Early prediction of endocrine responsiveness in ER+/HER2-negative metastatic breast cancer (MBC): pilot study with 18F-fluoroestradiol (18F-FES) CT/PET.

BACKGROUND: 18F-fluoroestradiol (FES) positron emission tomography (PET)/computed tomography (CT) is considered an accurate diagnostic tool to determine whole-body endocrine responsiveness. In the endocrine therapy (ET)-FES trial, we evaluated 18F-FES PET/CT as a predictive tool in estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC). PATIENTS AND METHODS: Eligible patients underwent an 18F-FES PET/CT at baseline. Patients with standardized uptake value (SUV) ≥ 2 received single-agent ET until progressive disease; patients with SUV < 2 were randomized to single-agent ET (arm A) or chemotherapy (ChT) (arm B). The primary objective was to compare the activity of first-line ET versus ChT in patients with 18F-FES SUV < 2. RESULTS: Overall, 147 patients were enrolled; 117 presented with 18F-FES SUV ≥ 2 and received ET; 30 patients with SUV < 2 were randomized to ET or ChT. After a median follow-up of 62.4 months, 104 patients (73.2%) had disease progression and 53 died (37.3%). Median progression-free survival (PFS) was 12.4 months [95% confidence interval (CI) 3.1-59.6 months] in patients with SUV < 2 randomized to arm A versus 23.0 months (95% CI 7.7-30.0 months) in arm B, [hazard (HR) = 0.71, 95% CI 0.3-1.7 months]; median PFS was 18.0 months (95% CI 11.2-23.1 months) in patients with SUV ≥ 2 treated with ET. Median overall survival (OS) was 28.2 months (95% CI 14.2 months-not estimable) in patients with SUV < 2 randomized to ET (arm A) versus 52.8 months (95% CI 16.2 months-not estimable) in arm B (ChT). Median OS was not reached in patients with SUV ≥ 2. 60-month OS rate was 41.6% (95% CI 10.4% to 71.1%) in arm A, 42.0% (95% CI 14.0% to 68.2%) in arm B, and 59.6% (95% CI 48.6% to 69.0%) in patients with SUV ≥ 2. In patients with SUV ≥ 2, 60-month OS rate was 72.6% if treated with aromatase inhibitors (AIs) versus 40.6% in case of fulvestrant or tamoxifen (P < 0.005). CONCLUSIONS: The ET-FES trial demonstrated that ER+/HER2- MBC patients are a heterogeneous population, with different levels of endocrine responsiveness based on 18F-FES CT/PET SUV.

Electronic circular dichroism from real-time propagation in state space.

In this paper, we propose to compute the electronic circular dichroism (ECD) spectra of chiral molecules using a real-time propagation of the time-dependent Schrödinger equation (TDSE) in the space of electronic field-free eigenstates, by coupling TDSE with a given treatment of the electronic structure of the target. The time-dependent induced magnetic moment is used to compute the ECD spectrum from an explicit electric perturbation. The full matrix representing the transition magnetic moment in the space of electronic states is generated from that among pairs of molecular orbitals. In the present work, we show the ECD spectra of methyloxirane, of several conformers of L-alanine, and of the Λ-Co(acac)3 complex, computed from a singly excited ansatz of time-dependent density functional theory eigenstates. The time-domain ECD spectra properly reproduce the frequency-domain ones obtained in the linear-response regime and quantitatively agree with the available experimental data. Moreover, the time-domain approach to ECD allows us to naturally go beyond the ground-state rotationally averaged ECD spectrum, which is the standard outcome of the linear-response theory, e.g., by computing the ECD spectra from electronic excited states.

Spatial, temporal and network analyses provide insights into the dynamics of the bacterial communities associated with two species of Caribbean octocorals and indicate possible key taxa.

Despite the current decline of scleractinian coral populations, octocorals are thriving on reefs in the Caribbean Sea and western North Atlantic Ocean. These cnidarians are holobiont entities, interacting with a diverse array of microorganisms. Few studies have investigated the spatial and temporal stability of the bacterial communities associated with octocoral species and information regarding the co-occurrence and potential interactions between specific members of these bacterial communities remain sparse. To address this knowledge gap, this study investigated the stability of the bacterial assemblages associated with two common Caribbean octocoral species, Eunicea flexuosa and Antillogorgia americana, across time and geographical locations and performed network analyses to investigate potential bacterial interactions. Results demonstrated that general inferences regarding the spatial and temporal stability of octocoral-associated bacterial communities should not be made, as host-specific characteristics may influence these factors. In addition, network analyses revealed differences in the complexity of the interactions between bacteria among the octocoral species analyzed, while highlighting the presence of genera known to produce bioactive secondary metabolites in both octocorals that may play fundamental roles in structuring the octocoral-associated bacteriome. Supplementary Information: The online version contains supplementary material available at 10.1007/s13199-023-00923-x.

