Higher levels of Zidovudine resistant HIV in the colon compared to blood and other gastrointestinal compartments in HIV infection.
BACKGROUND
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 drug-resistant HIV-1 variants.


METHODS
Gut 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.


RESULTS
Phylogenetic 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.


CONCLUSIONS
This 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.
van Marle
Guido
G
Department of Microbiology and Infectious Diseases, University of Calgary, Calgary, Alberta, Canada. vanmarle@ucalgary.ca
Church
Deirdre L
DL
Nunweiler
Kali D
KD
Cannon
Kris
K
Wainberg
Mark A
MA
Gill
M John
MJ
D019380:Anti-HIV Agents / Q000494:pharmacology*; D001769:Blood / Q000821:virology*; D003106:Colon / Q000821:virology*; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification; D024882:Drug Resistance, Viral; D004386:Duodenum / Q000821:virology; D004947:Esophagus / Q000821:virology; D015658:HIV Infections / Q000821:virology*; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects / Q000302:isolation & purification*; D006801:Humans; D008198:Lymph Nodes / Q000821:virology; D008297:Male; D020125:Mutation, Missense; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D013270:Stomach / Q000821:virology; D019562:Viral Load; D015215:Zidovudine / Q000494:pharmacology*
D019380:Anti-HIV Agents; D004279:DNA, Viral; D015215:Zidovudine; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase