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Are People With Low CD4s Getting Left Behind in Cure Research?

I had mixed feelings about the announcement a few days ago about two new clinical trials being launched by Sangamo Biosciences, which is in hot pursuit of a functional cure for HIV.

On the plus side it pleases me tremendously that Sangamo is moving swiftly with their technology--where CD4s or stem cells can be modified to resist HIV infection though the use of zinc fingers. Their pace compared to other similar biotechs has been pretty fast. So far, there have been no hiccups or signs of a problem. There have, however, been some intriguing findings.

In one trial of heavily treatment-experienced individuals, some of the study participants had stunning and sustained increases in their CD4 counts. In a second study, one of the participants by chance carried a natural mutation in his CD4s that made the cells partially resistant to infection. This is because the participants' CD4 cells have fewer functional CCR5 co-receptors on their surface, a coreceptor HIV needs to infect the cells. It looks like this study participant might have started controlling his virus almost completely during an interruption in his antiretroviral (ARV) therapy following the zinc finger treatment. If a person could go months or years without the need for ARVs this would, in essence, be a type of functional cure.

The two new trials announced by Sangamo represent a logical next step. The company is going to test their therapy in an entire group of people who have the same mutation as the patient mentioned above and then let them stay off of ARV therapy as long as their virus stays under control. A second similar study will be attempted in people without the mutation, but researchers will first give the participants a mildly immunosuppressive drug to make "space" for the new zinc-finger-modified CD4 cells.

While neither study would automatically (based on publicly available information) exclude people who's CD4s never rose very high on ARV therapy--a group scientists refer to as immunologic non-responders--both studies are emphasizing that success will only be measured based on people's viral load responses. In essence, if they can't get at least some people to undetectable and keep them there, the trials could be seen as a failure and this very promising development plan could be brought to a standstill.

I understand the need to aim for quick and demonstrative success when you don't have deep pockets and must constantly look for investments or partnership opportunities with bigger companies. That said, I would be happier if Sangamo would launch a third trial with the primary goal being to significantly elevate CD4 responses in immunologic non-responders and to look in more intensive ways at how functional those new CD4s are in protecting those individuals from health problems and opportunistic infections. Right now there are few promising treatments under study to boost CD4s in immunologic non-responders and I'd hate to see one of them demolished under the weight of lofty ambitions.

About four years ago at the International AIDS Conference in Mexico City, Tony Fauci gave a much-lauded talk about the possibility of a cure and his belief in it. In that talk, he highlighted that a functional cure or one that actually removed every last trace of HIV from the body (a sterilizing cure), would be most likely in people we caught within days or weeks after infection. I turned to a top AIDS researcher at the conference and asked whether this meant that people who'd lived with HIV for a really long time, particularly immunologic non-responders, would get left in the dust in the search for a cure. He winced, then said, "I hope not."

Me too.


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Comments on David Evans's blog entry "Are People With Low CD4s Getting Left Behind in Cure Research?"


My Viral Load has been undetectable since 2003; yet, I remain severely immunologically compromised. My CD4 is currently 84 and the high was 143 April 2009. The percentage has been 15, 16, 17 for the past 3 years. I have not been severely ill since September 2002 when I was critical.

My ARV medications are Truvada and Viramune.

I tell you all this because, I, too would like the research to include me. Where are the clinical trials being done and who can be a candidate?

Please keep me up-to-date.

I'd like to be included as a candidate as well. I've been HIV since 1986, Aids since 1994 (t-cells 6) and never have had a T cell count over 485 Right now 380, my Doctor say's this is "MY NEW NORMAL" I've been HCV since 2002 and failed on the interferon
I'm always depressed and have very little hope in the future. Maybe my being on a trial would help someone in the future.



I too have had a low CD4 count even though I have been undetectable since June of 1997. I have went off my treatment for a year at a time with no viral load rebound (I stayed un-detectable) but my t-cells would slowly go down while off treatment. The most my t-cells have been is around 300 but usually around 250.

keep me informed about the break through

Dear David,

This is an exciting discovery! My viral load has been undetectable for many years now; however, my CD4 count remains at a low around 300 and seem to raising extremely slow. Fortunately I have not had any opportunistic infections. How would it be possible to become apart of this trail study?


