Almost 30 years ago, the human immunodeficiency virus (HIV) was discovered and described as the causative agent of AIDS. Since then, a lot of efforts have been made to find a cure for HIV infection. However, eradication of HIV from infected individuals has not been achieved so far. Even though antiviral therapy (ART) is available for patients in many countries, this therapy has to be sustained lifelong. Furthermore, there is scientific evidence for a reservoir of cryptic viral replication in the face of highly active antiretroviral therapy (HAART).
The aim of this project was to define the anatomical reservoir of covert viral replication in HIV-1 infected individuals on HAART. Therefore, we examined the presence of viral replication intermediates (1- and 2-LTR episomal cDNA) in gut-associated lymphoid tissue (GALT), lymph nodes and peripheral blood mononuclear cells (PBMCs) obtained on initiation of therapy and after six months of undetectable viremia. We compared the frequencies of episomal cDNA at baseline and at six months post HAART initiation and found that ongoing replication persisted during HAART in all patients. Especially in ileum and lymph nodes elevated frequencies of episomal HIV DNA were detected and also PBMCs contained episomal HIV DNA. The antiretroviral drug regimen used in this study was not able to suppress viral replication efficiently. Therapy might have to be intensified and other classes of antiretroviral drugs are needed to suppress this ongoing replication.
HIV reservoirs are a major obstacle that has to be overcome to be able to eradicate HIV from infected patients. This study aimed to improve the knowledge about HIV reservoirs of ongoing infection in the face of HAART.