Éditeur(s) : HAL CCSD Lippincott, Williams & Wilkins
Résumé : International audience
The aim of the study was to investigate the impact of first-line combined antiretroviral therapy (cART) regimen on the course of CD8 + T-cell counts in human immunodeficiency virus (HIV)-infected patients. A retrospective observational study conducted on the French DAT'AIDS Cohort of HIV-infected patients. We selected 605 patients initiating a first-line cART between 2002 and 2009, and which achieved a sustained undetectable HIV plasma viral load (pVL) for at least 12 months without cART modification. The evolution of CD8 + T-cell counts according to cART regimen was assessed. CD8 + T-cell counts were assessed in 572 patients treated with 2NRTIs+1PI/r (n= 297), 2NRTIs+1NNRTI (n= 207) and 3NRTIs (n= 68). In multivariate analysis, after 12 months of follow-up, the 3NRTIs regimen was associated with a significantly smaller decrease of CD8 + T-cell count compared with NNRTI-containing regimens (–10.2 cells/mL in 3NRTIs vs –105.1 cells/mL; P=0.02) but not compared with PI-containing regimens (10.2 vs –60.9 cells/mL; P=0.21). After 24 months, the 3NRTIs regimen was associated with a smaller decrease of CD8 + T-cell count and % compared with PI/r-and NNRTI-containing regimens (0.2 in 3NRTIs vs –9.9 with PI/r-regimens, P=0.001, and vs –11.1 with NNRTI-regimens, p < 0.0001). A focus analysis on 11 patients treated with an INSTI-containing cART regimen during the study period showed after 12 months of follow-up, a median decrease of CD8 + T-cell count of –155 [inter quartile range: –302; –22] cells/mL. Our data highlight the fact that cART regimens have differential effects on CD8 pool down regulation. Abbreviations: cART = combined antiretroviral therapy, HIV = human immunodeficiency virus, INSTI = integrase strand transfer inhibitor, NNRTI = non-nucleotide reverse transcriptase inhibitor, NRTI = nucleotide reverse transcriptase inhibitor, PI/r = Ritonavir-boosted protease inhibitor, pVL = plasma viral load.
ISSN: 0025-7974

inserm-01408002
http://www.hal.inserm.fr/inserm-01408002
http://www.hal.inserm.fr/inserm-01408002/document
http://www.hal.inserm.fr/inserm-01408002/file/2016%2C%20Poizot-Martin%20-%20First-line%20cART%20regimen%20impacts%20the%20course%20of%20CD8%2B%20T-cell%20counts%20in%20HIV-infected%20patients.pdf
DOI : 10.1097/MD.0000000000005087

Éditeur(s) : HAL CCSD American Academy of Neurology
Résumé : International audience
OBJECTIVE: We examined if the CNS Penetration-Effectiveness (CPE) score of antiretroviral drugs was associated with survival after a diagnosis of HIV-related encephalopathy, progressive multifocal leukoencephalopathy (PML), cerebral toxoplasmosis, or cryptococcal meningitis. METHODS: Using data from the FHDH-ANRS CO4, we compared the survival of 9,932 HIV-infected patients diagnosed with a first neurologic AIDS-defining event in the pre-combination antiretroviral therapy (cART) (1992-1995), early cART (1996-1998), or late cART (1999-2004) periods. Follow-up was subdivided (CPE < 1.5 and CPE ≥ 1.5), and relative rates (RR) of death were estimated using multivariable Poisson regression models. RESULTS: In the pre-cART and early cART periods, regimens with CPE ≥ 1.5 were associated with lower mortality after HIV-related encephalopathy (RR 0.64; 95% confidence interval [CI] 0.47-0.86 and RR 0.45; 95% CI 0.35-0.58) and after PML (RR 0.79; 95% CI 0.55-1.12 and RR 0.45; 95% CI 0.31-0.65), compared to regimens with CPE < 1.5, while in the late cART period there was no association between the CPE score and the mortality. A higher CPE score was also associated with a lower mortality in all periods after cerebral toxoplasmosis (RR 0.68, 95% CI 0.56-0.84) or cryptococcal meningitis (RR 0.50, 95% CI 0.34-0.74). Whatever the neurologic event, these associations were not maintained after adjustment on updated plasma HIV-RNA (missing, <500, ≥500 copies/mL) with RR ranging from 0.82 (95% CI 0.36-1.91) to 1.02 (0.69-1.52). CONCLUSION: At the beginning of the cART era, the CPE score was of importance for survival after severe neurologic event, while in the late cART period, the additional effect of CPE score vanished with more powerful antiretroviral regimens associated with plasma viral load control.
ISSN: 0028-3878

