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Objectives To assess genotypic sensitivity scores (GSSs), plasma antiretroviral concentrations (PACs) and immunovirological outcomes at Week 96 (W96) in patients with persistent low-level viraemia (LLV). Methods On 1 January 2017, we analysed data from patients on three-drug regimens with persistent LLV defined as at least two consecutive plasma viral loads (pVLs) between 21 and 200 copies/mL (including one pVL of ≥50 copies/mL), at the Pitié-Salpêtrière Hospital. Outcomes were: GSS, PACs and HIV-DNA load at study entry; and virological status and proportion of patients with resistance-associated mutations (RAMs) at W96. Results Fifty-seven patients were included, with median age of 52.6 years (IQR 45.2–57.9), last CD4 count of 658 cells/mm3 (IQR 462–909) and total ART duration of 10.2 years (IQR 5.7–15.2). LLV duration was 14.0 months (IQR 5.5–22.3). GSS was 3 in 46/57 (81%) patients and PACs were adequate in 53/57 (93%) patients. Median total HIV-DNA was 2.65 log10 copies/106 cells (IQR 2.44–2.86). During follow-up, 26/57 (46%) had experienced ART modifications. At W96, 38/57 (67%) patients remained with LLV, 15/60 (26%) had achieved confirmed pVL of Conclusions A substantial number of patients harbouring LLV had no resistance to ART and adequate PACs. Two-thirds of these patients remained with this LLV status.

International audience

Introduction In recent years, children born to HIV-infected mothers have been receiving antiretroviral treatment (ART) with limited or no virologic monitoring, which increases the likelihood of development and accumulation of drug resistance mutations, which itself may limit the effectiveness of future ART. The objective of this study was to evaluate the prevalence of resistance mutations in children infected with HIV-1 experiencing virological failure to second-line ART in the Pediatric Department of Gabriel Toure Hospital in Mali. Methods Children aged from 5 to 18 infected with HIV-1 on second-line antiretroviral therapy and whose viral load was greater than 1000 copies/mL after observance reinforcement were enrolled. The protease and reverse transcriptase genes were sequenced with ViroSeq®. The results were interpreted according to the last version of the Stanford algorithm in 2018. The study was approved by the Ethics Committee of the Faculty of Medicine and Dentistry, University of Sciences, Techniques and Technologies of Bamako (Mali). Results Of 216 children, 33 (15.3%) who had a viral load (VL) > 1000 copies/mL in second line were recruited and included in the study. The median plasma viral load was 77,000 copies/mL [IQR (28,000–290,000)] and the median CD4 cell count was 310 cells/mm3 [IQR (152–412)]. The median age was 12 years; 48.5% of patients were treated with a combination of stavudine/lamivudine/nevirapine (Triomune®) for first-line treatment and 60.6% with abacavir/lamivudine/lopinavir/ritonavir for the second-line ART. The median treatment duration was 8.5 years [range, 3–13]. Of the 33 children whose treatment failed, the predominant HIV-1 subtype was CRF02_AG (66.7%). The prevalence of resistance to ART classes was 60.61% (20/33) to nucleoside reverse transcriptase inhibitors (NRTIs), 54.51% (18/33) to nonnucleoside reverse transcriptase inhibitors (NNRTIs), and 51.52% (17/33) to protease inhibitors (PIs). Of the patients studied, 90.9% were exposed to lopinavir/ritonavir (LPV/r) but only 15.2% (5/33) developed resistance to LPV/r. Conclusions This study demonstrated that LPV/r remains active in most patients after second-line ART failure. In children whose second-line ART fails, particular attention should be paid to their ART and adherence history when considering the next treatment option.

International audience; Active cancer and ongoing antineoplastic treatments are major factors for severe COVID-19 and death, reasons why the SARS-CoV-2 vaccination remains a priority in cancer patients (CPs). However, immunocompromised patients were excluded from major studies on mRNA vaccines, and could have a decreased response to vaccination, as recently demonstrated in solid organ transplant recipients. Herein, we aimed to assess the proportion of antibody response 4 weeks after the first injection of the BNT162b2 (Pfizer-BioNTech) vaccine in CPs and health care workers (HCWs) as the control population.

Objectives We aimed to evaluate the immune response of HIV-1 positive patients to a single injection of HAV vaccine in a context of vaccine shortage during the 2017 European outbreak. Methods We retrospectively enrolled all HIV-1 positive patients vaccinated by a single injection of HAV vaccine Vaqta 50®. HAV serology was performed before and > 30 days after the vaccine injection. Results Among the 73 patients, HIV-1 viral load was ≤ 50 copies/mL in 93.2% of the cases. Medians of CD4 and median ratio of T CD4/CD8 cells were 658/mm3 and 0.9, respectively. A low immune response rate (59.7%) was observed among the patients. Responders had a significantly higher CD4/CD8 cell ratio than non-responders. Conclusions A serologic control should be recommended in this population in the event of a single injection vaccination schedule. During routine follow-up, and prior to any untoward event, physicians should assess the vaccination coverage of HIV-infected patients.