I have been Positive for over 25 years.
I have not responded to ARV's in the past. Within the last year my Doctor started on what he called the last combo's they could find.
Whithin a month my viral load was undetectable for the first time since infection.
Interestingly I have had succes in the past raising my CD4's but not viral. Now it is the opposite my CD4's are about 84. Just to add in my viral load was 365,000 pre new meds.
If there is a chance that I could participate in this study I would be very interested.

Mi edad es de 54 años,soy VIH positivo desde 1984, después de atacarme una neumonia me dijeron que era SIDA. Posteriormente he estado bajo tratamiento y aunque regularmente mis CD4 no han aumentado más de 250, mi carga viral esta indetectable. No tengo resfrios, ni diarreas, ni ningún otro padecimiento. Mi estado de salud es normal. El tratamiento que tengo es Norvir, Isentress, Truvada,Prezista y como profilácticos Acyclovir y Dapsone.
Me gustaría saber que posibilidades habria de poder participar en el estudio. Estoy cansado de tomar tanto medicamento.

Limiting "The Cure" to people who started treatment within "weeks" of infection is worthless to almost everyone who is and will become infected. The HIV establishment has been too cozy with this man for too long, and it shows in his cavalier attitude, complacency and pessimism. Why doesn't anyone start demanding this guy step aside? What does it say about our own "advocates" that he gets away with these sorts of statements?

As for Sangamo, has anyone asked whether they have any plans to eventually test this on non responders if it should prove effective?

I too would like to be a part of this study.

I am currently on a cocktail of kaletra, truvada (more so because I have chronic hep B and the truvada keeps my hep B vl in check) and isentress. I have had an undetectable HIV vl for years but my cd4 count continues to languish around 300.

Let me know if I would be a candidate for the trials.


I have been undetectable for 3 years, but my CD4's have fluctuated between 230 to 330. Presently it is at 260. My medications are Isentress, Viramume, Truvada. I have been very healthy with no health issues. I am 58 years old.

I too would like to be part of the trial study.


I would probably not be a candidate. I tested poz in 03. Viral load was undetectable 4 times before starting meds, but t cells gradually declined. Started meds in 09, Issentress and Truvada, after awful stint with Atripla, Immediately undetectable from the meds although, my t cells continued to fall into the AIDS zone...They have fluctuated in the upper 100s and mid two hundreds with the lowest being 140 and the most recent being 173. Its lame when you ask your docs why your tcells continue to fall and they just look at you like you're speaking another language. More research would be swell.

This is exciting and it loks like there is light at the end of the tunnel. Where is the study taking place. I am in Africa and zambia, How could we participate?

I would like more information about this study as well. I have been poz for 10 years now, have a CD4 of about 350. Have not taken any ARVs to date.

i would like to know when exactly this new development is going to be introduce in the market for we people living with HIV to buy? from Africa

I have been HIV positive for 27 years. My labs listed undetectable for about 10 years. I reached 825 CD4 once in 2007 but usually hover around 550-650. My percent remains around 28%.

Apparently, ranges vary for each person to match their "normal".

I like the new Idea of SB 928T Iam looking forwards for good news soon. I have been poz for 10 year and my CD4 last time was 565 and I never been in ARV meds and hopefully will go higher by God grace. Good job doctors keep pressing on.

This trial.sounds interesting to me. I am in Michigan and have not heard this til your article. I am undetectable but have a cd4 count of roughly 200. Information would be nice.

Andrew Soullier

Hi folks,

There is currently no study by Sangamo focused on people with low CD4s despite good ARV therapy. If they do respond to requests from me and other advocates I will definitely write a post and let you all know about it.

Warm regards,

My viral load has been undetectable since 2005 shortly after I began ARV therapy; yet like others who struggle with low counts, my CD4 has never been higher than 380. I've had no health issues thankfully. My doctor keeps assuring me that my counts will improve with time. Wishful thinking?

I have a son who is hiv positive and presently
in jail for a parole violation regarding drugs.

He has suffered through 2 strokes and I pray
for him everyday that he stays safe until he comes home in July. I pray for everyone with this disease and their familys. You have to stay
positive and never give up hope that one day
there will be a cure to end all the suffering.
take care of yourself to the best of your ability
I hope everyone has someone to talk to and lean on in the tough moments.

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About this Entry

This page contains a single entry by David Evans published on January 13, 2012 5:33 PM.

Could 10 Minutes of Your Time Help Cure HIV? was the previous entry in this blog.

New Rules Could Slash Care for Thousands With HIV is the next entry in this blog.

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