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Introduction: Since the advent of HIV pre‐exposure prophylaxis (PrEP), stigma has been shown to be a major barrier to its uptake and adherence. It is therefore essential to define the proportion of users who consider that PrEP can negatively impact their image and the factors associated with this perception. Method: We performed a multivariable logistic regression on data from the 2567 participants in the ANRS‐PREVENIR study who answered the outcome question. Results: Almost one‐third of the sample (comprising mostly cisgender men who have sex with men [94.3%]) considered that taking PrEP could give others a negative image of them. Younger participants (adjusted odds ratio [aOR] 0.98; 95% confidence interval [CI] 0.97–0.99) and more psychologically vulnerable participants (i.e., lower self‐esteem score [aOR 0.98; 95% CI 0.96–0.99] and higher depression score [aOR 1.02; 95% CI 1.00–1.03]) were also more likely to have this perception. In contrast, participants encouraged to take PrEP by their main partner (aOR 0.67; 95% CI 0.51–0.88) and friends (aOR 0.79; 95% CI 0.66–0.95), and those who protected themselves more because they had knowledge of their most recent sexual partner's HIV status (aOR 0.83; 95% CI 0.69–0.99) and systematic use of PrEP and/or condoms during intercourse in the previous 3 months (aOR 0.80; 95% CI 0.67–0.96) were less likely to have this perception. Discussion: Given the strong interrelation between stigmatization (real or perceived), risky behaviours and adherence, our results emphasize the need for HIV prevention campaigns to promote a positive image of PrEP users. They also show that stigmatization and its effects need to be fully considered to improve HIV prevention offers to current and potential PrEP users who are most likely to be psychologically vulnerable. [ABSTRACT FROM AUTHOR]

Background: In recent years, dolutegravir monotherapy has been explored as a drug-reduced regimen for HIV patients.Methods: This was a retrospective observational study, including patients virologically suppressed for ≥6 months, without previous virological failure (VF) under integrase inhibitors (INIs), who had been switched to dolutegravir monotherapy (50 mg/day). The primary aim was to report the proportion of VF at week 48 (W48) and week 96 (W96) of dolutegravir monotherapy. The evolution from baseline to W48 of residual viraemia on ultra-deep sequencing and HIV DNA was also evaluated.Results: Sixty-one patients were included. Prior to switching to dolutegravir monotherapy, they had a median (IQR) of 15.4 (6.5-19.9) years of antiretroviral exposure, 5.8 (3.2-10.3) years of viral suppression and 687 (461-848) CD4+ cells/mm3. They remained on dolutegravir monotherapy for a median (IQR) of 100 (29-148) weeks. Forty-two out of 61 patients (68.9%) reached W48 and 32 out of 61 patients (52.5%) reached W96. VF occurred in three patients, with the emergence of INI resistance. VF occurred before W24 and in patients pre-exposed to INIs. At W48, the probability of VF (Kaplan-Meier analysis) was 5.6% (95% CI = 1.8%-16.4%). The same result was obtained at W96. Detectable residual viraemia did not increase and median HIV DNA did not change significantly (2.4 log/106 cells at baseline and 2.3 log/106 cells at W48). Dolutegravir plasma concentration was above the IC90 in 41/41 samples, from 22 patients.Conclusions: Long-term follow-up showed a low risk of VF under dolutegravir monotherapy, in a selected population of patients with previous long-term virological suppression and low HIV reservoir. [ABSTRACT FROM AUTHOR]

