Patricia García de Olalla

Impact of adherence and highly active antiretroviral therapy on survival in HIV-infected patients

Objectives: To assess the effect of antiretroviral therapy (ART) adherence on survival in HIV‐infected patients. Design: Cohort study at a single hospital in Barcelona, Spain. Methods: Data on HIV‐infected patients older than 18 years of age who began ART during the period 1990 to 1999 were analyzed. Patients were considered nonadherent if the total dose of antiretroviral drug was less than 90% of that prescribed. Adherence was assessed through self‐report and hospital pharmacy appointments. Cox regression with time‐dependent variables was used. Results: A total of 1219 patients were included. The first ART was with monotherapy in 23.7% of cases, with two drugs in 30.5%, and with triple therapy in 45.8%. In multivariate analysis, the variables that presented significant differences with respect to mortality were clinical stage at the beginning of treatment (AIDS: relative hazard (RH) = 2.97; 95% confidence interval [CI]: 2.14‐4.13), CD4 cell count (<200 cells/&mgr;L: RH = 5.89; CI: 3.44‐10.10), type of treatment (monotherapy: RH = 9.76; CI: 4.56‐20.90; bi‐therapy: RH = 9.12; CI: 4.23‐19.64), and adherence (nonadherence: RH = 3.87; CI: 1.77‐8.46). Conclusions: The modifiable factors most strongly associated with survival were type of treatment and adherence. It would be desirable to accompany therapy with intervention strategies intended to improve adherence.

Salud e inmigración: nuevas realidades y nuevos retos

The new social and demographic framework in Spain that has appeared since the arrival of new migrant populations, raises the need to improve the knowledge of their health status and to identify preventive measures and priorities in heath services. A bibliographic review of the available information on migration and health in Spain is performed, together with an analysis of their contents from a Public Health point of view. The high proportion of new borns from foreign mothers, the mental needs, deficits in oral and dental health, and the increase of tuberculosis in migrants, together with limited vaccine coverage in children, define the main health needs of these populations. The analysis of health services, reveals a high use of pediatric, obstetric and gynecologic resources by migrant populations. Conclusions; although no particular health needs have been identified for migrants, special attention for tuberculosis, mother and child health and health promotion and prevention, have to be funded for specific migrant populations. Health resources and services have to be reinforced with health agents, human resources, and specialized education for health professionals.

Tuberculosis importada: una enfermedad emergente en países industrializados

Fundamento Describir las caracteristicas de la tuberculosis importada en Barcelona durante 1999 y 2000. Material y metodo Encuesta epidemiologica. Resultados En el ano 2000 se detectaron449 casos de tuberculosis en poblacion autoctona(incidencia 29,5/100.000) y 121 eninmigrantes (incidencia 555,9/100.000).Entre 1999 y 2000 la tuberculosis ha disminuidoun 7,9% en la poblacion autoctonade Barcelona, mientras que ha aumentadoun 47,2% en inmigrantes. Hubo tres brotesepidemicos: una comunidad hindu (11 casos),dos familias dominicanas (4 casos) yuna escuela (dos casos) cuyo caso indice fueuna cooperante. Las cepas de Mycobacteriumtuberculosis del primer brote fueron sensiblesa todos los farmacos, las del segundo resistentesa los de primera linea y las del terceroresistentes a isoniacida. Conclusiones La evolucion de la tuberculosisen Barcelona en el ultimo bienio confirma laemergencia de casos importados que demandanuna revision de las medidas de control.

Long-term Mortality in HIV-Positive Individuals Virally Suppressed for >3 Years With Incomplete CD4 Recovery

BACKGROUND Some human immunodeficiency virus (HIV)-infected individuals initiating combination antiretroviral therapy (cART) with low CD4 counts achieve viral suppression but not CD4 cell recovery. We aimed to identify (1) risk factors for failure to achieve CD4 count >200 cells/µL after 3 years of sustained viral suppression and (2) the association of the achieved CD4 count with subsequent mortality. METHODS We included treated HIV-infected adults from 2 large international HIV cohorts, who had viral suppression (≤500 HIV type 1 RNA copies/mL) for >3 years with CD4 count ≤200 cells/µL at start of the suppressed period. Logistic regression was used to identify risk factors for incomplete CD4 recovery (≤200 cells/µL) and Cox regression to identify associations with mortality. RESULTS Of 5550 eligible individuals, 835 (15%) did not reach a CD4 count >200 cells/µL after 3 years of suppression. Increasing age, lower initial CD4 count, male heterosexual and injection drug use transmission, cART initiation after 1998, and longer time from initiation of cART to start of the virally suppressed period were risk factors for not achieving a CD4 count >200 cells/µL. Individuals with CD4 ≤200 cells/µL after 3 years of viral suppression had substantially increased mortality (adjusted hazard ratio, 2.60; 95% confidence interval, 1.86-3.61) compared with those who achieved CD4 count >200 cells/µL. The increased mortality was seen across different patient groups and for all causes of death. CONCLUSIONS Virally suppressed HIV-positive individuals on cART who do not achieve a CD4 count >200 cells/µL have substantially increased long-term mortality.

