Epidemiology and determinants of reemerging bacterial sexually transmitted infections (STIs) and emerging STIs in Europe.

In this scoping review, we offer a comprehensive understanding of the current and recent epidemiology, challenges, and emerging issues related to bacterial sexually transmitted infections (STIs) in the WHO European Region. We endeavour in collating data from both EU/EEA and non- EU/EEA countries, thereby giving a complete picture of the region which highlights the higher notification rates in Northern and Western countries than other regions, likely due to differences in testing, access to testing, and surveillance capacity. We provide an up-to-date review on the current knowledge of determinants and persistent inequities in key populations as well as the use of molecular epidemiology for identifying transmission networks in gonorrhoea and syphilis, and detecting chlamydia mutations that evade molecular diagnosis. Finally, we explore the emerging STIs in the region and the evolving transmission routes of food and waterborne diseases into sexual transmission. Our findings call for harmonized STI surveillance systems, proactive strategies, and policies to address social factors, and staying vigilant for emerging STIs.

Implementation of the HepClink test-and-treat community strategy targeting Pakistani migrants with hepatitis C living in Catalonia (Spain) compared with the current practice of the Catalan health system: budget impact analysis.

OBJECTIVES: To perform a budget impact analysis of the HepClink test-and-treat strategy in which community health agents offer hepatitis C virus (HCV) testing, diagnosis and treatment to the Pakistani population living in Catalonia compared with the current practice of the Catalan health system (without targeted screening programmes). METHODS: We estimated the population of adult Pakistani migrants registered at the primary care centres in Catalonia by means of the Information System for the Development of Research in Primary Care (n=37 972 in 2019, Barcelona health area). This cohort was followed for a time period of 10 years after HCV diagnosis (2019-2028). The statistical significance of the differences observed in the anti-HCV positivity rate between screened and non-screened was confirmed (α=0.05). The budget impact was calculated from the perspective of the Catalan Department of Health. Sensitivity analyses included different levels of participation in HepClink: pessimistic, optimistic and maximum. RESULTS: The HepClink scenario screened a higher percentage of individuals (69.8%) compared with the current scenario of HCV care (39.7%). Viraemia was lower in the HepClink scenario compared with the current scenario (1.7% vs 2.5%, respectively). The budget impact of the HepClink scenario was €884 244.42 in 10 years. CONCLUSIONS: Scaling up the HepClink strategy to the whole Catalan territory infers a high budget impact for the Department of Health and allows increasing the detection of viraemia (+17.8%) among Pakistani migrants ≥18 years. To achieve a sustainable elimination of HCV by improving screening and treatment rates, there is room for improvement at two levels. First, taking advantage of the fact that 68.08% of the Pakistani population had visited their primary care physicians to reinforce targeted screening in primary care. Second, to use HepClink at the community level to reach individuals with reluctance to use healthcare services.

Monitoring health and health behaviors among adolescents in Central Catalonia: DESKcohort protocol.

The objective of the prospective cohort study (the DESKcohort project) is to describe and monitor health, health behaviors, and their related factors among 12 and 19-year-old adolescents schooled at centers of Compulsory Secondary Education or post-compulsory secondary education in Central Catalonia, considering social determinants of health. The DESKcohort survey is administered biannually between the months of October and June, and the project has been running for three years. We have interviewed 7319 and 9265 adolescents in the academic years 2019/20 and 2021/22, respectively. They responded a questionnaire created by a committee of experts, that included the following variables: sociodemographic factors, physical and mental health, food, physical activity, leisure and mobility, substance use, interpersonal relationships, sexuality, screen use and digital entertainment, and gambling. The results are presented to educational centers, county councils, municipalities, and health and third sector entities to plan, implement, and evaluate prevention and health promotion actions that address the identified needs.

Population-based assessment of SARS-CoV-2 infection among people living with HIV and the general population of Catalonia (March-December, 2020).

INTRODUCTION: It is unclear if SARS-CoV-2 has affected people living with HIV (PLWH) more. METHODS: We compared SARS-CoV-2 testing, test positivity, hospitalisation, intensive care unit (ICU) admission, and mortality between PLWH and the general HIV-negative population of Catalonia, Spain from March 1 to December 15, 2020. RESULTS: SARS-CoV-2 testing was lower among PLWH 3556/13,142 (27.06%) compared to the general HIV-negative population 1,954,902/6,446,672 (30.32%) (p<0.001) but test positivity was higher among PLWH (21.06% vs. 15.82%, p<0.001). We observed no significant differences between PLWH and the general population in terms of hospitalisation (13.75% vs. 14.97%, p=0.174) and ICU admission (0.93% vs. 1.66%, p=0.059). Among positive cases, we found a lower mortality rate among PLWH compared to the general population (1.74% vs 3.64%, p=0.002). CONCLUSION: PLWH tested less frequently for SARS-CoV-2, had a higher test positivity, similar ICU admission and hospitalisation rates, and lower SARS-CoV-2-associated mortality compared to the general HIV-negative population.

