ABSTRACT
OBJECTIVES: Low HIV reservoirs may be associated with viral suppression under a lower number of antiretroviral drugs. We investigated tenofovir disoproxil fumarate/emtricitabine as a maintenance strategy in people living with HIV (PLHIV) with low HIV-DNA. METHODS: TRULIGHT (NCT02302547) was a multicentre, open-label, randomized trial comparing a simplification to tenofovir disoproxil fumarate/emtricitabine versus a triple regimen continuation (tenofovir disoproxil fumarate/emtricitabine with a third agent, control arm) in virologically suppressed adults with HIV-DNA <2.7 log10 copies/106 PBMCs and no prior virological failure (VF). The primary endpoint (non-inferiority margin 12%) was the percentage of participants with a plasma viral load (pVL) <50 copies/mL in ITT (Snapshot approach) and PP analyses at Week 48 (W48). RESULTS: Of the 326 participants screened, 223 (68%) were randomized to the tenofovir disoproxil fumarate/emtricitabine arm (n = 113) or control arm (n = 110). At W48, the tenofovir disoproxil fumarate/emtricitabine and control arms maintained a pVL < 50 copies/mL in 100/113 (88.5%) and 100/110 (90.9%) participants, respectively (ITT difference 2.4%, 95% CI -5.9 to 10.7; PP difference 3.4%, 95% CI -4.2 to 11.0). Six VFs occurred in the tenofovir disoproxil fumarate/emtricitabine arm (two with emerging mutations M184V and K65R) versus two in the control arm (ITT difference 3.5%, 95% CI -1.9 to 9.4). All VFs were resuppressed after treatment modification. CONCLUSIONS: Although non-inferiority was shown, simplification to tenofovir disoproxil fumarate/emtricitabine should not be used for most PLHIV because of a low risk of VF with resistance.
Subject(s)
Anti-HIV Agents , HIV Infections , HIV-1 , Adenine/therapeutic use , Adult , Anti-HIV Agents/therapeutic use , DNA , Emtricitabine/therapeutic use , HIV Infections/drug therapy , HIV-1/genetics , Humans , Tenofovir/therapeutic use , Treatment Outcome , Viral LoadABSTRACT
BACKGROUND: We investigated whether dolutegravir (DTG) monotherapy could be used to maintain virological suppression in people living with human immunodeficiency virus (HIV) on a successful dolutegravir-based triple therapy. METHODS: MONCAY (MONotherapy of TiviCAY) was a 48-week, multicentric, randomized, open-label, 12% noninferiority margin trial. Patients with CD4 nadir >100/µL, plasma HIV-1 RNA <50 copies/mL for ≥12 months, and stable regimen with DTG/abacavir (ABC)/lamivudine (3TC) were 1:1 randomized to continue their regimen or to DTG monotherapy. The primary endpoint was the proportion of patients with HIV RNA <50 copies/mL at week 24 in intention-to-treat snapshot analysis. Virologic failure (VF) was defined as 2 consecutive HIV RNA >50 copies/mL within 2 weeks apart. RESULTS: Seventy-eight patients were assigned to DTG monotherapy and 80 to continue DTG/ABC/3TC. By week 24, 2 patients in the DTG group experienced VF without resistance to the integrase strand transfer inhibitor (INSTI) class; 1 patient discontinued DTG/ABC/3TC due to an adverse event. The success rate at week 24 was 73/78 (93.6%) in the DTG arm and 77/80 (96.3%) in the DTG/ABC/3TC arm (difference, 2.7%; 95% confidence interval [CI], -5.0 to 10.8). During subsequent follow-up, 5 additional VFs occurred in the DTG arm (2 of which harbored emerging resistance mutation to INSTI). The cumulative incidence of VF at week 48 was 9.7% (95% CI, 2.8 to 16.6) in the DTG arm compared with 0% in the DTG/ABC/3TC arm (P = .005 by the log-rank test). The Data Safety Monitoring Board recommended to reintensify the DTG arm with standardized triple therapy. CONCLUSIONS: Because the risk of VF with resistance increases over time, we recommend avoiding DTG monotherapy as a maintenance strategy among people living with chronic HIV infection. CLINICAL TRIALS REGISTRATION: NCT02596334 and EudraCT 2015-002853-36.
Subject(s)
Anti-HIV Agents/therapeutic use , Dideoxynucleosides/therapeutic use , HIV Infections/drug therapy , Heterocyclic Compounds, 3-Ring/therapeutic use , Lamivudine/therapeutic use , Adult , Confidence Intervals , Drug Resistance, Viral/genetics , Female , Humans , Male , Middle Aged , Mutation/genetics , Oxazines , Piperazines , PyridonesABSTRACT
Background: Screening for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) at pharyngeal, urogenital, and anorectal sites is recommended for men who have sex with men (MSM). Pooling samples is a promising technique, but no data are available when pooled screening also includes Mycoplasma genitalium (MG). The main objective of this study was to examine the sensitivity of pooled samples for detecting CT, NG, and MG in MSM using nucleic acid amplification versus single-site testing. Methods: In this multicenter study, MSM with a positive result for CT, NG, or MG were recalled to the clinic for treatment and were asked to participate in this study. Separate samples were sent to a central virological department that proceeded to form the pooled samples. Testing was performed using the multiplex real-time polymerase chain reaction Allplex STI Essential Assay (Seegene, Seoul, Korea), which can simultaneously detect 7 pathogens. Results: A total of 130 MSM with at least 1 positive test for CT, NG, or MG were included. A total of 25.4% had a coinfection. The sensitivities of pooled-sample testing were 94.8% for CT, 97.0% for NG, and 92.3% for MG. Pooling failed to detect 8 infections, but pooled-sample analysis missed detecting only samples with a low bacterial load (cycle threshold >35). Conclusions: Pooling samples from MSM to detect CT, NG, and MG is as sensitive as individual-site testing for these 3 pathogens using the Allplex assay. Missed infections with a very low bacterial load could have a low impact on further transmission. Clinical Trials Registration. NCT03568695.