Imported malaria in a cosmopolitan European city: A mirror image of the world epidemiological situation

BackgroundInternational travel and migration have been related with an increase of imported malaria cases. There has been considerable immigration to Barcelona from low-income countries (LIC) in recent years. The objective is to describe the epidemiology and to determine the trends of the disease in Barcelona.MethodsAnalysis of the cases notified among city residents between 1989 and 2005. Patients were classified as: tourists, voluntary workers, resident immigrants (visiting friends and relatives, VFR) and recently arrived immigrants. An analysis was conducted using the chi2 test and comparison of means. As a measure of association we calculated the Relative Risk (RR) and Odds Ratio (OR) with a Confidence Interval of 95% (CI) and carried out a trends analysis.ResultsOf the total of 1,579 imported cases notified, 997 (63.1%) lived in Barcelona city, and 55.1% were male. The mean age of patients was 32.7 years. The incidence increased from 2.4 cases/100,000 in 1989 to 3.5 cases/100,000 in 2005 (RR 1.46 CI:1.36–1.55). This increase was not statistically significant (trends analysis, p = 0.36). In terms of reason for travelling, 40.7% were VFR, 33.6% tourists, 12.1% voluntary workers and 13.6% were recently arrived immigrants. The most frequent species found was Plasmodium falciparum (71.3%), mainly in visitors to Africa (OR = 2.3, CI = 1.7–3.2). The vast majority (82.2%) had had some contact with Africa (35.9% with Equatorial Guinea, a Spanish ex-colony) and 96.6% had not completed chemoprophylaxis. Six deaths were observed, all tourists who had travelled to Africa and not taken chemoprophylaxis (3.9% fatality rate).ConclusionOver the period studied there is an increase in malaria incidence, however the trend is not statistically significant. Lack of chemoprophylaxis compliance and the association between Africa and P. falciparum are very clear in the imported cases. Most of the patients with malaria did not take chemoprophylaxis.

Factors that influence current tuberculosis epidemiology.

According to WHO estimates, in 2010 there were 8.8 million new cases of tuberculosis (TB) and 1.5 million deaths. TB has been classically associated with poverty, overcrowding and malnutrition. Low income countries and deprived areas, within big cities in developed countries, present the highest TB incidences and TB mortality rates. These are the settings where immigration, important social inequalities, HIV infection and drug or alcohol abuse may coexist, all factors strongly associated with TB. In spite of the political, economical, research and community efforts, TB remains a major global health problem worldwide. Moreover, in this new century, new challenges such as multidrug-resistance extension, migration to big cities and the new treatments with anti-tumour necrosis alpha factor for inflammatory diseases have emerged and threaten the decreasing trend in the global number of TB cases in the last years. We must also be aware about the impact that smoking and diabetes pandemics may be having on the incidence of TB. The existence of a good TB Prevention and Control Program is essential to fight against TB. The coordination among clinicians, microbiologists, epidemiologists and others, and the link between surveillance, control and research should always be a priority for a TB Program. Each city and country should define their needs according to the epidemiological situation. Local TB control programs will have to adapt to any new challenge that arises in order to respond to the needs of their population.

Changes in the incidence of tuberculosis in a cohort of HIV-seroconverters before and after the introduction of HAART.

Objective:To analyse incidence and determinants of tuberculosis in HIV-seroconverters before and after the introduction of HAART. Methods:Data from a multicenter cohort study of 2238 HIV-seroconverters between the 1980s and 2004 were analysed and censored by December 2004. Calendar year at risk intervals were pre-1992, 1992–1996 and 1997–2004. Incident tuberculosis was calculated as cases per 1000 person-years (p-y). Survival analyses using Kaplan–Meier and multivariate Cox regression allowing for late-entry were used. Proportional hazards assumptions were checked with tests based on Schoenfeld residuals. Results:Overall, 173 (7.7%) patients developed tuberculosis over 23 698 p-y at a rate of 7.3 cases per 1000 p-y [95% confidence interval (CI), 6.3–8.5]. Incident tuberculosis was higher in intravenous drug-users (IDUs), 12.3 per 1000 p-y compared with persons infected sexually, 3.8 per 1000 p-y (P < 0.001), and persons with clotting disorders (PCD), 2.7 per 1000 p-y (P < 0.001). A decreasing tuberculosis incidence trend was observed from 1995 in all categories. Highest tuberculosis rates, 44 per 1000 p-y, were observed prior to 1997 in IDUs infected with HIV for 11 years. In multivariable analyses women were less likely to develop tuberculosis [relative hazard (RH), 0.62; 95% CI, 0.41–0.96; P < 0.05) and IDUs were more likely to develop tuberculosis (RH, 3.0; 95% CI, 1.72–5.26, P < 0.001). In the HAART era, the hazard of developing tuberculosis was 70% lower (RH, 0.31; 95% CI, 0.17–0.54; P < 0.001). Before 1997, the risk of tuberculosis increased with time since HIV seroconversion, whereas it remained nearly constant in the HAART era. Conclusions:Since the mid-1990s important decreases in tuberculosis have been observed in HIV-seroconverters that probably reflect the impact of both HAART and tuberculosis control programmes.