Who is lost to follow-up in HIV care? Assessment of care retention over time and the impact of COVID-19. Longitudinal analysis of the PISCIS cohort.

INTRODUCTION: People living with HIV who are lost to follow-up have a greater risk of health deterioration, mortality, and community transmission. OBJECTIVE: Our aim was to analyse both how rates of loss to follow-up (LTFU) changed between 2006 and 2020 and how the COVID-19 pandemic affected these rates in the PISCIS cohort study of Catalonia and the Balearic Islands. METHODS: We analysed socio-demographic and clinical characteristics of LTFU yearly and with adjusted odds ratios to assess the impact of these determinants on LTFU in 2020 (the year of COVID-19). We used latent class analysis to categorize classes of LTFU based on their socio-demographic and clinical characteristics at each year. RESULTS: In total, 16.7% of the cohort were lost to follow-up at any time in the 15 years (n = 19 417). Of people living with HIV who were receiving follow-up, 81.5% were male and 19.5% were female; of those who were lost to follow-up, 79.6% and 20.4% were male and female, respectively (p < 0.001). Although rates of LTFU increased during COVID-19 (1.11% vs. 0.86%, p = 0.024), socio-demographic and clinical factors were similar. Eight classes of people living with HIV who were lost to follow-up were identified: six for men and two for women. Classes of men (n = 3) differed in terms of their country of birth, viral load (VL), and antiretroviral therapy (ART); classes of people who inject drugs (n = 2) differed in terms of VL, AIDS diagnosis, and ART. Changes in rates of LTFU included higher CD4 cell count and undetectable VL. CONCLUSIONS: The socio-demographic and clinical characteristics of people living with HIV changed over time. Although the circumstances of the COVID-19 pandemic increased the rates of LTFU, the characteristics of these people were similar. Epidemiological trends among people who were lost to follow-up can be used to prevent new losses of care and to reduce barriers to achieve Joint United Nations Programme on HIV/AIDS 95-95-95 targets.

Population-based assessment of SARS-CoV-2 infection among people living with HIV and the general population of Catalonia (March-December, 2020).

Introduction: It is unclear if SARS-CoV-2 has affected people living with HIV (PLWH) more. Methods: We compared SARS-CoV-2 testing, test positivity, hospitalisation, intensive care unit (ICU) admission, and mortality between PLWH and the general HIV-negative population of Catalonia, Spain from March 1 to December 15, 2020. Results: SARS-CoV-2 testing was lower among PLWH 3556/13,142 (27.06%) compared to the general HIV-negative population 1,954,902/6,446,672 (30.32%) (p < 0.001) but test positivity was higher among PLWH (21.06% vs. 15.82%, p < 0.001). We observed no significant differences between PLWH and the general population in terms of hospitalisation (13.75% vs. 14.97%, p = 0.174) and ICU admission (0.93% vs. 1.66%, p = 0.059). Among positive cases, we found a lower mortality rate among PLWH compared to the general population (1.74% vs 3.64%, p = 0.002). Conclusion: PLWH tested less frequently for SARS-CoV-2, had a higher test positivity, similar ICU admission and hospitalisation rates, and lower SARS-CoV-2-associated mortality compared to the general HIV-negative population.

Introducción: No está claro si el SARS-CoV-2 ha afectado más a las personas que viven con VIH (PVV). Métodos: Se compararon los test realizados de SARS-CoV-2, la positividad de la prueba, la hospitalización, los ingresos en la unidad de cuidados intensivos (UCI), las tasas de mortalidad entre PVV y la población general de Cataluña desde el 1 de marzo hasta el 15 de diciembre de 2020. Resultados: Los test realizados de SARS-CoV-2 fueron menos entre PVV 3.556/13.142 (27.06%) comparado con la población general de Cataluña 1.954.902/6.446.672 (30,32%) (p < 0,001), pero la positividad de la prueba de SARS-CoV-2 fue mayor entre las PVV (21,06 vs. 15,82%; p < 0,001). No se observaron diferencias estadísticamente significativas entre PVV y la población general en cuanto a hospitalizaciones (13,75 vs. 14,97%; p = 0,174) e ingresos en la UCI (0,93 vs. 1,66%; p = 0,059). Entre los casos positivos, se encontró una menor tasa de mortalidad entre las PVV en comparación con la población general (1,74 vs. 3,64%; p = 0,002). Conclusiones: Las PVV fueron testadas menos frecuentemente por SARS-CoV-2 que la población general, tuvieron una tasa de positividad más elevada, tasas similares de hospitalización e ingresos en la UCI, y menos mortalidad asociada al SARS-CoV-2.

Feasibility of an online antigen self-testing strategy for SARS-CoV-2 addressed to health care and education professionals in Catalonia (Spain). The TESTA'T- COVID Project.

We aimed to assess the feasibility of TESTA'T COVID strategy among healthcare and education professionals.in Spain during the peak of the 6th wave caused by Omicron variant. Kits were ordered online and sent by mail, participants answered an online acceptability/usability survey and uploaded the picture of results. 492 participants ordered a test, 304 uploaded the picture (61.8%). Eighteen positive cases were detected (5.9%). 92.2% were satisfied/very satisfied with the intervention; and 92.5% found performing the test easy/very easy. We demonstrated that implementing online COVID-19 self-testing in schools and healthcare settings in Spain is feasible.

