MegaHAART at Acute HIV Infection
An interview of Jintanat Ananworanich, MD, PhD, Director of SEARCH and Deputy Director in Scientific Affairs of HIV-NAT, The Thai Red Cross AIDS Research Center, Bangkok, Thailand
Acute HIV infection is a unique moment in the history of HIV disease, the only moment when the retrovirus meets an intact immune system. Furthermore, as we know that the HIV reservoir is established early, at this disease stage, therapeutic interventions initiated at acute HIV infection have the potential to influence the natural history of the disease. Dr Jintanat Ananworanich has agreed to answer our questions on this issue.
Alain Lafeuillade: Could you please introduce a little bit yourself and the research you perform?
Jintanat Ananworanich: I received training in pediatrics, and allergy and immunology in the US and during the past 10 years, I have been coordinating clinical trials in Bangkok on antiretroviral therapy in children and adults. My main areas of interests are treatment of acute HIV infection and of multi-drug resistant HIV. The acute HIV infection work is done as part of a collaboration between the Thai Red Cross AIDS Research Center and the US Military HIV Research Program.
AL: What is, in your view, at stake during acute HIV infection?
JA: There are two key points that are at stake during acute HIV infection. One is to understand early HIV events, which includes knowing the types of HIV immune responses that occur and the dynamics of HIV virus. This could be crucial to inform treatment and vaccine immunogen choices. Number two is to test interventions during acute HIV infection that may shape disease burden and ultimately disease outcome. Interventions to reduce HIV-associated destruction and preserve HIV-specific immunity may be a prerequisite to achieving function cure or drug-free remission of HIV.
AL: What are the current proofs that ART should be initiated at this stage of the disease?
JA: We need more data before we can conclude that ART is beneficial in acute HIV infection. Evidence so far suggest that the massive gut immune destruction and microbial translocation during acute HIV infection sets the stage for ongoing immune activation and CD4 destruction in chronic HIV infection. The studies evaluating early ART have not shown a clear impact on HIV clinical outcome. These studies have some limitations. They were predominantly non-randomized studies, the sample sizes were small and the ART used were sometimes mono/dual NRTI and they did not consist of new drug classes. More importantly, many studies included patients who had been HIV-infected for as long as 6 months which may be too late. Therefore, it will be important to evaluate ART treatment with new drugs in a randomized study and in a population that is identified early, even before they seroconvert.
AL: How long should this therapy course last?
JA: There is not enough information to answer this question, but in order to know whether treating early will result in drug-free remission, treatment interruption will be necessary. The risk for serious non-AIDS events due to treatment interruption seen in the SMART study continues to be a concern; however, this may be less in early-treated AHI subjects who have preserved immunity and a limited HIV reservoir. The ongoing SPARTEC study that randomized acutely and recently infected patients to different lengths of ART will provide important insight into how long treatment needs to be.
AL: Is triple-drug therapy enough or do you have data showing that more is better?
JA: Our group is conducting a study in which we randomized acutely infected patients to a 5-drug (megaHAART) vs. a 3-drug regimen (standard HAART) during the first 6 months followed by standard HAART. The standard HAART regimen is tenofovir, emtricitabine and efavirenz whereas the megaHAART regimen adds raltegravir and maraviroc. We hope that this will provide some insight on whether adding drugs that block multiple phases of the viral life cycle will be more beneficial in limiting immune destruction and HIV reservoir.
Our preliminary immunologic data on megaHAART-treated patients will be presented at this year’s CROI in Boston
AL: What results can we expect in terms of HIV reservoirs reduction and drug-free remission?
JA: There are ongoing studies being conducted by IAVI and other groups that will provide insight into this question. Our preliminary immunologic data on megaHAART-treated patients will be presented at this year’s CROI in Boston. We found an increase in gut CD4+ CCR5+ T cells and a reduction in viral burden evidenced in both gut and plasma HIV RNA and DNA. Our next step is to assess this in more details and in the megaHAART vs. HAART groups. Our future plan is to interrupt treatment and evaluate drug-free remission.
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Key words: acute hiv infection, hiv reservoirs, megahaart