Journal Article

Safety and immunogenicity of the RTS,S/AS01 malaria vaccine in infants and children identified as HIV-infected during a randomized trial in sub-Saharan Africa

Masoud, Nahya Salim, Sorgho, Hermann, Sacarlal, Jahit, Asante, Kwaku Poku, Aide, Pedro, Vandoolaeghe, Pascale, Owusu-Agyei, Seth, Otieno, Godfrey Allan, Agbenyega, Tsiri, Berkley, James A, Lanaspa, Miguel, Adjei, Samuel, Akoo, Pauline, Kremsner, Peter, Njuguna, Patricia, Guerra Mendoza, Yolanda, Mtoro, Ali Takadir, Malabeja, Anangisye, Gesase, Samwel, Kaali, Seyram, Tanner, Marcel, Kariuki, Simon, Agnandji, Selidji Todagbe, Kamthunzi, Portia, Oneko, Martina, Otieno, Lucas, Tinto, Halidou, Otieno, Walter, Schuerman, Lode, Valea, Innocent, Ansong, Daniel, Lell, Bertrand, Lievens, Marc, Ofori-Anyinam, Opokua, Hamel, Mary J., Lusingu, John, Hoffman, Irving

2020

Overview

•The RTS,S/AS01 malaria vaccine was assessed in a phase 3 trial in sub-Saharan Africa.•We evaluated the vaccine in a subset of children identified as HIV+ in this trial.•The safety of RTS,S/AS01 in HIV+ children was similar to that of comparator vaccines.•RTS,S/AS01 was immunogenic in HIV+ children.•Antibody levels in HIV+ children were lower than in children with unknown HIV status. We assessed the safety and immunogenicity of the RTS,S/AS01 malaria vaccine in a subset of children identified as HIV-infected during a large phase III randomized controlled trial conducted in seven sub-Saharan African countries. Infants 6–12 weeks and children 5–17 months old were randomized to receive 4 RTS,S/AS01 doses (R3R group), 3 RTS,S/AS01 doses plus 1 comparator vaccine dose (R3C group), or 4 comparator vaccine doses (C3C group) at study months 0, 1, 2 and 20. Infants and children with WHO stage III/IV HIV disease were excluded but HIV testing was not routinely performed on all participants; our analyses included children identified as HIV-infected based on medical history or clinical suspicion and confirmed by polymerase chain reaction or antibody testing. Serious adverse events (SAEs) and anti-circumsporozoite (CS) antibodies were assessed. Of 15459 children enrolled in the trial, at least 1953 were tested for HIV and 153 were confirmed as HIV-infected (R3R: 51; R3C: 54; C3C: 48). Among these children, SAEs were reported for 92.2% (95% CI: 81.1–97.8) in the R3R, 85.2% (72.9–93.4) in the R3C and 87.5% (74.8–95.3) in the C3C group over a median follow-up of 39.3, 39.4 and 38.3 months, respectively. Fifteen HIV-infected participants in each group (R3R: 29.4%, R3C: 27.8%, C3C: 31.3%) died during the study. No deaths were considered vaccination-related. In a matched case-control analysis, 1 month post dose 3 anti-CS geometric mean antibody concentrations were 193.3 EU/mL in RTS,S/AS01-vaccinated HIV-infected children and 491.5 EU/mL in RTS,S/AS01-vaccinated immunogenicity controls with unknown or negative HIV status (p = 0.0001). The safety profile of RTS,S/AS01 in HIV-infected children was comparable to that of the comparator (meningococcal or rabies) vaccines. RTS,S/AS01 was immunogenic in HIV-infected children but antibody concentrations were lower than in children with an unknown or negative HIV status. Clinical trial registration: ClinicalTrials.gov: NCT00866619.

• Publisher: Elsevier Ltd,Elsevier Limited
• Subject: Africa South of the Sahara / Age / Allergy and Immunology / Antibodies / Antiretroviral drugs / Case-Control Studies / Children / Circumsporozoite protein / Double-Blind Method / Enrollments / Family medical history / Female / Health facilities / HIV / HIV infections / HIV Infections - epidemiology / Human immunodeficiency virus / Humans / Immunization / Immunogenicity / Immunogenicity, Vaccine / Infant / Infants / Infections / Malaria / malaria vaccines / Malaria Vaccines - administration & dosage / Malaria Vaccines - adverse effects / Malaria Vaccines - immunology / Malaria, Falciparum - prevention & control / Male / medical history / Medical tests / Pediatrics / Polymerase chain reaction / Public health / Rabies / randomized clinical trials / RTS / S/AS01 vaccine / Safety / Sub-Saharan Africa / Tropical diseases / Vaccination / Vaccines / Vaccines, Synthetic - administration & dosage / Vaccines, Synthetic - adverse effects / Vaccines, Synthetic - immunology / Vector-borne diseases