Factors associated with the use of cannabis for self-medication by adults: data from the French TEMPO cohort study.

BACKGROUND: Medical cannabis, legalized in many countries, remains illegal in France. Despite an experiment in the medical use of cannabis that began in March 2021 in France, little is known about the factors associated with the use of cannabis for self-medication among adults. METHODS: Data came from the French TEMPO cohort and were collected between December 2020 and May 2021. Overall, 345 participants aged 27-47 were included. Cannabis for self-medication was defined using the following questions: 'Why do you use cannabis?' and 'In what form do you use cannabis?'. The penalized regression method "Elastic net" was used to determine factors associated with the use of cannabis for self-medication, with the hypothesis that it is mainly used for pain in individuals who have already used cannabis. RESULTS: More than half of the participants reported having ever used cannabis (58%). Only 10% used it for self-declared medical reasons (n = 36). All self-medication cannabis users, except one, were also using cannabis for recreational purposes. The main factors associated with cannabis use for self-medication vs. other reasons included cannabis use trajectories, the presence of musculoskeletal disorders, tobacco smoking, and parental divorce. CONCLUSIONS: Engaging in cannabis use during adolescence or early adulthood may increase the likelihood of resorting to self-medication in adulthood. Due to the propensity of individuals with cannabis use during adolescence to resort to uncontrolled products for self-medication, this population should be more systematically targeted and screened for symptoms and comorbidities that may be associated with cannabis use.

Comparisons between diluted thrombin time, ecarin chromogenic assays, and UPLC-MS for plasma level dabigatran quantification: Results from DRIVING study.

INTRODUCTION: The knowledge of dabigatran levels is helpful for decision-making in specific situations such as urgent surgery or when the question of reversal arises (uncontrolled bleeding, eligibility for thrombolysis). However, a limited number of observational studies are available regarding comparisons between quantification methods. The objective of the study was to compare dabigatran plasma levels using three assays including the reference method (high-performance liquid chromatography coupled with mass spectrometry), focusing on the agreement around the 30-50 ng/mL clinically relevant thresholds. METHODS: Sixty healthy volunteers from DRIVING trial (NCT01627665) were given a single 300-mg dabigatran etexilate dose. Serial blood samplings were performed at pre-defined time points (0 to 24 h). We analyzed plasma samples using ultra-performance-liquid chromatography coupled with tandem mass spectrometry (UPLC-MS) (dabigatran reference method); ii/diluted thrombin time (dTT) (Hemoclot-DTI-Hyphen-Biomed); iii/ecarin-based chromogenic assay (ECA-II-Stago). RESULTS: Nine hundred sixty samples were analyzed using the three assays (2759 values). dTT and ECA-II values were highly correlated with those of UPLC-MS (Deming regression). Most values >50 ng/mL were higher using dTT and ECA-II compared to UPLC-MS: biases were constant, +14% and +16% with dTT and ECA-II, respectively (Bland-Altman plots), suggesting that active metabolites accounted for ~15% of thrombin inhibition. Regarding values <30 ng/mL, 30-50 ng/mL, or ≥50 ng/mL, the agreement probability between dTT and ECA-II was of 90.6% [88.4-92.5] (Cohen's kappa coefficient 0.84). CONCLUSION: dTT and ECA-II assays rapidly provide accurate dabigatran-level results for clinical practice, both assays being suitable in emergency, taking into account the thrombin inhibitory effect of dabigatran metabolites.

Sustainable return to work among breast cancer survivors.

PURPOSE: This study assessed sustainable return to work (SRTW) of breast cancer survivors (BCS). METHODS: We used data from the prospective French cohort, CANTO. We included 1811 stage I-III BCS who were <57 years old and employed at the moment of diagnosis and working 2 years after diagnosis. Using logistic regression, we investigated the role of clinical, health and socio-economic factors, and the work environment on SRTW 3 years after diagnosis. We compared having any sick leave with having worked continuously and being unemployed to having worked continuously between 2 and 3 years after diagnosis. RESULTS: Overall, 77% (n = 1395) worked continuously after return to work (RTW). Out of the other 416 BCS, 66% had any sick leave period, 33% had been unemployed, 4% had an early retirement, 2% a disability and 1% another status (multiple situations possible). Being on sick leave was associated with age > 50 (OR = 0.59; 95%CI = 0.43-0.82), stage III (2.56; 1.70-3.85), tumour subtype HR+/HER2+ (0.61; 0.39-0.95), severe fatigue (1.45; 1.06-1.98), workplace accommodations (1.63; 1.14-2.33) and life priorities (0.71; 0.53-0.95). Unemployment was associated with age > 50 (0.45; 0.29-0.72), working in the public sector (0.31; 0.19-0.51), for a small company (3.00; 1.74-5.20) and having a fixed-term contract (7.50; 4.74-11.86). CONCLUSIONS: A high number of BCS have periods of sick leave or unemployment after RTW. The determinants differ between sick leave and unemployment. IMPLICATIONS FOR CANCER SURVIVORS: BCS need to be supported even after RTW, which should be regarded as a process.

