Publications by authors named "Jean-Michel Molina"

328 Publications

Switching to Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (DOR/3TC/TDF) Maintains HIV-1 Virologic Suppression Through Week 144 in the DRIVE-SHIFT Trial.

J Acquir Immune Defic Syndr 2021 Feb 17. Epub 2021 Feb 17.

Medstar Georgetown University Hospital, Div. of Infectious Diseases and Travel Medicine, Washington DC, USA Royal Free Hospital, Department of HIV Medicine, London UK Saint-Louis and Lariboisière Hospitals, APHP, University of Paris, INSERM U944, Paris, France ASST Fatebenefratelli Sacco Hospital, Department of Infectious Diseases, Milan, Italy Fundación Huésped and Buenos Aires University, Buenos Aires, Argentina Infektiologikum, Centre for Infectious Diseases, Frankfurt, Germany; Merck & Co., Inc., Kenilworth, NJ USA.

Background: In the primary analysis of the DRIVE-SHIFT trial, switching to doravirine/lamivudine/ tenofovir disoproxil fumarate (DOR/3TC/TDF) maintained suppression of HIV-1 through Week 48. Here we present long-term efficacy and safety outcomes through Week 144 of the DRIVE-SHIFT trial.

Methods: This phase 3, randomized, open-label trial evaluated switching from a stable antiretroviral regimen to once-daily DOR/3TC/TDF in adults with HIV-1 suppressed for ≥6 months and no previous virologic failure. Participants switched at Day 1 (immediate-switch group [ISG]; n=447) or Week 24 (delayed-switch group [DSG]; n=209). Nine ISG participants who completed Week 48 but did not enter Extension-1 were excluded from Week 144 efficacy analyses.

Results: At Week 144, HIV-1 RNA <50 copies/mL was maintained in 80.1% of the ISG (351/438) and 83.7% of the DSG (175/209), while 2.7% (12/438) and 4.8% (10/209), respectively, had HIV-1 RNA ≥50 copies/mL (FDA Snapshot). Protocol-defined virologic failure after switch occurred in 2.1% of ISG (9/438) and 3.3% of DSG (7/209); no viral resistance to doravirine was detected in four participants with samples available. Reductions in fasting lipids were observed at 24 weeks post-switch and maintained through Week 144. Mean weight change from switch to Week 144 was +1.4 kg for ISG and +1.2 kg for DSG. The most common adverse events were nasopharyngitis (16.2%), headache (12.3%) and diarrhea (9.1%). Overall, 4.1% discontinued due to adverse events, and no deaths occurred.

Conclusions: These results confirm that switching to once-daily DOR/3TC/TDF is a generally well-tolerated option for maintaining viral suppression in adults considering a change in therapy.

Registration: ClinicalTrials.gov NCT02397096.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/QAI.0000000000002642DOI Listing
February 2021

Commentary title: COVID-19 research, Africa, and global health.

J Virus Erad 2021 Mar 3;7(1):100030. Epub 2021 Feb 3.

Forum for Collaborative Research, 1608 Rhode Island Avenue NW, Suite 212, Washington, DC, 20036, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jve.2021.100030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857035PMC
March 2021

Low level of baseline resistance in recently HCV-infected men who have sex with men with high-risk behaviours.

J Glob Antimicrob Resist 2021 Feb 2;24:311-315. Epub 2021 Feb 2.

Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), AP-HP, Hôpital Pitié-Salpêtrière, Laboratoire de virologie, F-75013 Paris, France. Electronic address:

Objectives: Presence of baseline hepatitis C virus (HCV) resistance-associated substitutions (RASs) can impair treatment outcome of direct-acting antivirals. We investigated the prevalence of pre-treatment HCV resistance among recently HCV-infected men who have sex with men (MSM) with high risk behaviours, either human immunodeficiency virus (HIV) co-infected or at high risk of HIV acquisition and under pre-exposure prophylaxis (PrEP).

Methods: NS5A and NS3 fragments were deep sequenced on pre-treatment samples of 72 subjects using Illumina MiSeq paired-end sequencing technology. Ultra-deep sequencing data were analysed by SmartGene® platform. RASs mentioned in the literature were analysed and interpreted depending on genotype (GT) at 10% cut-off.

Results: HCV genotyping showed 36 (50.0%) GT1a, 31 (43.1%) GT4d and 5 (6.9%) GT3a infections. Fifty-five patients (76.4%) were co-infected with HIV and 15 (20.8%) received PrEP. In GT1a viruses, NS3 RASs were found in 4/30 viruses (13.3%; S122 G/N, R155 K and I170 V) and Q80 K polymorphism was present in 14/30 viruses (46.7%). No NS3 RASs were detected in GT4d and GT3a viruses. NS5A RASs were detected in 3/36 GT1a viruses (8.3%; Q30E/R, L31 M and H58 L). NS5A subtype-specific polymorphisms L30R and T58 P were found at high frequencies in 31/31 (100%) and 16/31 (51.6%) GT4d viruses, respectively. One RAS M31 L was also observed along with the polymorphisms L30R and T58 P. No NS5A RASs were detected in GT3a viruses.

Conclusion: A low level of RASs to NS3 and NS5A inhibitors in pre-treatment samples was detected in the study population. Our findings reassure the clinical management of HCV infection in this high-risk population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jgar.2021.01.012DOI Listing
February 2021

Identification of 16S rRNA mutations in Mycoplasma genitalium potentially associated with tetracycline resistance in vivo but not selected in vitro in M. genitalium and Chlamydia trachomatis.

J Antimicrob Chemother 2021 Feb 4. Epub 2021 Feb 4.

Univ. Bordeaux, INRAE, IHMC, EA, 3671, F-33000 Bordeaux, France.

Objectives: Tetracyclines are widely used for the treatment of bacterial sexually transmitted infections (STIs) and recently have been used successfully for post-exposure prophylaxis of STIs in MSM. We investigated the in vitro and in vivo development of tetracycline resistance in Chlamydia trachomatis and Mycoplasma genitalium and evaluated 16S rRNA mutations associated with acquired resistance in other bacteria.

Methods: In vitro selection of resistant mutants of reference strains of C. trachomatis and M. genitalium was undertaken by serial passage in medium containing subinhibitory concentrations of tetracycline or doxycycline, respectively. The 16S rRNA gene of the two microorganisms was amplified and sequenced at different passages, as were those of 43 C. trachomatis- and 106 M. genitalium-positive specimens collected in France from 2013 to 2019.