Neutralizing antibody responses against SARS-CoV-2 spike receptor-binding domain 13 months after the recovery from the disease.

BACKGROUND: Information regarding the kinetics and longevity of acquired immunity in recovered COVID-19 patients requires thorough analysis and documentation. This is an update to an ongoing monocentric pilot observational study, that longitudinally analyzed the presence of antibodies after SARS-CoV-2 infection. STUDY DESIGN: Antibody titers against nucleocapsid protein (NCP) of SARS-CoV-2 analyzed at 8 months was followed by adoption of a more specific immunoassay, anti-Spike-Receptor binding domain IgG CLIA for analysis at 12 and 13 months post infection. METHODS: MAGLUMI® SARS-CoV-2 S-RBD IgG Chemiluminescence immunoassay (CLIA) was adopted for measurement of antibody titres at 12 and 13 months after SARS-CoV-2 infection. RESULTS: 97% (34 out of 35) patients resulted positive for anti-SARS-CoV-2 RBD IgG at 12 and 13 months. DISCUSSION AND CONCLUSIONS: In areas with vaccine and resource scarcity, vaccination could be prioritized for those individuals who have never been infected or for the ones who have recovered but show the absence of protective antibodies.

Antibody persistency and trend post-SARS-CoV-2 infection at eight months.

Introduction: A large amount of recent research has focused on the nature of immunity elicited by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, particularly its robustness and the duration of protection it offers. As a vaccine's efficacy relies on its ability to induce a protective immune response, these questions remain particularly pertinent. An improved understanding of the immunity offered by the antibodies developed against SARS-CoV-2 in recovered patients is critical for the development of diagnostic tests and vaccines. Methods: Our study aimed at the longitudinal analysis of antibody presence, persistence and its trend over eight months in a group of 30 COVID-19 recovered patients who tested positive by real-time quantitative PCR for SARS-CoV-2 in the period 1-30 March 2020. The subjects were divided into two groups based on disease severity: mild (n=17 subjects) and moderately-severe (n=13 subjects). The MAGLUMI 2019-nCoV lgM/lgG chemiluminescent analytical system (CLIA) assay was used to analyze these antibody titres. Results: IgG antibody persistency was demonstrated in 76.7 % of the subjects (23 out of 30) at eight months post-infection. For the moderately-severe group, the titre trends for both IgM and IgG changed in a statistically significant way throughout the time period with IgM below and IgG above the set cut-off. Conclusions: The results of this study highlight an important point in terms of the association between humoral immune response and disease severity. Patients who have experienced a relatively severe infection might develop a stronger immune response that could persist for a longer period.

Revealing the electronic properties of the B-B bond: the bis-catecholato diboron molecule.

The electronic properties of a diboron molecule, namely bis(catecholato)diboron (2-(1,3,2-benzodioxaborol-2-yl)-1,3,2-benzodioxaborole) (B2Cat2), have been studied by comparing the results of photoemission (XPS) and near edge X-ray absorption spectroscopy (NEXAFS) experiments with the outcome of DFT calculations. The B 1s, C 1s and O 1s K-edges have been investigated for both the isolated gas phase molecule and the adsorbed one on the Au(111) surface. The main features of the polarized NEXAFS spectra at each of the three edges considered are not significantly affected by the presence of the substrate, with respect to the isolated molecule, indicating that the molecule-gold interaction is weak. Moreover, the comparison between the observed dichroism in the NEXAFS spectra of the adsorbed B2Cat2 and that in the NEXAFS spectra of the isolated molecule has confirmed the orbital symmetry assigned in the gas phase absorption spectra. The transitions to π(B-B) bonding and π*(B-B) anti-bonding final states represent the most relevant probe of the chemistry of the B2Cat2 molecule. We show that their theoretical description requires that the treatment of the relaxation changes among different excited state configurations, which we successfully implemented by using ΔSCF-DFT (ΔSCF) calculations.

Epidemiology of emergency calls for time-dependent acute illnesses during COVID-19 outbreak in Umbria region (Italy).

