Estimating mother-to-child HIV transmission rates in Cameroon in 2011: a computer simulation approach.

BACKGROUND: Despite the progress in the Prevention of the Mother-to-Child Transmission of HIV (PMTCT), the paediatric HIV epidemic remains worrying in Cameroon. HIV prevalence rate for the population of pregnant women was 7.6% in 2010 in Cameroon. The extent of the paediatric HIV epidemic is needed to inform policymakers. We developed a stochastic simulation model to estimate the number of new paediatric HIV infections through MTCT based on the observed uptake of services during the different steps of the PMTCT cascade in Cameroon in 2011. Different levels of PMTCT uptake was also assessed. METHODS: A discrete events computer simulation-based approach with stochastic structure was proposed to generate a cohort of pregnant women followed-up until 6 weeks post-partum, and optionally until complete breastfeeding cessation in both prevalent and incident lactating HIV-infected women. The different parameters of the simulation model were fixed using data sources available from the 2011 national registry surveys, and from external cohorts in Cameroon. Different PMTCT coverages were simulated to assess their impact on MTCT. Available data show a low coverage of PMTCT services in Cameroon in 2011. RESULTS: Based on a simulation approach on a population of 995, 533 pregnant women, the overall residual MTCT rate in 2011 was estimated to be 22.1% (95 % CI: 18.6%-25.2%), the 6-week perinatal MTCT rate among prevalent HIV-infected mothers at delivery is estimated at 12.1% (95% CI: 8.1%-15.1%), with an additional postnatal MTCT rate estimated at 13.3% (95% CI: 9.3%-17.8%). The MTCT rate among children whose mothers seroconverted during breastfeeding was estimated at 20.8% (95% CI: 14.1%-26.9%). Overall, we estimated the number of new HIV infections in children in Cameroon to be 10, 403 (95% CI: 9, 054-13, 345) in 2011. When PMTCT uptake have been fixed at 100%, 90% and 80%, global MTCT rate failed to 0.9% (9% CI: 0.5%-1.7%), 2.0% (95% CI: 0.9%-3.2%) and 4.3% (95% CI: 2.4%-6.7%) respectively. CONCLUSIONS: This model is helpful to provide MTCT estimates to guide the national HIV policy in Cameroon. Increasing supply and uptake of PMTCT services among prevalent HIV infected pregnant women, as well as HIV-prevention interventions including the offer and acceptance of HIV testing and counselling in lactating women could reduce significantly the residual HIV MTCT in Cameroon. A public health effort should be made to encourage health care workers and pregnant women to use PMTCT services until complete breastfeeding cessation.

Relative survival multistate Markov model.

Prognostic studies often have to deal with two important challenges: (i) separating effects of predictions on different 'competing' events and (ii) uncertainty about cause of death. Multistate Markov models permit multivariable analyses of competing risks of, for example, mortality versus disease recurrence. On the other hand, relative survival methods help estimate disease-specific mortality risks even in the absence of data on causes of death. In this paper, we propose a new Markov relative survival (MRS) model that attempts to combine these two methodologies. Our MRS model extends the existing multistate Markov piecewise constant intensities model to relative survival modeling. The intensity of transitions leading to death in the MRS model is modeled as the sum of an estimable excess hazard of mortality from the disease of interest and an 'offset' defined as the expected hazard of all-cause 'natural' mortality obtained from relevant life-tables. We evaluate the new MRS model through simulations, with a design based on registry-based prognostic studies of colon cancer. Simulation results show almost unbiased estimates of prognostic factor effects for the MRS model. We also applied the new MRS model to reassess the role of prognostic factors for mortality in a study of colorectal cancer. The MRS model considerably reduces the bias observed with the conventional Markov model that does not permit accounting for unknown causes of death, especially if the 'true' effects of a prognostic factor on the two types of mortality differ substantially.

Hazard perception at high- and low-risk road sites: a pilot study of interurban roads in Pakistan and Cameroon.