Results: No tetracycline- or doxycycline-resistant strains of C. trachomatis and M. genitalium, respectively, were obtained after 30 serial passages. The tetracycline and doxycycline MICs were unchanged and analysis of the 16S rRNA gene, the molecular target of tetracyclines, of C. trachomatis and M. genitalium revealed no mutation. No mutation in the 16S rRNA gene was detected in C. trachomatis-positive specimens. However, six M. genitalium-positive specimens harboured a mutation potentially associated with tetracycline resistance without known prior tetracycline treatment for patients.

Conclusions: Tetracyclines did not select in vitro-resistant mutants of C. trachomatis or M. genitalium. However, 16S rRNA mutations either responsible for or associated with tetracycline resistance in other bacteria, including mycoplasma species, were identified in several M. genitalium-positive specimens.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jac/dkab016DOI Listing
February 2021

SARS-CoV-2 induces human plasmacytoid predendritic cell diversification via UNC93B and IRAK4.

J Exp Med 2021 04;218(4)

Université de Paris, Institut de Recherche Saint-Louis, Institut National de la Santé et de la Recherche Médicale U976, Hôpital Saint-Louis, Paris, France.

Several studies have analyzed antiviral immune pathways in late-stage severe COVID-19. However, the initial steps of SARS-CoV-2 antiviral immunity are poorly understood. Here we have isolated primary SARS-CoV-2 viral strains and studied their interaction with human plasmacytoid predendritic cells (pDCs), a key player in antiviral immunity. We show that pDCs are not productively infected by SARS-CoV-2. However, they efficiently diversified into activated P1-, P2-, and P3-pDC effector subsets in response to viral stimulation. They expressed CD80, CD86, CCR7, and OX40 ligand at levels similar to influenza virus-induced activation. They rapidly produced high levels of interferon-α, interferon-λ1, IL-6, IP-10, and IL-8. All major aspects of SARS-CoV-2-induced pDC activation were inhibited by hydroxychloroquine. Mechanistically, SARS-CoV-2-induced pDC activation critically depended on IRAK4 and UNC93B1, as established using pDC from genetically deficient patients. Overall, our data indicate that human pDC are efficiently activated by SARS-CoV-2 particles and may thus contribute to type I IFN-dependent immunity against SARS-CoV-2 infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1084/jem.20201387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7849819PMC
April 2021

Household Coronavirus Disease 2019 (COVID-19) Prevalence.

Clin Infect Dis 2021 02;72(3):539

Paris University, Paris, France.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cid/ciaa688DOI Listing
February 2021

SARS-CoV-2 induces human plasmacytoid pre-dendritic cell diversification via UNC93B and IRAK4.

bioRxiv 2021 Jan 8. Epub 2021 Jan 8.

Université de Paris, Institut de Recherche Saint-Louis, INSERM U976, Hôpital Saint-Louis, 75010 Paris, France.

Several studies have analyzed antiviral immune pathways in late-stage severe COVID-19. However, the initial steps of SARS-CoV-2 antiviral immunity are poorly understood. Here, we have isolated primary SARS-CoV-2 viral strains, and studied their interaction with human plasmacytoid pre-dendritic cells (pDC), a key player in antiviral immunity. We show that pDC are not productively infected by SARS-CoV-2. However, they efficiently diversified into activated P1-, P2-, and P3-pDC effector subsets in response to viral stimulation. They expressed CD80, CD86, CCR7, and OX40 ligand at levels similar to influenza virus-induced activation. They rapidly produced high levels of interferon-α, interferon-λ1, IL-6, IP-10, and IL-8. All major aspects of SARS-CoV-2-induced pDC activation were inhibited by hydroxychloroquine. Mechanistically, SARS-CoV-2-induced pDC activation critically depended on IRAK4 and UNC93B1, as established using pDC from genetically deficient patients. Overall, our data indicate that human pDC are efficiently activated by SARS-CoV-2 particles and may thus contribute to type I IFN-dependent immunity against SARS-CoV-2 infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1101/2020.07.10.197343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7805442PMC
January 2021

Evaluation of drug abuse by hair analysis and self-reported use among MSM under PrEP: Results from a French sub-study of the ANRS-IPERGAY trial.

J Acquir Immune Defic Syndr 2020 Dec 23;Publish Ahead of Print. Epub 2020 Dec 23.

Département des Maladies Infectieuses, Hôpital Tenon, AP-HP, Paris, France; INSERM SC10 US19, Villejuif, France; Département de Pharmacologie - Toxicologie, Hôpital Raymond Poincaré, AP-HP, et MassSpecLab, Plateforme de Spectrométrie de Masse, Inserm U-1173, UFR des Sciences de la Santé Simone Veil, Université Paris-Saclay (Versailles Saint-Quentin-en-Yvelines), Garches, France; Département de Pharmacologie - Toxicologie, Hôpital Bichat Claude Bernard, AP-HP, et IAME, INSERM, UMRS1137, Université de Paris, Paris, France Aix Marseille Université, INSERM, IRD, SESSTIM, Sciences Economiques & Sociales de la Santé & Traitement de l'Information Médicale, Marseille, France; ORS PACA, Observatoire régional de la santé Provence-Alpes-Côte d'Azur, Marseille, France; Département des Maladies Infectieuses, Hôpital de l'Archet, Nice, France; Département des Maladies Infectieuses, Hôpital de la Croix Rousse, Hospices Civils de Lyon, Lyon, France; Département des Maladies Infectieuses, Hôpital G Dron, Centre Hospitalier Universitaire de Tourcoing, Tourcoing, France; Université Paris Sud, Paris, France; Hôtel-Dieu, Département des Maladies Infectieuses, Nantes, France; Sorbonne Université; Département de Maladies Infectieuses, Hôpital Lariboisière Saint-Louis, Paris, France; Université de Paris, Paris, France; INSERM U944, Paris, France.

Abstract.

Background: We used the ANRS-IPERGAY trial in order to qualitatively and quantitatively measure drug use among MSM under PrEP using two different methods, in order to better understand and collectively respond to risky practices.

Method: We included 69 voluntaries of ANRS-IPERGAY trial. We measured drug use by two methods: (1) Drug detection by hair analysis; (2) Reported drug use by self-reported drug consumption.

