A rapidly expanding pandemic In early December 2019, several local health facilities first reported pneumonia cases of unknown origin in Wuhan, China. This new coronavirus infectious disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first reported on December 1, 2020 and identified as a previously unknown betacoronavirus (1, 2). Since then, studies have increasingly demonstrated that SARS-CoV-2 can be transmitted effectively among humans through aerosol or fomites (3-5). With transmission capabilities even before symptom onset (6, 7), this pandemic is rapidly evolving and expanding. As of April 2, 2020, a total of 962,977 confirmed cases of COVID-19 and 49,180 deaths have been reported across 180 countries and regions. Recent models indicated that as much as 86% of all infections early in the spread were undocumented, suggesting the real number of infections is likely much greater (8). As a public health emergency of international concern, COVID-19 was declared a pandemic by the World Health Organization. Public health authorities around the globe are now racing to contain the spread.
There is intense interest in developing curative interventions for HIV. How such a cure will be quantified and defined is not known. We applied a series of measurements of HIV persistence to the study of an HIV-infected adult who has exhibited evidence of cure after allogeneic hematopoietic stem cell transplant from a homozygous CCR5Δ32 donor. Samples from blood, spinal fluid, lymph node, and gut were analyzed in multiple laboratories using different approaches. No HIV DNA or RNA was detected in peripheral blood mononuclear cells (PBMC), spinal fluid, lymph node, or terminal ileum, and no replication-competent virus could be cultured from PBMCs. However, HIV RNA was detected in plasma (2 laboratories) and HIV DNA was detected in the rectum (1 laboratory) at levels considerably lower than those expected in ART-suppressed patients. It was not possible to obtain sequence data from plasma or gut, while an X4 sequence from PBMC did not match the pre-transplant sequence. HIV antibody levels were readily detectable but declined over time; T cell responses were largely absent. The occasional, low-level PCR signals raise the possibility that some HIV nucleic acid might persist, although they could also be false positives. Since HIV levels in well-treated individuals are near the limits of detection of current assays, more sensitive assays need to be developed and validated. The absence of recrudescent HIV replication and waning HIV-specific immune responses five years after withdrawal of treatment provide proof of a clinical cure.
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