ABSTRACT
Introdução Testes de neutralização têm se tornado a principal referência para avaliar proteção após exposição ao SARS-CoV-2 ou após a vacinação. Alguns estudos sugerem que pessoas que vivem com HIV (PVHIV) têm menor probabilidade de soroconversão após a vacinação para COVID-19, porém a resposta humoral após infecção natural é pouco conhecida. Objetivo Avaliar a positividade e títulos de anticorpos neutralizantes em PVHIV e controles com IgG positivo identificados no Estudo Prevent, realizado antes da implementação das vacinas para COVID-19 no Brasil. Método O Estudo Prevent incluiu PVHIV sob tratamento ARV e contactantes próximos sem diagnóstico de infecção por HIV acompanhados por 120 dias com avaliação clínica semanal e avaliação sorológica (IgM/IgG) ao início (TS1) e final (TS2) do seguimento, entre abril/2020 e janeiro/2021. Todas as amostras com IgG reagente (+) foram submetidas a um teste correlato de anticorpos neutralizantes (TCAN). Resultados Um total de 74 amostras tiveram IgG reagente;entre PVHIV, 9 tiveram TS1+ e TS2 não reagente (NR);14 tiveram TS1+ e TS2+;e 18 tiveram TS1 NR e TS2+. No grupo controle, 6 tiveram TS1+/TS2 NR;5 tiveram TS1+ e TS2+ e apenas 2 tiveram TS1 NR e TS2+. Quanto à avaliação do TCAN, houve positividade em 39/56 (69%;IC95% 56-81) amostras de PVHIV, e em 14/18 (78%;IC95% 52-94) amostras de controles. 21 amostras foram positivas no TS e negativas no TCAN (17 PVHIV e 4 controles) além de 1 amostra TNeutrAc indeterminada após TS positivo (PVHIV). Embora as medianas de porcentagens de neutralização tenham sido mais altas entre controles em relação a PVHIV tanto nas amostras iniciais quanto ao término do estudo, essa diferença não atingiu significância estatística. Conclusão Testes de neutralização para SARS-CoV-2 ainda possuem aplicabilidade e interpretação controversos. Entretanto, até o momento consistem na metodologia mais aceita para avaliar níveis de proteção contra o vírus. Nossos resultados sugerem tendência a resposta neutralizante inferior entre PVHIV comparadas com controles.
ABSTRACT
BACKGROUND: People living with HIV might have a poor or delayed response to vaccines, mainly when CD4 cell counts are low, and data concerning COVID-19 vaccines in this population are scarce. This prospective cohort study assessed the safety and immunogenicity of the inactivated SARS-CoV-2 vaccine CoronaVac in people with HIV compared with people with no known immunosuppression. METHODS: In this prospective cohort study, adults (aged ≥18 years) living with HIV who were regularly followed up at the University of Sao Paulo HIV/AIDS outpatient clinic in Sao Paulo, Brazil, were included in the study. Eligibility for people with HIV was independent of antiretroviral use, HIV viral load, or CD4 cell count. Adults with no known immunosuppression with CoronaVac vaccination history were included as a control group. CoronaVac was given intramuscularly in a two-dose regimen, 28 days apart. Blood was collected before vaccine administration and 6 weeks after the second dose (day 69). Immunogenicity was assessed at baseline (day 0), before second vaccine (day 28), and 6 weeks after second vaccine dose (day 69) through SARS-CoV-2 IgG titre and seroconversion, neutralising antibody (NAb) positivity and percentage activity, and factor increase in IgG geometric mean titres (FI-GMT). We investigated whether HIV status and CD4 count (<500 or ≥500 cells per µL) were associated with CoronaVac immunogenicity by use of multivariable models adjusted for age and sex. FINDINGS: Between Feb 9, 2021, and March 4, 2021, 776 participants were recruited. Of 511 participants included, 215 (42%) were people with HIV and 296 (58%) were people with no known immunosuppression. At 6 weeks after the second vaccine dose (day 69), 185 (91%) of 204 participants with HIV and 265 (97%) of 274 participants with no known immunosuppression had seroconversion (p=0·0055). 143 (71%) of 202 participants with HIV were NAb positive compared with 229 (84%) of 274 participants with no known immunosuppression (p=0·0008). Median IgG titres were 48·7 AU/mL (IQR 26·6-88·2) in people with HIV compared with 75·2 AU/mL (50·3-112·0) in people with no known immunosuppression (p<0·0001); and median NAb activity was 46·2% (26·9-69·7) compared with 60·8% (39·8-79·9; p<0·0001). In people with HIV who had CD4 counts less than 500 cells per µL seroconversion rates, NAb positivity, and NAb activity were lower than in those with CD4 counts of at least 500 cells per µL. In multivariable models for seroconversion, NAb positivity, IgG concentration, and NAb activity after a complete two-dose regimen, adjusted for age and sex, people with HIV who had CD4 counts of at least 500 cells per µL and people with no known immunosuppression had higher immunogenicity than did people with HIV with CD4 counts less than 500 cells per µL. No serious adverse reactions were reported during the study. INTERPRETATION: Immunogenicity following CoronaVac in people with HIV seems strong but reduced compared with people with no known immunosuppression. Our findings highlight the need for strategies to improve vaccine immunogenicity in people with HIV. FUNDING: Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), and B3-Bolsa de Valores do Brasil.