Results: New Psychoactive Substances (NPS) and conventional drugs were detected in 53/69 (77%) by hair analysis and in 39/69 (57%) by questionnaires. On the 219 hair segments analyzed, the most commonly used drugs were cocaine in 47/69 (68%), MDMA/ecstasy in 31/69 (45%), NPS in 27/69 (39%). On the 1,061 collected questionnaires, the most commonly used drugs were cocaine in 31/69 (45%), MDMA/ecstasy in 29/69 (42%) and NPS in 16/69 (23%). Hair analysis detects more conventional drugs and/or NPS use (p<0.05). Drug use identified by hair was significantly associated with a higher number of sexual partners in the past two months (p≤0.001), more often casual partners (p≤0.001), condomless anal sex (p≤0.005), hardcore sexual practices (p≤0.001), a higher number of STIs and chemsex (p≤0.05).

Conclusion: Self-report drug use by questionnaires remains the reference tool for harm reduction at the individual level due to its feasibility and low cost. However, hair analysis is more sensitive, objectively assessing consumption and is interesting in order to understand uses and to be able to collectively respond to risky practices with adapted messages.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/QAI.0000000000002610DOI Listing
December 2020

Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (TDF) Versus Efavirenz/Emtricitabine/TDF in Treatment-naive Adults With Human Immunodeficiency Virus Type 1 Infection: Week 96 Results of the Randomized, Double-blind, Phase 3 DRIVE-AHEAD Noninferiority Trial.

Clin Infect Dis 2020 Dec 18. Epub 2020 Dec 18.

Merck & Co., Inc., Kenilworth, New Jersey, USA.

Background: Doravirine (DOR) is a nonnucleoside reverse-transcriptase inhibitor. In the phase 3 DRIVE-AHEAD trial in treatment-naive adults with human immunodeficiency virus type 1 (HIV-1) infection, DOR demonstrated noninferior efficacy compared with efavirenz (EFV) and superior profiles for neuropsychiatric tolerability and lipids at 48 weeks. We present data through week 96.

Methods: DRIVE-AHEAD is a phase 3, multicenter, double-blind, noninferiority trial in antiretroviral treatment-naive adults with HIV-1 RNA ≥1000 copies/mL. Participants were randomized to a daily fixed-dose tablet of DOR (100 mg), lamivudine (3TC; 300 mg) and tenofovir disoproxil fumarate (TDF; 300 mg) (DOR/3TC/TDF) or EFV (600 mg), emtricitabine (FTC; 200 mg) and TDF (300 mg) (EFV/FTC/TDF). The efficacy end point of interest at week 96 was the proportion of participants with HIV-1 RNA levels <50 copies/mL (Food and Drug Administration Snapshot Approach) with a predefined noninferiority margin of 10% to support week 48 results. Safety end points of interest included prespecified neuropsychiatric adverse events and the mean change in fasting lipids at week 96.

Results: Of 734 participants randomized, 728 received study drugs and were included in analyses. At week 96, HIV-1 RNA <50 copies/mL was achieved by 77.5% of DOR/3TC/TDF vs 73.6% of EFV/FTC/TDF participants, with a treatment difference of 3.8% (95% confidence interval, -2.4% to 10%). Virologic failure rates were low and similar across treatment arms, with no additional resistance to DOR observed between weeks 48 and 96. Prespecified neuropsychiatric adverse events and rash were less frequent in DOR/3TC/TDF than in EFV/FTC/TDF participants through week 96. At week 96, fasting low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol (HDL-C) levels increased in the EFV/FTC/TDF group but not in the DOR/3TC/TDF group; the mean changes from baseline in total cholesterol/HDL-C ratio were similar.

Clinical Trials Registration: NCT02403674.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cid/ciaa822DOI Listing
December 2020

Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in Adults With HIV and M184V/I Mutation.

J Acquir Immune Defic Syndr 2021 Apr;86(4):490-495

Gilead Sciences, Foster City, CA.

Background: The ability of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) to maintain virologic suppression in participants with M184V and/or M184I resistance mutations from historical genotypic reports when switching from a tenofovir disoproxil fumarate-based or abacavir (ABC)-based regimen was investigated.

Setting: Phase IIIb, 48-week, open-label, single-arm, multicenter, clinical trial (NCT02616029).

Methods: Virologically suppressed adults with HIV and documented M184V/I on historical genotypic records switched to E/C/F/TAF from a tenofovir disoproxil fumarate-based or ABC-based regimen. The primary end point was HIV-1 RNA of <50 copies per milliliter at week 12 using pure virologic response (PVR). Secondary end points included HIV-1 RNA of <50 copies per milliliter at weeks 24/48 (PVR) and at weeks 12, 24, and 48 (Food and Drug Administration snapshot algorithm), and change in CD4+ count at weeks 12, 24, and 48.

Results: M184V alone was reported in 82.8% of 64 participants; 9.4% and 7.8% had M184I and M184V/I, respectively, and 43.8% had archived M184V/I (baseline DNA). All (62/62 with available data, 100%, 95% confidence interval 94.2% to 100%) participants maintained PVR at weeks 12, 24, and 48. By Food and Drug Administration snapshot algorithm, one participant had HIV-1 RNA of ≥50 copies per milliliter (week 12); confirmatory HIV-1 RNA was <50 copies per milliliter. No significant changes were observed in CD4+ cell count. Drug-related adverse events (AEs) were reported by 10 (15.6%) participants. Six (9.4%) and 5 (7.8%) participants had grade 3-4 AEs or serious AEs, respectively (none drug related).

Conclusions: The presence of the resistance mutations M184V/I did not jeopardize the efficacy of switching to E/C/F/TAF in virologically suppressed adults. High rates of virologic suppression were maintained throughout 48 weeks of therapy and treatment was well tolerated.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/QAI.0000000000002595DOI Listing
April 2021

High Prevalence and High Rate of Antibiotic Resistance of Mycoplasma genitalium Infections in Men who Have Sex with Men. A Sub-Study of the ANRS Ipergay PrEP Trial.

Clin Infect Dis 2020 Dec 11. Epub 2020 Dec 11.

INSERM UMR 941, Department of Infectious Diseases, University of Paris, Saint-Louis and Lariboisière Hospitals, APHP, Paris, France.

Background: Mycoplasma genitalium (MG) is an emerging pathogen among men who have sex with men (MSM) with raising rates of antibiotic resistance. In this study, we assessed the prevalence and incidence of MG infection in MSM enrolled in the open-label phase of the ANRS IPERGAY trial with on demand TDF/FTC for HIV prevention and the impact of doxycycline post-exposure prophylaxis (PEP).

Methods: 210 subjects were tested at baseline and at 6 months by real-time PCR assays for MG detection in urine samples, oro-pharyngeal and anal swabs. Resistance to azithromycin (AZM), to fluoroquinolones (FQ) and to doxycycline were investigated in the French National Reference Centre of bacterial STI.