ABSTRACT
We describe the third case of prosthetic infection due to Erysipelothrix rhusiopathiae. The patient, a 68-year-old woman, had had total knee arthroplasty 12 months before diagnosis. She had been in contact with swine at home. We review the seven previous reports of septic arthritis due to E. rhusiopathiae.
Subject(s)
Arthritis, Infectious/diagnosis , Erysipelothrix Infections/diagnosis , Erysipelothrix/isolation & purification , Knee Joint/microbiology , Prosthesis-Related Infections/diagnosis , Aged , Animals , Arthritis, Infectious/microbiology , Erysipelothrix Infections/microbiology , Female , Humans , Knee Joint/pathology , Prosthesis-Related Infections/microbiology , SwineABSTRACT
BACKGROUND: In France, the estimated annual incidence of infective endocarditis (IE) is 33.8 cases per million residents. Valvular surgery is frequently undergone. We report an epidemiological and economic study of IE for 2007-2009 in a French region, using the hospital discharge database (HDD). METHODS: The population studied concerned all the patients living in Centre region, France, hospitalized for IE. We extracted hospital stay data for IE from the regional HDD, with a definition based on IE-related diagnosis codes. The predictive positive value (PPV) and sensitivity (Se) of the definition were 87.4% and 90%, respectively, according to the Duke criteria (definite IE frequency 74.4%). Hospitalization costs were estimated, taking into account the fixed hospital charges of the diagnosis-related group (DRG) and supplementary charges due to intensive care unit (ICU) stay. RESULTS: The analysis included 578 patients. The annual average incidence was 45.4 cases per million residents. Valvular surgery was performed in 19.4% of cases. The hospital mortality was 17.6%. Multivariate analysis identified as risk factors for mortality an age ≥ 70 years (odds ratio (OR) = 3.03, 95% confidence interval (CI) = 1.78-5.18), staphylococcal IE (OR = 3.3, 95% CI = 1.9-5.7), chronic renal insufficiency (OR = 2.04, 95% CI = 1.00-4.15), ischemic stroke (OR = 2.55, 95% CI = 1.19-5.47), and hemorrhagic stroke (OR = 5.7, 95% CI = 1.9-17.3). The average cost per episode was $20 103 (15 281). CONCLUSIONS: We report a higher incidence of IE than described by the French national study of 2008. Valvular surgery was considerably less frequent than in the published data, whereas mortality was similar. IE generates substantial costs.
Subject(s)
Endocarditis/economics , Endocarditis/therapy , Adolescent , Adult , Aged , Aged, 80 and over , Child, Preschool , Diagnosis-Related Groups , Endocarditis/mortality , Female , France/epidemiology , Hospital Mortality , Humans , Incidence , Infant , Infant, Newborn , Length of Stay/economics , Male , Middle Aged , Multivariate Analysis , Risk Factors , Survival Analysis , Treatment Outcome , Young AdultABSTRACT
BACKGROUND: Schools are a source of epidemic seasonal dissemination-in particular gastroenteritis among children and the general population. We assessed the impact of an alcohol-based sanitizer on gastroenteritis and its subsequent consequences. METHODS: A study was conducted in 2 primary schools over a 17-week period, before and throughout the seasonal gastroenteritis period. The intervention, under strict teacher supervision and in a realistic and long lasting manner, consisted of 1 school rubbing an alcohol-based sanitizer into the hands of the school children. The primary outcome was the proportion of children without any occurrence of gastroenteritis during the study period both in the treated group and the control group, which were 2 separate schools. A Cox proportional hazards model was used to assess the hazard ratio. Secondary outcomes were the number of gastroenteritis episodes, doctor appointments, absenteeism, and working days lost by a parent. RESULTS: Four thousand six hundred fifty-four weekly questionnaires were collected. One hundred fifty-five children presented with at least 1 occurrence of gastroenteritis during the study period: 64 of 259 in the treatment group and 91 of 217 in the control group (χ2 = 16.4, P < 0.0001). The instantaneous risk of primary infection, at any time of the study, for children receiving the treatment was multiplied by 0.52 (95% CI: [0.37,0.71]) compared with children not receiving the treatment. The average number of gastroenteritis episodes was 0.31 in the treatment group and 0.53 in the control group (P < 0.001). CONCLUSIONS: Systematic and controlled use of alcohol-based sanitizers during the epidemic season could significantly reduce the incidence of gastroenteritis in primary school children.