Background: The virus responsible of severe acute respiratory syndrome named SARS-CoV-2 and causing the new coronavirus disease (COVID-19) has gone global within three months. The current gold standard technique used to detect SARS-CoV-2 is real-time reverse transcription-polymerase chain reaction (rRT-PCR) from naso-pharyngeal swabs but it may be negative in up to 30% of COVID-19 patients. Detection of specific antibodies against SARS-CoV-2 may therefore enhance sensitivity of the current biological diagnosis, as well as monitor the extent of the epidemics in global or specific population, such as health-care worker. Many serological assays are currently available, but their clinical performances are still to be evaluated. Material and Method: A total of 2,594 serum samples collected from patients with SARS-CoV-2 infection documented by a positive rRT-PCR were enrolled in this study. They were tested for IgM/IgG/IgA against SARS-CoV-2 using 31 commercial assays. Antibody response was assessed depending on the onset of symptoms. In addition, 1,996 pre-epidemic serum samples expected to be negative were tested to assess specificity. Results: Rapid tests for qualitative detection of anti-SARS-CoV-2 antibodies (RDTs) achieved 77.4-100%, and ELISA/CLIA (ELISA) assays 58.8-100% for SARS-CoV-2-specific total antibodies (TAb) specificity. From 15 days after onset of symptoms, 13/18 RDT and 8/13 ELISA reached sensitivity > 90%. However, only 4 RDT and 3 ELISA assays fitted both sensitivity (> 90%) and specificity (> 98%) criteria according to French recommendations. Conclusions: Serology may offer valuable information during the course of COVID-19 pandemic, at the condition that commercial assays give reliable results. Contrasted performances were observed among the 31 commercial assays we evaluated, which underlines the importance of independent evaluation before clinical implementation. Funding Statement: This study was funded by the Agence Nationale de Recherche sur le SIDA et les Hepatites Virales (ANRS, AC43)". Declaration of Interests: JM Pawlotsky has served as an advisor and/or a speaker for Abbvie, Gilead, GlaxoSmithKline, Merck, Regulus and Siemens Healthcare. C Vauloup-Fellous served as un expert (rubella and CMV serology) for Abbott Diagnostics, Roche Diagnostics, Siemens Healthcare and DiaSorin. No other authors have any competing interests to declare. Ethics Approval Statement: The study was carried out in accordance with the Declaration of Helsinki. This work was a retrospective non-interventional study with no addition to standard care procedures. Reclassification of biological remnants into research material after completion of the ordered virological tests was approved by the local interventional review board of hospital. According to the French Public Health Code (CSP Article L.1121-1.1) such protocols are exempted from individual informed consent.

Background Integrase strand transfer inhibitors (INSTIs) are recommended by international guidelines as first-line therapy in antiretroviral-naive and -experienced HIV-1-infected patients. Objectives This study aimed at evaluating the prevalence at failure of INSTI-resistant variants and the impact of baseline minority resistant variants (MiRVs) on the virological response to an INSTI-based regimen. Methods Samples at failure of 134 patients failing a raltegravir-containing (n = 65), an elvitegravir-containing (n = 20) or a dolutegravir-containing (n = 49) regimen were sequenced by Sanger sequencing and ultra-deep sequencing (UDS). Baseline samples of patients with virological failure (VF) (n = 34) and of those with virological success (VS) (n = 31) under INSTI treatment were sequenced by UDS. Data were analysed using the SmartGene platform, and resistance was interpreted according to the ANRS algorithm version 27. Results At failure, the prevalence of at least one INSTI-resistant variant was 39.6% by Sanger sequencing and 57.5% by UDS, changing the interpretation of resistance in 17/134 (13%) patients. Among 53 patients harbouring at least one resistance mutation detected by both techniques, the most dominant INSTI resistance mutations were N155H (45%), Q148H/K/R (23%), T97A (19%) and Y143C (11%). There was no difference in prevalence of baseline MiRVs between patients with VF and those with VS. MiRVs found at baseline in patients with VF were not detected at failure either in majority or minority mutations. Conclusions UDS is more sensitive than Sanger sequencing at detecting INSTI MiRVs at treatment failure. The presence of MiRVs at failure could be important to the decision to switch to other INSTIs. However, there was no association between the presence of baseline MiRVs and the response to INSTI-based therapies in our study.

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.

Introduction La persistance d’une symptomatologie chez des patients suspects d’une infection à SARS-COV-2 est fréquente y compris chez des patients sans diagnostic virologique initial. L’organisation d’une consultation dite « post-COVID » initiée en mai 2020 et son évaluation constitue l’objectif de cette étude. Matériels et méthodes Étude rétrospective de cohorte des patients > 18 ans, présentant une histoire clinique compatible avec une infection à SARS-COV-2, une symptomatologie persistante ≥ 30 j du j0 et vus en consultation post-COVID entre mai–juin 2020. Le diagnostic d’infection à SARS-COV-2 a été définie par une RT-PCR SARS-COV-2 positive et/ou une sérologique positive en IgG (Architect, Abbott ; sensibilité 100 % [IC95 : 95,8–100 %] ; spécificité 99,6 % [IC95 : 99,0–99,9 %]). Les variables continues sont présentées en médiane et IQR. L’analyse présentée compare les caractéristiques des patients confirmés au SARS-COV-2 (COVID-19 positif) à ceux non confirmés (COVID-19 négatif). Résultats Un total de 83 patients (71 femmes [86 %], 46 ans [38–52]) ont consulté dans un délai 61 jours (j) (49–78) après le début des symptômes. Les manifestations cliniques persistantes après j30 les plus fréquentes étaient : asthénie/myalgies (n = 58, 70 %), toux (n = 34, 41 %), dyspnée (n = 45, 54 %) et douleur thoracique (n = 43, 52 %). Parmi eux, 32/83 (39 %) avaient eu une PCR SARS-COV-2 positive et 51/83 (61 %) n’avait pas de preuve virologique d’infection. Une sérologie réalisée chez 78 patients (27 avec PCR positive antérieure et 51 sans preuve virologique) montre la présence d’Ac anti-SARS-CoV chez 37/78 (47 %) : 26/27 (97 %) des patients avec PCR initiale positive et 11/51 (22 %) des patients sans preuve virologique initiale. Au total, 43/83 (52 %) patients de la consultation post-COVID ont eu un COVID-19 confirmé. Le groupe COVID-19 positif (n = 43, 33 femmes [77 %], 49 ans [44–59]) était significativement plus âgé (p = 0,005) avec un délai de consultation plus court par rapport au j0 (55 j [45–70] vs 73 j [53–82], p = 0,007) que les COVID-19 négatif (n = 40, 29 femmes [73 %], 42 ans [35–49]) avec à j0, significativement plus souvent de la toux (n = 36 [84 %] vs n = 25 [63 %], p = 0,028), une anosmie/dysgueusie (n = 29 [67 %] vs n = 8 [20 %], p

