HIV persistence
Thursday 16 April 2009
Project
The introduction of highly active antiretroviral therapy (HAART) around 1996 has led to a significant decline in morbidity and mortality as a result of AIDS. However, total eradication of the virus is impossible with current HAART regimens due to viral persistence in various cellular reservoirs such as resting memory CD4+ T cells. Replication competent viruses could be isolated from CD4+ T cells even after 8 years of successful HAART. One potential mechanism by which HIV‑1 can persist for long periods in CD4+ T cells is latency. In this case, HIV‑1 preferentially infects activated CD4+ T cells and although most of them die as a result of the cytopathic effects of HIV‑1 infection, some infected effector cells return to a resting memory state carrying integrated proviral DNA.
One suggested mechanism to maintain the latent reservoir is a low level of ongoing viral replication. Viral replication under selective pressure of HAART will ultimately lead to emergence of drug-resistant viruses. Early studies have reported the appearance of these HIV-1 variants in patients after one year of HAART. More recently, however, it has been shown that clinically successful HAART may result in an arrest in viral replication and evolution. So far no study on the appearance of drug resistance has been performed for a period up to 8 years. Follow up over such a long period might be necessary to rule out viral evolution and emergence of drug resistance at a very low pace.
The goal of this project is to gain insight into the mechanisms that maintain the latent reservoir. Therefore, evolution of and acquisition of drug resistance mutations in protease and RT sequences will be determined in patient samples obtained before and after an average of 8.3 years of HAART.
Techniques
DNA/RNA isolation, Taqman real-time PCR, sequence analysis, phylogenetic analyses, HIV-1 infection
Duration
6 or 9 months
Contact
Dr. H.S.L.M. Nottet, tel. 088 75 535 05, H.S.L.M.Nottet@umcutrecht.nl
Dr. H.Snippe, tel. 088 75 576 28, H.Snippe@umcutrecht.nl
More info
Website UMC Utrecht - Medical Microbiology
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