A Potential Cure for HIV?
By Hilary Leung
Hoping to embark on a career in healthcare, many sixth form students have been paying attention to recent developments in medicine. Earlier this year, a case report was published regarding the ‘London patient’, who was ‘cured’ of HIV with a stem cell transplant. The male London patient, who wishes to remain anonymous, was diagnosed with HIV in 2003 and advanced Hodgkin’s lymphoma (a rare cancer that develops in lymphocytes, a type of white blood cell) in 2012. Along with chemotherapy, his cancer was treated with a stem cell transplant, through which he received stem cells from a donor who was HIV resistant.
HIV infections result in the depletion of helper T (Th) cells, the host cells which aid the replication of the virus. The entry of HIV into the host Th cells is dependent on the virus binding to the CD4 receptor and CCR5 co-receptor on the Th cell’s plasma membrane. This interaction triggers the fusion of the viral and host cell membranes, allowing HIV entry.
HIV resistance arises from a mutation of the CCR5 gene, called CCR5-Δ32. This is a 32 base-pair deletion leading to a premature stop codon, terminating the synthesis of the polypeptide chain early. A non-functional CCR5 receptor is therefore produced, inhibiting HIV entry. Currently, 1% of the European population are HIV resistant as they are homozygous for the mutant allele (have two copies of the allele); 10% of the European population have a slower progression to AIDS as they are heterozygous for the mutant allele (only have one copy of the allele).
The stem cells that the London patient received were homozygous for the mutant CCR5-Δ32 allele, meaning that the Th cells produced from those stem cells are HIV resistant. As the patient’s own Th cells were being replaced by the HIV resistant Th cells, his HIV has been undetectable for 18 months. During this time, he has stopped taking the antiretroviral medication that inhibits replication of HIV, without which he previously would not have survived. However, as it is still too early to call this a cure, doctors consider him to be in ‘long term remission’.
This is the second successful case after Timothy Brown, then called the ‘Berlin patient’, who over a decade ago underwent a similar procedure and made history as the first person to be ‘cured’ of HIV. This suggests that the Berlin patient’s success was not anomalous. Although this is exciting, doctors do not consider the procedure an appropriate standard treatment for the millions living with HIV. Stem cell transplants entail considerable risks and side effects, which are not justifiable considering the effectiveness of current treatments for HIV, such as antiretroviral drugs. Having said this, more valuable is the understanding of HIV resistance and why this procedure works better for some than others, which may ultimately contribute to the development of a cure for HIV.