OBJECTIVES: Interurban roads account for a significant proportion of traffic deaths in developing countries. In this pilot study, hazard perceptions of interurban road sites involved in ≥3 injury road traffic crashes were compared with those not involved in road traffic crashes on the same road sections. SETTINGS: Karachi-Hala (Pakistan) and Yaoundé-Douala (Cameroon) road sections were the main study settings. DATA: Videos of 26 high-risk sites and 26 low-risk sites from Karachi-Hala (Pakistan) and Yaoundé-Douala (Cameroon) roads, matched for the road section, were shown to 100 voluntary Pakistani drivers. Variations in perceived site hazardousness and preferred speed for each site pair were assessed. Analyses Factors associated with incorrect hazard perception of high-risk sites (perceived as safe) were assessed by multinomial logistic regression analyses. RESULTS: Drivers reported a higher hazard perception and a lower preferred speed for high-risk sites than for their matched low-risk sites in less than half of pairs (n=12, p≤0.02). Factors associated with increased likelihood of identifying a high-risk site as safe were as follows: flat road profile (adjusted OR=2.00, 95% CI 1.55 to 2.57), intersections (OR=1.96, 95% CI 1.43 to 2.68), irregular road surface (OR=3.56, 95% CI 2.68 to 4.71), nearby road obstacles (OR=2.57, 95% CI 1.96 to 3.39) and visible rain (OR=1.85, 95% CI 1.48 to 2.32). CONCLUSION: The methods used in this study might be useful in prioritising cost-effective improvements at high-risk sites.

Bayesian multi-response nonlinear mixed-effect model: application of two recent HIV infection biomarkers.

Since the discovery of the human immunodeficiency virus (HIV) 35 years ago, the epidemic is still ongoing in France. To monitor the dynamics of HIV transmission and assess the impact of prevention campaigns, the main indicator is the incidence. One method to estimate the HIV incidence is based on biomarker values at diagnosis and their dynamics over time. Estimating the HIV incidence from biomarkers first requires modeling their dynamics since infection using external longitudinal data. The objective of the work presented here is to estimate the joint dynamics of two biomarkers from the PRIMO cohort. We thus jointly modeled the dynamics of two biomarkers (TM and V3) using a multi-response nonlinear mixed-effect model. The parameters were estimated using Bayesian Hamiltonian Monte Carlo inference. This procedure was first applied to the real data of the PRIMO cohort. In a simulation study, we then evaluated the performance of the Bayesian procedure for estimating the parameters of multi-response nonlinear mixed-effect models.

Severe morbidity and mortality in untreated HIV-infected children in a paediatric care programme in Abidjan, Côte d'Ivoire, 2004-2009.

BACKGROUND: Clinical evolution of HIV-infected children who have not yet initiated antiretroviral treatment (ART) is poorly understood in Africa. We describe severe morbidity and mortality of untreated HIV-infected children. METHODS: All HIV-infected children enrolled from 2004-2009 in a prospective HIV programme in two health facilities in Abidjan, Côte d'Ivoire, were eligible from their time of inclusion. Risks of severe morbidity (the first clinical event leading to death or hospitalisation) and mortality were documented retrospectively and estimated using cumulative incidence functions. Associations with baseline characteristics were assessed by competing risk regression models between outcomes and antiretroviral initiation. RESULTS: 405 children were included at a median age of 4.5 years; at baseline, 66.9% were receiving cotrimoxazole prophylaxis, and 27.7% met the 2006 WHO criteria for immunodeficiency by age. The risk of developing a severe morbid event was 14% (95%CI: 10.7 - 17.8) at 18 months; this risk was lower in children previously exposed to any prevention of mother-to-child-transmission (PMTCT) intervention (adjusted subdistribution hazard ratio [sHR]: 0.16, 95% CI: 0.04 - 0.71) versus those without known exposure. Cumulative mortality reached 5.5% (95%CI: 3.5 - 8.1) at 18 months. Mortality was associated with immunodeficiency (sHR: 6.02, 95% CI: 1.28-28.42). CONCLUSIONS: Having benefited from early access to care minimizes the severe morbidity risk for children who acquire HIV. Despite the receipt of cotrimoxazole prophylaxis, the risk of severe morbidity and mortality remains high in untreated HIV-infected children. Such evidence adds arguments to promote earlier access to ART in HIV-infected children in Africa and improve care interventions in a context where treatment is still not available to all.

A multi-state Markov model using notification data to estimate HIV incidence, number of undiagnosed individuals living with HIV, and delay between infection and diagnosis: Illustration in France, 2008-2018.