Objectives: Given the effectiveness of treatment of HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, there are considerable benefits associated with determining HIV/HBV/HCV status. We evaluated the feasibility and acceptability of systematic screening and subsequent care in an oral and maxillofacial surgery department. Methods: The anaesthesiologists proposed screening for HIV, HBV and HCV to all individuals of unknown infection status undergoing surgery between 19 April 2016 and 19 April 2017. The endpoints were the rates of test offer, acceptance/refusal and new diagnoses. Seropositive individuals were referred to infectious disease specialists. Associations between age, sex or surgery type and test offer (eligible individuals) or acceptance/refusal (those offered testing) were investigated. Results: Of the 1407 individuals attending the department, 1322 were eligible for inclusion in the study. Testing was proposed to 899 individuals [68%; 95% confidence interval (CI) 65–71%], 831 of whom accepted the offer (92.4%; 95% CI 90.5–94.1%). Results were obtained for 787 individuals (41 samples were uncollected and three were invalid). Age was the only factor associated with test offer in multivariable analysis [odds ratio (OR) 0.90; 95% CI 0.84–0.97, per additional 10 years], and no factor was associated with acceptance. Of the five, three and eight individuals testing positive for HIV, HBV and HCV, four, two and one patient, respectively, reported prior knowledge of seropositivity. The new diagnosis rate was 0.13% (95% CI 0–0.7%) for HIV and HBV, and 0.89% (95% CI 0.36–1.82%) for HCV [three positive polymerase chain reaction (PCR) tests]. All individuals newly diagnosed with HIV or HCV infection received specific antiviral treatment. Conclusions: Rates of screening offer and acceptance were high. Substantial screening resources are required to decrease the impact of the hidden epidemics of HIV, HBV and HCV infections. [ABSTRACT FROM AUTHOR]

Objectives: High rates of clinical acute rejection after kidney transplantation have been reported in people living with HIV (PLHIV), probably as a consequence of drug interactions. We therefore investigated the incidence of acute rejection within 6 months of transplantation in HIV‐infected recipients treated with a protease‐inhibitor‐free raltegravir‐based regimen. Methods: The Agence Nationale de Recherche sur le Sida et les Hépatites Virales (ANRS) 153 TREVE (NCT01453192) study was a prospective multicentre single‐arm trial in adult PLHIV awaiting kidney transplantation, with viral load < 50 HIV‐1 RNA copies/mL, CD4 T‐cell count > 200 cells/μL, and HIV‐1 strains sensitive to raltegravir, aiming to demonstrate 6‐month clinical acute rejection rates < 30%. Time to transplantation was compared with that for uninfected subjects matched for age, sex and registration date. Results: In total, 61 participants were enrolled in the study, and 26 underwent kidney transplantation. Two participants experienced clinical acute rejection, corresponding to an estimated clinical acute rejection rate of 8% [95% confidence interval (CI) 2–24%] at 6 and 12 months post‐transplantation. HIV infection remained under control in all but one participant, who temporarily stopped antiretroviral treatment. Median time to transplantation was longer in PLHIV than in controls (4.3 versus 2.8 years, respectively; P = 0.002) and was not influenced by blood group. Conclusions: Acute rejection rates were low after kidney transplantation in PLHIV treated with a raltegravir‐based regimen. However, PLHIV have poorer access to transplantation than HIV‐uninfected individuals after registration on the waiting list. [ABSTRACT FROM AUTHOR]

Background: Darunavir/ritonavir is a potent PI with a high genetic barrier and pharmacological robustness favourably investigated as monotherapy. Whether darunavir could be dose reduced in the context of monotherapy deserves investigation.Methods: Patients with HIV suppressed viraemia (plasma viral load <50 copies/mL for 12 months) under ART who had switched to darunavir/ritonavir monotherapy at 600/100 mg/day between 2013 and 2015 were included in this observational 48 week single-centre study. The primary outcome was the proportion of patients with virological success (defined as plasma viral load <50 copies/mL) at week 24. Secondary outcomes included treatment strategy success and resistance.Results: Thirty-one patients were included with the following baseline characteristics [median (IQR)]: age 52 years (47-57), CD4+ 649 cells/mm3 (463-813), ART duration 16.3 years (9.2-22.3), nadir CD4+ 195 cells/mm3 (144-261) and duration of HIV suppression 7.8 years (4.8-9.7). Prior to switch, ART consisted of PI monotherapy for 28 of 31 patients [darunavir/ritonavir 800/100 mg/day (n = 26), lopinavir/ritonavir (n = 1) and atazanavir/ritonavir (n = 1)] and a triple drug regimen for 3 of 31 patients. Within the 48 weeks of follow-up, no virological failure occurred and two patients discontinued 600/100 mg of darunavir/ritonavir due to side effects at week 16 and 40, leading to a virological suppression rate of 100% (95% CI = 89-100) at weeks 24 and 48. Strategy success rates were 96.8% (95% CI = 83.3-99.9) at week 24 and 93.5% (95% CI = 78.6-99.2) at week 48. Median (IQR) Ctrough values of 800/100 mg of darunavir/ritonavir and 600/100 mg of darunavir/ritonavir were 1537 ng/mL (1286-1724) and 1255 ng/mL (873-2161), respectively.Conclusions: A lower dose of darunavir/ritonavir used as monotherapy (600/100 mg/day) was highly effective in virologically suppressed HIV-infected patients. Further studies are needed to confirm these data. [ABSTRACT FROM AUTHOR]