hal-00875434
https://hal.archives-ouvertes.fr/hal-00875434
DOI : 10.1212/WNL.0b013e31820c3089
PUBMED : 21248274

Éditeur(s) : HAL CCSD International Medical Press
Résumé : International audience
BACKGROUND: Psychiatric disorders are relatively common among HIV-infected patients. However, there are few studies about their potential risk factors. This analysis aimed to measure the incidence of severe psychiatric events (PE) among patients receiving combination antiretroviral therapy (cART) of the French APROCO-COPILOTE (ANRS CO8) cohort, and to identify the medical and socio-behavioural correlates of their first episode of depression, suicide or suicide attempt (D/S/SA). METHODS: APROCO-COPILOTE is a cohort of patients started on a protease inhibitor regimen between 1997 and 1999, with prospective medical standardized records and self-administered questionnaires collecting socio-demographic and socio-behavioural data. This analysis included all 11-year follow-up visits for 1,095 patients having completed baseline self-administered questionnaires. A proportional hazard Cox model was used to identify the correlates of a first D/S/SA event. RESULTS: The overall prevalence of severe PE remained low: 50 patients experienced 67 events (incidence rate [95% CI] =1.04 [0.82, 1.32] per 100 person-years). Depression (n=16), suicides (n=5) and suicide attempts (n=14) were the most frequently diagnosed PE (0.54 [0.39, 0.76] per 100 person-years) among 25 patients. Multivariate results showed that unemployment, unstable housing, detectable viral load and smoking more than 20 cigarettes/day were independently associated with D/S/SA. CONCLUSIONS: Although the incidence of severe PE remained relatively low among the patients of APROCO-COPILOTE cohort, this study's results underline a clinically important problem in HIV-infected patients receiving cART. Furthermore, our findings not only emphasize the importance of comprehensive care, especially for socially vulnerable patients, but may also help future studies designed to assess the effectiveness of interventions in reducing the risk of PE during cART.
ISSN: 1359-6535

hal-00875183
https://hal.archives-ouvertes.fr/hal-00875183
DOI : 10.3851/IMP2102
PUBMED : 22544079

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
OBJECTIVES: The aims of the study were to assess in patients with advanced HIV disease receiving antiretroviral therapy (ART) intensification with enfuvirtide (i) resistance at virological failure (VF), (ii) impact of baseline tropism on immunovirological response, and (iii) HIV-1 DNA tropism evolution during ART. METHODS: The ANRS 130 APOLLO randomized trial evaluated in naive patients the immunovirological impact of standard ART without (control arm) or with enfuvirtide. Tropism was determined on RNA and DNA by V3-loop sequencing interpreted using the Geno2Pheno algorithm. RESULTS: At baseline the median CD4 cell count was 30 cells/mm(3). Among the 170 patients assessable in this virological substudy, HIV-1 RNA tropism was as follows: 60% of viruses were R5 and 40% were R5X4/X4. HIV-1 DNA tropism was as follows: 54% were R5 and 46% were R5X4/X4. At week 24, 39% and 49% of patients experienced VF in the enfuvirtide and control arms, respectively. In the enfuvirtide arm, only resistance-associated mutations to enfuvirtide were detected. In the control arm, two patients displayed drug-resistant viruses at the time of VF. No impact of baseline tropism was observed on immunovirological response, regardless of the study arm. Among the 25 patients experiencing DNA tropism switch between baseline and week 24, 16 (64%) switched from R5 to R5X4/X4. These latter were mostly successfully suppressed patients receiving enfuvirtide and exhibiting poorer immunological response. CONCLUSIONS: Baseline RNA tropism had no impact on the immunovirological response. Drug resistance mutations were only detected for the fusion inhibitor. Finally, the mechanism of replenishment of the viral cellular reservoir with X4 viruses observed needs to be further analysed.
ISSN: 0305-7453

hal-00875130
https://hal.archives-ouvertes.fr/hal-00875130
DOI : 10.1093/jac/dks455
PUBMED : 23152480

