Compartmentalization of HIV resistance between blood and semen

Jade GHOSN, MD, Service des Maladies Infectieuses du Pr Bricaire, CHU Pitié-Salpétrière, 47-83 Boulevard de l’Hôpital, 75013 Paris (France).

Background: One consequence of HIV resistance development is the increasing risk of sexually transmitted resistant viral strains. Given the possible HIV compartmentalization, we wanted to compare the genotypic mutational pattern of both circulating and archived strains between blood and semen in heavily pretreated HIV-infected men. Material and Methods: Paired blood and semen samples were collected from HIV-infected patients harbouring resistant viral strains in blood plasma (BP). Quantification and genotypic resistance testing of HIV RNA were performed in BP and in seminal plasma (SP); and of proviral DNA in PBMC and in semen cells (SC). Clones of HIV protease gene were obtained to explore the diversity of viral quasi-species through a phylogenetic analysis. Pharmacological measurements of antiretroviral drugs were performed in both compartments. Results: Twenty HIV-infected men with therapeutic failure were enrolled. They had previously received a median of seven antiretroviral regimens. At inclusion, fifteen patients (75%) were on a median-four-drug combination, and five were off treatment. Median BP HIV RNA, PBMC proviral DNA, SP HIV RNA and SC proviral DNA loads were respectively: 4.77, 3.65, 3.16 and 1.77 log₁₀. Resistant HIV strains were found in the BP and PBMC of all patients, in the SP of 14, and in the SC of 5 patients. Overall, the blood and genital compartments exhibited different genotypic resistance patterns for six men (30%), with additional resistance mutations in semen for 4/6 patients. The phylogenetic analysis of clones of HIV protease gene proved viral strains in SP originated not only from a passive diffusion from BP, but also from a local production in semen. Despite optimal concentrations in BP, and unlike previously described, amprenavir and efavirenz achieved poor concentrations in SP. In contrast, tenofovir proved to concentrate in SP. Conclusion: Resistant HIV strains are frequent (70%) in the semen of heavily pretreated men, with genotypic resistance pattern diversity confirming HIV compartmentalization. Thus, the storage of archived proviruses might differe according to the anatomic reservoir considered. In the issue of sexual transmission, we also show that seminal plasma and semen cells may be differently involved in the spread of HIV.