Results: The all-site prevalence of MG at baseline was 10.5% [6.3% in urine samples, 4.3% in anal swabs and 0.5% in throat swabs] and remained unchanged at 6 months whether or not PEP was used: 9.9% overall, 10.2% with PEP and 9.6% without. The overall rate of MG resistance (prevalent and incident cases) to AZM and FQ was 67.6% and 9.1%, respectively, with no difference between arms. An in vivo mutation of the MG 16S rRNA which could be associated with tetracycline resistance was observed in 12.5% of specimens tested.

Conclusions: The prevalence of MG infection among MSM on PrEP was high and its incidence was not decreased by doxycycline prophylaxis with a similar high rate of AZM- and FQ-resistance, raising challenging issues for the treatment of this STI and supporting current recommendations to avoid testing or treatment of asymptomatic MG infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cid/ciaa1832DOI Listing
December 2020

Persistence of monocyte activation under treatment in people followed since acute HIV-1 infection relative to participants at high or low risk of HIV infection.

EBioMedicine 2020 Dec 26;62:103129. Epub 2020 Nov 26.

Université Paris-Saclay, UVSQ, Inserm, CESP, 94807 Villejuif, France; Service de Santé Publique, AP-HP, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France. Electronic address:

Background: Interpretation of the increase in certain inflammatory markers in virally suppressed HIV-infected individuals must rely on an appropriate uninfected control group well characterized for non-HIV-related factors that contribute to chronic inflammation, e.g. smoking, alcohol consumption, or being overweight. We compared the inflammatory profiles of HIV-infected participants under long-term antiretroviral therapy (ART) with those of two HIV-uninfected groups with contrasting health behaviours.

Methods: We studied 150 HIV-infected participants (42 women, 108 men) under long-term ART (median, 6 years) followed in the ANRS PRIMO cohort since acute/early HIV-1 infection (AHI) diagnosis. Sex and age-matched controls were sampled from i) the ANRS IPERGAY pre-exposure prophylaxis trial among men at high risk for HIV infection and with high frequencies of non-HIV factors of inflammation ii) the ANRS COHVAC cohort of volunteers in vaccine trials with a low-risk profile for HIV infection. We measured the plasma levels of ten inflammatory markers.

Findings: After adjusting for smoking, alcohol use and body mass index, both HIV-infected men and women had higher levels of sCD14, sCD163, sTNFRII and I-FABP than their high-risk IPERGAY and low-risk COHVAC counterparts. Hierarchical clustering showed a subset of 15 PRIMO participants to have an inflammatory profile similar to that of most HIV-negative participants. These participants already had favourable markers at AHI diagnosis.

Interpretation: Long-term ART, even when initiated at a low level of immunodeficiency, fails to normalize monocyte/macrophage activation and gut epithelial dysfunction. Persistent inflammation under treatment may be related to an increased inflammatory profile since AHI.

Funding: ANRS and Paris-Saclay University.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ebiom.2020.103129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704414PMC
December 2020

Fosfomycin-trometamol (FT) or fluoroquinolone (FQ) as single-dose prophylaxis for transrectal ultrasound-guided prostate biopsy (TRUS-PB): A prospective cohort study.

Int J Infect Dis 2021 Jan 29;102:269-274. Epub 2020 Oct 29.

APHP, Infectious Diseases and Tropical medicine department, Saint-Louis Hospital, F-75010, Paris, France. Electronic address:

Objectives: The increasing incidence of fluoroquinolones (FQ) resistance may lower its efficacy in preventing UTI following transrectal ultrasound-guided prostate biopsy (TRUS-PB). We assessed the efficacy and safety of FQ and fosfomycin-trometamol (FT) in patients undergoing TRUS-PB.

Methods: A prospective observational study was conducted between April 2017 and June 2019 and enrolled men undergoing TRUS-PB and receiving a single-dose of FQ (FQ-arm) or FT (FT-arm) for UTI prophylaxis per physician's choice. The primary efficacy endpoint was self-reported TRUS-PB UTI. We assessed baseline factors associated with UTI with logistic regression.

Results: A total of 222 men were enrolled, 141/222 (64%) received FQ, and 81/222 (36%) FT. The median age was 67.6 years [IQR, 61.4-72.1] and the Charlson score was 3 [IQR, 3-5]. The overall incidence of self-reported TRUS-PB UTI was 12% (24/197, (95%CI, 8%-17%)): 15% (17/116, (95% CI, 10%-17%)) in FQ-arm, versus 9% (7/81, 95% CI (5%-13%)) in FT-arm (RR = 0.55 (95% CI, 0.22-1.40), p-value = 0.209). No baseline characteristic was significantly associated with TRUS-PB UTI. Safety was similar between the arms: the rate of the reported adverse event was 31% (36/116, (95% CI, 25%-37%) in the FQ-arm versus 36% (28/81, (95% CI, 28%-41%)) in the FT-arm (RR = 1.17 (95% CI, 0.64-2.15), p = 0.602).

Conclusions: TRUS-PB UTI prophylaxis with FT and FQ has similar efficacy and safety. A randomized comparison of these two antibiotics is warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijid.2020.10.065DOI Listing
January 2021

Safety and efficacy of the HIV-1 attachment inhibitor prodrug fostemsavir in heavily treatment-experienced individuals: week 96 results of the phase 3 BRIGHTE study.

Lancet HIV 2020 11;7(11):e740-e751

ViiV Healthcare, Branford, CT, USA.

Background: Fostemsavir, a prodrug of the first-in-class attachment inhibitor, temsavir, is indicated for heavily treatment-experienced individuals with multidrug-resistant HIV-1. We previously reported superior efficacy of fostemsavir versus placebo in the randomised cohort of the BRIGHTE study after 8-day functional monotherapy (primary endpoint); here we report planned interim analyses through week 96.

Methods: BRIGHTE (NCT02362503) is an ongoing multicentre, two-cohort, phase 3 trial, done at 108 centres in 22 countries. We enrolled heavily treatment-experienced adults (≥18 years) failing antiretroviral therapy (HIV-1 RNA ≥400 copies per mL) into two cohorts: the randomised cohort, in which patients with one or two fully active antiretrovirals remaining received oral fostemsavir (600 mg twice a day) or placebo in combination with their failing regimen for 8 days, followed by fostemsavir plus optimised background therapy; or the non-randomised cohort, in which patients with no remaining antiretroviral options received oral fostemsavir (600 mg twice a day) plus optimised background therapy from day 1. Endpoints for the week 96 interim analyses included the proportions of participants with plasma HIV-1 RNA of less than 40 copies per mL, changes from baseline in CD4 cell counts, and the frequency of adverse events, adverse events leading to discontinuation, and deaths. The intention-to-treat exposed population and the safety population both included all participants who received at least one dose of study treatment. The response rates (proportion of participants with HIV-1 RNA <40 copies per mL) in the intention-to-treat exposed population were calculated via snapshot analysis at weeks 24, 48, and 96.

