvant (HepB-alum vaccine) in people with HIV and prior nonresponse to HepB-alum vaccine. Design, Setting, and Participants This phase 3, open-label, randomized clinical trial included people with HIV receiving antiretroviral therapy (CD4 cell count ≥100 cells/μL and HIV RNA &amp;amp;lt;1000 copies/mL) without past or present serological evidence of having HBV or a response to hepatitis B vaccine. From December 2020 to February 2023, 561 adults were enrolled in the study at 41 sites in 10 countries in Africa, Asia, North America, and South America with follow-up for the primary outcome analysis through September 4, 2023. Interventions Participants were randomly assigned to receive 2 doses of HepB-CpG vaccine administered intramuscularly at weeks 0 and 4; 3 doses of HepB-CpG vaccine administered intramuscularly at weeks 0, 4, and 24; or 3 doses of HepB-alum vaccine administered intramuscularly at weeks 0, 4, and 24. Main Outcomes and Measures The primary outcome was a seroprotection response to hepatitis B vaccine (defined as level of antibody titer against hepatitis B surface antigen [HBsAg] ≥10 mIU/mL) at week 12 for the 2-dose regimen (8 weeks after dose 2) and at week 28 for 3-dose regimens (4 weeks after dose 3). Key secondary outcomes included seroprotection response at additional time points, antibody titer against HBsAg, and adverse events within 4 weeks of hepatitis B vaccination. Results Of 561 participants included in the analysis (median age, 46 years [IQR, 31-56 years]); 64% were male; 17% of participants were Asian, 42% were Black, and 35% were White), a seroprotection response was achieved in 93.1% who received 2 doses of HepB-CpG vaccine (n = 174), in 99.4% who received 3 doses of HepB-CpG vaccine (n = 169), and in 80.6% who received 3 doses of HepB-alum vaccine (n = 165). The stratified difference in seroprotection response between the 2-dose HepB-CpG vaccine group and the 3-dose HepB-alum vaccine group was 12.5% (97.5% CI, 4.1%-20.9%), achieving noninferiority and indicating superiority. The 3-dose HepB-CpG vaccine regimen was superior to the 3-dose HepB-alum vaccine regimen (stratified difference in seroprotection response, 18.4% [repeated 97.5% CI, 10.4%-26.2%]). By week 12, more than 90% of participants who received HepB-CpG vaccine achieved a seroprotection response. The 3-dose regimen of HepB-CpG vaccine achieved a higher proportion of participants with antibody titer against HBsAg greater than 1000 mIU/mL (78.1%) vs the other 2 regimen groups (26.4% for 2 doses of HepB-CpG vaccine and 35.2% for 3 doses of HepB-alum vaccine). No unexpected safety issues were observed. Conclusions and Relevance Among people with HIV and nonresponse to prior hepatitis B vaccination, both the 2-dose and 3-dose regimens of HepB-CpG vaccine achieved a superior seroprotection response compared with 3 doses of HepB-alum vaccine. Trial Registration ClinicalTrials.gov Identifier: NCT04193189