Background: Individuals presenting for care with severe immunosuppression typically have high plasma HIV viral load (pVL) and may transmit HIV before and after initiation of combination antiretroviral therapies (cART).Patients and Methods: Using risk equations and data collected in the IMEA 040 DATA trial on sexual behaviour and pVL level of 84 HIV-infected patients (23 women), we estimated monthly rates of HIV transmission for each virologically unsuppressed participant (pVL >50 copies/mL) who reported sex with HIV-negative or unknown serostatus (HNUS) partners at cART initiation, 24 weeks (W24) and W48 after; rates were considered negligible for other participants.Results: At cART initiation, median pVL was 5.4 log10 copies/mL. The percentage of virologically unsuppressed patients decreased, from 100% at cART initiation to 27% (95% CI 16%-43%) for heterosexuals and 8% (95% CI 2%-22%) for MSM at W48 (P < 0.001). The percentage of patients reporting sex with HNUS partners increased between cART initiation and W48, from 23% (95% CI 10%-42%) to 42% (95% CI 25%-61%) for heterosexuals (P = 0.042) and from 41% (95% CI 21%-64%) to 73% (95% CI 52%-88%) for MSM (P = 0.004). Median monthly HIV transmission rates were 0.0540 (IQR 0.0339-0.0742) for MSM and 0.0018 (IQR 0.0014-0.0191) for heterosexuals at cART initiation, and were reduced by 95% (95% CI 87%-100%) for heterosexuals and 98% (95% CI 95%-100%) for MSM as early as W24.Conclusions: Risk of onward transmission for severely immunosuppressed individuals is high before and within the first weeks of cART, and persists, at a substantially reduced level, beyond 24 weeks of cART for some individuals. Earlier cART and protecting HIV-negative partners until full viral suppression is achieved could reduce HIV transmission. [ABSTRACT FROM AUTHOR]

Background: Surveillance of HIV-1 resistance in treated patients with a detectable viral load (VL) is important to monitor, in order to assess the risk of spread of resistant viruses and to determine the proportion of patients who need new antiretroviral drugs with minimal cross-resistance.Methods: The HIV-1 protease and reverse transcriptase (RT) and integrase genes were sequenced in plasma samples from 782 consecutive patients on failing antiretroviral regimens, seen in 37 specialized centres in 2014. The genotyping results were interpreted using the ANRS v24 algorithm. Prevalence rates were compared with those obtained during a similar survey conducted in 2009.Results: The protease and RT sequences were obtained in 566 patients, and the integrase sequence in 382 patients. Sequencing was successful in 60%, 78%, 78% and 87% of patients with VLs of 51-200, 201-500, 501-1000 and >1000 copies/mL, respectively. Resistance to at least one antiretroviral drug was detected in 56.3% of samples. Respectively, 3.9%, 8.7%, 1.5% and 3.4% of patients harboured viruses that were resistant to any NRTI, NNRTI, PI and integrase inhibitor (INI). Resistance rates were lower in 2014 than in 2009. Resistance was detected in 48.5% of samples from patients with a VL between 51 and 200 copies/mL.Conclusion: In France in 2014, 90.0% of patients in AIDS care centres were receiving antiretroviral drugs and 12.0% of them had VLs >50 copies/mL. Therefore, this study suggests that 6.7% of treated patients in France might transmit resistant strains. Resistance testing may be warranted in all treated patients with VL > 50 copies/mL. [ABSTRACT FROM AUTHOR]

