Identification of the HIV Reservoir in Lymph Nodes Using Single Cell RNA-Seq

Kwazulu-Natal Research Institute Tb-Hiv, Durban

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Abstract

MODIFIED PROJECT SUMMARY HIV persistence in the face of antiretroviral therapy (ART) necessitates lifelong treatment of infected individuals because of a reservoir of HIV infected cells. The Covid-19 pandemic has resulted in the critical need to better understand the interaction between HIV and SARS-CoV-2. Our preliminary data indicates that poorly controlled HIV infection leads to prolonged SARS-CoV-2 infection which evolves variant-like mutations. It also interferes with the neutralizing antibody response elicited by Covid-19 vaccines. As there is no sign that SARS-CoV-2 will be eliminated anytime soon, these questions are critical for both the health of people living with HIV and possibly to prevent continued emergence of SARS-CoV-2 variants. MODIFIED ABSTRACT HIV infection is currently lifelong due to the persistence of the infection in the face of ART because of a reservoir of HIV infected cells which is insensitive to antiretroviral drugs [1]. South Africa has a high proportion of people living with HIV (PLWH), with about one-third of the population in the Durban area being PLWH [2, 3]. Due Covid-19 and other factors, many individuals are not fully suppressed with ART and about 10% of PLWH in our Durban based cohort of confirmed SARS-CoV-2 infected cases have long-term unsuppressed HIV infection culminating in advanced HIV disease [2]. Incomplete suppression of HIV replication would lead to HIV reservoirs being replenished and maintained by ongoing HIV replication [1]. Furthermore, it may compromise immune responses to SARS-CoV-2 [4, 5]. This leads to long-term SARS-CoV-2 infection which we and others have found to evolve neutralizing antibody escape mutations in the SARS-CoV-2 spike protein [6]. Such evolution may form variants. In addition to causing prolonged SARS-CoV-2 infection, we have preliminary data showing that mRNA vaccines do not elicit an effective neutralizing immune response in PLWH with poorly suppressed HIV infection. There may also be unknown consequences to HIV reservoirs and the ability of ART to suppress the HIV reservoir in different anatomical compartments if SARS-CoV-2 infection is long and causes extensive immune activation. Given these unexpected developments which are the consequence of the Covid-19 pandemic, we propose to modify the current study Aims to understand the impact of HIV status and level of suppression on the immune response to SARS-CoV-2 infection and vaccines, as well as determine the effect of long-term SARS-CoV-2 infection on HIV reservoir suppression.