Biomarkers for Dysbiosis-Related HIV-Associated Cognitive Disorders among Persons Who Inject Drugs in Puerto Rico

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ABSTRACT As of March 25, the novel SARS-CoV-2 coronavirus disease 2019 (COVID-19) has infected almost 125 million individuals causing over 2.7 million deaths worldwide. Puerto Rico's population is at a heightened risk of COVID- 19 due to the existing health disparity in the population and its higher proportion of elderly people compared to the US as a whole. There are now over 105,000 confirmed cases of COVID-19, a substantial increase from the 64 infected cases reported just over year ago on March 22, 2020. It is expected that the cases will continue to increase even though vaccines are provided by the local governor to slow the spread of the disease but only about 10% of the population were fully vaccinated so far. This dire situation is coupled to the ongoing opioid epidemic that parallels the current opioid injection incidence in the many other parts of the United States. It is well established that people who inject drugs (PWID) are at high risk for infectious diseases, including HIV-1, and now possibly COVID-19. These co-infected individuals are likely to have disease progression very different from those who do not inject. It is known that HIV-1 infection is associated with lymphoid depletion in tissues and induces systemic inflammation. The resulting inappropriate immune activation in PWID upon SARS-CoV-2 infection may enhance HIV-1 replication, lead to premature aging of T cells to promote HIV-1 disease progression, and likely potentiate the effects of inflammation and disease course due to COVID-19. The proposed study will make use of a well-established cohort of injection drug users in Puerto Rico, where there is a historically high level of injection drug use and an HIV incidence rate that is disproportionately associated with drug use. The overall objective of our proposed supplement study is to expand and leverage our current longitudinal study on PWID with and without HIV-1, to determine the prevalence of SARS-CoV-2 infection and its HIV-1 viral load, inflammation, disease progression due to both COVID-19 and HIV-1 infections. The current ongoing longitudinal cohort study of PWID in Puerto Rico will allow our team to test the hypothesis that SARS-CoV-2 infection of HIV+ PWID intensifies inflammation that, in turn, exacerbates HIV replication, disease progression and HIV treatment failures. This hypothesis will be tested via three specific aims: Aim 1, Expand our current cohort study of HIV-1 infected PWID, with a non-PWID HIV uninfected control group to support a prospective evaluation of the incidence and the effects of COVID-19 at baseline and at follow-ups. Aim 2, Quantify the SARS-CoV-2 and HIV- 1 viral loads, cellular immune-phenotypes and inflammatory mediators in blood samples, and microbial dysbiosis at baseline and longitudinally followed these cases for HIV disease progression. Aim 3, Correlate the effects of COVID-19 on the HIV-1 viral loads, cellular immunophenotypes, inflammatory mediators and neurocognitive functions, as well as disease progression, while controlling for HIV and injection drug use status and socio-behavioral factors associated with drug use. The results is translatable to other states in the U.S. and may lead to the development of strategies to prevent HIV and COVID-19 disease progression in HIV+ PWID.