Background Recent studies have independently implicated the chemokine CXCL12 and its receptors, CXCR4 and CXCR7, in the pathophysiology of Kaposi sarcoma ( KS). Objectives We investigated whether the CXCL12/ CXCR4- CXCR7 protein trio could constitute KS biomarkers. Methods Endothelial and spindle cells positive for CXCL12/ CXCR4- CXCR7, human herpesvirus-8 latency-associated nuclear antigen ( LANA), Ki67 antigen (proliferation) and vascular endothelial growth factor ( VEGF) were quantitated in skin lesions from patients with AIDS-associated KS, patients with classic KS and patients with angiomas, using immunohistochemistry and quantitative image analysis (16, 21 and 20 skin lesions, respectively). Plasma CXCL12 concentrations were measured by enzyme-linked immunosorbent assay from 20 patients with AIDS- KS, 12 HIV-infected patients without KS and 13 healthy donors' samples. Results Cells positive for CXCL12, CXCR4, CXCR7, LANA, Ki67 and VEGF were significantly enriched in patients with AIDS-associated KS and classic KS vs. angiomas ( P < 0·001), and in nodular vs. macular/papular KS lesions ( P < 0·05). CXCL12, CXCR4 and CXCR7 detection correlated with LANA, Ki67 and VEGF detection ( r > 0·4; P < 0·05). However, plasma CXCL12 concentrations did not differ between patients with AIDS-associated KS, HIV-infected patients without KS, and healthy donors. Conclusions The CXCL12/ CXCR4- CXCR7 trio is upregulated in KS and correlates with KS pathophysiological markers and the severity of skin lesions. Histological assessment of the CXCL12 axis could serve as a valuable biomarker for KS diagnosis and progression. [ABSTRACT FROM AUTHOR]

Background: Etravirine (ETR) is recommended as twice-daily dosing in pretreated patients. There are no data regarding the use of ETR once daily in HIV-experienced patients with prior resistance to first-generation non-nucleoside reverse transcripase inhibitors (NNRTIs). Objectives: To evaluate the capacity of once-daily ETR to maintain suppressed viremia over 48 weeks after switching from ETR twice daily in NNRTI-experienced patients. Methods: In this pilot open-label study, patients with plasma viral load (pVL) <50 copies/mL on a stable ETR 200 mg bid regimen were enrolled to switch to ETR 400 mg qd and followed up over 48 weeks. The primary endpoint was the proportion of patients with pVL <50 copies/mL at week 24. Secondary endpoints included the rate of pVL< 50 copies/mL at week 48, ETR pharma-cokinetic parameters, and tolerability and resistance profile. Results: Twenty-four patients were included. They had extensive antiretroviral treatment for a median of 14 years (range, 1-19). All except for 2 had prior resistance to NNRTIs. Seven patients discontinued ETR once daily prior to week 48 for virological failure (3), protocol deviation (3), and side effects (1). At week 24, 95% of patients maintained pVL< 50 copies/mL (95% Cl, 78.4-99.7) and 85% at week 48 (95%Cl, 65.6-95.8). Two of the 3 patients with virological failure had ETR resistance mutations prior to initiation. The median ETR Ctrough level remained stable after switching from twice daily 515 ng/mL (340-758) to once daily 422 ng/mL (264-655). Conclusion: These results suggest that ETR is effective as a once-daily regimen in patients with prior NNRTI experience when HIV is sensitive to ETR. The stability of Ctrough concentrations on a once-daily regimen confirms the once-daily profile of the drug in experienced patients. [ABSTRACT FROM AUTHOR]

A double-blinded, controlled study of vaccination of untreated patients with chronic human immunodeficiency virus type 1 (HIV-1) infection with 3 doses of autologous monocyte-derived dendritic cells (MD-DCs) pulsed with heat inactivated autologous HIV-1 was performed. Therapeutic vaccinations were feasible, safe, and well tolerated. At week 24 after first vaccination (primary end point), a modest significant decrease in plasma viral load was observed in vaccine recipients, compared with control subjects (P = .03). In addition, the change in plasma viral load after vaccination tended to be inversely associated with the increase in HIV-specific T cell responses in vaccinated patients but tended to be directly correlated with HIV-specific T cell responses in control subjects. [ABSTRACT FROM AUTHOR]