Is this a valid principle of curing HIV?

Question

I have a set of questions actually, it will be very helpful if you answer them in order.

1. Where does the HIV virus hide (during incubation period)? Let answer be X cell.

2. Is X cell in the bloodstream?

3. What parts of the HIV are constant for all its version? (I suspect it's Reverse Transcription Protein, Glycoprotein 120 and 41) Let answer be Y.

4. Is there a chemical that can destroy Y?

5. Is Y present in the normal Human body?

6. If Answer to question 2 is yes and that to question 5 is no can we inject the said drug into the bloodstream so that it can wipe out the virus?

Answer 1

HIV hides in a number of known cells and unknown cells. Although most of the damage of HIV is caused by its infection of shorter lived cells, long lived cells which it infects includes anything with adequate receptors including memory T cells, dendritic cells, macrophages and some glial cells too. These cells are found widespread in the body from tissues to the blood stream. HIV also infects an as of yet unknown pool, which is thought to be the cause of rebound after HART (Highly Active Retroviral Therapy) is stopped.

The constant parts are not exactly there. Every part of HIV can essentially mutate and does. In functional HIV particles (which surprisingly make up a tiny proportion of total HIV particles in an infected individual), the epitopes you mentioned are mostly constant.

Destroying them is impossible as of yet and hence no cure for HIV. It is hard to destroy a particular protein. We could make HIV that doesn't make these proteins (it would then rapidly mutate until it did, or be non-functional to the point it was an awful vaccine not inducing a particularly adept CD8 response). Otherwise we could block either these proteins themselves or that which they bind. There is a group of individuals with the delta 32 mutation which blocks CCR5 preventing infection, however this is rare. For the most part most individuals are susceptible as CD4 and CCR5 are highly conserved amongst humans. We would benefit therefore from inhibitors of these proteins themselves, however due to glycosylation generally our antibodies are terrible at inhibiting the glycoproteins. Reverse transcriptase inhibitors exist and are in fact very important as part of HART.

HIV came from chimpanzees. In their natural host the HIV equivalent (SIV) doesn't cause immunosuppression. HIV doesn't infect quite a few primates due to restriction factors which do not exist in humans or do not target the same things. Then of course there's the matter of the lack of the correct receptors. There's ongoing research if there's a chemical that does cure HIV however there isn't a subset of individuals where this occurs to study. HIV resistance is normally due to elite control of the virus due to specific genetic features that make the immune system target the best least variable, most deleterious (if HIV mutates them to escape) epitopes. If we could get everyone to respond to these epitopes that would be great (see a billion vaccine trials for HIV) otherwise if we could flush out the cells where it hides latently integrated (our current therapy and the immune system can only target cells where HIV is constantly replicating).

Answer 2

To answer your title question: Yes, that is a valid principle of curing HIV. In fact that's pretty much the basic idea behind treating any infection.

• 1) HIV strains use a combination of two receptors to enter a cell: CD4 and either CXCR4 or CCR5. It can infect and hide out in any cell which expresses both of these receptors; namely CD4+ T cells and some macrophages.

• 2) Yes. Except that there are populations of dormant CD4+ T cells in some hard-to-reach tissues such as lymph nodes.

• 3 & 4) There are currently five strategies against HIV, and each strain may be vulnerable against one of them but not another - or may develop resistance during treatment. This is why HAART (highly active anti-retroviral therapy) always comprises drugs of three different strategies. An article recommended to me on this is Shattock and Rosenberg, 2012: Microbicides: Topical Prevention against HIV. Or in particular, this graphic from the article is a great summary: http://perspectivesinmedicine.org/content/2/2/a007385/F1.expansion.html. Briefly: Drugs either inhibit viral entry into a cell by blocking the receptors mentioned above; or they target the viral reverse transcriptase (two strategies for this one), integrase or protease. *)

• 5) No - although partial activity by the drugs against human enzymes is the cause of side effects.

• 6) Yes, and we are doing so already (or rather, take them orally - no need for bothersome injections). The only problem is that the above-mentioned dormant cell populations are already infected and have integrated HIV, but it is not being active and hence not noticed by the immune system and not affected by our drugs. As long as HAART is maintained, viral loads in the blood are reduced to near-zero and the patient is for all intents and purposes healthy (including not transmitting HIV) - any latent virus that activates will immediately be wiped out. However, when HAART is interrupted even briefly, the virus can relapse.

Reaching those dormant populations is the focus of current research. If a person starts HAART very shortly after initial infection, before the virus can reach those populations, it is possible to cure them.

In terms of third world, the problem is not the drugs but getting them to the people who need them (money, transport, distribution, legal systems, civil wars etc.)

*) These are not simply 'chemical X from virus' and 'destroy chemical X'. Our drugs do not destroy the viral particles themselves but prevent them from replicating in a live system. If you mix HIV particles and the drugs in a test tube, leave it for 20min, filter the particles out and inject them into somebody, you will still infect them. There has probably been research into antibodies to target viral particles but I don't know any detail of this.