Thirty-five years since the discovery of the human immunodeficiency virus (HIV), the epidemic is still ongoing in France. To guide HIV prevention strategies and monitor their impact, it is essential to understand the dynamics of the HIV epidemic. The indicator for reporting the progress of new infections is the HIV incidence. Given that HIV is mainly transmitted by undiagnosed individuals and that earlier treatment leads to less HIV transmission, it is essential to know the number of infected people unaware of their HIV-positive status as well as the time between infection and diagnosis. Our approach is based on a non-homogeneous multi-state Markov model describing the progression of the HIV disease. We propose a penalized likelihood approach to estimate the HIV incidence curve as well as the diagnosis rates. The HIV incidence curve was approximated using cubic M-splines, while an approximation of the cross-validation criterion was used to estimate the smoothing parameter. In a simulation study, we evaluate the performance of the model for reconstructing the HIV incidence curve and diagnosis rates. The method is illustrated in the population of men who have sex with men using HIV surveillance data collected by the French Institute for Public Health Surveillance since 2004.

Perception of Physical Child Abuse Among Parents and Professionals in a French Emergency Department.

France has not prohibited all forms of corporal punishment, and the point at which an act is regarded as physical abuse is not clearly determined. The aim of our study was to compare perception of a caregiver's violent behavior toward his child by professionals and parents in an emergency department and determine characteristics associated with that perception. A cross-sectional study was conducted from November 2013 to October 2014 in the emergency department of the pediatric university hospital in Bordeaux, France. An anonymous self-administered questionnaire, including vignettes describing hypothetical situations of violent interaction between a parent and child, and items related to sociodemographic and family characteristics, was administered to professionals and parents. Vignettes included varying child's age and behavior, frequency of caregiver's behavior, hitting with/without an object, and targeted child's body part. Violent behavior was restricted to hitting for reasons of feasibility. Respondents were asked to rate the acceptability of situations on a 100-mm visual analog scale. Analyses were multivariate mixed Poisson regressions. A total of 1,001 participants assessed the vignettes. Participants were predominantly females (64%), married or living with a partner (87%), with a median age of 34 years. Professionals assessed vignettes as acceptable significantly more than parents (mean rating 2.8 times higher; p < .001). For both professionals and parents, all vignette characteristics were significantly associated with acceptability. Parents who had a child below 1 year old, those who had visited an emergency department many times in the past year, and those who had fewer children were less tolerant. Such findings indicate the need for additional research to better appreciate consequences and severity of violent behavior toward children, and the need to educate parents and professionals.

Prevalence and factors associated with psychological distress among key populations in Togo, 2017.

OBJECTIVES: Mental health is a largely neglected issue among in Sub-Saharan Africa, especially among key populations at risk for HIV. The aim of this study was to estimate the prevalence of psychological distress (PD) and to assess the factors associated among males who have sex with males (MSM), female sex workers (FSW) and drug users (DU) in Togo in 2017. STUDY DESIGN: A cross-sectional bio-behavioral study was conducted in August and September 2017 using a respondent-driven sampling (RDS) method, in eight cities in Togo. METHODS: A standardized questionnaire was used to record sociodemographic characteristics and sexual behaviors. The Alcohol Use Disorders Identification Test (AUDIT) and a subset of questions from the Tobacco Questions for Survey were used to assess alcohol and tobacco consumption respectively. PD was assessed with the Kessler Psychological Distress Scale. A blood sample was taken to test for HIV. Descriptive statistics, univariable and multivariable ordinal regression models were used for analysis. RESULTS: A total of 2044 key populations including 449 DU, 952 FSW and 643 MSM with a median age of 25 years, interquartile range (IQR) [21-32] were recruited. The overall prevalence of mild PD among the three populations was 19.9% (95%CI = [18.3-21.8]) and was 19.2% (95%CI = [17.5-20.9]) for severe/moderate PD. HIV prevalence was 13.7% (95%CI = [12.2-15.2]). High age (≥ 25 years) [aOR = 1.24 (95% CI: 1.02-1.50)], being HIV positive [aOR = 1.80 (95% CI: 1.31-2.48)] and hazardous alcohol consumption [aOR = 1.52 (95% CI: 1.22-1.87)] were risk factors for PD. Secondary [aOR = 0.52 (95% CI: 0.42-0.64)] or higher [aOR = 0.46 (95% CI: 0.32-0.64)] education levels were protective factors associated with PD. FSW [OR = 0.55 (95% CI: 0.43-0.68)] and MSM [OR = 0.33 (95% CI: 0.24-0.44)] were less likely to report PD compared with DU. CONCLUSION AND RECOMMENDATIONS: This is the first study conducted among a large, nationally representative sample of key populations in Togo. The prevalence of PD is high among these populations in Togo and was associated to HIV infection. The present study indicates that mental health care must be integrated within health programs in Togo with a special focus to key populations through interventions such as social support groups.