Association between Sleep Disturbances During Childhood and Smoking Trajectories During Adulthood: The Longitudinal TEMPO Cohort Study.

OBJECTIVE: This study examined the longitudinal association between child sleep disturbances from ages 3 to 16 and smoking in adulthood among subjects from a French cohort study. METHODS: Data from 2,134 subjects who participated in the French TEMPO cohort from 1991 to 2018 were used. Sleep disturbances observed from ages 3 to 16 years defined our exposure. Tobacco consumption trajectories constitute our outcomes and were ascertained by using Group-Based Trajectory Modeling, a semiparametric probabilistic method that hypothesizes the existence of distinct developmental trajectories over time within one population. The impact of SDs in childhood on adulthood's Tobacco consumption were studied using multinomial logistic regression. RESULTS: Sleep disturbances at 16 years or under were observed in 26.5% of participants. Five smoking trajectories were defined: "non-smokers", "decrease in consumption at age 20 years", "low-level tobacco use", "smoking followed by cessation at age 30 years" and "high-level tobacco use". No statistically significant association between sleep disturbances and smoking trajectories was found. Compared with nonsmokers, adjusted odds-ratios and 95% Confidence Intervals for each trajectory were respectively: 0.81 [0.52-1.26], 1.28 [0.74-2.22], 1.37 [0.88-2.15] and 1.01 [0.60-1.69]. CONCLUSION: These results suggest that smoking in adulthood may not be related to sleep disturbances in childhood.

Occurrence and severity of cocaine-induced hallucinations: Two distinct phenotypes with shared clinical factors but specific genetic risk factors.

Cocaine-induced transient hallucinations (CIH) are a frequent complication following cocaine intake that is associated with addiction severity. METHODS: Two hundred and forty-two non-psychotic and Caucasian lifetime cocaine users were included in a French multicentric study. Clinical variables and dopamine pathway genotype data were extracted and tested with CIH scores using a zero-inflated binomial model, which allows for the exploration of factors associated with occurrence and severity separately. RESULTS: Cocaine dependence (poccurrence= 6.18 × 10-5, pseverity= 9.25 × 10-8), number of cocaine dependence DSM IV-Tr criteria (poccurrence= 1.22 × 10-7, pseverity= 5.09 × 10-6), and frequency of intake during the worst period of misuse (poccurrence= 8.51 × 10-04, pseverity= 0.04) were associated with greater occurrence and higher severity of CIH. The genetic associations did not yield significant results after correction for multiple tests. However, some nominal associations of SNPs mapped to the VMAT2, DBH, DRD1, and DRD2 genes were significant. In the multivariate model, the significant variables were the number of cocaine dependence criteria, lifetime alcohol dependence, and the nominally associated SNPs. CONCLUSION: Our study shows that CIH occurrence and severity are two distinct phenotypes, with shared clinical risk factors; however, they likely do not share the same genetic background.

Adolescent cannabis experimentation and unemployment in young to mid-adulthood: Results from the French TEMPO Cohort study.