Background In Africa a high percentage of HIV-infected children continue to experience HIV treatment failure despite enormous progress. In Benin (West Africa), there are currently no data on HIV drug resistance at failure in paediatric populations. Objectives To assess the frequency and patterns of HIV drug resistance among children with virological ART failures. Methods Dried blood spots from 62 HIV-infected children with virological failure were collected at the paediatric clinic of the National Hospital Center in Cotonou for genotyping and plasma drug concentration determination. Results Characteristics of the population show a median age of 10 years (IQR 6-13) and a median duration on ART of 5 years (IQR 3-7). Viruses from 53 children were successfully amplified. Of these, 76% of patients were on an NNRTI-based regimen and 24% on a boosted PI-based regimen. NRTI, NNRTI and dual-class resistance was present in 71%, 84% and 65% of cases, respectively. Only 4% of the children had major resistance mutations to PIs and none had major resistance mutations to integrase inhibitors. Among the participants, 25% had undetectable antiretroviral concentrations. Conclusions Our results showed that the development of drug resistance could be one of the main consequences of high and continuous viral replication in HIV-infected children in Benin. Thus, inadequate attention to monitoring lifelong ART in children may prevent achievement of the goal of the United Nations Program on HIV and AIDS (UNAIDS) of 90% viral suppression among patients receiving ART.

Objectives There is no consensus about the performances of genotypic rules for predicting HIV-1 non-B subtype tropism. Three genotypic methods were compared for CRF01_AE HIV-1 tropism determination. Methods The V3 env region of 207 HIV-1 CRF01_AE and 178 B subtypes from 17 centers in France and 1 center in Switzerland was sequenced. Tropism was determined by Geno2Pheno algorithm with false positive rate (FPR) 5% or 10%, the 11/25 rule or the combined criteria of the 11/25, net charge rule and NXT/S mutations. Results Overall, 72.5%, 59.4%, 86.0%, 90.8% of the 207 HIV-1 CRF01_AE were R5-tropic viruses determined by Geno2pheno FPR5%, Geno2pheno FPR10%, the combined criteria and the 11/25 rule, respectively. A concordance of 82.6% was observed between Geno2pheno FPR5% and the combined criteria for CRF01_AE. The results were nearly similar for the comparison between Geno2pheno FPR5% and the 11/25 rule. More mismatches were observed when Geno2pheno was used with the FPR10%. Neither HIV viral load, nor current or nadir CD4 was associated with the discordance rate between the different algorithms. Conclusion Geno2pheno predicted more X4-tropic viruses for this set of CRF01_AE sequences than the combined criteria or the 11/25 rule alone. For a conservative approach, Geno2pheno FPR5% seems to be a good compromise to predict CRF01_AE tropism.

Objectives To investigate the dynamics of HIV-1 variants archived in cells harbouring drug resistance-associated mutations (DRAMs) to lamivudine/emtricitabine, etravirine and rilpivirine in patients under effective ART free from selective pressure on these DRAMs, in order to assess the possibility of recycling molecules with resistance history. Patients and methods We studied 25 patients with at least one DRAM to lamivudine/emtricitabine, etravirine and/or rilpivirine identified on an RNA sequence in their history and with virological control for at least 5 years under a regimen excluding all drugs from the resistant class. Longitudinal ultra-deep sequencing (UDS) and Sanger sequencing of the reverse transcriptase region were performed on cell-associated HIV-1 DNA samples taken over the 5 years of follow-up. Results Viral variants harbouring the analysed DRAMs were no longer detected by UDS over the 5 years in 72% of patients, with viruses susceptible to the molecules of interest found after 5 years in 80% of patients with UDS and in 88% of patients with Sanger. Residual viraemia with

Objectives The aim of the study was to assess the impact of rapid and sustained viral control produced by combination antiretroviral therapy (cART) on HIV-associated immune activation and inflammation. Methods In this longitudinal observational study, we examined changes in interleukin-6 (IL-6), interferon-γ-inducible protein-10 (IP-10), monokine induced by interferon-γ (MIG) and soluble CD14 (sCD14) levels during 2 years of effective first-line cART. Biomarker levels before and after cART were compared with those observed in healthy subjects, using the Wilcoxon signed rank test. Elevated biomarker levels were defined with respect to values for healthy subject (mean + 2 standard deviations). Factors associated with persistently elevated biomarker levels after 2 years of cART were identified by logistic regression. Results We included in the study 139 patients with a median HIV-1 RNA level of 4.8 log10 HIV-1 RNA copies/mL and a median CD4 cell count of 294 cells/μL at cART initiation [day 0 (D0)]. At D0, all biomarker levels were higher than in healthy subjects (P 75% of patients. In contrast, sCD14 levels did not change significantly (0.18 × 106 pg/mL; P = 0.102) and remained elevated. Older age was associated with elevated levels of IP-10 [odds ratio (OR) 1.60 per 10 years older; P = 0.047] and MIG (OR 1.92 per 10 years older; P = 0.007) after 2 years of cART. Conclusions The rapid and sustained viral suppression produced by first-line cART reduced IL-6, IP-10 and MIG to normal levels, while sCD14, a marker of monocyte activation, remained elevated. High levels of IP-10 and MIG tended to persist in older patients.