The transport of high amounts of vascular endothelial growth factor by blood platelets underlines their potential contribution in systemic sclerosis angiogenesis.

OBJECTIVES: Altered angiogenesis is a characteristic feature in SSc and remains ill-understood. VEGF is believed to play a central role. Serum VEGF is elevated in SSc patients but questions remain concerning the source of circulating VEGF. Here we investigated platelet activation and the role of platelets as a source of VEGF and other angiogenic mediators in this disease. METHODS: A cohort of 40 patients with SSc was included. Age- and sex-matched healthy subjects and subjects presenting a primary RP were included as controls. Platelets were isolated, activated with thrombin and the secretion of VEGF, platelet derived growth factor, homodimeric form BB (PDGF-BB), TGF-beta1 and angiopoietins-1 and -2 measured. Plasma concentrations of these mediators and the functionality of platelet-derived VEGF were also studied. Platelet activation was assayed by measuring plasma beta-thromboglobulin and expression of P-selectin on platelets. The effect of iloprost on VEGF secretion by platelets was studied. RESULTS: Platelets from SSc patients, in contrast to controls, secreted large amounts of VEGF when activated, but not PDGF-BB, TGF-beta1 or angiopoietins. Increased expression of membrane P-selectin confirmed platelet activation in the patients. Iloprost inhibited VEGF secretion by platelets both in vivo and in vitro, through inhibition of platelet activation. CONCLUSIONS: Platelets transport high levels of VEGF in SSc. They may contribute to circulating VEGF because of ongoing activation in the course of the disease. If activated at the contact of injured endothelium, platelets may be important in the altered angiogenesis associated with the disease through the secretion of high levels of VEGF.

Morbidity before and after HAART initiation in Sub-Saharan African HIV-infected adults: a recurrent event analysis.

The incidence and determinants of severe morbidity recurrence in sub-Saharan African HIV-infected adults on antiretroviral therapy (ART) have never been reported. In a prospective cohort study of HIV-infected adults in Abidjan the association of severe morbidity occurrence and recurrence with follow-up CD4 counts and ART on/off status was analyzed by means of multivariate failure analysis for recurrent events (Prentice, Williams, and Peterson model). A total of 608 patients (median CD4 290/mm3 ) was followed off ART for 1824 person-years (PY). Of these 187 started HAART (median CD4 174/mm3 ) and were followed for 328 PY. The incidence of first, second, and third severe morbidity events was 40.6/100 PY, 68.4/100 PY, and 93.9/100 PY during the off-ART period, and 28.4/100 PY, 39.4/100 PY, and 37.6/100 PY during the on-ART period, respectively. The rates of recurrences were higher than the rates of first episodes for almost all diseases, even after stratifying by CD4 count and by ART on/off status. In multivariate analysis, the time-updated CD4 count was independently associated with increasing rates of morbidity first events and recurrences, after adjustment on other covariates (p > 10(4) ). By contrast, there was no association between the ART on/off status and the morbidity rates after adjustment for CD4 count (p = 0.37). Introducing ART led to a clear reduction in morbidity, mainly related to the ART-induced increase in CD4 count. In HIV-infected patients on ART, the incidence of severe morbidity varied with the past history of morbidity. The past history of morbidity should be taken into account when comparing HIV morbidity rates before and after ART initiation.

Decrease of human immunodeficiency virus prevalence in antenatal clinics in Abidjan, Côte d'Ivoire, 1995-2002.

Antenatal HIV seroprevalence surveys are important tools to understand the extent of the HIV epidemic in Africa. The main objective is to describe HIV prevalence trends from 1995-2002 in pregnant women consulting antenatal clinics in Abidjan, Côte d'Ivoire. We proposed HIV test to pregnant women consulting antenatal clinics in Abidjan from 1995-2002 in a programme of prevention of mother-to-child transmission of HIV. Yearly prevalence was estimated. Overall, 36,442 women were tested. Prevalence decreased from 14-15% in 1995-96 to 11% in 2002. The prevalence among 18-22-year-old women dropped from 15% in 1995 to 8% in 2002, while for older women it increased slightly, or remained stable from 1995-1999 and decreased thereafter. HIV prevalence among women consulting antenatal clinics has been decreasing overall. This is the first such report among pregnant women in Abidjan, probably the result of different phenomena: ageing of the epidemic and behaviour changes (disease awareness and prevention campaigns).