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
BACKGROUND: HIV cohort collaborations, which pool data from diverse patient cohorts, have provided key insights into outcomes of antiretroviral therapy (ART). However, the extent of, and reasons for, between-cohort heterogeneity in rates of AIDS and mortality are unclear. METHODS: We obtained data on adult HIV-positive patients who started ART from 1998 without a previous AIDS diagnosis from 17 cohorts in North America and Europe. Patients were followed up from 1 month to 2 years after starting ART. We examined between-cohort heterogeneity in crude and adjusted (age, sex, HIV transmission risk, year, CD4 count and HIV-1 RNA at start of ART) rates of AIDS and mortality using random-effects meta-analysis and meta-regression. RESULTS: During 61 520 person-years, 754/38 706 (1.9%) patients died and 1890 (4.9%) progressed to AIDS. Between-cohort variance in mortality rates was reduced from 0.84 to 0.24 (0.73 to 0.28 for AIDS rates) after adjustment for patient characteristics. Adjusted mortality rates were inversely associated with cohorts' estimated completeness of death ascertainment [excellent: 96-100%, good: 90-95%, average: 75-89%; mortality rate ratio 0.66 (95% confidence interval 0.46-0.94) per category]. Mortality rate ratios comparing Europe with North America were 0.42 (0.31-0.57) before and 0.47 (0.30-0.73) after adjusting for completeness of ascertainment. CONCLUSIONS: Heterogeneity between settings in outcomes of HIV treatment has implications for collaborative analyses, policy and clinical care. Estimated mortality rates may require adjustment for completeness of ascertainment. Higher mortality rate in North American, compared with European, cohorts was not fully explained by completeness of ascertainment and may be because of the inclusion of more socially marginalized patients with higher mortality risk.
ISSN: 0300-5771

hal-00875138
https://hal.archives-ouvertes.fr/hal-00875138
DOI : 10.1093/ije/dys164
PUBMED : 23148105

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
Two of the crucial aspects of human immunodeficiency virus (HIV) infection are (i) viral persistence in reservoirs (precluding viral eradication) and (ii) chronic inflammation (directly associated with all-cause morbidities in antiretroviral therapy (ART)-controlled HIV-infected patients). The objective of the present study was to assess the potential involvement of adipose tissue in these two aspects. Adipose tissue is composed of adipocytes and the stromal vascular fraction (SVF); the latter comprises immune cells such as CD4+ T cells and macrophages (both of which are important target cells for HIV). The inflammatory potential of adipose tissue has been extensively described in the context of obesity. During HIV infection, the inflammatory profile of adipose tissue has been revealed by the occurrence of lipodystrophies (primarily related to ART). Data on the impact of HIV on the SVF (especially in individuals not receiving ART) are scarce. We first analyzed the impact of simian immunodeficiency virus (SIV) infection on abdominal subcutaneous and visceral adipose tissues in SIVmac251 infected macaques and found that both adipocytes and adipose tissue immune cells were affected. The adipocyte density was elevated, and adipose tissue immune cells presented enhanced immune activation and/or inflammatory profiles. We detected cell-associated SIV DNA and RNA in the SVF and in sorted CD4+ T cells and macrophages from adipose tissue. We demonstrated that SVF cells (including CD4+ T cells) are infected in ART-controlled HIV-infected patients. Importantly, the production of HIV RNA was detected by in situ hybridization, and after the in vitro reactivation of sorted CD4+ T cells from adipose tissue. We thus identified adipose tissue as a crucial cofactor in both viral persistence and chronic immune activation/inflammation during HIV infection. These observations open up new therapeutic strategies for limiting the size of the viral reservoir and decreasing low-grade chronic inflammation via the modulation of adipose tissue-related pathways
ISSN: 1553-7366