OBJECTIVES This observational study in antiretroviral treatment-experienced, HIV-1-infected adults explored the efficacy of etravirine plus darunavir/ritonavir (DRV group; n = 999) vs. etravirine plus an alternative boosted protease inhibitor (other PI group; n = 116) using pooled European cohort data. METHODS Two international (EuroSIDA; EUResist Network) and five national (France, Italy, Spain, Switzerland and UK) cohorts provided data (collected in 2007-2012). Stratum-adjusted (for confounding factors) Mantel-Haenszel differences in virological responses (viral load < 50 HIV-1 RNA copies/mL) and odds ratios (ORs) with 95% confidence intervals (CIs) were derived. RESULTS Baseline characteristics were balanced between groups except for previous use of antiretrovirals (≥ 10: 63% in the DRV group vs. 49% in the other PI group), including previous use of at least three PIs (64% vs. 53%, respectively) and mean number of PI resistance mutations (2.3 vs. 1.9, respectively). Week 24 responses were 73% vs. 75% (observed) and 49% vs. 43% (missing = failure), respectively. Week 48 responses were 75% vs. 73% and 32% vs. 30%, respectively. All 95% CIs around unadjusted and adjusted differences encompassed 0 (difference in responses) or 1 (ORs). While ORs by cohort indicated heterogeneity in response, for pooled data the difference between unadjusted and adjusted for cohort ORs was small. CONCLUSIONS These data do not indicate a difference in response between the DRV and other PI groups, although caution should be applied given the small size of the other PI group and the lack of randomization. This suggests that the efficacy and virology results from DUET can be extrapolated to a regimen of etravirine with a boosted PI other than darunavir/ritonavir.

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

International audience; Objectives: Transmitted drug resistance (TDR) can impair the response to first-line antiretroviral therapy. In treatment-naïve patients chronically infected with HIV type 1 (HIV-1), it was previously shown through Sanger sequencing that TDR was more common in men who have sex with men (MSM) than in other transmission risk groups. We aimed to compare two HIV-1 transmission groups in terms of the presence of TDR mutations.Methods: We investigated, through Sanger sequencing and ultradeep sequencing (UDS), the presence of resistance mutations, both in majority (> 20%) and in minority (1−20%) proportions, in 70 treatment-naïve MSM and 70 treatment-naïve heterosexual patients who recently screened positive for HIV-1.Results: The global prevalence of TDR was not significantly different between the two groups, either by Sanger or by UDS. Nevertheless, a higher frequency of nucleoside reverse transcriptase inhibitor TDR was observed among heterosexual patients (P = 0.04). There was also a trend for a higher frequency of TDR among MSM infected with HIV-1 subtype B compared with MSM infected with HIV-1 non-B subtypes (P = 0.06).Conclusions:Ultradeep sequencing UDS allowed sensitive monitoring of TDR, and highlighted some disparities between transmission groups.

OBJECTIVES To evaluate whether a dual nucleoside reverse transcriptase inhibitor (NRTI) strategy can control HIV replication in antiviral therapy (ART)-naive HIV-infected patients with a high CD4 cell count and a low viral load (VL). METHODS This observational study included all HIV-infected treatment-naive patients with a CD4 cell count >300 cells/mm(3), a plasma HIV RNA between 1000 copies/mL and 30,000 copies/mL and wild-type virus who initiated dual NRTI ART between January 2008 and December 2012. HIV RNA and CD4 cell count were assessed at Day 0, Week (W) 4, W12, W24 and W48. The primary endpoint was the proportion of patients with a plasma VL (pVL)

To treat human immunodeficiency virus (HIV)-infected patients, international guidelines recommend the combination of two nucleos(t)ide reverse transcriptase inhibitors [N(t)RTIs] and a third agent [non-NRTI (NNRTI), boosted protease inhibitor (r/PI) or integrase inhibitor (INI)] for initial treatment. The objective of this study was to compare the selection of resistance to antiretrovirals (ARVs) for regimens containing or lacking N(t)RTIs in patients experiencing their first virological failure. Eligible patients had a first virological failure, defined as the occurrence of two consecutive HIV plasma viral loads ≥50copies/mL. Genotypic resistance testing was performed at the time of virological failure (on the second sample with detectable viral load ≥50copies/mL) in patients failing regimens of N(t)RTIs+r/PI or NNRTI or INI, r/PI+NNRTI or INI, and INI+NNRTI. Among 434 virological failures analysed, resistance testing results were available in 416 cases (95.9%). Higher rates of drug resistance were observed in patients receiving N(t)RTI-sparing regimens. When the combination of N(t)RTIs+r/PI was used, PIs protect themselves and the associated N(t)RTIs from the selection of resistance; however, this was not observed with the NNRTI+r/PI combination. The same phenomenon was observed for raltegravir: when used in combination with N(t)RTIs, INI resistance mutations were less frequently selected compared with its use in combination with PIs or NNRTIs. In conclusion, regimens of the ARV classes combined impact the frequency of resistance development. Lower resistance is observed for N(t)RTI-based regimens, with more therapeutic options for subsequent regimens after failure.

