HIV CURE.........not so easy as they thought

[buginme2]

Anyway, Johns Hopkins just published a study yesterday that the whole "reservoir issue" is worse than previously thought and due to this a "cure" for HIV is a lot further away than previously thought.



There is always a silver lining and in this case I think it can help with further drug development.  It seemed as though with all the cure talk lately that new treatments had been put on the back burner.  Hopefully they can continue working on better treatments.

http://www.fiercebiotech.com/story/hopkins-study-reports-setback-hivaids-cure/2013-10-25

[Jeff G]

Not as easy as they thought ... snickers to self .

[Joe K]

...There is always a silver lining and in this case I think it can help with further drug development.  It seemed as though with all the cure talk lately that new treatments had been put on the back burner.  Hopefully they can continue working on better treatments...

Hey Bug,

While the news about the cure is disappointing, I do not think it is fair to characterize that new treatments are not being pursued, simply because there is work also being done on a possible cure.  Drugs take years to reach markets and for every one that makes it, there are another dozen or so that do not make it.  With all the new drugs that have come onto the market, it would seem that treatment research is fairly constant.

I realize the HIV funding is finite, however, we do not have to claim that searching for a cure, is somehow detrimental to further treatment development.

Joe

[Tadeys]

This news is not so new --Siciliano's team poster-published these findings in March of this year at some conference-- nor is this a surprise really to those in the field.  It just shows that the shock and kill approach is going to be somewhat dificult in and of itself without a therapeutic vaccine or some other help; Siliciano suggested this last year when he used a therapeutic vaccine with some shock and kill drug.
http://www.hiv-reservoir.net/index.php/the-news/353-hiv-reservoir-larger-than-previously-estimated.html

I kind of got a little depressed after reading this yesterday and got me thinking.  And then I remembered reading last month on how an antifungal med was used to induce apoptosis of viraly infected HIV cells and how it erradicated the reservoir in vitro...since there was no viral rebound 90 after stopping the medication; this has never been seen. I read the whole article last night (Drug-Induced Reactivation of Apoptosis Abrogates HIV-1 Infection) .Basically, this team at Rutgers is focusing on meds that induce apopotosis (cellular suicide) of HIV infected cell; this is diferent from the Shock and Kill approach. And this is somewhat similar to what was done a few months ago by Dr.  andrea Saravino and his team when they functionally cured monkeys: "adding to antiretroviral therapy two existing drugs, i.e. the gold salt auranofin and the chemosensitizing agent buthionine sulfoximine (BSO), an Italian and American research team, led by Dr. Andrea Savarino at the Italian NIH (www.iss.it), observed, after therapy suspension, a drug-free remission of the disease in the macaque AIDS model (i.e. the animal model most closely resembling human AIDS)." These drugs attack the infected cell instead of attacking the virus. It should be noted that Dr. Savarino had given up on Shock and Kill approach a few years ago.
 http://www.hiv-reservoir.net/index.php/the-news/430-drug-free-remission-of-aids-in-monkeys.html

Both Andrea Saravino and the team at Rutgers talk also about a form of auto vaccination that occurs when these viraly infected cells are killed en mass. This is new and fascinating. This mass killing of infected cells gets the immune system to kill HIV infected cells. These drugs are creating a therapeutic vaccine scenario in the body just by using medication.

The paper I read yesterday also gives some very promising information on a proof-of-concept trial that a co-autor --Saxena-- headed in South Africa using another apoptosis inducing medication(DEF) on HIV patients. The findings are unpublished thus far. Don't know why. But from what I read, the results seem big.

The following is some clips of information on the trail:
"In vivo, absent rebound is a rare event, achieved only by total lymphoid tissue ablation with subsequent transplantation of HIV-1 resistant CCR5n32/n32 stem cells [194,195], by complementing cART with hydroxyurea [148], or by very early start of cART [1]. Importantly, absent re-acquisition of pre- treatment HIV-1 RNA levels was also noted after DEF monotherapy in the proof-of-concept trial (Saxena et al., unpublished data)."