BACKGROUND: France accounts for one of the highest levels of recreational cannabis use, with almost 40% of youth aged 17 reporting having experimented with cannabis. We investigated the impact of early cannabis experimentation (defined as first-time use ≤ 16 years) on future probability of unemployment in young to mid-adulthood using a longitudinal, community sample over the span of 9 years. METHODS: Data were obtained from the French TEMPO Cohort study, set up in 2009 among young adults aged 22-25 years old. Participants who reported information on age of cannabis experimentation and employment status in at least one study wave (2009, 2011, 2015 and 2018) were included in the statistical analyses (N = 1487, 61.2% female). RESULTS: In A-IPW-adjusted analyses, early cannabis experimenters (≤ 16 years) had 1.71 (95% CI: 1.46-2.02) times higher odds of experiencing unemployment compared to late cannabis experimenters (> 16 years) and 2.40 (95% CI: 2.00 - 2.88) times higher odds of experiencing unemployment compared to non-experimenters. Late cannabis experimenters experienced 1.39 (95% CI: 1.17-1.68) times higher odds of being unemployed compared to non-experimenters, and early cannabis experimenters experienced 3.84 (95%CI: 2.73-5.42) times higher odds of experiencing long-term unemployment (defined as unemployed at least twice) compared to non-experimenters. CONCLUSIONS: Participants who ever used cannabis, especially at or before the age of 16, had higher odds of experiencing unemployment, even when accounting for many psychological, academic and family characteristics which preceded cannabis initiation.

Diagnosis, risk factors and management of diabetes mellitus in HIV-infected persons in France: A real-life setting study.

BACKGROUND: Diabetes mellitus (DM) is a major and increasing public health problem that may be underdiagnosed and undertreated among persons living with HIV (PLWH). OBJECTIVE: To describe the diagnosis, treatment and follow-up of DM among PLWH. METHODS: This study was performed inside a monocentric cohort of 1494 PLWH. DM was defined as having a FG ≥126 mg/dL twice or a HbA1c ≥6.5%, or a history of diabetes, or receiving antidiabetic treatment. The first visit mentioning a diagnosis of DM was considered as the baseline visit. Chi-Square or Fisher exact test were used to examine the association between categorical variables and DM, Wilcoxon or Student t-test were used for continuous variables. RESULTS: 156 PLWH with DM were included. Compared to non-diabetic participants, they were more likely to be native of Sub Saharan Africa (31.6% vs. 22.4%, p = 0.027) and older (54.6 vs. 49.9 years, p<0.001), to have a higher BMI (> 25 for 46.1% vs. 35.3%, p = 0.020) and a poorer control of HIV (HIV RNA<50 copies/mL: 80.1% vs. 89.5%, p<0.001). The diagnosis of DM was missed in 37.8% of PLWH, and 47.2% of PLWH treated for DM did not reach a HbA1c<7%. PLWH with DM were more frequently on antihypertensive and/or lipid-lowering medications: 94.2% had a LDL-cholesterol <70 mg/dL and 60.9% had a blood pressure <140/90 mmHg. CONCLUSION: In a setting of HIV-control, HIV care providers should focus on metabolic issues. The management of DM and associated risk factors is mandatory to prevent cardiovascular disease in PLWH.

Lean Body Mass and Endocrine Status But Not Age Are Determinants of Resting Energy Expenditure in Patients with Non-Small Cell Lung Cancer.

BACKGROUND: Cancer and aging are both frequently associated with malnutrition, a factor of poor prognosis. In adult cancer patients, this may be related in part to impaired energy metabolism, with higher than predicted resting energy expenditure (REE) in about 50% of patients. We hypothesized that frequently impaired energy metabolism in elderly patients could potentiate cancer-associated hypermetabolism, further promoting risk of malnutrition. OBJECTIVE: To study the hypermetabolic response to cancer in a predominantly aged population and the potential underlying determinants. METHODS: This was a cross-sectional exploratory study in patients with non-small-cell lung cancer. REE was measured by indirect calorimetry. Body composition was determined from a single CT scan imaging at L3 level. Endocrine, inflammatory, nutritional and metabolic status were evaluated. RESULTS: Twenty-seven patients, of median age 68 years (range 32-81) completed the study. In this population, mean measured REE was 7.5% higher than calculated REE. Sex and weight accounted for about 51% of REE variations, whereas age accounted only for 4%. However, these parameters did not explain the REE-to-lean body mass (LBM) ratio variations, suggesting that they influenced REE only through their effect on LBM. Among the other parameters evaluated, only the thyroid-stimulating hormone and interleukin-6 plasma levels appeared to have an influence on REE. The study of the consequences of this increase in REE-to-LBM ratio showed a growing inability of patients to meet their energy needs but showed no effect on nutritional markers such as transthyretin. CONCLUSIONS: The results of this pilot study suggest that in our population, age was not an important factor of REE. The elevated energy metabolism was associated with patients' failure to increase their energy intakes sufficiently, which can contribute to the development of cachexia. CLINICAL TRIAL: This trial is registered at clinicaltrials.gov under NCT0314.