Epidemiological characteristics and predictors of late presentation of HIV infection in Barcelona (Spain) during the period 2001-2009

BackgroundEarly diagnosis of HIV infection can prevent morbidity and mortality as well as reduce HIV transmission. The aim of the present study was to assess prevalence, describe trends and identify factors associated with late presentation of HIV infection in Barcelona (Spain) during the period 2001-09.MethodsDemographic and epidemiological characteristics of cases reported to the Barcelona HIV surveillance system were analysed. Late presentation was defined for individuals with a CD4 count below 350 cells/ml upon HIV diagnosis or diagnosis of AIDS within 3 months of HIV diagnosis. Multivariate logistic regression were used to identify predictors of late presentation.ResultsOf the 2,938 newly diagnosed HIV-infected individuals, 2,507 (85,3%) had either a CD4 cell count or an AIDS diagnosis available. A total of 1,139 (55.6%) of the 2,507 studied cases over these nine years were late presenters varying from 48% among men who have sex with men to 70% among heterosexual men. The proportion of late presentation was 62.7% in 2001-2003, 51.9% in 2004-2005, 52.6% in 2006-2007 and 52.1% in 2008-2009. A decrease over time only was observed between 2001-2003 and 2004-2005 (p = 0.001) but remained constant thereafter (p = 0.9). Independent risk factors for late presentation were older age at diagnosis (p < 0.0001), use of injected drugs by men (p < 0.0001), being a heterosexual men (p < 0.0001), and being born in South America (p < 0.0001) or sub-Saharan Africa (p = 0.002).ConclusionLate presentation of HIV is still too frequent in all transmission groups in spite of a strong commitment with HIV prevention in our city. It is necessary to develop interventions that increase HIV testing and facilitate earlier entry into HIV care.

Predictors of death among patients who completed tuberculosis treatment: a population-based cohort study.

Background Mortality among patients who complete tuberculosis (TB) treatment is still high among vulnerable populations. The objective of the study was to identify the probability of death and its predictive factors in a cohort of successfully treated TB patients. Methods A population-based retrospective longitudinal study was performed in Barcelona, Spain. All patients who successfully completed TB treatment with culture-confirmation and available drug susceptibility testing between 1995–1997 were retrospectively followed-up until December 31, 2005 by the Barcelona TB Control Program. Socio-demographic, clinical, microbiological and treatment variables were examined. Mortality, TB Program and AIDS registries were reviewed. Kaplan-Meier and a Cox regression methods with time-dependent covariates were used for the survival analysis, calculating the hazard ratio (HR) with 95% confidence intervals (CI). Results Among the 762 included patients, the median age was 36 years, 520 (68.2%) were male, 178 (23.4%) HIV-infected, and 208 (27.3%) were alcohol abusers. Of the 134 (17.6%) injecting drug users (IDU), 123 (91.8%) were HIV-infected. A total of 30 (3.9%) recurrences and 173 deaths (22.7%) occurred (mortality rate: 3.4/100 person-years of follow-up). The predictors of death were: age between 41–60 years old (HR: 3.5; CI:2.1–5.7), age greater than 60 years (HR: 14.6; CI:8.9–24), alcohol abuse (HR: 1.7; CI:1.2–2.4) and HIV-infected IDU (HR: 7.9; CI:4.7–13.3). Conclusions The mortality rate among TB patients who completed treatment is associated with vulnerable populations such as the elderly, alcohol abusers, and HIV-infected IDU. We therefore need to fight against poverty, and promote and develop interventions and social policies directed towards these populations to improve their survival.

Increase in the Non-HIV-Related Deaths Among Aids Cases in the HAART Era

OBJECTIVE To analyze the factors associated with survival and to describe the specific causes of death in a large cohort of individuals with Acquired Immune Deficiency Syndrome (AIDS) in the Highly Active Antiretroviral Therapy (HAART) era. METHODS Subjects over 13 years old recorded in the AIDS registry of Barcelona and diagnosed between 1997-2005 were included. Survival analysis was performed. Causes of death were classified as being HIV-related or non-HIV-related. RESULTS A total of 1,759 cases were analyzed, 640 (36.3%) of them died during the follow-up. The cumulative probability of survival at five years was of 64% (95% C.I. 62%-67%). The cause of death was non-HIV-related in 28.9% of the cases, among which the most frequent were cancers (20.8%) and liver diseases (18.8%). CONCLUSION An increase in the proportion of non-HIV-related deaths has been observed compared to that in the pre-HAART era. The case management of HIV-infected people must be re-directed to influence the risk factors associated with these increasing causes of death.