OBJECTIVES In resource-limited settings, few data are available on virological failure after long-term first-line antiretroviral therapy. This study characterized the genotypic resistance patterns at the time of failure after at least 36 months of a first-line regimen in Mali, West Africa. METHODS Plasma samples from 84 patients who were receiving first-line antiretroviral treatment and with an HIV-1 RNA viral load (VL) >1000 copies/mL were analysed. Genotypic resistance testing was performed and HIV-1 drug resistance was interpreted according to the latest version of the National Agency for HIV and Hepatitis Research algorithm. RESULTS At the time of resistance testing, patients had been treated for a median of 60 months (IQR 36-132 months) and had a median CD4 cell count of 292 cells/mm(3) (IQR 6-1319 cells/mm(3)), a median HIV-1 RNA level of 28266 copies/mL (IQR 1000-2 93 495 copies/mL) and a median genotypic susceptibility score of 1 (IQR 1-4). The prevalence of nucleoside reverse transcriptase inhibitor (NRTI) and non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance mutations was 78% and 82%, respectively. Viruses were resistant to at least one drug in 92% of cases. Although etravirine and rilpivirine were not used in the first-line regimens, viruses were resistant to etravirine in 34% of cases and to rilpivirine in 49% of cases. The treatment duration, median number of NRTI and NNRTI mutations and some reverse transcriptase mutations (T215Y/F/N, L210W, L74I, M41L and H221Y) were associated with the VL at virological failure. CONCLUSIONS This study demonstrated a high level of resistance to NRTIs and NNRTIs, compromising second-generation NNRTIs, for patients who stayed on long-term first-line regimens. It is crucial to expand the accessibility of virological testing in resource-limited settings to limit the expansion of resistance and preserve second-line treatment efficacy.

Background HIV screening is recommended at time of cancer diagnosis. Moreover, HBV screening, is recommended during immunotherapy due to its risk of reactivation. Furthermore, HCV screening, before using immunotherapy is justified by the prevalence of dysimmune disorders during HCV infection. The main objective of this survey was to evaluate screening practices for HIV, HBV and HCV in cancer patients. Methods A cross-sectional study carried- out across 16 French regions between 25/10/2018 and 31/12/2018, evaluating performance of HIV, HBV and HCV systematic screening at time of cancer diagnosis and/or before immunotherapy. An electronic questionnaire was sent to participants in multidisciplinary concertation meetings. Results The responses of 290 participants (including 101 surgeons, 61 organ specialists, 50 oncologists, 30 radiotherapists, 21 hematologists and 13 general practitioners) were analyzed. Of the 16 regions targeted, 8 of them are represented by 160 participants (55%). A systematic screening for HIV, HBV and HCV at time of cancer diagnosis was reported by 59 (20%), 66 (23%) and 63 (22%) respondents, respectively. A screening on a case by case for HIV, HBV and HCV was reported by 113, 103 and 102 respondents, respectively while 117 respondents stated to never prescribe HIV testing (40%), 121, HBV testing (42%) and 125 HCV testing (43%). Before immunotherapy, 122 respondents stated that they were not concerned and 89 routinely screened for HIV (31%), 97 for HBV (33%) and 94 for HCV (32%). A screening on a case by case for HIV, HBV, and HCV was reported by 38, 36 and 34 respondents, respectively while 40 respondents stated to never prescribe HIV testing (14%), 34, HBV testing (12%) and 39, HCV testing (13%). Conclusions This survey highlights the insufficiency of HIV, HBV and HCV systematic screening at time of cancer diagnosis and/or before immunotherapy. There is a need to raise awareness about the importance of systematic screening in health care providers. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

Recent studies have independently implicated the chemokine CXCL12 and its receptors, CXCR4 and CXCR7, in the pathophysiology of Kaposi sarcoma (KS).We investigated whether the CXCL12/CXCR4-CXCR7 protein trio could constitute KS biomarkers.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.Cells positive for CXCL12, CXCR4, CXCR7, LANA, Ki67 and VEGF were significantly enriched in patients with AIDS-associated KS and classic KS vs. angiomas (P0·001), and in nodular vs. macular/papular KS lesions (P0·05). CXCL12, CXCR4 and CXCR7 detection correlated with LANA, Ki67 and VEGF detection (r0·4; P0·05). However, plasma CXCL12 concentrations did not differ between patients with AIDS-associated KS, HIV-infected patients without KS, and healthy donors.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.

Background Several genotypic rules for predicting HIV-1 non-B subtypes tropism are commonly used, but there is no consensus about their performances. Objectives Three genotypic methods were compared for CRF02_AG HIV-1 tropism determination. Study design V3 env region of 178HIV-1 CRF02_AG from Pitie-Salpetriere and Saint-Antoine Hospitals was sequenced from plasma HIV-1 RNA. HIV-1 tropism was determined by Geno2Pheno algorithm, false positive rate (FPR) 5% or 10%, the 11/25 rule or the combined criteria of the 11/25 and net charge rule. Results A concordance of 91.6% was observed between Geno2pheno 5% and the combined criteria. The results were nearly similar for the comparison between Geno2pheno 5% and the 11/25 rule. More mismatches were observed when Geno2pheno was used with the FPR 10%. A lower nadir CD4 cell count was associated with a discordance of tropism prediction between Geno2pheno 5% and the combined criteria or the 11/25 rule ( p = 0.02 and p = 0.03, respectively). A lower HIV-1 viral load was associated with some discordance for the comparison of Geno2pheno 10% and the combined rule ( p = 0.02). Conclusion Geno2pheno FPR 5% or 10% predicted more X4-tropic viruses for this set of CRF02_AG sequences than the combined criteria or the 11/25 rule alone. Furthermore, Geno2pheno FPR 5% was more concordant with the 11/25 rule and the combined rule than Geno2pheno 10% to predict HIV-1 tropism. Overall, Geno2pheno 5% could be used to predict CRF02_AG tropism as well as other genotypic rules.