Association Between Electronic Cigarette Use and Smoking Reduction in France.

IMPORTANCE: The electronic cigarette (EC) has become popular among smokers who wish to reduce their tobacco use levels or quit smoking, but its effectiveness as a cessation aid is uncertain. OBJECTIVE: To examine the association of regular EC use with the number of cigarettes smoked per day, smoking cessation among current smokers, and smoking relapse among former smokers. DESIGN, SETTING, AND PARTICIPANTS: The CONSTANCES (Consultants des Centres d'Examens de Santé) cohort study, based in France, began recruiting participants January 6, 2012, and is currently ongoing. Participants were enrolled in CONSTANCES through 2015, and included 5400 smokers (mean [SD] follow-up of 23.4 [9.3] months) and 2025 former smokers (mean [SD] follow-up of 22.1 [8.6] months) at baseline who quit smoking in 2010, the year in which ECs were introduced in France, or afterward. Analyses were performed from February 8, 2017, to October 15, 2018. MAIN OUTCOMES AND MEASURES: The association between EC use and the number of cigarettes smoked during follow-up was studied using mixed regression models. The likelihood of smoking cessation was studied using Poisson regression models with robust sandwich variance estimators. The association between EC use and smoking relapse among former smokers was studied using Cox proportional hazards regression models. All statistical analyses were adjusted for sociodemographic characteristics, duration of follow-up, and smoking characteristics. RESULTS: Among the 5400 daily smokers (2906 women and 2494 men; mean [SD] age, 44.9 [12.4] years), regular EC use was associated with a significantly higher decrease in the number of cigarettes smoked per day compared with daily smokers who did not use ECs (-4.4 [95% CI, -4.8 to -3.9] vs -2.7 [95% CI, -3.1 to -2.4]), as well as a higher adjusted relative risk of smoking cessation (1.67; 95% CI, 1.51-1.84]). At the same time, among the 2025 former smokers (1004 women and 1021 men; mean [SD] age, 43.6 [12.1] years), EC use was associated with an increase in the rate of smoking relapse among former smokers (adjusted hazard ratio, 1.70; 95% CI, 1.25-2.30). CONCLUSIONS AND RELEVANCE: This study's findings suggest that, among adult smokers, EC use appears to be associated with a decrease in smoking level and an increase in smoking cessation attempts but also with an increase in the level of smoking relapse in the general population after approximately 2 years of follow-up.

Indoor tetrachloroethylene levels and determinants in Paris dwellings.

There is growing public health concern about indoor air quality. Tetrachloroethylene (PERC), a chlorinated volatile organic compound widely used as a solvent in dry cleaning facilities, can be a residential indoor air pollutant. As part of an environmental investigation included in the PARIS (Pollution and asthma Risk: an Infant Study) birth cohort, this study firstly aimed to document domestic PERC levels, and then to identify the factors influencing these levels using standardized questionnaires about housing characteristics and living conditions. Air samples were collected in the child's bedroom over one week using passive devices when infants were 1, 6, 9, and 12 months. PERC was identified and quantified by gas chromatography/mass spectrometry. PERC annual domestic level was calculated by averaging seasonal levels. PERC was omnipresent indoors, annual levels ranged from 0.6 to 124.2 µg/m3. Multivariate linear and logistic regression models showed that proximity to dry cleaning facilities, do-it-yourself activities (e.g.: photographic development, silverware), presence of air vents, and building construction date (<1945) were responsible for higher domestic levels of PERC. This study, conducted in an urban context, provides helpful information on PERC contamination in dwellings, and identifies parameters influencing this contamination.

Formaldehyde exposure and lower respiratory infections in infants: findings from the PARIS cohort study.