The recent literature reported an inverse correlation between COVID-19 pandemic and hospital admissions for Acute Coronary Syndromes (ACS).

Daily music listening to reduce work-related stress: a randomized controlled pilot trial.

BACKGROUND: Literature shows that music can reduce stress conditions. This pilot study investigated the effects of music listening on work-related stress and well-being in healthcare professionals. METHOD: A total of 45 subjects were randomly assigned to three treatment groups: No Music, Individualized Music and Melomics-Health Listening. Music groups experienced a daily 30-min-playlist listening for 3 weeks at home. The Maugeri Stress Index-Revised (MASI-R) and the Psychological General Well-Being Index (PGWBI) were administered at baseline, after 3 weeks and after 7 weeks (follow-up). Longitudinal data were analyzed by means of a nested ANOVA model, testing the main effects of time and treatment and the interaction between them. RESULTS: MASI-R scores showed a positive trend in music groups and a worsening in the control group. Only the interaction time/treatment emerged as supporting a trend toward statistical significance (P = 0.07). PGWBI showed a stability in music groups and a clear decline in controls, without significant effects. CONCLUSIONS: Results from the study support the need for a larger clinical trial: it is suggested that daily music listening could be implemented to reduce work-related stress and that the effects may be related, not only to individual musical preferences and familiarity, but also to specific music structures and parameters.

Spontaneous perception of numerosity in pre-school children.

There is strong evidence that humans can make rough estimates of the numerosity of a set of items, almost from birth. However, as numerosity covaries with many non-numerical variables, the idea of a direct number sense has been challenged. Here we applied two different psychophysical paradigms to demonstrate the spontaneous perception of numerosity in a cohort of young pre-school children. The results of both tasks showed that even at that early developmental stage, humans spontaneously base the perceptual choice on numerosity, rather than on area or density. Precision in one of these tasks predicted mathematical abilities. The results reinforce strongly the idea of a primary number sense and provide further evidence linking mathematical skills to the sensory precision of the spontaneous number sense, rather than to mechanisms involved in handling explicit numerosity judgements or extensive exposure to mathematical teaching.

How do Swiss medical schools prepare their students to become good communicators in their future professional careers: a questionnaire and interview study involving medical graduates, teachers and curriculum coordinators.

BACKGROUND: Since 2011, the Swiss Catalogue of Learning Objectives (SCLO) has provided the framework for assessing communication skills in the Swiss Medical Federal Licensing Examination (FLE). This study evaluates how far the communication curricula of five Swiss medical schools match the SCLO and international recommendations. It also explores their strengths, weaknesses, opportunities and threats (SWOT). METHODS: A mixed method approach was used. In a first step, curriculum coordinators/key communication skills teachers and medical graduates were asked to fill out a questionnaire based on communication related objectives from the SCLO and a review of European consensus statements on communication training. Second, information was collected from all Swiss medical schools to identify which communication skills were taught in which formats and at what time points within the 6-year curricula. Finally, 3-4 curriculum coordinators/key communication skills teachers from each medical school were interviewed about their communication curriculum, using SWOT analysis. RESULTS: Sixteen teachers/coordinators (response rate 100%) and 389 medical graduates (response rate 43%) filled out the questionnaire. Both the teachers/coordinators and the graduates considered that two thirds of the communication items listed in the questionnaire were covered in their curricula. Between sixty and two hundred structured hours were dedicated to communication, predominantly in small group and experiential formats. Assessment relied on both MCQs and OSCEs. Most of the training occurred during the first three years of medical school. Teachers felt that the need for communication skills training was now well-recognized by their institution and was taught with appropriate teaching methods. However, recruitment and training of teachers, continuity of communication skills training during clinical years, and the adoption of a common frame of reference among the five medical schools, remained a challenge. CONCLUSION: Although the Swiss medical schools all offered a partly longitudinal communication skills training, with appropriate teaching methods, this study indicates that the communication skills actually taught do not fully match the SCLO or international recommendations. There was less training for complex communication skills training during the clinical years, and ensuring quality and coherence in the teaching remained a challenge.

Small bowel intussusception due to malignant melanoma: primary lesion or metastases? A case report.

Intussusception is a rare condition in the adult population: it is responsible for 1% of all bowel obstructions. In most of intussusceptions a malignant tumor is involved; a lot of studies show that approximately 50% of malignant metastases causing small bowel intussusception are metastatic melanomas. In present paper a case of a small bowel intussusception probably due to metastases of an occult melanoma, in a 69-year-old patient, is presented. Surgery resection, careful research of possible primitive neoplasms and an accurate follow-up program has been the treatment of choice. All the investigations carried out did not allow to identify a possible primitive neoplasm. The last whole body PET carried out 44 months after surgery resulted disease-free.