International audience; Background Reducing drug burden is a key challenge for achieving lifelong suppressive HIV therapy. Dolutegravir, with a high potency, long half-life and high genetic barrier, offers potential for monotherapy.Methods This observational single-centre study enrolled all patients with HIV RNA (viral load) 350 cells/mm3 and with no failure under integrase inhibitor therapy who had switched from suppressive ART to dolutegravir monotherapy (50 mg/day). Primary outcome was proportion of patients with viral load

OBJECTIVES There are few data on clinical and virological factors associated with maraviroc virological response (VR) in clinical practice. This study aimed to identify factors associated with VR in 94 treatment-experienced, but CCR5 inhibitor-naive, HIV-1 patients switched to maraviroc-containing regimens. METHODS Patients with HIV-1 RNA viral load (VL)

International audience; Objectives In the context of a rilpivirine/emtricitabine/tenofovir disoproxil fumarate switch in HIV-1-infected patients with at least 1 year of virological success, we determined whether proviral DNA is an alternative to plasma HIV RNA for resistance genotyping.Methods Resistance-associated mutations (RAMs) in DNA after at least 1 year of virological success [viral load (VL) 50 copies/mL). Kappa's coefficient was used to measure agreement between the DNA and RNA genotypes.Results In patients without VF (n = 130) and with VF (n = 114), RNA and DNA showed resistance to at least one drug of the rilpivirine/emtricitabine/tenofovir disoproxil fumarate combination in 8% and 9% and in 60% and 45%, respectively. For rilpivirine RAMs, correlation between RNA and DNA was higher in patients without VF than in patients with VF (kappa = 0.60 versus 0.19, P = 0.026). Overall, the prevalence of RAMs was lower in DNA than in RNA.Conclusions Incomplete information provided by the DNA genotypic test is more notable in patients with VF, suggesting that all resistance mutations associated with prior VF have not been archived in the proviral DNA or decreased to a level below the threshold of detection. In the case where no historical plasma genotypic test is available, DNA testing might be useful to rule out switching to rilpivirine/emtricitabine/tenofovir disoproxil fumarate.

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).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.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 pVL50 copies/mL at week 24. Secondary endpoints included the rate of pVL50 copies/mL at week 48, ETR pharmacokinetic parameters, and tolerability and resistance profile.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 pVL50 copies/mL (95% CI, 78.4-99.7) and 85% at week 48 (95%CI, 65.6-95.8). Two of the 3 patients with virological failure had ETR resistance mutations prior to initiation. The median ETR C(trough) level remained stable after switching from twice daily 515 ng/mL (340-758) to once daily 422 ng/mL (264-655).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 C(trough) concentrations on a once-daily regimen confirms the once-daily profile of the drug in experienced patients.

Objectives: To estimate the prevalence of transmitted drug resistance mutations and non-B subtype circulation in antiretroviral-naive chronically HIV-1-infected patients in France. Methods: Resistance mutations were sought in samples from 530 newly diagnosed HIV-1-infected patients from October 2006 to March 2007. Protease and reverse transcriptase mutations were identified from the 2007 Stanford Resistance Surveillance list. Results: Reverse transcriptase and protease resistance mutations were determined in 466 patients with duration of seropositivity

BACKGROUND Darunavir/ritonavir (darunavir/r) maintenance strategy, in patients with suppressed HIV RNA viremia, is a potential long-term strategy to avoid nucleoside analogue toxicities and to reduce costs. METHODS MONOtherapy Inhibitor protease is a prospective, open-label, noninferiority, 96-week safety and efficacy trial in virologically suppressed patients on triple therapy who were randomized to a darunavir/r triple drug regimen or darunavir/r monotherapy. The primary endpoint was the proportion of patients with HIV RNA less than 400 copies/ml at week 48; treatment failure was defined as two consecutive HIV RNA more than 400 copies/ml (time to loss of virologic response) or any change in treatment. The trial had 80% power to show noninferiority for the monotherapy arm (delta =-10%, 90% confidence interval). RESULTS A total of 242 patients were screened, 225 of whom were randomized. In the per protocol efficacy analysis, treatment success was 99% on darunavir/r triple drug versus 94% on darunavir/r monotherapy (delta = -4.9%, 90% confidence interval, from -9.1 to -0.8). Similar results were found in intent-to-treat population (92 versus 87.5%, delta = -4.5%, 90% confidence interval from -11.2 to 2.1). Three patients experienced virologic failure on darunavir/monotherapy and none on darunavir/r triple drug. No resistance to protease inhibitor emerged in patients with plasma viral load above 50 copies/ml. The two groups did not differ in the number of serious adverse events. CONCLUSION Darunavir/r monotherapy exhibited efficacy rate over 85% with concordant results in the magnitude of difference with darunavir/r triple drug regimen in both intent-to-treat and per protocol analyses, but discordant conclusions with respect to the noninferiority margin. Patients failing on darunavir/r monotherapy had no emergence of new darunavir resistance mutations preserving future treatment options.

