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# The only known case of an HIV cure

## Problem

For decades one of world’s deadliest infectious diseases has been AIDS, brought about by HIV. According to the World Health Organization, in 2012 there were an estimated 35, point, 3 million people living with HIV, and about 1, point, 6 million deaths due to AIDS. It is found on every inhabited continent, and while treatment has improved drastically, there is no known cure.
HIV is a cytopathic retrovirus – it carries its genetic information in RNA enclosed in a protein envelope surrounded with a heavy layer of glycosylation. Reverse transcriptase transcribes the RNA into DNA, which is then inserted into host cells. The main target of the virus are CD4 T cells, also known as T helper cells. HIV enters cells by binding receptor proteins on the host’s outer membrane. HIV proteins gp120 and gp41 bind the T cell’s CD4 receptor and a coreceptor. Most often, this coreceptor is chemokine receptor 5 (CKR-5). This co-receptor is coded for by the CCR-5 gene. Both receptors are required for the virus to enter and infect the cell.
Figure 1. Basic structure of HIV virus. RNA is contained within a capsid, surrounded by a lipid membrane. This envelope contains docking proteins such as gp120 and gp41. Image from wikimedia courtesy of the US National Institute of Health
Individuals homozygous or heterozygous for a mutation known as CKR-5Δ32 have shown resistance to certain strains of the virus. However, this mutation is only found in a small portion of the population.
Figure 2. Nucleotide sequence of CKR-5 wildtype (WT) and CKR-5Δ32
The only case of being cured of HIV is a man known as the Berlin Patient. In 2006, about 10 years after discovering he had HIV, Timothy Ray Brown was diagnosed with acute leukemia while living in Berlin. As part of his cancer therapy, Mr. Brown received two stem cell transplants from a donor who was homozygous for the CKR-5Δ32 mutation. At this time, he also stopped taking his antiretroviral therapy (ART) treatment. Within a year of the transplants, HIV was undetectable and the patient’s white blood count had drastically increased (Figure 3). Mr. Brown remains HIV-free to this day.
Figure 3. Genotype of CCR5 variants. The Berlin Patient’s CCR5 expression before and after stem cell transplant (SCT).