Evidence of genotypic resistance diversity of archived and circulating viral strains in blood and semen of pre-treated HIV-infected men.
OBJECTIVE
To study the genetic diversity of drug-resistant HIV strains present in blood and in semen, especially those archived in peripheral blood mononuclear cells (PBMC) and non-sperm cells (NSC).


METHODS
Paired blood and semen samples were collected from twenty heavily pre-treated HIV-infected men. HIV RNA in blood plasma (BP) and seminal plasma (SP), as well as proviral DNA in PBMC and NSC were quantified and used for resistance genotyping. Phylogenetic analysis of protease gene clones was used to explore the diversity of the viral quasi-species.


RESULTS
Median BP HIV RNA, PBMC proviral DNA, SP HIV RNA and non-sperm cell proviral DNA loads were respectively: 4.77, 3.65, 3.16 and 1.77 log10 copies per ml or per 10 cells. Resistant HIV strains were found in the BP and PBMC of all the patients, in the SP of 14 patients, and in the NSC of five patients. Overall, the blood and genital compartments exhibited different genotypic resistance patterns in six patients (30%), with additional resistance mutations in the semen of four patients. Phylogenetic analysis of clones of HIV protease gene showed that viral strains in SP originated not only from passive diffusion from BP, but also from local production in semen. The storage of archived proviruses differed according to the anatomic reservoir.


CONCLUSIONS
HIV resistant strains are frequent (70%) in the semen of heavily pre-treated men, and the diversity of genotypic resistance pattern confirms HIV compartmentalization. Thus, the risk of sexual transmission of resistant strains can only be partly predicted by standard tests applied to BP.
Ghosn
Jade
J
Laboratoire de Virologie, EA MRT 3620 Université R. Descartes, CHU Necker, Paris. jade.ghosn@psl.ap-hop-paris.fr
Viard
Jean-Paul
JP
Katlama
Christine
C
de Almeida
Marta
M
Tubiana
Roland
R
Letourneur
Franck
F
Aaron
Laurent
L
Goujard
Cécile
C
Salmon
Dominique
D
Leruez-Ville
Marianne
M
Rouzioux
Christine
C
Chaix
Marie-Laure
ML
D000328:Adult; D003430:Cross-Sectional Studies; D004279:DNA, Viral / Q000032:analysis; D024882:Drug Resistance, Viral / Q000235:genetics*; D014644:Genetic Variation; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D016333:HIV Protease / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000145:classification / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010802:Phylogeny; D010949:Plasma / Q000821:virology; D012367:RNA, Viral / Q000032:analysis; D012661:Semen / Q000821:virology
D004279:DNA, Viral; D012367:RNA, Viral; D054303:HIV Reverse Transcriptase; D016333:HIV Protease