More info:
"To determine whether any productively infected cells survived the suppressive effect of CPX monotherapy, we examined the possibility of viral resurgence following withdrawal of drug. Cultures were maintained for extended post-treatment observation periods and monitored for the re-emergence of HIV-1 RNA (Fig. 7, period 3). Strikingly, after drug cessation (asterisk in Fig. 7) HIV-1 infection did not recur during post-treatment observation periods extending up to 90 days. Similar results were obtained in repeated experiments (not shown). DEF likewise produced off- drug suppression and consistent with apoptotic ablation of infected cells, reduced HIV-1 DNA to the limit of detection (Saxena et al., unpublished data). By contrast, monotherapy with standard antiretrovirals (including zidovudine, lamivudine, nevirapine, delavirdine, loviride, tenofovir, ritonavir, indinavir, saquinavir, stavudine, festinavir, didanosine, or emitricitabine [108,109]) uniformly fails to delay resurgence of HIV-1 production for more than 3 days off drug, despite an initial report that HIV-1 ‘‘became negative’’ [110]. Marked reduction of HIV-1 RNA without off-drug resurgence requires combination of several of these antiretrovirals [104–106].
We conclude that the apparent functional sterilization of HIV- infected primary cultures treated with CPX or DEF correlates with the preferential apoptotic ablation of HIV-infected cells, and thus the destruction of the proviral reservoir, by each of these drugs."

And then again:

"In a double-blinded proof-of-concept trial, a one week- course of oral DEF caused an acute zidovudine-like reduction of viral load in individuals who attained the threshold serum level of the drug, defined according to the concentrations required in culture for inhibition of HIV-1 gene expression and induction of apoptosis in infected cells as documented here and elsewhere [22,23]. The viral load reduction persisted throughout seven weeks of monitoring AFTER cessation of DEF (Saxena et al., unpublished data). These data suggest that medicinal activation of apoptosis in pathogenic infected cells is a viable antiviral strategy, for which we propose the term ’therapeutic reclamation of apoptotic proficien- cy’ (TRAP). Related approaches using recombinant protein constructs rather than small molecules, have been tested against several viruses in cell culture and a mouse model [118,119]. We infer that the TRAP concept has general applicability for the termination of viral infections."
 

Why awaken the bee hive when it can be set on fire? 


http://www.plosone.org/article/fetchObject.action?uri=info%3Adoi%2F10.1371%2Fjournal.pone.0074414&representation=PDF

[buginme2]

Hey Bug,

While the news about the cure is disappointing, I do not think it is fair to characterize that new treatments are not being pursued, simply because there is work also being done on a possible cure.  Drugs take years to reach markets and for every one that makes it, there are another dozen or so that do not make it.  With all the new drugs that have come onto the market, it would seem that treatment research is fairly constant.

I realize the HIV funding is finite, however, we do not have to claim that searching for a cure, is somehow detrimental to further treatment development.

Joe

I want saying that due to funding.  I know research takes years. However, if you look at the drug dependent pipeline while there are a few compounds in phase two and three research there are not many new phase one studies to research new drug compounds.  There has been a reduction in hiv drug research as of late.  Hopefully, witha greater understanding that no, hiv is not being cured next week, the need of new compounds can be realized.

[GoForIt]

Technically this is a good thing.  More information is always better.  The more information the have about this virus the more they can understand it.  So its not going to be "easy".  It will take some real smart people to beat this.  But the more we know the better chance we have.

[geobee]

I've always thought the "shock and kill" approach to be a little iffy.  I mean, all it takes is one little virion to reignite the infection.  In a few weeks you could have a high VL and you're back where you started.

My money is on that guy in Oregon -- Picker? -- who's working with the CMV cross-bred with HIV.  Seems to me we're going to need a virus, such as CMV, that spreads to all parts of the body that is constantly priming us with antibodies to wipe out HIV.

PS -- don't say it often but I like this forum a lot.  Check it every day!

[WillyWump]

Technically this is a good thing.  More information is always better.  The more information the have about this virus the more they can understand it.  .

I agree with this. While disappointing, this "reservoir issue" being more difficult than previously thought, can move us forward and allow us to look at other avenues or more novel ways to attack the reservoirs. ANY new discoveries in this field is progress.

-Will (disappointed but hopeful)

[Hoyland]

Though this news is disappointing all is not lost. While HIV may hide away in the DNA of more cell than was originally known about, the new treatments being trialled by Calimmune and the CoH are both DNA based. So while the virus may be able to initiate replication from within more cells, so to the treatment is constantly being produced in the body. This means that if these new treatments work, they have the potential to prevent re-infection without the need for further mediation. This means that the size of the reservoir would have no impact on the outcome of the treatment.

[sensual1973]

we can still live on meds,and meds are getting better (period).

[buginme2]

Technically this is a good thing. 

Way to make lemonade out of a lemon.

There is always a silver lining.  I absolutely agree that all research even the ones that show something doesn't work move the science forward and in the long run can be beneficial. 

Even after thirty plus years there is still a lot we/they don't know about this virus. 

Personally, I think all the cure talk over the past year may have got ahead of itself.

[Zoob626]

  after more than 30 years  and now thy say its not so easy as they thought !!!
WE knows its not so easy  We need smart researchers to eradicate HIV not some news after many many years thy say  not so easy at we thought