Findings: Between Feb 23, 2015, and Aug 11, 2016, 371 participants were enrolled and treated, of which 272 participants were in the randomised cohort and 99 in the non-randomised cohort. 320 (86%) of 371 reported a history of AIDS. In the randomised cohort, rates of virological suppression (HIV-1 RNA <40 copies per mL) increased from 53% (144 of 272) at week 24 to 60% (163 of 272) at week 96. Response rates in the non-randomised cohort were 37% (37 of 99) at week 24 and week 96. Mean increases in CD4 counts from baseline at week 96 were 205 cells per μL (SD 191) in the randomised cohort and 119 cells per μL (202) in the non-randomised cohort. Mean CD4/CD8 ratio increased from 0·20 at baseline to 0·44 at week 96 in the randomised cohort. Few adverse events led to discontinuation (26 [7%] of 371). 12 (4%) of 272 people in the randomised cohort and 17 (17%) of 99 in the non-randomised cohort died; the median baseline CD4 count for participants who died was 11 cells per μL.

Interpretation: In heavily treatment-experienced individuals with advanced HIV-1 disease and limited treatment options, fostemsavir-based antiretroviral regimens were generally well tolerated and showed a distinctive trend of increasing virological and immunological response rates through 96 weeks; these findings support fostemsavir as a treatment option for this vulnerable population.

Funding: ViiV Healthcare.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S2352-3018(20)30240-XDOI Listing
November 2020

Safety and efficacy of fumagillin for the treatment of intestinal microsporidiosis. A French prospective cohort study.

J Antimicrob Chemother 2021 Jan;76(2):487-494

Department of Infectious Diseases, St-Louis Hospital, APHP and University of Paris, France.

Background: Intestinal microsporidiosis due to Enterocytozoon bieneusi is a cause of chronic diarrhoea in immunocompromised patients. Fumagillin has been approved in France for its treatment.

Objectives: To investigate the efficacy and safety of fumagillin in a real-life setting.

Methods: As required by the French Medicine Agency, all patients receiving fumagillin were enrolled in a prospective study to evaluate its efficacy and safety. Stool examination with identification of E. bieneusi by PCR was performed at baseline, end of treatment and monthly thereafter for 6 months. Safety was monitored up to 6 months and full blood counts were monitored up to 42 days after treatment initiation. The primary endpoint was safety. Parasite clearance and relapses were secondary endpoints.

Results: From 2007 to 2018, 166 patients received fumagillin, including 6 children. Patients were transplant recipients (84%), HIV-infected patients (13%) or had another cause of immunosuppression (5%). Serious adverse events were reported in 41 patients (25%), mainly thrombocytopenia (15%) and neutropenia (5%), with two haemorrhagic events leading to one death. Severe thrombocytopenia (<50 G/L) developed in 50 patients (29.6%), neutropenia (<1 G/L) in 20 patients (11.8%) and severe anaemia (<8 g/dL) in 21 patients (12.4%). At the end of treatment, 94% of patients with available stool examination (n = 132) had no spores detected. Among 99 patients with available follow-up after the end of treatment, three parasite relapses were documented.

Conclusions: E. bieneusi microsporidiosis was mainly diagnosed in transplant recipients. Fumagillin was associated with haematological toxicity but showed high efficacy with a low relapse rate.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jac/dkaa438DOI Listing
January 2021

Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults: 2020 Recommendations of the International Antiviral Society-USA Panel.

JAMA 2020 10;324(16):1651-1669

University of California, San Francisco.

Importance: Data on the use of antiretroviral drugs, including new drugs and formulations, for the treatment and prevention of HIV infection continue to guide optimal practices.

Objective: To evaluate new data and incorporate them into current recommendations for initiating HIV therapy, monitoring individuals starting on therapy, changing regimens, preventing HIV infection for those at risk, and special considerations for older people with HIV.

Evidence Review: New evidence was collected since the previous International Antiviral (formerly AIDS) Society-USA recommendations in 2018, including data published or presented at peer-reviewed scientific conferences through August 22, 2020. A volunteer panel of 15 experts in HIV research and patient care considered these data and updated previous recommendations.

Findings: From 5316 citations about antiretroviral drugs identified, 549 were included to form the evidence basis for these recommendations. Antiretroviral therapy is recommended as soon as possible for all individuals with HIV who have detectable viremia. Most patients can start with a 3-drug regimen or now a 2-drug regimen, which includes an integrase strand transfer inhibitor. Effective options are available for patients who may be pregnant, those who have specific clinical conditions, such as kidney, liver, or cardiovascular disease, those who have opportunistic diseases, or those who have health care access issues. Recommended for the first time, a long-acting antiretroviral regimen injected once every 4 weeks for treatment or every 8 weeks pending approval by regulatory bodies and availability. For individuals at risk for HIV, preexposure prophylaxis with an oral regimen is recommended or, pending approval by regulatory bodies and availability, with a long-acting injection given every 8 weeks. Monitoring before and during therapy for effectiveness and safety is recommended. Switching therapy for virological failure is relatively rare at this time, and the recommendations for switching therapies for convenience and for other reasons are included. With the survival benefits provided by therapy, recommendations are made for older individuals with HIV. The current coronavirus disease 2019 pandemic poses particular challenges for HIV research, care, and efforts to end the HIV epidemic.

Conclusion And Relevance: Advances in HIV prevention and management with antiretroviral drugs continue to improve clinical care and outcomes among individuals at risk for and with HIV.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jama.2020.17025DOI Listing
October 2020

Acute Hepatitis B Infection After a Switch to Long-Acting Cabotegravir and Rilpivirine.

Open Forum Infect Dis 2020 Sep 25;7(9):ofaa367. Epub 2020 Sep 25.

Department of Infectious Diseases, Saint-Louis Hospital, University of Paris Diderot, Paris, France.