Droits : http://creativecommons.org/licenses/by/
hal-01207287
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01207287
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01207287/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01207287/file/journal.ppat.1005153.pdf
DOI : 10.1371/journal.ppat.1005153

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
Although semen is the principal vector of human immunodeficiency virus (HIV) dissemination worldwide, the origin of the infected leukocytes and free viral particles in this body fluid remain elusive. Here we review the accumulated evidence of the genital origin of HIV in semen from therapy naive individuals and men receiving suppressive highly active antiretroviral therapy (HAART), summarize the data on the detection and localization of HIV/SIV within the male genital tract, discuss the potential involvement of each genital tissue as a source of infected cells and virions in semen in the absence and presence of HAART, and suggest further studies. Deciphering the exact sources of HIV in semen will be crucial to improving HIV transmission prevention strategies.
ISSN: 0022-1899

hal-01121761
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01121761
PUBMED : 25414416
DOI : 10.1093/infdis/jiu328

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
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 time.
ISSN: 0305-7453

hal-00875092
https://hal.archives-ouvertes.fr/hal-00875092
DOI : 10.1093/jac/dkt033
PUBMED : 23404192

Éditeur(s) : HAL CCSD Taylor & Francis (Routledge): STM, Behavioural Science and Public Health Titles
Résumé : International audience
The aim of this study was to determine factors associated with complete satisfaction with the care provided (satisfaction with physicians and satisfaction with services and organization) among HIV-infected patients followed up in the French ANRS CO8 APROCO-COPILOTE cohort. Analyses focused on cross-sectional data collected during the ninth year of cohort follow-up. Satisfaction with care, sociodemographic characteristics, and behavioral data were collected using self-administered questionnaires, while clinical data were derived from medical records. Complete satisfaction with care was defined as being 100% satisfied. Two logistic regression models were used to identify predictors of (1) complete satisfaction with physicians (n=404) and (2) complete satisfaction with services and organization (n=396). Sixteen percent of patients were completely satisfied with physicians, while 15.9% were completely satisfied with services and organization. Being older and reporting fewer discomforting antiretroviral therapy (ART) side effects were factors independently associated with complete satisfaction with both physicians and services and organization. Strong support from friends and absence of hepatitis C (HCV) co-infection were independently associated with complete satisfaction with physicians, while strong support from one's family and comfortable housing conditions were independently associated with complete satisfaction with services and organization. Even after nine years of follow-up, social vulnerabilities still strongly influence HIV-infected patients' interactions with the health care system. Day-to-day experience with the disease, including perceived treatment side effects, appears to play a key role in the quality of these interactions. More attention should be given to patient satisfaction, especially for socially vulnerable patients, in order to avoid potentially detrimental consequences such as poor adherence to ART.
AIDS Care

hal-00875619
https://hal.archives-ouvertes.fr/hal-00875619
DOI : 10.1080/09540121.2011.613909
PUBMED : 21999644

Éditeur(s) : HAL CCSD American College of Physicians
Résumé : International audience
BACKGROUND: Most clinical guidelines recommend that AIDS-free, HIV-infected persons with CD4 cell counts below 0.350 × 10(9) cells/L initiate combined antiretroviral therapy (cART), but the optimal CD4 cell count at which cART should be initiated remains a matter of debate. OBJECTIVE: To identify the optimal CD4 cell count at which cART should be initiated. DESIGN: Prospective observational data from the HIV-CAUSAL Collaboration and dynamic marginal structural models were used to compare cART initiation strategies for CD4 thresholds between 0.200 and 0.500 × 10(9) cells/L. SETTING: HIV clinics in Europe and the Veterans Health Administration system in the United States. PATIENTS: 20, 971 HIV-infected, therapy-naive persons with baseline CD4 cell counts at or above 0.500 × 10(9) cells/L and no previous AIDS-defining illnesses, of whom 8392 had a CD4 cell count that decreased into the range of 0.200 to 0.499 × 10(9) cells/L and were included in the analysis. MEASUREMENTS: Hazard ratios and survival proportions for all-cause mortality and a combined end point of AIDS-defining illness or death. RESULTS: Compared with initiating cART at the CD4 cell count threshold of 0.500 × 10(9) cells/L, the mortality hazard ratio was 1.01 (95% CI, 0.84 to 1.22) for the 0.350 threshold and 1.20 (CI, 0.97 to 1.48) for the 0.200 threshold. The corresponding hazard ratios were 1.38 (CI, 1.23 to 1.56) and 1.90 (CI, 1.67 to 2.15), respectively, for the combined end point of AIDS-defining illness or death. Limitations: CD4 cell count at cART initiation was not randomized. Residual confounding may exist. CONCLUSION: Initiation of cART at a threshold CD4 count of 0.500 × 10(9) cells/L increases AIDS-free survival. However, mortality did not vary substantially with the use of CD4 thresholds between 0.300 and 0.500 × 10(9) cells/L.
ISSN: 0003-4819