Paget's disease of the male breast: case report and a point of view from actual literature.

INTRODUCTION: Paget disease of the nipple in man is a very rare breast cancer, and there are not standard procedures or guidelines. In any cases, a Paget's disease could hide an invasive ductal breast cancer. CASE DESCRIPTION: We report the case of a 77-years old man affected by Alzheimer's disease, who presented to our attention because of an ulcerated palpable mass in the right nipple. A biopsy of the lesion showed "intra-epidermic proliferation of epitelioid cells, associated with linfo-plasmacellular infiltration of superficial dermis, compatible with Paget's disease (pTis)". We discussed the case in the multidisciplinary meeting and decided to subject the patient to surgery, so a right mastectomy plus sentinel lymph node biopsy (SLNB) were performed. Histo-pathological examination revealed "invasive ductal carcinoma of the breast, associated with a small component of in situ ductal carcinoma and Paget's disease of the nipple with superficial ulceration". Resection margins were free. Sentinel lymph node was negative. Biological features were as follows: ER 95%, PR 60%, Her-2/neu 1+, Ki-67 35%. The patient was discharged in the third post-operative day in good conditions. In the following weeks the patient's healing process was good and free of complications. CONCLUSIONS: Clinical recognition of Paget's disease is very important also in man, because it can be the alarm bell for an underlying invasive ductal breast cancer, often more aggressive than in woman.

Insoluble fibres, satiety and food intake in cats fed kibble diets.

Fibre is generally considered to dilute food energy, alter intestinal transit time and promote satiety; however, in cats, conflicting results have been found. In this study, two insoluble fibres were evaluated in four feline diets: control (no added fibre); diet with 10% sugar cane fibre; diet with 20% sugar cane fibre; and diet with 10% cellulose. The experiment was conducted with 32 cats, eight animals per diet, over 42 days: 1-7 for diet adaptation; 8-14 for total collection of faeces for digestibility; 15-17 for fresh faeces collection for fermentation products measurements; 18-20 for gastrointestinal transit time determination; 21 and 37 to evaluate the pattern of food intake; and 22 and 42 to assess satiety. Means were compared by analysis of variance and orthogonal contrasts, and the pattern of food intake was compared by repeated-measures analysis of variance (p < 0.05). The cats exhibited increased food intake after fibre addition to the diets (p < 0.05), achieving similar energy consumption. Cellulose and the two levels of sugar cane fibre reduced nutrient availability and energy digestibility, but only sugar cane fibre reduced fat digestibility (p < 0.05). Faecal output and the number of defecations per day increased with fibre inclusion (p < 0.05). Gastrointestinal transit time did not change with sugar cane fibre inclusion, but it was reduced with cellulose addition (p = 0.032). The pattern of food intake did not change, but cats fed fibre-supplemented diets exhibited greater consumption of a challenge meal, increasing energy intake (p < 0.01) when exposed to a palatable, energy-dense food.

Beet pulp intake and hairball faecal excretion in mixed-breed shorthaired cats.

Hairball formation may induce vomiting and intestinal obstruction in predisposed cats. Some insoluble fibres as sugarcane fibre and cellulose can prevent hairball formation. The aim of this study was to evaluate the effect of beet pulp consumption, a moderate soluble and fermentable fibre source, on faecal trichobezoars excretion in adult shorthaired cats fed kibble diets. Eighteen mixed-breed shorthaired cats and three extruded diets were used as follows: a basal diet without added fibre source (PB0-8.8% dietary fibre); BP8-8% inclusion of beet pulp (17.5% of dietary fibre); BP16-16% inclusion of beet pulp (23.8% of dietary fibre). The cats were fed during 31 days and faeces quantitatively collected during three periods of 3 days each (from days 3-5; 15-17; 26-28). Gastrointestinal transit time was determined in the last 3 days of study (from days 29-31). The trichobezoars were separated from faeces, collected, dried and washed in ether for complete removal of all faecal material. The results were submitted to repeated-measure analysis of variance and means evaluated by polynomial contrast (p < 0.05). Beet pulp increased faecal production (p < 0.001) and reduced gastrointestinal transit time (p = 0.003). No alterations were found on trichobezoar faecal excretion, both as considered in number per cat per day of mg per cat per day (p > 0.05). Beet pulp intake did not reduce the number or the size of hairballs eliminated via faeces of shorthaired cats.