Maintenance antiretroviral therapy with combination of two injectable long-acting drugs, cabotegravir and rilpivirine, is a new strategy addressing the challenges of daily adherence to oral pills that has shown non-inferior efficacy to standard of care therapy in patients with suppressed HIV-infection. Patients co-infected with hepatitis B virus (HBV) are not eligible for this dual therapy since it has no activity against HBV, but this strategy should also be restricted to patients with anti-HBs antibodies since people with HIV are still at risk of HBV acquisition due to high risk behavior and since HBV vaccination does not always elicit anti-HBs antibodies, as highlighted in the case report below.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ofid/ofaa367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7518369PMC
September 2020

Emerging and Reemerging Sexually Transmitted Infections.

N Engl J Med 2020 08;383(8):793-794

Saint-Louis Hospital, Paris, France

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1056/NEJMc2022699DOI Listing
August 2020

Emtricitabine and tenofovir alafenamide vs emtricitabine and tenofovir disoproxil fumarate for HIV pre-exposure prophylaxis (DISCOVER): primary results from a randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial.

Lancet 2020 07;396(10246):239-254

Department of Adult and Family Medicine, Kaiser Permanente San Francisco Medical Center, San Francisco, CA, USA.

Background: Tenofovir alafenamide shows high antiviral efficacy and improved renal and bone safety compared with tenofovir disoproxil fumarate when used for HIV treatment. Here, we report primary results from a blinded phase 3 study evaluating the efficacy and safety of pre-exposure prophylaxis (PrEP) with emtricitabine and tenofovir alafenamide versus emtricitabine and tenofovir disoproxil fumarate for HIV prevention.

Methods: This study is an ongoing, randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial done at 94 community, public health, and hospital-associated clinics located in regions of Europe and North America, where there is a high incidence of HIV or prevalence of people living with HIV, or both. We enrolled adult cisgender men who have sex with men and transgender women who have sex with men, both with a high risk of acquiring HIV on the basis of their self-reported sexual behaviour in the past 12 weeks or their recent history (within 24 weeks of enrolment) of bacterial sexually transmitted infections. Participants with current or previous use of PrEP with emtricitabine and tenofovir disoproxil fumarate were not excluded. We used a computer-generated random allocation sequence to randomly assign (1:1) participants to receive either emtricitabine (200 mg) and tenofovir alafenamide (25 mg) tablets daily, with matched placebo tablets (emtricitabine and tenofovir alafenamide group), or emtricitabine (200 mg) and tenofovir disoproxil fumarate (300 mg) tablets daily, with matched placebo tablets (emtricitabine and tenofovir disoproxil fumarate group). As such, all participants were given two tablets. The trial sponsor, investigators, participants, and the study staff who provided the study drugs, assessed the outcomes, and collected the data were masked to group assignment. The primary efficacy outcome was incident HIV infection, which was assessed when all participants had completed 48 weeks of follow-up and half of all participants had completed 96 weeks of follow-up. This full analysis set included all randomly assigned participants who had received at least one dose of the assigned study drug and had at least one post-baseline HIV test. Non-inferiority of emtricitabine and tenofovir alafenamide to emtricitabine and tenofovir disoproxil fumarate was established if the upper bound of the 95·003% CI of the HIV incidence rate ratio (IRR) was less than the prespecified non-inferiority margin of 1·62. We prespecified six secondary bone mineral density and renal biomarker safety endpoints to evaluate using the safety analysis set. This analysis set included all randomly assigned participants who had received at least one dose of the assigned study drug. This trial is registered with ClinicalTrials.gov, NCT02842086, and is no longer recruiting.

Findings: Between Sept 13, 2016, and June 30, 2017, 5387 (92%) of 5857 participants were randomly assigned and received emtricitabine and tenofovir alafenamide (n=2694) or emtricitabine and tenofovir disoproxil fumarate (n=2693). At the time of the primary efficacy analysis (ie, when all participants had completed 48 weeks and 50% had completed 96 weeks) emtricitabine and tenofovir alafenamide was non-inferior to emtricitabine and tenofovir disoproxil fumarate for HIV prevention, as the upper limit of the 95% CI of the IRR, was less than the prespecified non-inferiority margin of 1·62 (IRR 0·47 [95% CI 0·19-1·15]). After 8756 person-years of follow-up, 22 participants were diagnosed with HIV, seven participants in the emtricitabine and tenofovir alafenamide group (0·16 infections per 100 person-years [95% CI 0·06-0·33]), and 15 participants in the emtricitabine and tenofovir disoproxil fumarate group (0·34 infections per 100 person-years [0·19-0·56]). Both regimens were well tolerated, with a low number of participants reporting adverse events that led to discontinuation of the study drug (36 [1%] of 2694 participants in the emtricitabine and tenofovir alafenamide group vs 49 [2%] of 2693 participants in the emtricitabine and tenofovir disoproxil fumarate group). Emtricitabine and tenofovir alafenamide was superior to emtricitabine and tenofovir disoproxil fumarate in all six prespecified bone mineral density and renal biomarker safety endpoints.

Interpretation: Daily emtricitabine and tenofovir alafenamide shows non-inferior efficacy to daily emtricitabine and tenofovir disoproxil fumarate for HIV prevention, and the number of adverse events for both regimens was low. Emtricitabine and tenofovir alafenamide had more favourable effects on bone mineral density and biomarkers of renal safety than emtricitabine and tenofovir disoproxil fumarate.

Funding: Gilead Sciences.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S0140-6736(20)31065-5DOI Listing
July 2020

COVID-19-Related IgA Vasculitis.

Arthritis Rheumatol 2020 11 22;72(11):1952-1953. Epub 2020 Sep 22.

Hôpital Saint-Louis, AP-HP and Université de Paris, Paris, France.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/art.41428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7361577PMC
November 2020

Household COVID-19 Prevalence.

Clin Infect Dis 2020 May 31. Epub 2020 May 31.

Paris University, Paris, France.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cid/ciaa688DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7314252PMC
May 2020

Coverage of Sex Acts by Event-Driven Pre-exposure Prophylaxis: A Sub-Study of the ANRS IPERGAY Trial.

AIDS Behav 2020 Nov;24(11):3244-3251

Hôpital Saint-Louis, Maladies infectieuses, Paris, France.

We assessed the coverage of sex acts by event-driven pre-exposure prophylaxis (ED-PrEP) over a 2-month period in 54 participants in the open label phase of the ANRS Ipergay trial. Participants received an electronic monitoring system device to record bottle openings. Self-questionnaires collected daily information on PrEP intake and sexual behavior. Intake was also estimated through returned pill counts. Full coverage of sex acts was defined as at least one pill taken both within 24 h before and within 48 h following sex. There was a strong correlation (r =  - 0.92) between the number of bottle openings and returned pill counts. During the study, 42 participants (78%) practiced ED-PrEP and 12 (22%) daily PrEP with bottle openings at least 5 days/week whatever their sexual activity. Out of the 154 reported receptive anal sex acts, 81% were condomless: among them, PrEP coverage was hight: 97% among those practicing daily PrEP and 82% among those using ED-PrEP.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10461-020-02890-6DOI Listing
November 2020

Changes in Sexual Behaviors in Men Who Have Sex with Men: A Comparison Between the Double-Blind and Open-Label Extension Phases of the ANRS-IPERGAY Trial.