Biases in observational studies of the effect of prenatal treatment for congenital toxoplasmosis.

The paper reviews methodological difficulties that arise when using observational studies to evaluate the effect of prenatal screening and treatment. The principle of each difficulty is described and then illustrated by a clinical example of toxoplasmosis in pregnancy and its consequences. Methods to deal with these difficulties are described. Given the limitations of existing observational studies and lack of randomised controlled trials, a systematic review of cohort studies offers the best approach for exploring potential biases.

The disablement process: factors associated with progression of disability and recovery in French elderly people.

PURPOSE: To study the factors associated with progression, recovery and death from different grades of disability in elderly people. METHOD: The sample included 3198 participants of the PAQUID ('Personnes Agées QUID') cohort, aged 65 and over and community-dwellers at baseline. Subjects were re-interviewed 1, 3, 5, 8 and 10 years after baseline. A five-state Markov model was used to estimate transition intensities between four grades of disability and toward death. We used a hierarchic scale of disability, which combines basic and instrumental activities of daily living and mobility. Several explanatory variables were investigated: medical, personal and environmental factors. RESULTS: The factors associated with progression and/or no recovery of disability were cardiovascular diseases, stroke and diabetes, low cognition, visual impairment and dyspnoea (for pathologies and impairments), older age, female gender, low educational level (for risk factors), depression (for intra-individual factor) and being married, recent hospitalization and number of drugs (for extra-individual factors). Older age, male gender, tobacco consumption and living in an urban area were associated with mortality. CONCLUSIONS: These findings confirm the independent contribution of each group of variables in the disablement process and stress their different impact on progression of disability or on recovery from different grades of disability.

Predictors of virological rebound in HIV-1-infected patients initiating a protease inhibitor-containing regimen.

OBJECTIVE: To study the predictors of virological rebound in patients having early virological response to protease inhibitor (PI)-containing regimen. DESIGN AND METHODS: APROCO cohort study prospectively enrolled 1283 HIV-infected patients starting a PI-containing regimen in 1997-1999. Adherence to therapy was measured with self-administered questionnaires after 4 months of therapy (M4). Virological rebound was defined as a viral load (VL) > 500 copies/ml in patients having early virological response, defined as a VL < 500 copies/ml at M4. Predictors of time to virological rebound were studied with multivariate proportional hazards model. RESULTS: During a median follow-up of 20 months, virological rebound was observed in 32% of the 830 patients with early virological response. Virological rebound was more frequent when patients had received previous antiretroviral treatment [adjusted hazards ratio (HR) = 2.4; P < 0.0001], were younger (HR = 1.4 per each 10 years younger; P < 0.0001), had baseline CD4 cell count < 500 x 106/l (HR = 2.3; P < 0.001), had higher baseline VL (HR = 1.4 per each log10 copies/ml higher; P < 0.001), reported low adherence to therapy at M4 (HR = 2.1; P < 0.001) or had stopped PI at M4 (HR = 1.7; P = 0.04). CONCLUSION: Initiation of treatment at a stage of preserved immunity is associated with a more durable virological response under protease inhibitor. Every effort should be made to monitor and strengthen adherence to therapy, even in patients having early virological response.

Twenty-four month efficacy of a maternal short-course zidovudine regimen to prevent mother-to-child transmission of HIV-1 in West Africa.

OBJECTIVE: To assess the 24 month efficacy of a maternal short-course zidovudine regimen to prevent mother-to-child transmission (MTCT) of HIV-1 in a breastfeeding population in West Africa. METHODS: Data were pooled from two clinical trials: DITRAME-ANRS049a conducted in Abidjan, Côte d'Ivoire and Bobo-Dioulasso, Burkina-Faso and RETRO-CI, conducted in Abidjan. Between September 1995 and February 1998, consenting HIV-1-seropositive women were randomly assigned to receive zidovudine (300 mg) or placebo: one tablet twice daily from 36-38 weeks' gestation until delivery, then in DITRAME only, for 7 more days. Paediatric HIV-1 infection was defined as a positive HIV-1 polymerase chain reaction, or if aged > or =15 months, a positive HIV-1 serology. Cumulative risks (CR) of infection were estimated using a competing risk approach with weaning as a competing event. RESULTS: Among 662 live-born children, 641 had at least one HIV-1 test. All but 12 children were breastfed. At 24 months, overall CR of MTCT were 0.225 in the zidovudine and 0.302 in the placebo group, a 26% significant reduction. Among children born to women with CD4 cell counts < 500/ml at enrollment, CR of MTCT were similar, 0.396 in the zidovudine and 0.413 in the placebo group. Among children born to women with CD4 cell counts > or =500/ml, CR of MTCT were 0.091 in the zidovudine and 0.220 in the placebo group, a significant 59% reduction. CONCLUSION: A maternal short-course zidovudine regimen reduces MTCT of HIV-1 at age 24 months, despite prolonged breastfeeding. However, efficacy was observed only among women with CD4 cell counts > or =500/ml. New interventions should be considered to prevent MTCT, especially for African women with advanced HIV-1 immunodeficiency.

