To the question 1 the answer is you are correct. Here is a summary of the stages:

HIV entry into a human cell requires the following steps in sequence.

The binding of HIV surface protein gp120 to the CD4 receptor

1.A conformational change in gp120, which both increases its affinity for a co-receptor and exposes gp41

2.The binding of gp120 to a co-receptor either CCR5 or CXCR4

3.The penetration of the cell membrane by gp41, which approximates the membrane of 4.HIV and the T cell and promotes their fusion

The entry of the viral core into the cell. 

Not sure what SNPs mean.

http://perspectivesinmedicine.cshlp.org/content/2/8/a006866.full

http://glycopedia.eu/e-chapters/Human-Immunodeficiency-Virus-the/The-mechanism-of-HIV-entry-to-the

Thank you so much Jeganathan and Daniel for your responses and papers. By SNPs I meant single nucleotide polymorphisms in the CD4 receptor. On a population level I would imagine there are SNP-variations in the CD4 itself, I was wondering if anyone has shown it to be associated with enhanced or diminished HIV-1 entry.  Going by what you sent Daniel, seems to me that there is substantial heterogeneity in the co-receptor usage (CXCR4, CCR5, CCR3 etc.) However, it is absolutely imperative that the virus binds to CD4?

Here's an empirical fact: In its Phase 2b trial, CytoDyn, Inc. demonstrated that a self-injected MAB that blocks CCR5 is an effective monotherapy for suppressing HIV viremia for at least 6 months (the duration of the trial).

Here's an empirical fact: In its Phase 2b trial, CytoDyn, Inc. demonstrated that a self-injected MAB that blocks CCR5 is an effective monotherapy for suppressing HIV viremia for at least 6 months (the duration of the trial).

HIV entry into cells is based on binding of gp120 to various receptors on the T cells and other cells of the macrophage/mononuclear lineage. For the latter, the virus utilises other receptors (example: DC-SIGN) for dendritic cells. For T cells, it utilises CD4 as the major receptor. That is the reason that only CD4 T cells allow HIV entry and replication. However, as suggested before, the binding of gp120 to CD4 alone does not lead to internalisation of the viral capsid. It requires a co-receptor which approximates the two membranes and allows gp41 to penetrate and causing fusion of both membranes. Although there are a number of these co-receptors, the most important are CCR5 and CXCR4.

Normally, during early infection, the virus is R5 tropic, which means that it utilises the CCR5 co-receptor for infecting cells. As the infection progresses and (normally after a number of years) for reasons not completely known as yet, the virus starts to utilise CXCR4 as well (either exclusively, and known as X4 tropic or both co-receptors, and hence known dual tropic). It is thought that when the virus becomes X4 tropic, it becomes more pathogenic and at this point, if the patient was in the latent phase of the disease, the viral load would start to go up and the CD4 count will start to drop. The patient is likely to be entering the late phase, when he/she would require treatment.

There are patients who have a 32 base pair deletion in the CCR5 co-receptor. Patients who are homozygous for this, are naturally resistant to HIV infection. The delta32-CCR5 mutation is found in around 1% of the population and first came to light in the early phases of the epidemic when it was shown that some sex workers, despite extensive exposure to HIV, rarely developed the infection, and seemed to be resistant to viral acquisition. The Berlin patient who is the only person who has been "cured" of HIV infection, has been given a delta32-CCR5 mutated leucocyte transplant on two different occasions.

There is only one inhibitor which is commercially available and that works by inhibiting co-receptor binding. This is Maraviroc and works by inhibiting binding to CCR5 only. It is a second/third line agent that is used if first line agents are not working. Due to its activity against one co-receptor only, the drug is only indicated following a tropism assay that shows that the virus in the particular patient uses only this co-receptor. Since Maraviroc is only used in highly experienced patients and as suggested above, the longer the patient has been infected the more likely it is for the virus to become dual tropic or X4, I am not sure how this seems to work in such individuals. Needless to say, Maraviroc cannot be used alone and has to be used in combination (hence, may explain why it works).

A good article that discusses HIV entry and use of co-receptors is:

Aiamkitsumrit B, Dampier W et al. Bioinformatic analysis of HIV-1 entry and pathogenesis. Curr HIV res 2014; 12(2): 132-161

Some other alternative coreceptors have been involved for viral entry... A lot of them...

Look for this review: "Use of (alternative) coreceptors for HIV entry" from Georgios Pollakis and William A. Paxton.

There is also a paragraph on host variations involving in viral entry (and there is a lot of them: deletion 32, coreceptors density at cells surface, ...)

But, if HIV seems to be able to use these alternative coreceptors in vitro, they don't seem to have a huge impact in vivo... Or, at least, they don't seem to have a huge impact on maraviroc efficacy on R5 HIV-1 strains.

I hope it will help.

Thank you all for such insightful responses. If I may extend these points, can it be argued then that it will be very difficult to prevent HIV-1 entry by these receptor-co-receptor analog-vaccines (it's not technically a vaccine) as shown by this paper which got a lot of attention? I'd like to know everyone's thoughts on this. 

http://www.nature.com/nature/journal/v519/n7541/full/nature14264.html

http://www.nature.com/nature/journal/v519/n7541/full/nature14205.html?WT.ec_id=NATURE-20150305

Maraviroc has very good results, had shown a non-inferiority compared to other HIV treatment and is used in real life since now a couple of years. It is not widely used today because of a very complex dosing and the necessity of tropism testing before any use (and that's not so easy to perform in clinical practice, for many reasons). Antibodies again CCR5 have also already shown their efficiency.

So... In my opinion, the limiting point of this approach is not the possible alternative coreceptor use (again these alternative coreceptors have still not demonstrated their role in vivo at this time), the limiting point may be the tolerability and feasability of such treatment in human... Wait and see...