The role of hysteroscopy in unexplained infertility.

PURPOSE OF INVESTIGATION: To evaluate pregnancy rate after diagnostic and operative hysteroscopy in nulliparous patients with inter- tility of unknown cause. MATERIALS AND METHODS: The authors conducted this study on 92 nulliparous patients with unexplained infer- tility that underwent diagnostic hysteroscopy which showed an uterine lesion (submucous fibroids, uterine septa, polyps, synechias) and underwent operative hysteroscopy to remove the lesion between 2007 and 2011. Patients' data were retrospectively extrapolated from patient's charts, then the patients were called to ask if they had pregnancies after hysteroscopic surgery. RESULTS: The present study showed a significant increase in pregnancy rate after hysteroscopic surgery (85% during the two years after the surgery). The most common endocavitary lesions were endometrial polyps (21%), uterine septa (25%), and submucous myomas (18%). CONCLUSIONS: Ac- cording to the present data, hysteroscopic evaluation of nulliparous women with unexplained infertility could be useful to detect lesions not diagnosed with other tests, and the treatment of these endocavitary lesions plays an important role in the diagnostic and therapeutic iter. The results show-a pregnancy rate of 85% in the patients treated for endocavitary lesions, but 15% of the patients, despite a normal uterine cavity, continue to have unexplained infertility and are classified as idiopathic infertility.

Benefits of task-shifting HIV care to nurses in terms of health-related quality of life in patients initiating antiretroviral therapy in rural district hospitals in Cameroon [Stratall Agence Nationale de Recherche sur le SIDA (ANRS) 12110/Ensemble pour une Solidarité Thérapeutique Hospitalière en Réseau (ESTHER) substudy].

OBJECTIVES: The World Health Organization (WHO) recommends task-shifting HIV care to nurses in low-resource settings with limited numbers of physicians. However, the effect of such task-shifting on the health-related quality of life (HRQL) of people living with HIV (PLHIV) has seldom been evaluated. We aimed to investigate the effect of task-shifting HIV care to nurses on HRQL outcomes in PLHIV initiating antiretroviral therapy (ART) in rural district hospitals in Cameroon. METHODS: Outcomes in PLHIV were longitudinally collected in the 2006-2010 Stratall trial. PLHIV were followed up for 24 months by nurses and/or physicians. Six HRQL dimensions were assessed during face-to-face interviews using the WHO Quality of Life (WHOQOL)-HIV BREF scale: physical health; psychological health; independence level; social relationships; environment; and spirituality/religion/personal beliefs. The degree of task-shifting was estimated using a consultant ratio (i.e. the ratio of nurse-led to physician-led visits). The effect of task-shifting and other potential correlates on HRQL dimensions was explored using a Heckman two-stage approach based on linear mixed models to adjust for the potential bias caused by missing data in the outcomes. RESULTS: Of 1424 visits in 440 PLHIV (70.5% female; median age 36 years; median CD4 count 188 cells/µL at enrolment), 423 (29.7%) were task-shifted to nurses. After multiple adjustment, task-shifting was associated with higher HRQL level for four dimensions: physical health [coefficient 0.7; 95% confidence interval (CI) 0.1-1.2; P = 0.01], psychological health (coefficient 0.5; 95% CI 0.0-1.0; P = 0.05), independence level (coefficient 0.6; 95% CI 0.1-1.1; P = 0.01) and environment (coefficient 0.6; 95% CI 0.1-1.0; P = 0.02). CONCLUSIONS: Task-shifting HIV care to nurses benefits the HRQL of PLHIV. Together with the previously demonstrated comparable clinical effectiveness of physician-based and nurse-based models of HIV care, our results support the WHO recommendation for task-shifting.

Secondary Cytoreduction in Platinum-Resistant Recurrent Ovarian Cancer: A Single-Institution Experience.

