Journal
ANNALS OF INTERNAL MEDICINE
Volume 175, Issue 1, Pages 95-+Publisher
AMER COLL PHYSICIANS
DOI: 10.7326/L21-0297
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Funding
- National Institutes of Health (NIH) [HL134539, AI116228, AI078799, DA047034, AI155171, AI150396]
- Bill & Melinda Gates Foundation [INV-002703]
- NIH [AI135940, AI114235, AI117841, AI120008, AI152979, AI130005, DK120387, AI155233]
- amfAR [110181-69-RGCV]
- Frederick National Laboratory for Cancer Research [HHSN261200800001E]
- Intramural Research Program of the NIH, Frederick National Laboratory, Center for Cancer Research
- National Institutes of Health Delaney AIDS Research Enterprise (DARE) Collaboratory [UM1AI126611]
- National Health and Medical Research Council (NHMRC) of Australia [GNT1149990]
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The study evaluated persistent HIV-1 reservoir cells in an elite controller, revealing the absence of genome-intact and replication-competent HIV-1, suggesting a potential natural sterilizing cure of HIV-1 infection.
Background: A sterilizing cure of HIV-1 infection has been reported in 2 persons living with HIV-1 who underwent allogeneic hematopoietic stem cell transplantations from donors who were homozygous for the CCR5D32 gene polymorphism. However, this has been considered elusive during natural infection. Objective: To evaluate persistent HIV-1 reservoir cells in an elite controller with undetectable HIV-1 viremia for more than 8 years in the absence of antiretroviral therapy. Design: Detailed investigation of virologic and immunologic characteristics. Setting: Tertiary care centers in Buenos Aires, Argentina, and Boston, Massachusetts. Patient: A patient with HIV-1 infection and durable drug-free suppression of HIV-1 replication. Measurements: Analysis of genome-intact and replication-competent HIV-1 using near-full-length individual proviral sequencing and viral outgrowth assays, respectively; analysis of HIV-1 plasma RNA by ultrasensitive HIV-1 viral load testing. Results: No genome-intact HIV-1 proviruses were detected in analysis of a total of 1.188 billion peripheral blood mononuclear cells and 503 million mononuclear cells from placental tissues. Seven defective proviruses, some of them derived from clonally expanded cells, were detected. A viral outgrowth assay failed to retrieve replication-competent HIV-1 from 150 million resting CD4(+) T cells. No HIV-1 RNA was detected in 4.5 mL of plasma. Limitations: Absence of evidence for intact HIV-1 proviruses in large numbers of cells is not evidence of absence of intact HIV-1 proviruses. A sterilizing cure of HIV-1 can never be empirically proved. Conclusion: Genome-intact and replication-competent HIV-1 were not detected in an elite controller despite analysis of massive numbers of cells from blood and tissues, suggesting that this patient may have naturally achieved a sterilizing cure of HIV-1 infection. These observations raise the possibility that a sterilizing cure may be an extremely rare but possible outcome of HIV-1 infection.
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