hal-00875307
https://hal.archives-ouvertes.fr/hal-00875307
PUBMED : 21502648
DOI : 10.7326/0003-4819-154-8-201104190-00001

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
OBJECTIVES: To compare virological effectiveness in patients who continued on a virologically successful first-line boosted protease inhibitor (PI)-containing combination antiretroviral therapy (cART) regimen or who switched to a PI-free cART including efavirenz, nevirapine or abacavir. METHODS: From the French Hospital Database on HIV, we selected 439 patients with undetectable viral load (VL) on a first-line boosted PI-containing cART regimen who switched to a PI-free combination including efavirenz, nevirapine or abacavir. Each of these patients was matched with three patients who continued to take their first-line cART regimen, on the basis of gender, age, CD4 cell count, VL, date of cART initiation and the duration of VL undetectability. Time to virological failure (VF) was analysed with Kaplan-Meier curves and Cox models. RESULTS: The 12 month probabilities of VF were 3.7% and 5.7% in non-switch and switch patients, respectively, and 3.9%, 7.2% and 9.0% in patients switching to efavirenz-, nevirapine- and abacavir-containing cART, respectively. After adjustment, only patients switching to abacavir-containing cART had a higher risk of VF than non-switch patients (adjusted hazard ratio, 1.99; 95% confidence interval, 1.05-3.79). CONCLUSIONS: Switching from a virologically successful first-line boosted PI-containing cART regimen to a non-nucleoside reverse transcriptase inhibitor-containing cART regimen containing either efavirenz or nevirapine is virologically safe, while switching to abacavir-containing cART should be avoided.
ISSN: 0305-7453

hal-00875284
https://hal.archives-ouvertes.fr/hal-00875284
DOI : 10.1093/jac/dkr208
PUBMED : 21636583

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
BACKGROUND: The male genital tract is suspected to constitute a viral sanctuary as persistent HIV shedding is found in the semen of a subset of HIV-infected men receiving effective antiretroviral therapy (HAART). The origin of this persistent shedding is currently unknown. Phylogenetic studies indicated that HIV in semen from untreated men arises from local sources and/or passive diffusion from the blood. We previously demonstrated in human and macaque low levels and localized infection of several semen-producing organs by HIV/SIV. Using a macaque model, this study investigates the impact of short term HAART (2-4 weeks) initiated either during the asymptomatic chronic stage or 4 h post-intravenous inoculation of SIVmac251 on the infection of male genital organs. METHODOLOGY/PRINCIPAL FINDINGS: Short term HAART during the chronic stage decreased blood viral load. No major impact of HAART was observed on SIV DNA levels in male genital organs using a sensitive nested PCR assay. Using in situ hybridization, SIV RNA+ cells were detected in all male genital tract organs from untreated and treated animals with undetectable blood viral load following HAART. Infected CD68+ myeloid cells and CD3+ T lymphocytes were detected pre- and post-HAART. In contrast, short term HAART initiated 4 h post-SIV exposure led to a drastic decrease of the male genital tissues infection, although it failed to prevent systemic infection. In both cases, HAART tended to decrease the number of CD3+ T cells in the male organs. CONCLUSIONS: Our results indicate that the established infection of male genital organs is not greatly impacted by short term HAART, whereas the same treatment during pre-acute phase of the infection efficiently impairs viral dissemination to the male genital tract. Further investigations are now needed to determine whether infection of male genital organs is responsible for long term persistent HIV shedding in semen despite HAART.
ISSN: 1932-6203

hal-00876945
https://hal.archives-ouvertes.fr/hal-00876945
https://hal.archives-ouvertes.fr/hal-00876945/document
https://hal.archives-ouvertes.fr/hal-00876945/file/Impactsur Short-Term-accepted.pdf
DOI : 10.1371/journal.pone.0037348