BACKGROUND: Certain chemical pollutants can exacerbate lower respiratory tract infections (LRIs), a common childhood ailment. Although formaldehyde (FA) is one of the most common air pollutants found in indoor environments, its impact on infant health is uncertain. OBJECTIVE: Our aim was to determine the impact of FA exposure on the LRI incidence during the first year of life of infants from the Pollution and Asthma Risk: an Infant Study (PARIS) birth cohort. METHODS: FA was measured in a random sample of 196 infants' dwellings, and exposure to this pollutant was estimated for 2,940 infants using predictive models based on measurements and data about potential determinants of FA levels. Health data were collected from parents by regular self-administered questionnaires. We used multivariate logistic regressions to estimate associations between FA exposure and the occurrence of LRI and wheezy LRI (wLRI), adjusting for potential confounders/risk factors. RESULTS: During the first year of life, 45.8% of infants had at least one LRI, and LRI occurred simultaneously with wheezing in 48.7% of cases. The FA predictive models correctly classified 70% of dwellings as having high or low exposure, and we estimated that 43.3% of infants were exposed throughout the first year to levels of FA > 19.5 µg/m3. FA exposure was significantly associated with LRI and wLRI before and after adjustment for known LRI risk factors/confounders. For an interquartile increase in FA levels (12.4 µg/m3), we estimated a 32% [95% confidence interval (CI): 11, 55] and 41% (95% CI: 14, 74) increase in the incidence of LRI and wLRI, respectively. CONCLUSION: The findings of this study suggest that infants exposed to FA at an early age have an increased incidence of LRI.

IL-2 therapy: potential impact of the CD4 cell count at initiation on clinical efficacy--results from the ANRS CO4 cohort.

OBJECTIVES: We investigated why, despite its beneficial effect on the CD4 cell count, IL-2 therapy had no clinical benefit as shown in the ESPRIT and SILCAAT trials. We focused on subgroups of patients defined according to CD4 cell counts at baseline and over time to assess the threshold above which IL-2 therapy was no longer beneficial in a large cohort of HIV-1 infected patients. METHODS: Within the French Hospital Database on HIV, a total of 953 IL-2-treated patients were compared with 27 750 IL-2-untreated patients, matched for the date of enrolment, sex, age, and the baseline CD4 cell count and plasma HIV-1 RNA level. The risk of clinical progression, defined as the occurrence of a new AIDS-defining event or death, was studied with multivariable Cox proportional hazards models and Poisson regression models. RESULTS: We found no clinical benefit in patients starting IL-2 with CD4 count ≥200 cells/mm(3) [hazard ratio (HR) =1.13; 95% confidence interval (CI), 0.81-1.57], while a benefit was observed in patients with CD4 count <200 cells/mm(3) (HR=0.64; 95% CI, 0.48-0.86). The observed benefit was due to the risk reduction in the 100-350/mm(3) stratum of updated CD4 cell counts (relative rate=0.30; 95% CI, 0.09-1.03). CONCLUSIONS: Higher CD4 cell counts at enrolment and shorter follow-up with low to intermediate CD4 cell counts may explain why IL-2 therapy had no observed clinical benefit in the SILCAAT study. Our findings suggest that the benefit of IL-2 is restricted to a narrow range of CD4 cell counts, arguing against the use of IL-2 in HIV infection to reduce the risk of clinical events.

Use of an anti-hepatitis C virus (HCV) IgG avidity assay to identify recent HCV infection.

There is no reliable and simple diagnostic marker available to diagnose recent hepatitis C virus (HCV) infection. It has been shown that the avidity of specific IgG antibody is low in primary viral infection and increases with time. We report the development of an anti-HCV avidity assay derived from a commercially available test. A panel of 117 sera was first examined for IgG avidity. It was composed of samples from patients with recent (group 1, n = 14), chronic (group 2, n = 70), and resolved (group 3, n = 33) HCV infections. Avidity index (AI) values observed in recently infected patients were significantly lower (12.0% +/- 9.2% [mean +/- standard deviation]) than those found in chronic carriers (83.1% +/- 15.2%). Using a threshold of 43.0%, this assay distinguished between groups 1 and 2 with very high sensitivity (98%) and specificity (100%). For group 3, a broader distribution of the AI values was observed (54.8% +/- 27.3%), suggesting that this index would not be useful in HCV RNA-negative patients. Blind validation of the test was carried out with a panel of 36 serum samples from 17 HCV seroconverters. The assay described here is a useful tool to distinguish recent from chronic infection in HCV-viremic patients.

Interleukine-2 therapy does not increase the risk of Hodgkin or non-Hodgkin lymphoma in HIV-infected patients: results from FHDH ANRS CO4.