AIDS Behav 2020 Nov;24(11):3093-3106

Aix Marseille Univ, INSERM, IRD, SESSTIM, Sciences Economiques & Sociales de la Santé & Traitement de L'Information Médicale, Marseille, France.

Pre-Exposure Prophylaxis (PrEP) is changing the landscape of HIV prevention, and may bring changes in sexual behaviors. The double-blind phase (DBP) and open-label extension (OLE) study of the ANRS-IPERGAY trial allowed us to assess changes in sexual behavior of men who have sex with men (MSM) taking sexual activity-based (i.e., on-demand) PrEP. Generalized Estimating Equation (GEE) models found a significant decrease in the number of sexual partners (Coefficient [CI95%], p value; - 0.37[- 0.70 to - 0.04], p = 0.03) between the DBP and OLE as well as in the number of sexual relations (- 0.25 [- 0.49 to 0.00], 0.04). GEE estimates also showed that respondents' most recent sexual relation was less likely to have been with an unknown casual partner during the OLE than during the DBP (Odds Ratio [CI95%], p value: 0.75[0.62-0.92], 0.005). Furthermore, they showed an increase in the proportion of condomless anal sex in the OLE (1.32[1.04-1.67], 0.02), a decrease in the proportion of 'suboptimal PrEP adherence' over time (0.75[0.58-0.97], p = 0.03), a decrease in PrEP only use (0.73[0.55-0.96], 0.03) and in both PrEP and condom use over time (0.70[0.51-0.95], 0.02) and finally, a decrease in alcohol consumption between the DBP and OLE (0.74[0.61-0.90], 0.002). We observed both protective and risky behaviors in terms of HIV and STI risk after on-demand PrEP uptake in the OLE phase. Our findings are consistent with results from previous PrEP trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10461-020-02864-8DOI Listing
November 2020

Changes in Sexual Behaviors in Men Who Have Sex with Men: A Comparison Between the Double-Blind and Open-Label Extension Phases of the ANRS-IPERGAY Trial.

AIDS Behav 2020 Nov;24(11):3093-3106

Aix Marseille Univ, INSERM, IRD, SESSTIM, Sciences Economiques & Sociales de la Santé & Traitement de L'Information Médicale, Marseille, France.

Pre-Exposure Prophylaxis (PrEP) is changing the landscape of HIV prevention, and may bring changes in sexual behaviors. The double-blind phase (DBP) and open-label extension (OLE) study of the ANRS-IPERGAY trial allowed us to assess changes in sexual behavior of men who have sex with men (MSM) taking sexual activity-based (i.e., on-demand) PrEP. Generalized Estimating Equation (GEE) models found a significant decrease in the number of sexual partners (Coefficient [CI95%], p value; - 0.37[- 0.70 to - 0.04], p = 0.03) between the DBP and OLE as well as in the number of sexual relations (- 0.25 [- 0.49 to 0.00], 0.04). GEE estimates also showed that respondents' most recent sexual relation was less likely to have been with an unknown casual partner during the OLE than during the DBP (Odds Ratio [CI95%], p value: 0.75[0.62-0.92], 0.005). Furthermore, they showed an increase in the proportion of condomless anal sex in the OLE (1.32[1.04-1.67], 0.02), a decrease in the proportion of 'suboptimal PrEP adherence' over time (0.75[0.58-0.97], p = 0.03), a decrease in PrEP only use (0.73[0.55-0.96], 0.03) and in both PrEP and condom use over time (0.70[0.51-0.95], 0.02) and finally, a decrease in alcohol consumption between the DBP and OLE (0.74[0.61-0.90], 0.002). We observed both protective and risky behaviors in terms of HIV and STI risk after on-demand PrEP uptake in the OLE phase. Our findings are consistent with results from previous PrEP trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10461-020-02864-8DOI Listing
November 2020

Fostemsavir in Adults with Multidrug-Resistant HIV-1 Infection.

N Engl J Med 2020 03;382(13):1232-1243

From Yale University School of Medicine and the Veterans Affairs Connecticut Healthcare System, New Haven (M.K.), and ViiV Healthcare, Branford (P.A., C.L., M.L.) - all in Connecticut; Icahn School of Medicine at Mount Sinai, New York (J.A.); Hôpital Tenon, Assistance Publique-Hôpitaux de Paris (AP-HP) (G.P.), and Hôpital Saint Louis, AP-HP, and University of Paris Diderot Paris 7 (J.-M.M.), Paris; Fundación Huesped, Buenos Aires (P.C.); AIDS Research Consortium of Atlanta, Atlanta (M.T.); Instituto de Pesquisa Clínica Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro (B.G.), and Federal University of São Paulo, São Paulo (R.D.); San Raffaele Scientific Institute, Milan (A.C.); Georgetown University Hospital, Washington, DC (P.K.); Maxwell Center, Durban, South Africa (G.L.); Orlando Immunology Center, Orlando, FL (E.D.); GlaxoSmithKline, Upper Providence, PA (M. Gummel); and ViiV Healthcare, Research Triangle Park, NC (M. Gartland, A.P.).

Background: Among some patients with human immunodeficiency virus type 1 (HIV-1) infection who have undergone multiple antiretroviral therapies and have limited options for treatment, new classes of antiretroviral drugs with novel mechanisms of action are needed. Fostemsavir is the prodrug of temsavir, a first-in-class investigational HIV-1 attachment inhibitor.

Methods: In this ongoing phase 3 trial in 23 countries, we enrolled patients with multidrug-resistant HIV-1 infection in two cohorts, according to their remaining treatment options. In the first cohort, we assigned (in a 3:1 ratio) patients who had the option of using at least one fully active, approved antiretroviral drug in at least one but no more than two antiretroviral classes to add either fostemsavir (at a dose of 600 mg twice daily) or placebo to their failing regimen for 8 days, followed by open-label fostemsavir plus optimized background therapy (randomized cohort). In the second cohort, patients who had no remaining antiretroviral options were started on open-label fostemsavir plus optimized background therapy on day 1 (nonrandomized cohort). The primary end point was the mean change in the HIV-1 RNA level from day 1 through day 8 in the randomized cohort.