Objectives The aim of this analysis was to review the evidence and update a meta-analysis evaluating the efficacy and safety results from randomized controlled trials of ritonavir-boosted protease inhibitor (PI/r) monotherapy. Methods A PubMed/EMBASE search was conducted to find randomized trials of PI/r monotherapy vs. triple therapy in patients with HIV-1 RNA suppression at baseline (

Objectives To evaluate the benefits of therapeutic drug monitoring (TDM) in association with genotypic resistance testing and expert advice to optimize therapy in multiexperienced patients infected with HIV-1. Methods Patients with a viral load>1000 HIV-1 RNA copies/mL and an unchanged antiretroviral therapy regimen over the last 3 months were randomized into two groups: a genotypic group (G) and a geno-pharmacological group (GP). Treatment was selected by an expert committee according to genotypic resistance testing (the G and GP groups) and TDM (the GP group) at week 4. Treatment could be modified at each visit according to toxicity, poor virological response and TDM. Results of TDM were withheld from the G group until week 12. The primary endpoint of the study was the percentage of patients with viral load

Background. The consequences of a prior human herpesvirus-8 (HHV-8) infection in kidney-transplant recipients are still partially unknown. The aim of this monocentric study was to determine the prevalence of HHV-8-seropositive patients at the time of transplantation and to identify the main clinical events of these HHV-8 + recipients. Methods. From January 1,1990 to December 31, 1996, antibodies to HHV-8 latent nuclear antigen were detected by indirect immunofluorescent method in serum samples collected just before kidney transplantation from 400 consecutive patients. Conventional double or triple immunosuppressive treatment was prescribed. For the group of HHV-8 + recipients, data including death rate, graft survival, and occurrence of Kaposi's sarcoma (KS) were retrospectively collected until December 31, 1998. Cofactors associated with KS were studied in univariate and multivariate analyses using a Cox model. Results. Thirty-two patients (8%) had antibodies to HHV-8 in their sera at the time of transplantation. Among these 32, 3 years after transplantation, graft survival was 72%, and KS prevalence was 28% (KS incidence: 8.2/yr/100 HHV-8 + recipients). Multivariate analysis identified bacterial and/or Pneumocystis carinii infection (odds ratio: 8.6; P=0.019) and female gender (odds ratio: 5.34; P=0.047) as factors associated with KS. No KS was observed in patients without anti-HHV-8 antibodies at the time of transplantation. Conclusions. The low graft survival and the high prevalence of KS within the studied population of HHV-8 + transplant recipients are strong arguments for systematic screening of HHV-8 serologic features before transplantation, especially in patients of African origin. HHV-8 + transplant recipients should be closely monitored to severe infections.

H-932. American Society for Microbiology, Washington, DC, USA. 10 Nouhin J, Donchai T, Hoang KT et al. Natural polymorphisms of HIV-1 CRF01_AE integrase coding region in ARV-naive individuals in Cambodia, Thailand and Vietnam: an ANRS AC12 working group study. Infect Genet Evol 2011; 11: 38–43. 11 Wainberg MA, Brenner BG. Role of HIV subtype diversity in the development of resistance to antiviral drugs. Viruses 2010; 2: 2493–508. Research letter

Long-term results at week 96 are needed to evaluate the capacity of the darunavir/ritonavir monotherapy strategy to maintain a sustained control of the HIV-1 viral load.MONOI is a prospective, open-label, non-inferiority, randomized, 96 week trial comparing darunavir/ritonavir monotherapy versus a darunavir/ritonavir triple-therapy strategy to maintain HIV-1 viral load suppression in HIV-1-infected patients.NCT00412551.From 225 randomized patients, 219 patients reached the 48 week follow-up and 211 reached the 96 week follow-up (106 patients in the darunavir monotherapy arm and 105 in the darunavir triple-therapy arm). Baseline characteristics were well balanced between the two treatment groups. At week 96, in intent-to-treat analysis, 91/103 patients (88%, 95% CI 81-94) allocated to the darunavir/ritonavir monotherapy arm and 87/104 patients (84%, 95% CI 75-90) allocated to the darunavir triple-therapy arm achieved an HIV-1 viral load50 copies/mL, with no statistical difference between the two groups. Throughout the 96 week follow-up, 66/112 patients (59%, 95% CI 49-68) and 79/113 patients (70%, 95% CI 61-78) consistently had HIV-1 RNA50 copies/mL with darunavir/ritonavir monotherapy and darunavir/ritonavir triple therapy, respectively.The MONOI study establishes darunavir/ritonavir monotherapy as durable and efficacious for maintaining virological suppression in HIV-1 patients. Darunavir/ritonavir monotherapy should be considered as a (tailored) treatment option for standard triple-therapy patients who have had a substantial period of viral suppression.

The large underestimations of HIV RNA quantification observed in 17 patients with the first version of Cobas TaqMan assay have been successfully corrected in the upgraded version 2.0. In comparison with the Abbott RealTime assay, the mean difference that was 1.18 log 10 copies/ml is now zero. The discrepancies have disappeared.