Postnatal transmission of HIV-1 after a maternal short-course zidovudine peripartum regimen in West Africa.

BACKGROUND: To assess the postnatal transmission (PT) risk of HIV-1 after a maternal short-course zidovudine regimen in a breastfeeding population. METHODS: Data were pooled from two trials: ANRS 049a DITRAME (Abidjan, Côte d'Ivoire and Bobo-Dioulasso, Burkina-Faso) and RETROCI (Abidjan). Consenting HIV-1 seropositive women were randomized at 36-38 weeks' gestation between September 1995 and February 1998, to receive oral zidovudine or placebo: one tablet twice daily until delivery, and in DITRAME only, for 7 more days. A PT case was infection in a child with a negative HIV-1 PCR at age >/= 30 days who later became infected as defined by a positive HIV-1 PCR, or if aged >/= 15 months, a positive HIV serology. Cumulative risks (CR) of PT were computed using a competing risk approach with weaning as a competing event. FINDINGS: At age 24 months, CR for PT were similar in the zidovudine (9.8%, n = 254) and placebo groups (9.1%, n = 225). In a multivariate model of PT risk factors, the treatment effect was not significant, maternal CD4 cell count < 500 x 10(6)/l at entry tripled the hazard compared to women with CD4 cell counts >/= 500 x 10(6)/l [hazard ratio (HR), 3.14; 95% confidence interval (CI), 1.31-7.49] as well as an increased maternal plasma viral load at entry (HR, 2.65 for 1 log(10) increase; CI, 1.75-4.00). INTERPRETATION: PT occurred at a similar rate between arms and therefore reduced the long-term overall efficacy of this peripartum zidovudine regimen at age 24 months. The higher risk of PT among women with low CD4 cell count emphasizes the importance of identifying interventions to prevent PT for these women.

HIV status disclosure and retention in care in HIV-infected adolescents on antiretroviral therapy (ART) in West Africa.

OBJECTIVE: We assessed the effect of HIV status disclosure on retention in care from initiation of antiretroviral therapy (ART) among HIV-infected children aged 10 years or more in Cote d'Ivoire, Mali and Sénégal. METHODS: Multi-centre cohort study within five paediatric clinics participating in the IeDEA West Africa collaboration. HIV-infected patients were included in this study if they met the following inclusion criteria: aged 10-21 years while on ART; having initiated ART ≥ 200 days before the closure date of the clinic database; followed ≥ 15 days from ART initiation in clinics with ≥ 10 adolescents enrolled. Routine follow-up data were merged with those collected through a standardized ad hoc questionnaire on awareness of HIV status. Probability of retention (no death or loss-to-follow-up) was estimated with Kaplan-Meier method. Cox proportional hazard model with date of ART initiation as origin and a delayed entry at date of 10th birthday was used to identify factors associated with death or loss-to-follow-up. RESULTS: 650 adolescents were available for this analysis. Characteristics at ART initiation were: median age of 10.4 years; median CD4 count of 224 cells/mm³ (47% with severe immunosuppression), 48% CDC stage C/WHO stage 3/4. The median follow-up on ART after the age of 10 was 23.3 months; 187 adolescents (28.8%) knew their HIV status. The overall probability of retention at 36 months after ART initiation was 74.6% (95% confidence interval [CI]: 70.5-79.0) and was higher for those disclosed compared to those not: adjusted hazard ratio for the risk of being death or loss-to-follow-up = 0.23 (95% CI: 0.13-0.39). CONCLUSION: About 2/3 of HIV-infected adolescents on ART were not aware of their HIV status in these ART clinics in West Africa but disclosed HIV status improved retention in care. The disclosure process should be thus systematically encouraged and organized in adolescent populations.

