Colliding pandemics and how to end them:Working towards a cure for HIV whilst navigating HIV care during the COVID-19 pandemic

This thesis investigates key areas that advance progress toward curing HIV, an as yet incurable disease and preventing morbidity from COVID 19 in people living with HIV. The insights aim to help end the HIV/AIDS pandemic by examining the HIV reservoir, cure strategies, and elite control, and by investigating approaches that mitigate COVID 19 related harm on top of HIV. The intersection of these pandemics is highlighted as critical for future threats. Using a multidimensional approach with multiple reservoir assays across molecular compartments, we map HIV reservoir dynamics during the first year on ART and link them to HIV specific immune responses. We gather clinical evidence on Latency Reversing Agents within the ‘Kick and Kill’ strategy to assess in vivo reactivation and effects on the reservoir. We also characterise the Rotterdam HIV 2 cohort and identify a novel elite controller phenotype. We evaluate SARS CoV 2 vaccine effectiveness in over a 1000 people living with HIV in the Netherlands in the largest study globally in this population during early rollout. On average, antibody responses are lower (especially in people with AIDS) than in controls without HIV, with relatively better performance of mRNA vaccines; an mRNA booster substantially improves responses in primary hyporesponders. We further analyse the impact of the first COVID 19 wave and lockdown on the first pillars of the HIV care cascade (diagnosis and linkage to care) at Erasmus MC, showing as first the disruption this novel pandemic had on testing and later entry into care. Together, these findings reveal parallels between the two pandemics and emphasise the need for personalized cure strategies, early diagnosis and treatment, and standardised, global collaboration to strengthen preparedness for future threats.