Treating Acute HIV Infection PDF Print E-mail
Written by Alain Lafeuillade   
Thursday, 24 March 2011 09:34

Treating Acute HIV Infection : where we are and where we go

An interview of Martin Markowitz, The Aaron Diamond AIDS Research Center, New York, USA

MarkowitzThe Markowitz Laboratory at the Aaron Diamond AIDS Research Center engages in translational and clinical research addressing issues of HIV-1 pathogenesis and treatment. Laboratory-based research is performed at the Aaron Diamond AIDS Research Center whereas all clinical studies are performed at The Rockefeller University Hospital. Apart from continuing to explore novel treatments for acute and early HIV-1 infection, the laboratory is also actively involved in the development of new agents to treat HIV-1 infection.

Following the recent presentation given by Martin Markowitz at CROI, he kindly accepted to answer a few questions... 


Alain Lafeuillade: what are the certainties in terms of benefits when treating at the acute stage of HIV-1 infection?
Martin Markowitz: As you are well aware we have been treating acute infection aggressively for many years. The certainties are that the intensity and duration of symptom in the acute phase will be reduced and shortened with ARVs. It is my opinion that patients treated during acute and early infection are more likely to have excellent treatment responses- both virologically and immunologically- for example after treating nearly 400 patients over the years we have had but 2 subjects who started treatment with drug susceptible virus and failed with drug resistant HIV (generally with just an M184V) and in both issues of non adherence were the cause.  Perhaps this is a reflection of the patient population that I see, however, this rate of virologic success is hard to duplicate. In addition in general the vast majority of patients treated during acute and early infection have normal CD4 levels and they restore their CD4/CD8 ratios above 1.0. As has been documented by many, HIV specific immune responses are preserved in those treated early. We also published over 10 years ago that persistent immune activation during treatment was higher in patients treated during chronic infection compared to those treated during acute infection- perhaps due to differences in residual viral burden which is higher in patients treated during chronic infection.

AL: Do we have any clues on the duration this treatment should have to be beneficial in the long-term?
MM: This is a tough question to answer- but at this point most of our patients who initiate treatment during acute and early infection stay on treatment. However a randomized study of early versus delayed treatment was just presented at the recent CROI in Boston (abstract 161 by Girjsen et al) which showed that 24 weeks of treatment resulted in lower viral setpoints and reduced time on ARVs when compared to no treatment.

AL: At the last CROI you presented a study showing than 5 drugs do not perform better than 3 at this stage. Was it unexpected for you? Will your future trials at acute infection definitively contain only 3 anti-retrovirals?
MM: At the time I designed the study we asked whether persistent low level viremia was the result of ongoing cryptic viral replication- and thus the primary endpoint was powered to answer this question- by the time we were able to do the 48 week analyses the intensification studies had suggested that low level viremia was not a consequence of ongoing viral replication.
That said, we did a fair amount of additional virology to determine whether increasing the # of drugs from 3 to 5 would make a difference and at 48 weeks we are hard pressed to see differences.

AL: We would have expected a difference in proviral DNA levels in the 5 drugs arm due to the different mechanisms of action of maraviroc and raltegravir, how do you explain that it was not the case?
MM: I would differ with you here. Cells harboring proviral DNA were infected pretreatment and this pool persists during treatment. We would only expect a difference if there is ongoing replication during ART that is constantly replenishing a slowly decaying pool of latently infected cells. This does not seem to be the case.

AL: If the establishment of the HIV-1 reservoir cannot be prevented at acute infection, does that mean that any intervention is doomed to failure?
MM: It depends on your goals of therapy. I will say categorically that we cannot cure HIV infection with ARVs alone- be it 3-drug, 4-drug or 5-drug regimens. We will need to find adjunctive therapies to deal with persistently infected cells.

AL: What are the next strategies you plan to test at acute infection, if you can tell?
MM: We have gone back to the 3-drug model to suppress patients and reduce the total viral burden…we hope that adjunctive immune based therapies and purging agents may be developed…I have the right patients to test novel approaches.- however right now we are waiting for something new and exciting to emerge.



Key words: acute HIV infection, hiv reservoirs, proviral HIV DNA
Last Updated on Thursday, 24 March 2011 09:51
 

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