BACKGROUND: The purpose of this study was to observe the role of secondary cytoreductive surgery in platinum-resistant recurrent ovarian cancer (OC) patients. METHODS: We collected data of patients affected by recurrent OC treated between 1995 and 2013. Inclusion criteria were: invasive epithelial OC histologically documented, cytoreductive surgery and platinum-based chemotherapy at first-line treatment with evidence of complete response to treatment, disease-free interval <6 months, and no concomitant neoplasia. Patients considered susceptible of cytoreductive surgery (group A) were compared with a historical series of patients with similar characteristics but not eligible for surgery (group B). RESULTS: Of 122 platinum-resistant patients, 18 met the inclusion criteria for the study and were enrolled. They were compared with a historical series of 18 patients not surgically treated with analogous clinical and pathological features. The most frequent sites of relapse included pelvic and aortic lymph nodes (39 %), peritoneum (33 %), bowel (28 %), and pelvis (22 %). A low rate of intraoperative and postoperative complications was reported. No deaths were recorded. Overall survival was significantly longer in cytoreductive group when compared with the control group (P = 0.035). Median overall survival was 44 months. Estimated 5-year overall survival rates were 57 versus 23.5 % for groups A and B, respectively. CONCLUSIONS: Surgery could represent a useful adjunct to chemotherapy in the management of platinum-resistant recurrent OC patients, carefully selected, in highly selected centers. Larger prospective trials are needed to further confirm our experience.

PARP inhibition: A promising therapeutic target in ovarian cancer.

Ovarian cancer is burdened by the highest mortality rate among gynecological cancers. Gold standard is represented by the association of platinum-taxane -based chemotherapy and radical surgery. Despite several adjustments occurred in cytotoxic drug in last decades, most patients continue to relapse, and no significant enhancement has been reached in the overall survival. The development of drug resistance and the recurrence of disease have prompted the investigations of other targets that can be used in the treatment of ovarian cancers. Among such targets, polyadenosine diphosphate-ribose polymerase (PARP) represents a novel way to target specific patways involved in tumor growth. PARP accelerates the reaction of the polyADP-ribosylation of proteins implicated in DNA repair. PARP inhibitors have shown activity in cancers with BRCA mutations, with other deficient DNA repair genes or signaling pathways that modulate DNA repair, or in association with DNA damaging agents not involved in DNA repair dysfunction. A number of inhibitors for PARP has been developed, and such drugs are under investigation in clinical trials to identify their impact in the treatment of ovarian cancers. This review aims to summarize the recent researches and clinical progress on PARP inhibitors as novel target agents in ovarian cancer.

[Effective communication strategies to frame the trainer-trainee dialogue in the clinical setting]. / Stratégies de communication au service de la formation: quelques outils pratiques.

Communication between trainer and trainee plays a central role in teaching and learning in the clinical environment. There are various strategies to frame the dialogue between trainee and trainer. These strategies allow trainers to be more effective in their supervision, which is important in our busy clinical environment. Communication strategies are well adapted to both in- and out-patient settings, to both under- and postgraduate contexts. This article presents three strategies that we think are particularly useful. They are meant to give feedback, to ask questions and to present a case.

Patterns of adherence to antiretroviral therapy and HIV drug resistance over time in the Stratall ANRS 12110/ESTHER trial in Cameroon.

OBJECTIVES: The emergence of HIV drug resistance is a crucial issue in Africa, where second-line antiretroviral therapy (ART) is limited, expensive and complex. We assessed the association between adherence patterns and resistance emergence over time, using an adherence measure that distinguishes low adherence from treatment interruptions, in rural Cameroon. METHODS: We performed a cohort study among patients receiving nonnucleoside reverse transcriptase inhibitor (NNRTI)-based ART in nine district hospitals, using data from the Stratall trial (2006-2010). Genotypic mutations associated with antiretroviral drug resistance were assessed when 6-monthly HIV viral loads were > 5000 HIV-1 RNA copies/mL. ART adherence data were collected using face-to-face questionnaires. Combined indicators of early (1-3 months) and late (6 months to t - 1; t is the time point when the resistance had been detected) adherence were constructed. Multivariate logistic regression and Cox models were used to assess the association between adherence patterns and early (at 6 months) and late (after 6 months) resistance emergence, respectively. RESULTS: Among 456 participants (71% women; median age 37 years), 45 developed HIV drug resistance (18 early and 27 late). Early low adherence (< 80%) and treatment interruptions (> 2 days) were associated with early resistance [adjusted odds ratio (95% confidence interval) 8.51 (1.30-55.61) and 5.25 (1.45-18.95), respectively]. Early treatment interruptions were also associated with late resistance [adjusted hazard ratio (95% confidence interval) 3.72 (1.27-10.92)]. CONCLUSIONS: The emergence of HIV drug resistance on first-line NNRTI-based regimens was associated with different patterns of adherence over time. Ensuring optimal early adherence through specific interventions, adequate management of drug stocks, and viral load monitoring is a clinical and public health priority in Africa.