Objective: Activation of AT2 angiotensin II receptor release cytochrome P-450 arachidonic acid metabolites (CYP-AA). The presence of the AT2 receptor and its ability to mediate renal vasodilation through CYP-AA metabolites were evaluated. Methods: Vascular response to angiotensin II in the isolated perfused kidney of the rat was evaluated in the absence and presence of angiotensin II AT1 and AT2 receptor blockers. Results: Blockade of the AT1 receptor unmasked a vasodilatory response that was inhibited by AT2 receptor blockade and AA metabolism. Conclusion: The findings indicate that blockade of the AT1 angiotensin II receptor, activation of AT2 receptors, releases CYP-AA metabolites that induce renal vasodilation.

It is unclear how stable low-level viral replication and CD4 cell numbers can be maintained under highly active antiretroviral therapy (HAART). This study was designed to analyse whether HIV-specific responses in stable partially controlled patients during antiretroviral therapy (ART) differ from those observed in complete HAART failure and whether they contribute to the control of viral load (VL).Three groups of patients were selected according to plasma HIV RNA levels during 18 months of ART: persistently low VL (LoVL; HIV RNA10,000 copies/ml; n = 28), undetectable VL (UnVL; HIV RNA200 copies/ml; n = 29) and high VL (HiVL; HIV RNA10,000 copies/ml; n = 14). T-cell responses were studied using lymphoproliferative and interferon (IFN)-gamma-ELISpot assays against HIV-p24, -gp160, recall antigens, and 15 pools of HIV-(Gag + RT) peptides.Frequencies of IFN-gamma-producing CD4 T cells against HIV-p24 were higher in LoVL than in UnVL or HiVL groups [median, 131, 47 and 23 spot-forming cells (SFC)/1 x 10 peripheral blood mononuclear cells (PBMC), respectively; P = 0.012 and P = 0.047]. Lymphoproliferative responses to HIV-p24 and recall antigens were similar in LoVL and UnVL groups but lower in HiVL (P = 0.004). Frequencies of HIV-specific CD8 T cells were higher in LoVL than in UnVL (1340 versus 410 SFC/1 x 10 PBMC; P = 0.001). They correlated negatively with VL in the LoVL and HiVL (r, -0.393, P = 0.039 and r, -0.643, P = 0.024, respectively) and positively correlated with anti-HIV CD4 cell frequencies in the LoVL group only (r, 0.420; P = 0.026).Persistently low viral replication (10,000 copies/ml) during ART stimulates high frequencies of HIV-specific CD4 and CD8 T cells compared to full virus suppression or complete ART failure. The association of high anti-HIV activity with large numbers of HIV-specific CD8 T cells contribute to the control of viral replication.

ObjectiveTo evaluate the efficacy and tolerability of indinavir/ritonavir (IDV/RTV) 400/100 mg twice daily in combination with two nucleoside reverse transcriptase inhibitors in antiretroviral-naive patients.Design and methodsAntiviral therapy-naive patients with plasma HIV-1 RNA >5000 copies/ml were enrolled in this pilot, single-arm study. CD4 cell count and viral load were evaluated at weeks (W) 4, 12, 24 and every 3 months until W48. The primary end-point was the percentage (%) of patients with viral load ResultsForty patients were enrolled. Baseline median viral load was 5.36 log10copies/ml, median CD4 count was 84 cells/mm3. At W48 by ITT analysis, the % patients with viral load 10copies/ml (–0.1; –5.19) and the median increase in CD4 was +167 cells/mm3(6–474 cell/mm3). At W4 (34/40), the median IDV Cminwas 500 ng/ml (range 5–8100) with 91% of patients with an adequate IDV Cmin>150 ng/ml. Ten patients discontinued the study treatment before W48: adverse events (eight), patient's will (one) and simplification of therapy (one). Three patients were lost to follow-up. Only one virological failure occurred and was associated with poor compliance and sub-optimal concentrations of IDV/RTV.ConclusionsIDV/RTV 400/100 mg twice daily is an effective and safe first-line antiretroviral therapy. The simplicity and the low cost of IDV/RTV is of major interest particularly in countries with limited resources.

Background. Human herpesvirus-8 (HHV-8) is a new human herpesvirus that is clearly associated with Kaposi’s sarcoma (KS). A previous study has reported that the prevalence of KS in a cohort of renal transplant recipients with previous HHV-8 infection was 28% and two other studies have shown that KS can be linked to HHV-8 seroconversion after graft. The aim of this study was to evaluate the HHV-8 seroconversion rate in a cohort of renal allograft recipients in Paris. Methods. Two hundred eighty-seven patients who were HHV-8 seronegative before renal transplantation were tested for HHV-8 antibodies by an immunofluorescence assay 12 months after transplantation. Results. Of the 287 patients, 6 (2.09%) seroconverted after renal transplantation. None of these 6 patients developed KS within 3 years of the first HHV-8 positive serum. None of the clinical manifestations that could be associated with HHV-8 primary infection were observed during the seroconversion. Conclusions. Our results demonstrated that HHV-8 seroconversion can be observed even in a low HHV-8 prevalence area and confirmed the need to perform systematic screening for HHV-8 antibodies in renal graft donors and recipients.

BACKGROUND Common variable immunodeficiency (CVID) is a primary immune deficiency defined by defective antibody production. In most series, a small proportion of patients present with opportunistic infections (OIs). METHODS The French DEFI study has enrolled patients with primary hypogammaglobulinemia and allows a detailed clinical and immunologic description of patients with previous OIs and/or at risk for OIs. RESULTS Among 313 patients with CVID, 28 patients (8.9%) presented with late-onset combined immune deficiency (LOCID), defined by the occurrence of an OI and/or a CD4(+) T cell count