BACKGROUND: Concerns have been raised about a possible excess risk of lymphomas in HIV-infected patients exposed to interleukin 2 (IL-2) therapy. Here we compared the risks of non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) in IL-2-treated and IL-2-untreated HIV-infected patients. METHODS: Patients monitored through the French Hospital Database on HIV between May 1, 1995, and December 31, 2005, were enrolled in this study. Lymphomas that occurred between the day after study entry and the end of follow-up were eligible for analysis. Poisson regression models were used in 2 separate analyses to quantify the possible relationship between IL-2 therapy and the incidence of NHL and HL. RESULTS: The IL-2-treated group consisted of 861 patients and the IL-2-untreated group of 77,605 patients. Follow-up lasted a total of 3643 and 382,720 person-years, respectively. After adjustment for sex and time-updated age, period, the CD4 cell counts, the plasma HIV RNA levels, and AIDS status, the relative rates of NHL and HL associated with IL-2 therapy were 0.64 (95% confidence interval, 0.25 to 1.65) and 0.33 (95% confidence interval, 0.04 to 2.86), respectively. CONCLUSIONS: In this large observational study, IL-2 therapy did not increase the risk of lymphoma, either NHL or HL, in HIV-infected patients.

Evaluation of CLINDE as potent translocator protein (18 kDa) SPECT radiotracer reflecting the degree of neuroinflammation in a rat model of microglial activation.

BACKGROUND: The translocator protein (TSPO; 18 kDa), the new name of the peripheral-type benzodiazepine receptor, is localised in mitochondria of glial cells and expressed in very low concentrations in normal brain. Their expression rises after microglial activation following brain injury. Accordingly, TSPO are potential targets to evaluate neuroinflammatory changes in a variety of CNS disorders. PURPOSE: To date, only a few effective tools are available to explore TSPO by SPECT. We characterised here 6-chloro-2-(4'iodophenyl)-3-(N,N-diethyl)-imidazo[1,2-a]pyridine-3-acetamide or CLINDE in a rat model with different stages of excitotoxic lesion. METHODS: Excitotoxicity was induced in male Wistar rats by unilateral intrastriatal injection of different amounts of quinolinic acid (75, 150 or 300 nmol). Six days later, two groups of rats (n = 5-6/group) were i.v. injected with [(125)I]-CLINDE (0.4 MBq); one group being pre-injected with PK11195 (5 mg/kg). Brains were removed 30 min after tracer injection and the radioactivity of cerebral areas measured. Complementary ex vivo autoradiography, in vitro autoradiography ([(3)H]-PK11195) and immunohistochemical studies (OX-42) were performed on brain sections. RESULTS: In the control group, [(125)I]-CLINDE binding was significantly higher (p < 0.001) in lesioned than that in intact side. This binding disappeared in rats pre-treated with PK11195 (p < 0.001), showing specific binding of CLINDE to TSPO. Ex vivo and in vitro autoradiographic studies and immunohistochemistry were consistent with this, revealing a spatial correspondence between radioactivity signal and activated microglia. Regression analysis yielded a positive relation between the ligand binding and the degree of neuroinflammation. CONCLUSION: These results demonstrate that CLINDE is suitable for TSPO in vivo SPECT imaging to explore their involvement in neurodegenerative disorders associated with microglial activation.

Maintaining antiretroviral therapy reduces the risk of AIDS-defining events in patients with uncontrolled viral replication and profound immunodeficiency.

