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HIV-Elite-Controllers,

HIV Elite Controllers and Long-term Non-progressors

Elite controllers are defined as those individuals who have been infected with HIV but is able to achieve undetectable levels of virus (<50 copies/ml) without any medication. While long-term controllers are those who have been able to achieve low but detectable levels of HIV (<2000 copies/ml) without treatment.

There are many theories as to how these individuals are able to control the virus:

  • These individuals CD4 cells are less susceptible to infection by the HIV virus
  • Infected with defective strains of the HIV virus that makes the virus less able to produce copies of itself.
  • Individuals’ whose immune system is able to mount an effective response to the virus
  • Individuals’ immune system causes less inflammation when the HIV virus is encountered and thus limiting the exposure of the virus to CD4 cells.

There is a fair amount of evidence to suggest that perhaps the main mechanism that allows for control of the HIV virus is that an effective and potent immune response by an individual. Studies have shown that when only CD4 cells of elite controllers were isolated without CD8 cells, and then infected with HIV virus, the CD4 was just as easily infected as non-elite controllers thus giving evidence that the elite controllers CD4 cells were just as susceptible to HIV infection as non-elite individuals.

In recent months, researchers in Sydney, Australia has reported a case of a known HIV person who has spontaneously cleared HIV infection with no treatment. This patient was infected due to a blood transfusion back in 1981. The patient was able to suppress the HIV virus in his body through his own immune system and have undetectable levels of the virus since 1997. Most recently, they tried to look for traces of the HIV virus in his blood, intestines and lymph nodes but did not detect any traces of the virus, thus the researchers believe this is the first case of spontaneous clearance of HIV infection in humans.

So what factors may have contributed to this patient being able to clear the virus from his body?

  • The virus that originally infected that patient was lacking in a gene called nef. In HIV virus deficient in this gene, the virus replicates more slowly and thus is associated with lower viral loads.
  • The patient was born with 1 copy of a gene called CCR5. The gene is required for HIV to attach to human immune cells. Thus persons with only one copy of the gene would make it more difficult for the HIV virus to attach on to the immune cells. (See: CCR5 HIV Test)
  • It was also found that the patient’s immune cells were naturally more able to recognise a protein called gag made by the HIV virus. This protein is found on the surface of infected human cells. Thus allowing his immune system to better recognise cells that have been infected with HIV virus and aid in their destruction.
  • In addition, the patient was born with 2 specific immune-cell genes called HLA-B57 and HLA-DR13 and in combination allows his immune system to be more effective in responding to HIV infection.
  • As a result of his strong response by his CD4 cells as a result of the presence of the HLA-B57, he is able to mount a bigger immune response by his CD8 cells. CD8 cells are required to activate cytotoxic T cells which as the name suggests are immune cells that kills defective or infected human cells.

In essence, the combined effects of each of the above factors contributed to the clearance of the HIV virus from this particular patient. To replicate this combined effect artificially at this point in time is not possible. However, perhaps in the future with further development of gene therapy, we may be able to achieve this unique set of host factors to achieve clearance of HIV virus.


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