People With Mutated HIV More Likely To Survive

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Main Category: HIV / AIDS
Also Included In: Infectious Diseases / Bacteria / Viruses;  Genetics
Article Date: 21 Mar 2008 - 0:00 PDT

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According to a study published in the open-access journal PLoS Pathogens, South African researchers found higher survival rates for people who were infected with a mutated HIV strain that came from someone who has the genetic advantages to control the virus.

The investigators - CAPRISA (the Centre for the AIDS Program of Research in South Africa) researchers at the Universities of Cape Town, KwaZulu-Natal, Western-Cape and the National Institute of Communicable Diseases in South Africa - came to this conclusion after analyzing 24 newly infected people in Durban, South Africa and the genetic mutations in the virus.

Professor Salim Abdool Karim, Director of CAPRISA, notes that, "It is significant that the mutations to HIV which occur in a person with advantageous genes leads to a low viral load, even when the virus infects a new person who does not have these 'good' genes. Low viral load is a goal of several HIV vaccines as it means that these HIV infected people will be clinically well for longer and be less likely to spread the virus."

The HIV virus can avoid the immune system by mutating into forms that the human leukocyte antigen (HLA) system cannot notice. HLA genes tell the immune system that HIV is present, and therefore affect the rate that HIV progresses in infected individuals. Researchers do know that the virus can only avoid some versions of the HLA gene, such as HLA-B*57 and HLA-B*5801, if the virus mutates into a form with a smaller replication rate.

Two mutations - A146X and T242N in the Gag sequences of acutely infected HLA-B*57/5801 negative women - were used in the study and were associated with lower viral loads and higher CD4+ counts in these women up to a year post-infection. (HIV infection usually reduces the number of T cells possessing CD4 receptors.)

Both the A146X and T242N mutations have been previously identified as HLA-B*57/5801 immune evasion mutations, and the T242N mutation inhibits viral replication ability. Since the reproductive ability of the virus is compromised in people who are HLA-B*57 or HLA-B*5801 negative, they may have better survival prospects.

Team leader Williamson notes that there is a sophisticated interaction between the host and the virus that determines how a disease progressed. "While the role of host genetics is well established, this study shows that genetic polymorphisms in the transmitted virus can offer survival advantage to a newly infected person."

The study can ultimately change the way that HIV vaccines and immunotherapeutics are designed. If there is a complex network of mutations that can lead to better long-term survival rates, the knowledge can deeply affect what we know about the cause and development of HIV.

Transmission of HIV-1 CTL Escape Variants Provides HLA-Mismatched Recipients with a Survival Advantage
Chopera DR, Woodman Z, Mlisana K, Mlotshwa M, Martin DP, et al.
PLoS Pathogens (2008). 4(3):e1000033.
doi:10.1371/journal.ppat.1000033
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Written by: Peter M Crosta
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