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Fast Rebound After Treatment Interruption in 9 of 10 With Low HIV DNA Reservoir

June 1, 2016

Nine of 10 people with a cell-associated HIV DNA level below 100 copies/106 cells had an HIV RNA rebound within 12 weeks after antiretroviral therapy interruption. The 10th person maintained HIV RNA control without drugs for more than 48 weeks, according to a study published in AIDS.

The SMART trial and other studies established that interrupting antiretroviral therapy (ART) during chronic infection results in higher rates of AIDS and non-AIDS diseases when compared with continued therapy. Yet elite controllers safely keep HIV replication in check without ever starting ART, and long-term viral control has been documented in a few individuals after interruption of ART for primary infection. Collaborators from several Paris centers conducted the ULTRASTOP study to see if patients with low cell-associated HIV DNA levels and excellent immune status while taking ART could interrupt treatment for extended periods.

ULTRASTOP aimed to recruit 15 adults in three cohorts of five participants with plasma viremia below 50 copies/mL for more than two years on ART begun during early chronic infection. Everyone had an HIV DNA level below 100 copies/106 peripheral blood mononuclear cells (PBMCs). All had a CD4-count nadir above 300 cells/mm3, a current CD4 count above 500 cells/mm3 and a CD4/CD8 ratio above 0.9. They interrupted ART with the plan to resume therapy if plasma viremia rebounded above 400 copies/mL, CD4 count fell below 400 cells/mm3 or an AIDS illness developed.

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The Paris team planned to recruit five participants for the second cohort if one person in the first cohort maintained control of plasma viremia eight weeks after interrupting ART. They planned to begin recruitment of the third cohort if two of ten patients in the first two cohorts retained viral control for eight weeks without ART. The primary endpoint was the proportion of participants who did not have to resume ART 24 weeks after stopping.

The study began with recruitment of 10 potential participants in the first and second cohorts. They had a median CD4 count of 1118 cells/mm3 (range 608 to 1494), a median CD4/CD8 ratio of 2.1 (range 1.4 to 2.6) and a median HIV DNA level below 66 cells/106 PBMCs (range <66 to 66). Participants had taken ART for a median of more than five years and had undetectable plasma viremia for nearly five years.

One person reached the primary endpoint of viral control for 24 weeks without ART and remained aviremic to week 56 as of the time of this report. The remaining nine patients in the first two cohorts had viral rebounds within 12 weeks of ART interruption -- two at week 2, six at week 4, and one at week 12. Median time to rebound measured four weeks. Median HIV DNA at the time of HIV RNA rebound rose to 106 copies/106 PBMCs. Treatment interruption resulted in a median CD4-count decline of 124 cells/mm3. These results did not justify enrollment of five participants for the third cohort.

All nine rebounders resumed ART and regained a viral load below 50 copies/mL within 12 weeks. No grade 3 or 4 adverse events or antiretroviral resistance mutations emerged during the ART interruptions.

The single participant who retained control of plasma viremia through 56 weeks had a viral load of 282 copies/mL at week 48. His CD4 count fell from 915 to 727 cells/mm3 through 48 weeks. Before treatment interruption, his viral load measured 187 copies/mL and his highest recorded viral load was 3063 copies/mL. His HIV did not carry a delta 32 mutation. The researchers could not identify a specific reason for long ART-free viral control in this person.

Mark Mascolini writes about HIV infection.


Copyright © 2016 Remedy Health Media, LLC. All rights reserved.




 

Reader Comments:

Comment by: LG (Bethesda) Fri., Jan. 13, 2017 at 8:16 pm UTC
HI Mark,

Great article. Just one comment: In the last paragraph you say the non-rebound patient's "HIV did not carry a delta 32 mutation". I gather you wanted to say "CCR5".

best,

LG
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Comment by: Christian (London ) Wed., Jun. 8, 2016 at 5:38 pm UTC
Did the nine rebounders resume the same combination of ART that they were taking before the interruption?
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Comment by: Tom (Chicago) Tue., Jun. 7, 2016 at 9:07 pm UTC
Hi,
I'd like to see more effort on getting everyone's "CD4/CD8 ratio of [to] 2.1 (range 1.4 to 2.6)."

I find that exceptional, and would like to learn how this was accomplished on a patient-by-patient basis.

How did early (earlier?) treatment figure into that ratio?

How did genetics figure into that ratio?

Can we use therapeutic vaccines (TAT, DermaVir) to boost the ratio?

Why are such obvious progressive lines of research seemingly ignored decades-in and decades-out?

I recently saw my CD4/CD8 T cell ratio jump from 0.9 to 1.3, for the first time in nearly thirty years after receiving a TDaP vaccination.

Can someone supply a list of papers from doctors who ran clinical studies aimed at investigating ways to increase the CD4/CD8 T cell ratio? I wonder what has already been tried, and in what cohort it was tried in. I assume that cohorts of young, healthy, recently infected AND on EARLY TREATMENT has always been ignored. True?

Thank you,
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