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The Body PRO Covers: The 1st International AIDS Society Conference on HIV Pathogenesis and Treatment

Viral Reservoirs

July 9, 2001

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  • Monitoring Intracellular HIV-1 Replication in Blood and Lymphoid Tissue in Antiretroviral Naive Subjects Receiving Amprenavir (APV), Abacavir (ABC), and 3TC (COLA3003 Study) (Abstract 25)
    Speaker: B. Patterson
    Authored by Patterson, B.; Becker, S.; Snidow, J.; Pobiner, B.; Landay, A.; Children's Memorial Hospital, Chicago, Illinois, United States


At the International AIDS Conference in Vancouver in 1996 the excitement was all about viral eradication. Dr. David Ho and his colleagues from the Aaron Diamond Institute in NYC theorized that with sufficiently potent and not-so-prolonged antiretroviral therapy complete eradication of HIV might be feasible. Based on mathematical modeling of the dynamics of HIV and CD4 lymphocytes, Ho predicted that three to four years of HAART might be enough to do this.

Unfortunately we soon learned that this theory was wrong and wrong in one major area. Though the CD4 lymphocytes are the primary target of HIV, there are other cells (namely, peripheral blood mononuclear cells, PBMCs) that are also targeted. And some of these cells are especially long-lived which would prolong the time necessary to eradicate HIV to more than fifty years of treatment.

Indeed we have seen in recent studies that even after prolonged success with antiretroviral therapy (viral suppression below the level of detectability by the most sensitive assays for several years) the virus will rebound in the blood if treatment is discontinued. Patterson and his colleagues have previously reported that the cause of this rebound is the persistence of HIV replication in CD4 lymphocytes as well as PBMCs in the blood from individuals on stable HAART regimens with undetectable viral loads. This replication not only can re-seed the blood if treatment is interrupted but could also be the site for the development and evolution of resistance mutations. In this current study the authors attempt to quantify the amount of HIV in these cellular reservoirs. They speculate that if quantification of HIV in reservoir cells is possible, we might have another method to assess the success (or failure) of antiretroviral therapy.

They obtained blood as well as tonsil and lymph node biopsy specimens from five previously untreated individuals participating in a clinical trial of APV, ABC and 3TC. They used a commercially available technique, the ViroTect In Cell HIV-1 Detection System, to measure the amount of intracellular HIV (as opposed to plasma or blood HIV that is measured by conventional viral load assays) present in these specimens before and after treatment.

They showed that they could quantify the percent of PBMCs and CD4 lymphocytes that were infected and then show the response to initiation of ART. The antiviral response in PBMCs was significant at 24 and 48 weeks of treatment compared to pre-treatment baseline levels. They further demonstrated that different cell types responded differently. The percent of infected CD4 cells in the biopsy specimens fell, whereas the percent of infected macrophages rose.

Patterson concluded that the ability to quantify the degree of HIV infection in specific cell types in specific locations might help the understanding of long-term viral control and failure. This could also lead to drug-by-drug or regimen-by-regimen reports based on these assays. The control of replication in cellular reservoirs might lead to improved success in overall control of HIV.


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This article was provided by TheBodyPRO.com. It is a part of the publication The 1st International AIDS Society Conference on HIV Pathogenesis and Treatment.
 



Please note: Knowledge about HIV changes rapidly. Note the date of this summary's publication, and before treating patients or employing any therapies described in these materials, verify all information independently. If you are a patient, please consult a doctor or other medical professional before acting on any of the information presented in this summary. For a complete listing of our most recent conference coverage, click here.
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