Bacterial pneumonia among HIV-infected patients: decreased risk after tobacco smoking cessation. ANRS CO3 Aquitaine Cohort, 2000-2007.

BACKGROUND: Bacterial pneumonia is still a substantial cause of morbidity and mortality in HIV-infected patients in the era of combination Antiretroviral Therapy. The benefit of tobacco withdrawal on the risk of bacterial pneumonia has not been quantified in such populations, exposed to other important risk factors such as HIV-related immunodeficiency. Our objective was to estimate the effect of tobacco smoking withdrawal on the risk of bacterial pneumonia among HIV-infected individuals. METHODOLOGY/PRINCIPAL FINDINGS: Patients of the ANRS CO3 Aquitaine Cohort with >or= two visits during 2000-2007 and without bacterial pneumonia at the first visit were included. Former smokers were patients who stopped smoking since >or= one year. We used Cox proportional hazards models adjusted on CD4+ lymphocytes (CD4), gender, age, HIV transmission category, antiretroviral therapy, cotrimoxazole prophylaxis, statin treatment, viral load and previous AIDS diagnosis. 135 cases of bacterial pneumonia were reported in 3336 patients, yielding an incidence of 12 per thousand patient-years. The adjusted hazard of bacterial pneumonia was lower in former smokers (Hazard Ratio (HR): 0.48; P = 0.02) and never smokers (HR: 0.50; P = 0.01) compared to current smokers. It was higher in patients with <200 CD4 cells/microL and in those with 200 to 349 CD4 cells/microL (HR: 2.98 and 1.98, respectively; both P<0.01), but not in those with 350 to 499 CD4 cells/microL (HR: 0.93; P = 0.79), compared to those with >or=500 CD4 cells/microL. The interaction between CD4 cell count and tobacco smoking status was not statistically significant. CONCLUSIONS/SIGNIFICANCE: Smoking cessation dramatically reduces the risk of bacterial pneumonia, whatever the level of immunodeficiency. Smoking cessation interventions should become a key element of the clinical management of HIV-infected individuals.

A multistate approach for estimating the incidence of human immunodeficiency virus by using HIV and AIDS French surveillance data.

Before the introduction of highly active antiretroviral therapy (HAART) in 1996, monitoring the epidemics of HIV infection was extensively based on back-calculating the number of new HIV infections from AIDS surveillance data and knowledge of the AIDS incubation period distribution. However, the increase in the AIDS incubation period induced by HAART has complicated the use of AIDS diagnosis data only, and made it necessary to supplement these data with HIV diagnosis data. We explore the advantage of combining HIV and AIDS surveillance data in the context where the HIV diagnosis data are available only for the most recent years. Extending the earlier work of Aalen et al. (Statist. Med. 1997; 16(19):2191-2210) based on a discrete-time Markov model that describes simultaneously disease progression, HIV diagnosis and treatment intake, we propose a penalized likelihood approach to estimate smooth HIV incidence, together with HIV diagnosis rates. The smoothing parameter is chosen using an approximated cross-validation criterion. In a simulation study, we show that incorporation of HIV test information improves the precision of the estimation of the incidence of infections in recent periods. The method is illustrated using HIV and AIDS surveillance data collected by the Institut de Veille Sanitaire, France.

A new endpoint definition improved clinical relevance and statistical power in a vaccine trial.

OBJECTIVE: Endpoints used for the evaluation of immunogenicity in vaccine trials are often the proportion of individuals with immune response or geometric means of antibody concentrations for each serotype. When a vaccine includes several types of the same species, we illustrate how an endpoint combining all responses may improve clinical relevance and statistical power. STUDY DESIGN AND SETTINGS: The motivating example was the ANRS 114 Pneumovac trial where the effect of two vaccine strategies against Streptococcus pneumoniae was assessed in adults infected by the Human Immunodeficiency Virus. The power associated with several endpoints was calculated in the example and in simulations. A new endpoint based on four ordered levels is formulated and analyzed by using a proportional odds model. RESULTS AND CONCLUSION: The analysis of this new endpoint led to an odds ratio allowing detection of improvement and detriment. In the simulation study, this endpoint was associated with the largest statistical power by increasing the amount of information used as compared with usual endpoints. We recommend this new endpoint formulation in the formal development of a new vaccination regimen, whenever applicable.