Current SARS-CoV-2 vaccines, based on the ancestral Wuhan strain, were developed rapidly to meet the needs of a devastating global pandemic. People living with HIV (PLWH) have been designated as a priority group for SARS-CoV-2 vaccination in most regions and varying primary courses (2 or 3-dose schedule) and additional boosters are recommended depending on current CD4+ T cell count and/or detectable HIV viraemia. From the current published data, licensed vaccines are safe for PLWH, and stimulate robust responses to vaccination in those well controlled on antiretroviral therapy and with high CD4+ T cell counts. Data on vaccine efficacy and immunogenicity remain, however, scarce in PLWH, especially in people with advanced disease. A greater concern is a potentially diminished immune response to the primary course and subsequent boosters, as well as an attenuated magnitude and durability of protective immune responses. A detailed understanding of the breadth and durability of humoral and T cell responses to vaccination, and the boosting effects of natural immunity to SARS-CoV-2, in more diverse populations of PLWH with a spectrum of HIV-related immunosuppression is therefore critical. This article summarises focused studies of humoral and cellular responses to SARS-CoV-2 infection in PLWH and provides a comprehensive review of the emerging literature on SARS-CoV-2 vaccine responses. Emphasis is placed on the potential effect of HIV-related factors and presence of co-morbidities modulating responses to SARS-CoV-2 vaccination, and the remaining challenges informing the optimal vaccination strategy to elicit enduring responses against existing and emerging variants in PLWH. Lay Abstract People living with Human Immunodeficiency Virus (PLWH), appear to be at a higher risk (approximately 15%) of becoming more seriously unwell if they are infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the virus that causes COVID-19 disease, and at least twice as likely to die from COVID-19 as the rest of the population. SARS-CoV-2 vaccination and boosters are recommended for all PLWH. However, there is limited information about the protective immune responses to both vaccination (and actual infection), the protection against serious COVID-19 disease, and whether the safety profile of the vaccines, which are very safe in the general population, differs in PLWH. Here we summarise findings from studies which looked specifically at vaccine-related immune responses in PLWH, and discuss factors – such as age, known to impact negatively on immune responses in the general population, to see whether this effect is worse in PLWH. A better understanding of these issues will help guide tailored vaccination and prevention strategies for PLWH.
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