BACKGROUND: The benefits of continuing antiretroviral therapy are questionable in human immunodeficiency virus (HIV) type 1-infected patients with profound immunodeficiency and multiple treatment failure due to viral resistance. METHODS: From the French Hospital Database on HIV, we selected 12,765 patients with a CD4(+) cell count <200 cells/mm(3) who received a combination antiretroviral therapy (cART) during 2000-2005. Three groups of patients were defined: patients who interrupted cART at least once, patients who had at least 2 consecutive detectable viral loads (VLs) while receiving cART, and patients who had undetectable VL during treatment with cART. Incidence rates and risks of new acquired immunodeficiency syndrome-defining events (ADEs) were assessed among the 3 groups of patients, overall and after CD4(+) cell count stratification (<50 and 50-200 cells/mm(3)). RESULTS: The estimated incidence rates +/- standard deviation of ADEs were 18.5+/-1.9, 14.5+/-0.7, and 4.9+/-0.5, respectively, for patients who interrupted cART, patients who had detectable VL during treatment with cART, and patients who had undetectable VL during treatment with cART. These differences were observed in both CD4(+) cell count strata. Overall, after adjustment, risks of a new ADE in patients who had detectable VL and in patients who had undetectable VL while receiving cART were 22% and 62% lower, respectively, than in patients who stopped cART. Among patients with CD4(+) cell count <50 cells/mm(3), the risk of a new ADE was 22% lower in patients who continued to receive a failing cART regimen than in patients who stopped treatment with cART. Likewise, among patients with a CD4(+) cell count of 50-200 cells/mm(3), the risk was 34% lower in patients who continued to receive a failing cART regimen than in those who stopped taking cART. CONCLUSIONS: Even when effective virological control is no longer achievable, cART still reduces the risk of ADEs in profoundly immunodeficient HIV-infected patients.

Immunologic and clinical responses to highly active antiretroviral therapy over 50 years of age. Results from the French Hospital Database on HIV.

OBJECTIVE: To study immunologic and clinical responses to HAART in patients over 50 years old. DESIGN AND METHODS: A prospective cohort study which included 68 hospitals in France. A total of 3015 antiretroviral-naive patients, 401 of whom were aged 50 years or over, were enrolled following initiation of HAART. The influence of age on the mean CD4 cell count increase on HAART was studied by using a two-slope mixed model. Progression, defined by the occurrence of a new AIDS-defining event (ADE) or death, was studied by Cox multivariate analyses. RESULTS: Among patients with baseline HIV RNA above 5 log copies/ml, CD4 mean increase during the first 6 months on HAART was +42.9 x 10(6) cells/l per month in patients under 50 years and +36.9 x 10(6) cells/l per month in patients over 50 years (P < 0.0001); subsequently, the respective monthly changes were +17.9 and +15.6 x 10(6) cells/l per month (P < 0.0001). Similar trends were observed in patients with baseline HIV RNA below 5 log copies/ml, and also after stratification for the baseline CD4 cell count. After a median follow-up of 31.5 months, 263 patients had a new ADE and 44 patients died. After adjustment for baseline characteristics, older patients had a significantly higher risk of clinical progression (hazard ratio (HR) = 1.52 [95% confidence interval (CI), 1.15-2.00]) and were more likely to achieve a viral load below 500 copies/ml [HR = 1.23, (95% CI, 1.11-1.38)]. CONCLUSION: Patients over 50 years of age have an immunologic response to HAART. However, their CD4 cell reconstitution is significantly slower than in younger patients, despite a better virologic response. This impaired immunologic response may explain their higher risk of clinical progression.

Modeling the time course of CD4 T-lymphocyte counts according to the level of virologic rebound in HIV-1-infected patients on highly active antiretroviral therapy.

OBJECTIVE: To study the influence of the level of virologic rebound during combination antiretroviral therapy on the time course of the CD4 count. METHODS: Between January 1997 and December 1999, we enrolled 3736 patients from the French Hospital HIV Database who had an undetectable viral load on a first course of highly active antiretroviral therapy (HAART). Four levels of virologic rebound were defined on the basis of viral load values during the year following initial undetectability on HAART: group 1, all viral loads <500 copies/mL; group 2, all viral loads <5000 copies/mL; group 3, all viral loads <10,000 copies/mL; and group 4, at least 1 viral load >10,000 copies/mL. We developed a continuous time-homogeneous Markov process with 5 reversible stages defined by CD4 count intervals. RESULTS: CD4 counts increased continuously over time in each group. The smaller the virologic rebound, the stronger was the increase in the CD4 count (P < 0.0001). The mean CD4 cell count increments between months 2 and 6 were 26, 20, 11, and 2 cells/mm3 in groups 1, 2, 3, and 4, respectively. The rate of gain fell after month 6 and was almost nil in group 4. CONCLUSION: After achieving an undetectable viral load on HAART, immunologic reconstitution is possible whatever the subsequent level of viral replication, except among patients with high-level rebound, meaning that in patients with a long history of antiretroviral therapy and a reduced choice of antiretroviral drugs due to acquisition of resistances, delay in antiretroviral therapy switch can be possible in patients with low or intermediate rebound.