Results: A total of 371 patients were treated, including 272 in the randomized cohort and 99 in the nonrandomized cohort. At day 8, the mean decrease in the HIV-1 RNA level was 0.79 log copies per milliliter in the fostemsavir group and 0.17 log copies in the placebo group (P<0.001). At week 48, a virologic response (HIV-1 RNA level, <40 copies per milliliter) had occurred in 54% of the patients in the randomized cohort and in 38% of those in the nonrandomized cohort; the mean increase in the CD4+ T-cell count was 139 cells per cubic millimeter and 64 cells per cubic millimeter, respectively. Adverse events led to the discontinuation of fostemsavir in 7% of the patients. In the randomized cohort, glycoprotein 120 (gp120) substitutions were found in 20 of 47 patients (43%) with virologic failure.

Conclusions: In patients with multidrug-resistant HIV-1 infection with limited therapy options, those who received fostemsavir had a significantly greater decrease in the HIV-1 RNA level than those who received placebo during the first 8 days. Efficacy was sustained through 48 weeks. (Funded by Bristol-Myers Squibb and GSK/ViiV Healthcare; BRIGHTE ClinicalTrials.gov number, NCT02362503.).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1056/NEJMoa1902493DOI Listing
March 2020

Five-year follow-up of patients enrolled in the NEAT 001/ANRS 143 randomized clinical trial: NEAT 001/ANRS 143 LONG TERM study.

J Antimicrob Chemother 2020 06;75(6):1618-1622

Division of Infectious Diseases, Saint Pierre University Hospital, Université Libre de Bruxelles, Brussels, Belgium.

Background: Few long-term data are available in subjects having initiated ART with an NRTI-sparing regimen.

Objectives: Outcomes of subjects enrolled in the NEAT 001/ANRS 143 randomized clinical trial (comparing ritonavir-boosted darunavir + raltegravir versus ritonavir-boosted darunavir + tenofovir disoproxil fumarate/emtricitabine) were retrospectively collected, through anonymized electronic case report forms, up to 6 years post-enrolment.

Methods: The last NEAT 001 visit (Week 96) was conducted in 745/805 randomized subjects (363/401 ritonavir-boosted darunavir + raltegravir and 382/404 ritonavir-boosted darunavir + tenofovir disoproxil fumarate/emtricitabine). Of these, 430 were enrolled in NEAT 001/ANRS 143 LONG TERM (NLT) study (201 raltegravir, 229 tenofovir disoproxil fumarate/emtricitabine), with a median follow-up of 44.4 months.

Results: During NLT follow-up, the proportion of AIDS, non-AIDS events, virological rebound and serious adverse events, discontinuation for virological failure and for adverse events did not differ between groups; discontinuations for virological failure since NEAT 001 inclusion were more frequent in subjects with baseline CD4 <200 cells/mm3 (11.9% versus 5.3%; P = 0.077). At last follow-up, a quarter of subjects (22.2% for ritonavir-boosted darunavir + raltegravir and 29.7% for ritonavir-boosted darunavir + tenofovir disoproxil fumarate/emtricitabine) were still receiving their initial regimen. Integrase inhibitor exposure was not associated with weight gain (P = 0.48), while tenofovir disoproxil fumarate exposure was associated with a trend to higher creatinine increase (P = 0.067).

Conclusions: After a median of 5.6 years, subjects initiating ritonavir-boosted darunavir + raltegravir or ritonavir-boosted darunavir + tenofovir disoproxil fumarate/emtricitabine experienced few serious clinical adverse events. Most discontinuations were for reasons unrelated to adverse events or virological failure.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jac/dkaa056DOI Listing
June 2020

Perspectives of injectable long acting antiretroviral therapies for HIV treatment or prevention: understanding potential users' ambivalences.

AIDS Care 2020 05 19;32(sup2):155-161. Epub 2020 Mar 19.

Infectious Diseases Unit, Hôtel Dieu Hospital, Paris, France.

Recent clinical trial data showed that injectable long-acting antiretroviral treatment (LA-ART) every four or eight weeks could become an alternative option for HIV treatment or prevention. The purpose of our study was to explore perceptions and potential users' points of views of this new mode of administration through individuals' therapeutic itinerary and their singular history with ART. Between 2018 and 2019, a qualitative study was conducted in two University Hospitals in Paris, France. In-depth interviews were conducted with 15 virologically controlled People Living with HIV (PLWH) and 13 men on pre-exposure prophylaxis (PrEP) for at least six months. Interviews, focused on the daily experience with ART, were recorded, transcribed, and analyzed using thematic content analysis. Collected discourses were organized around three emergent concerns: social, material and experimental. Each of these concerns was perceived as ambivalent, balanced by skepticism and hope. It revealed the complexity of each individual's relationship to their HIV treatment or PrEP, leading to balance the injectable LA-ART popularity reported within clinical trials. This new mode of administration may be a suitable alternative for some PLWH and PrEP users, a "simplification" compared to the oral route. It opens a window for "customizable" ART-treatment according to individuals' lives.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/09540121.2020.1742869DOI Listing
May 2020

European confederation of medical mycology expert consult-An ECMM excellence center initiative.

Mycoses 2020 Jun 13;63(6):566-572. Epub 2020 Apr 13.

Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, Center for Integrated Oncology Aachen Bonn Cologne Dusseldorf (CIO ABCD), Excellence Center for Medical Mycology (ECMM), University of Cologne, Cologne, Germany.

Objectives: Difficult-to-treat invasive fungal infections require infectious diseases expert consultation to improve treatment outcome and increase survival rates.

Methods: The European Confederation of Medical Mycology (ECMM) intends to provide expert help free of charge by a newly founded ECMM Expert Consultation Service for medical centres around the globe seeking advice when there is no fungal infection consultant available. The expert consult will provide recommendations and broad expertise on difficult-to-treat invasive fungal infections (eg azole-resistant Aspergillus species, Candida auris, mucormycosis) to improve diagnostic and therapeutic management and outcome.

Results: The initiative plans global outreach through video conferencing between ECMM Excellence Centers and treating physicians. FungiScope registries will be used to structure case information and to evaluate the impact of the collegial advice system at regular intervals. Advice will follow recent guidelines, and EQUAL Scores will be used to measure guideline adherence.

Conclusions: Infectious diseases expert consultation should be an integral component of care for patients with difficult-to-treat invasive fungal infections. The ECMM Expert Consult will attend to this matter on a global scale.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/myc.13076DOI Listing
June 2020