Éditeur(s) : HAL CCSD International Medical Press
Résumé : International audience
Background: Although the role of clinical/biological factors associated with mortality has already been explored in HIV-infected patients on antiretroviral therapy (ART), to date little attention has been given to the potential role of social vulnerability. This study aimed to construct an appropriate measure of social vulnerability and to evaluate whether this measure is predictive of increased mortality risk in ART-treated patients followed up in the ANRS CO8 APROCO-COPILOTE cohort.Methods: The cohort enrolled 1,281 patients initiating a protease inhibitor-based regimen in 1997–1999. Clinical/laboratory data were collected every 4 months. Self-administered questionnaires collected psycho-social/behavioural characteristics at enrolment (month [M] 0), M4 and every 8–12 months thereafter. A multiple correspondence analysis using education, employment and housing indicators helped construct a composite indicator measuring social vulnerability. The outcome studied was all-cause deaths occurring after M4. The relationship between social vulnerability and mortality, after adjustment for other predictors, was studied using a shared-frailty Cox model, taking into account informative study dropout.Results: Over a median (IQR) follow-up of 7.9 (3.0–11.2) years, 121 deaths occurred among 1,057 eligible patients, corresponding to a mortality rate (95% CI) of 1.64 (1.37, 1.96)/100 person-years. Leading causes of death were non-AIDS defining cancers (n=26), AIDS (n=23) and cardiovascular diseases (n=12). Social vulnerability (HR [95% CI] =1.2 [1.0, 1.5]) was associated with increased mortality risk, after adjustment for other known behavioural and bio-medical predictors.Conclusions: Social vulnerability remains a major mortality predictor in ART-treated patients. A real need exists for innovative interventions targeting individuals cumulating several sources of social vulnerability, to ensure that social inequalities do not continue to lead to higher mortality.
ISSN: 1359-6535

hal-01299300
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01299300
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01299300/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01299300/file/Twelve-year%20mortality%20in%20HIV-infected%20patients_accepted.pdf
DOI : 10.3851/IMP2960

Éditeur(s) : HAL CCSD American Society for Investigative Pathology (ASIP)
Résumé : International audience
Semen represents the main vector of HIV dissemination worldwide, yet the origin of HIV in semen remains unclear. Viral populations distinct from those found in blood have been observed in semen, indicating local viral replication within the male genital tract. The seminal vesicles, the secretions of which constitute more than 60% of the seminal fluid, could represent a major source of virus in semen. This study is the first to investigate the susceptibility of human seminal vesicles to HIV infection both in vitro and in vivo. We developed and characterized an organotypic culture of human seminal vesicles to test for target cells and HIV infection, and, in parallel, analyzed the seminal vesicle tissues from HIV-infected donors. In vitro, in contrast to HIV-1 X4, HIV-1 R5 exposure induced productive infection. Infected cells consisted primarily of resident CD163(+) macrophages, often located close to the lumen. In vivo, HIV protein and RNA were also detected primarily in seminal vesicle macrophages in seven of nine HIV-infected donors, some of whom were receiving prolonged suppressive highly active antiretroviral therapy. These results demonstrate that human seminal vesicles support HIV infection in vitro and in vivo and, therefore, have the potential to contribute virus to semen. The presence of infected cells in the seminal vesicles of treated men with undetectable viremia suggests that this organ could constitute a reservoir for HIV.
American Journal of Pathology

inserm-00626549
http://www.hal.inserm.fr/inserm-00626549
DOI : 10.1016/j.ajpath.2011.08.005
PUBMED : 21925468