Is it HIV or an Immune System which causes an Onset of AIDS?

Highlights

• HIV triggers pathogenesis that leads to an onset of AIDS (Therefore, answer for the above question is yes, it is HIV)
• Fast mutation rates of HIV cannot be used always to explain the lack of protective immunity against them leading to AIDS, since the identical HIV cannot cause an onset of AIDS in certain individuals.
• An individual with a homozygous mutation of CCR5 (CCR5delta³² ) is not susceptible to AIDS even with high titer of HIV in an individual (no, it is not HIV)
• When HST is infected and depleted by HIV, it will lead to an onset of AIDS. However, as long as HST is spared by a depletion mediated by HIV or reconstituted by HST with a homozygous mutant form (CCR5^D32 ), there will be no AIDS (again, it is an immune system which plays a critical role of getting AIDS, especially of an availability of HST).
• But it all starts from HIV infection (yes, it is HIV)

The simple question posed above is a very important one and the correct answer will undoubtedly help us to design an effective vaccine against the HIV.  There is an apparent shortcoming in our understanding on a pathology triggered by an HIV infection, otherwise we should have had an HIV vaccine probably 20 years ago as initially claimed after identifying HIV as an AIDS causing virus.  At that time and still now, it may not be an unrealistic claim, since we routinely generate seasonal flu vaccine within a very short period of time, within a few months or so after identifying the disease-causing flu virus.  Apparently, it has not been easy for generating an HIV vaccine even after two long decades with extensive and expensive efforts. To identify what our shortcomings are and why it is so different from other viruses,  let's think about an apparent question first.

Does an HIV infection cause an onset of AIDS?  
The simple answer for this question is, yes and no.  It is yes, because without HIV infection, there is no onset of AIDS.  However it is no, because certain individual with high titers of HIV still does not suffer from AIDS.  An infection of the same rapidly-mutating and deadly HIV is no different from that of influenza virus for those lucky individuals.  Why that is the case?  Does HIV escape immune responses by their fast mutation rate?  If that is the reason, it is not easy to explain this discrepancy.  It is safe to say that HIV triggers initial punch leading to an AIDS.  However, there is a certain immunological basis that can explain why an HIV infection, unlike any other pathogens, causes an onset of AIDS.  Once we understand the immunological basis that was initially triggered by an HIV infection, we will be able to counteract correctly.  Don't we understand even after close to three decades of identification of HIV as an agent for AIDS?  I am afraid to say that we are not.  We do not know how to counteract with them.  But we repeat ourselves from old technologies and empirical lessons.  Waiting for miracles and hold onto tight to a small possible success, only can be visible by minute statistical differences.  

What kind of immune response make them HIV infection so dangerous and different from other infectious agents?
In one word, it is the type of target cells that HIV infects and destroys.  Unlike any other infectious agents, HIV, especially R5-tropic HIV (HIV that uses CCR5 and CD4 molecules as their target for initial attachment to infect cells) infects, expands initially and destroys them all at the mucosal effector sites, such as gut, lung and reproductive organs.  Once HIV is expanded, they hide as a latent form and sometimes change their phenotypes with their fast mutation rates.  I called those CCR5 expressing CD4 T cells as HST, HIV Susceptible CD4 T cells, meaning CD4 T cells that are susceptible to R5-tropic HIV.  Once HST is depleted with a fast and furious pace, there is no looking back. The titer of HIV is high in the system and HIV is waiting for available target cells for their propagation.  Even with Highly Active Antiretroviral Therapy (HAART) cannot rescue HST once gone, while plasma level of HIV can easily be controlled by it.  However, there is a possibility that newly formed HST can be protected by the lack of available HIV in the plasma by HAART.  That could be the reason that HAART needs to be very quick once infection occur and it require lifetime long treatment once infected by HIV.

Lessons learned from studies with non-human primates
Another strong case, which supports the the lack of immune system causes AIDS is derived from studies of non-human primates infected with SIV (human homolog of HIV).  Certain native species of non-human primates are not susceptible to AIDS-like syndrome even after SIV infection.  Although it is very difficult to test whether all SIV are identical or due to differences in virulence factor among different SIV species, it suggests that it is not all viruses that causes AIDS-like syndrome in non-human primates, but differences in preserving HST.  Some preserve HST by the lack of of expression of CCR5 (Sooty mangabey), while others express less CD4 molecules (African green monkey).  Clearly saving HST is the prime significance for not getting AIDS.  In all experimental infection of SIV study, Rhesus macaque (Chinese monkey) is used as a control, since they are prone to AIDS while losing the majority of CCR5 expressing CD4 T cells in a very fast pace.

Conclusion
AIDS is triggered by an infection of HIV.  Without HIV, there will be no AIDS for sure.  However,  AIDS won't happen if HST is spared even in the presence of HIV infection.  Therefore, it is for sure that HIV is the main agent that infects and depletes the HST.  
The answer to the original question is yes, it is HIV and yes it is the lack of immune system, in particular HST, which are destroyed by the presence of R5-tropic HIV.

Key words
Epitope, HIV, AIDS, vaccines, CCR5, HST, delta32 CCR5 homozygous, HAART, African green monkey, Sooty mangabey, Rhesus macaque,