‘How does HIV ‘hide’ to evade detection by the immune system?‘
HIV hardly ‘hides’ from or evades detection by the immune system. Rather, it preferentially targets and infects key immune cells, preferred ones being CD4, master orchestrator of immune responses, as well as a variety of such as and , cells critical in jumpstarting immune responses.
There’s more than one approach to study how HIV does what it does,
- A variety of experimental animal models with widely varying applicability to human HIV infection and AIDS.
- In vitro cellular and molecular studies that try to discern HIV interactions with different cell types.
- In silico modeling of how specific HIV molecules interact with host cell molecules.
Though they all help understand HIV, overall value of each such approach depends on the ratio of its pros and cons.
OTOH, though most HIV-infected individuals progress to irreversible, catastrophic AIDS without timely diagnosis and Rx with cART (Combination Antiretroviral Therapy), a few are either naturally resistant and prevent the infection itself or immunologically resistant and slow its progress considerably.
Such cases represent compelling natural experiments with the inbuilt incalculable advantage of having few or no experimental artifacts. Somewhat akin to examining a mirror image, understanding how HIV fails to subvert the immune systems of such patients offers a contrarian’s path to better treatments, maybe even functional cure as well as the realistic possibility of prophylactic or at least therapeutic vaccines.
Such natural HIV resistance can be broken down into tiers that track the infection cycle itself,
- The initial tier prevents infection.
- The next one prevents effective early viral replication.
- The last one controls chronic disease and asserts itself if given a helping hand with initial Rx.
The latter two tiers remain niche fields of research within HIV though given their ‘cure’ potential, they deserve far more attention and funding compared to the ever-burgeoning experimental animal model field with its surfeit of dubious results of questionable relevance to the human disease.
Natural HIV Resistance That Prevents Infection
Some individuals naturally resistant to HIV were found to have a 32 base pair deletion in thegene (1, , ). Called CCR5 ∆32, this discovery showed how important this cell-surface molecule is for human HIV infection to get going, namely, in entering T cells.
Natural HIV Resistance That Prevents Effective Early Viral Replication: Elite Controllers
Long-term non-progressors (LTNP) appear capable of resisting HIV to various degrees for anywhere from 7 to 20 years, even without antiretroviral Rx ().
This group includes the awkwardly labeled elite controllers (aka elite suppressors) and/or viremic controllers. Key hallmark of ECs is stable CD4+ T cell counts >500 cells/µl for >7 years. Within LTNPs, ECs ()
- Represent <1% of total HIV-1 infected population.
- Maintain circulating HIV-1 levels (as measured in plasma) at <50 copies/ml, which is below the limit of detection of standard commercial assays.
While some initially dismissed such relatively rare individuals as those who got infected with defective virus (6), understanding what is different about these individuals is now a fairly fertile research area simply because cumulative research data found that initial assertion to be inaccurate.
Rather, ECs appear to control HIV quite efficiently (see below from 6).
How? While a complete answer is still unavailable, studies that each examined relatively small groups of such individuals showed
- Noticeable quantitative and qualitative differences in adaptive immune responses, in both CD8 ( , , , ) as well as CD4 (11, ) T cells.
- Polymorphisms in important immunoregulatory genes such as HLA-B*5701 and HLA-B27 (13, 14, , , , ).
Natural HIV Resistance That Prevents Effective Late Viral Replication: Post-treatment Controllers
The most recent (first identified circa 2010), least studied and therefore least well-understood are the thus-far relatively tiny subsets of HIV patients who maintain control of virus replication for varying lengths of time after varying periods of initial cART (, , 21, , , 24), the so-called post-treatment controllers.
Advantages of this clinical picture simply write themselves. Reduced Rx cost while avoiding both the physical burden from long-term toxicity of cART as well as the possibility of developing viral resistance.
How to explain this phenomenon? By chance such patients might have started cART early enough after contracting HIV before it irreversibly damaged their immune system, such early intervention allowing their own anti-HIV immune responses to rebound and prevail (25,, ).
If such an observation pans out in independent, larger studies, better control, even functional cure of HIV may require not more protracted, expensive basic research nor newer, ever more expensive drugs but rather nothing more than a concerted public health effort to diagnose and treat HIV early in order to effectively tamp down early virus replication before it strikes body blows to the immune system’s capacity to control HIV by itself. Now wouldn’t that be a worthy Millennium goal?
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