Human prostate supports more efficient replication of HIV-1 R5 than X4 strains ex vivo

<p>Abstract</p> <p>Background</p> <p>In order to determine whether human prostate can be productively infected by HIV-1 strains with different tropism, and thus represent a potential source of HIV in semen, an organotypic culture of prostate from men undergoing prostatic adenomectomy for benign prostate hypertrophy (BPH) was developed. The presence of potential HIV target cells in prostate tissues was investigated using immunohistochemistry. The infection of prostate explants following exposures with HIV-1 R5, R5X4 and X4 strains was analyzed through the measure of RT activity in culture supernatants, the quantification of HIV DNA in the explants and the detection of HIV RNA+ cells <it>in situ</it>.</p> <p>Results</p> <p>The overall prostate characteristics were retained for 2^1/2weeks in culture. Numerous potential HIV-1 target cells were detected in the prostate stroma. Whilst HIV-1 R5_SF162strain consistently productively infected prostatic T lymphocytes and macrophages, the prototypic X4_IIIBstrain and a primary R5X4 strain showed less efficient replication in this organ.</p> <p>Conclusion</p> <p>The BPH prostate is a site of HIV-1 R5 replication that could contribute virus to semen. A limited spreading of HIV-1 X4 and R5X4 in this organ could participate to the preferential sexual transmission of HIV-1 R5 strains.</p

Prevalence of HIV-1 drug resistance in treated patients with viral load >50 copies/mL in 2009: a French nationwide study

Background Surveillance of HIV-1 drug resistance in treated patients with plasma viral load (VL) >50 copies/mL. Methods The protease and reverse transcriptase (RT) genes were systematically sequenced in samples from 756 patients with VL >50 copies/mL in 2009. The genotyping results were interpreted for each antiretroviral drug (ARV) by using the ANRS algorithm v21. Weighted analyses were used to derive representative estimates of percentages of patients. Prevalence rates were compared with those obtained in 2004 among patients with VL >1000 copies/mL. Results Sequences were obtained for 506 patients. Sequencing was successful in 45%, 80% and 96% of samples with VL of 51-500, 501-1000 and >1000 copies/mL, respectively. Resistance or possible resistance to at least one ARV was observed in 59% of samples. Overall, 0.9% of samples contained viruses resistant to all drugs belonging to at least three drug classes. All resistance prevalence rates were significantly lower in 2009 than in 2004. Conclusion In France, where 86% of patients were receiving combination antiretroviral therapy in 2009, only 15.0% of patients had a VL >50 copies/mL, suggesting that only 8.9% of treated patients could potentially transmit resistant viruses. Only 0.08% of patients harboured viruses fully resistant to at least three antiretroviral drug classes. Further studies are needed to determine whether resistance continues to decline over tim

HIV-1-infected patients from the French National Observatory experiencing virological failure while receiving enfuvirtide

Objectives We studied gp41 mutations associated with failing enfuvirtide salvage therapy. Methods This multicentre study involved patients with HIV-1 plasma viral load (pVL) > 5000 copies/mL after at least 3 months of uninterrupted enfuvirtide therapy and with plasma samples available at inclusion (T0), at initial enfuvirtide failure (T1) and at last follow-up visit during continued failing enfuvirtide therapy (T2). The HR-1 and HR-2 domains of the gp41 gene were sequenced at T0, T1 and T2. Results Ninety-nine patients were enrolled. At baseline, the median pVL and CD4 cell count were 5.1 log copies/mL and 72 cells/mm3, respectively. Based on the ANRS Resistance Group algorithm, the proportion of patients harbouring viruses with enfuvirtide resistance mutations increased significantly between T0 and T1. In the HR-1 domain, the V38A/M, Q40H, N42T, N43D and L45M mutations wereselected (P < 0.02). In the HR-2 domain, no mutations were significantly selected during the follow-up. None of the mutations was associated with a CD4 cell count increment. Conclusions Mutations selected during failing enfuvirtide salvage therapy are mainly located in the HR-1 domain of the gp41 gene, between codons 38 and 45. No mutations were associated with an increase in the CD4 cell coun

Place de l'atazanavir dans la prise en charge du patient infecté par le VIH-1 dans un service clinique

RENNES1-BU Santé (352382103) / SudocSudocFranceF

Impact des mutations de résistance sur la réponse virologique au Kaletra®

LYON1-BU Santé (693882101) / SudocRENNES1-BU Santé (352382103) / SudocSudocFranceF

Intérêt du génotype de résistance dans le choix d'une nouvelle stratégie thérapeutique incluant l'abacavir chez des patients VIH+ prétraités

LYON1-BU Santé (693882101) / SudocRENNES1-BU Santé (352382103) / SudocSudocFranceF

Données récentes sur le VIH-2 et intérêt de la quantification de l'ARN-VIH-2 plasmatique par RT-PCR en temps réel

LYON1-BU Santé (693882101) / SudocRENNES1-BU Santé (352382103) / SudocSudocFranceF

Evaluation de la prise en charge thérapeutique de la grossesse chez les femmes séropositives

LYON1-BU Santé (693882101) / SudocRENNES1-BU Santé (352382103) / SudocSudocFranceF

Etude d'une cohorte de patients infectés par des VIH-1 de sous-type non-B versus B (comparaison de données démographiques, du polymorphisme et caractérisation des mutations acquises à l'échec d'un premier traitement antirétroviral)

Alors que plus de 90% des infections VIH-1 dans le monde sont liées à des sous types non-B, les connaissances sur les mutations de résistance de ces virus et leurs implications cliniques sont encore limitées. Les données concernant 472 patients infectés par des VIH-1 Non-B (N=227) et B (N=245) ont été comparées dans le but de caractériser les mutations de résistance acquises à l'échec d'un premier traitement antirétroviral après avoir analysé le polymorphisme avant initiation de cette première c-ART. Des données épidémiologiques et immuno-virologiques sont également confrontées afin d'évaluer la réponse au traitement des deux groupes de patients. Bien que le polymorphisme naturel soit différent en fonction des sous-types, la réponse au traitement ne semble pas modifiée nos résultats suggèrent de plus que la diversité des VIH-1 ne joue pas un rôle majeur dans la sélection des mutations de résistance aux antirétroviraux.Despite the fact over 90% of HIV-1 infections worldwide are associated with non-B subtype, knowledge of resistance mutation in these viruses and their clinical implications are still limited. Data on 472 patients infected with HIV-1 Non-B (N=227) and B (N=245) were compared to characterize the resistance mutations acquired at failure of an initial antiretroviral therapy after having analyzed the polymorphism before initiation of the first HAART. Epidemiological and immuno-virological data also face to assess the response to a first HAART in both groups of patients. Although the natural polymorphism is different depending on the subtype, response to therapy does not appear to change. Our results also suggest that the genetic diversity of HIV-1 does not play a major rôle in the selection of resistance mutations to antiretroviral.LYON1-BU Santé (693882101) / SudocRENNES1-BU Santé (352382103) / SudocSudocFranceF

Multiple organ failure during primary HIV infection.

International audienceThe appearance of primary HIV infection ranges from an asymptomatic presentation to a symptomatic illness resembling infectious mononucleosis. Severe unusual presentations include acute myopericarditis, renal failure, and opportunistic infections such as esophageal candidiasis, cytomegalovirus infection, and Pneumocystis jirovecii pneumonia. We report a case of multiple organ failure during primary HIV infection