Abstract
BackgroundThe gut-associated lymphoid tissue (GALT) is the largest lymphoid organ infected by human immunodeficiency virus type 1 (HIV-1). It serves as a viral reservoir and host-pathogen interface in infection. This study examined whether different parts of the gut and peripheral blood lymphocytes (PBL) contain different drug-resistant HIV-1 variants.MethodsGut biopsies (esophagus, stomach, duodenum and colon) and PBL were obtained from 8 HIV-1 infected preHAART (highly active antiretroviral therapy) patients at three visits over 18 months. Patients received AZT, ddI or combinations of AZT/ddI. HIV-1 Reverse transcriptase (RT)-coding sequences were amplified from viral DNA obtained from gut tissues and PBL, using nested PCR. The PCR fragments were cloned and sequenced. The resulting sequences were subjected to phylogenetic analyses, and antiretroviral drug mutations were identified.ResultsPhylogenetic and drug mutation analyses revealed differential distribution of drug resistant mutations in the gut within patients. The level of drug-resistance conferred by the RT sequences was significantly different between different gut tissues and PBL, and varied with antiretroviral therapy. The sequences conferring the highest level of drug-resistance to AZT were found in the colon.ConclusionThis study confirms that different drug-resistant HIV-1 variants are present in different gut tissues, and it is the first report to document that particular gut tissues may select for drug resistant HIV-1 variants.
Highlights
Science has been confronted with the problem of drugresistance virtually since the introduction of the first antiretroviral drugs to treat infection by human immunodeficiency virus type 1 (HIV-1)
We recently showed that HIV-1 quasi-species varied within different parts of the GI tract of pre-HAART patients, indicating that HIV-1 replication in the gut is compartmentalized [23]
We have extended these observations to show that variability exists in the distribution of drug-resistant variants in different gut tissues and peripheral blood lymphocytes of these pre-HAART patients
Summary
Science has been confronted with the problem of drugresistance virtually since the introduction of the first antiretroviral drugs to treat infection by human immunodeficiency virus type 1 (HIV-1) (reviewed in [1]). The development of many new NRTI, non-nucleoside RT inhibitors (NNRTI), and protease inhibitors (PI) offered additional treatment options in cases of drug-resistance. It offered the possibility of combination therapies (i.e. highly active antiretroviral therapy (HAART)) able to. The gut-associated lymphoid tissue (GALT) is the largest lymphoid organ infected by human immunodeficiency virus type 1 (HIV-1). It serves as a viral reservoir and host-pathogen interface in infection. This study examined whether different parts of the gut and peripheral blood lymphocytes (PBL) contain different drugresistant HIV-1 variants
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