[Health status among immigrant in Catalonia from a gender perspective: PELFI project]. / Estado de salud de personas inmigrantes en Cataluña desde una perspectiva de género: Proyecto PELFI.

OBJECTIVE: The objective of the study is to assess the health status of immigrant men and women from non-EU countries living in the Metropolitan Area of Barcelona (Catalonia, Spain) and to identify the social determinants of health from a gender perspective. METHOD: Cross-sectional analysis from a cohort of immigrant families recruited in Badalona and Santa Coloma de Gramenet, in Spain (PELFI cohort). In 2015-2016, 167 immigrants answered the baseline epidemiological questionnaire and the 5-level EuroQol instrument (EQ-5D) which measures health status. To identify health determinants, Tobit models were constructed to the EQ-5D index. RESULTS: Women rated poorer self-perceived health (p=0.005). To be diagnosed with and illness was only associated with poor self-perceived health among men (p<0.05). Length of residence, domestic work, and especially double workload deteriorated women's health. After adjusting models by demographics and social determinants, permanent administrative status (-0.136; p=0.015) and social support (0.182; p=0.02) were associated with health status in both sexes. To have a job was associated with better health only in men. CONCLUSIONS: Non-EU immigrants living in the Metropolitan Area of Barcelona are a socially vulnerable group of population and present inequalities in health by sex. Social support and occupation are key factors of their health status. Interventions to reduce immigrant vulnerabilities and inequalities in health should promote their social inclusion and cohesion from a gender perspective.

Prevalence and Risk Factors for HIV Infection in a Population of Homosexual, Bisexual, and Other Men Who Have Sex with Men in the Metropolitan Region of Chile: A Re-emerging Health Problem.

According to the most recent UNAIDS report, the number of new HIV infections has increased by 34% since 2010 in Chile, representing the largest increase in the Americas. The objective of this study was to identify factors associated with HIV prevalence among men who have sex with men (MSM) in the metropolitan region (MR) of Santiago, Chile. Cross-sectional study of MSM living in the MR, recruited using respondent-driven sampling (RDS). Participants were tested using Human Immunodeficiency virus rapid test, and reactive cases were confirmed withELISA. Participants were interviewed using a questionnaire adapted for the Chilean population. Descriptive and logistic regression analyses were then performed. All applicable ethical norms were followed in the execution of this study. The total sample consisted of 375 individuals. HIV prevalence among MSM was 17.6% overall. Among the HIV-negative men, most (71.5%) had not been tested for sexually-transmitted diseases (STIs) other than HIV in the past 12 months, and 24.1% had never been tested for HIV. Participants who had been tested for an STI other than HIV in the past 12 months had a 3.56-fold greater OR for HIV-positive status than those who had not. Conversely, having had an HIV test in the past 12 months was a protective factor against positive HIV status (OR = 0.09). The high prevalence of HIV among MSM suggests a re-emergence of the disease in Chile, and cases are specifically concentrated among young MSM. Access to sexual health care and STI testing in Chile is insufficient. Targeted prevention efforts are urgently needed as part of the Chilean national strategy to combat the spread of HIV, including community-based testing programs.

Linked factors to access to sexual health checkups of female sex workers in the metropolitan region of Chile.

OBJECTIVES: To describe and compare the profile of female sex workers (FSWs) that access or do not access sexual health checkups (SHC). The research question was what are the factors linked to access to SHC for FSWs in the metropolitan region (RM) of Chile? METHODS: A cross-sectional study was conducted in the RM with FSWs over the age of 18. A sample of 370 FSWs was selected by using the time-location sampling method in closed venues and at street-level locations. A survey was applied, validated, and included clinical-epidemiological, behavioral and socio-demographic variables. RESULTS: 38.6% (n = 140) of FSWs that answered the question never used SHC and 37.6% (n = 84) received checkups in a specialized health center for FSWs. FSWs with no SHC were younger, prone to have more group sex, preferably with occasional or no stable partner, and did not know where to get an HIV test. CONCLUSIONS: FSWs have had uncertain access to sexual health controls. FSWs with no SHC and young FSWs presented higher-risk behaviors.

Undiagnosed HIV and Hepatitis C infection in people who inject drugs: From new evidence to better practice.

BACKGROUND: The objective of this study was to estimate the proportion of undiagnosed HIV or Hepatitis C virus (HCV) infection and to assess the risk factors associated with an undiagnosed infection. METHODS: A questionnaire was distributed among people who inject drugs (PWID) in harm reduction centres in Catalonia, Spain 2008-2012 (n=2243). Self-report of HIV and HCV was compared to oral fluid tests to calculate the proportion of undiagnosed infection. Associations of undiagnosed HIV and HCV with age, origin, risk and protective factors of infection and services use were calculated using a Poisson regression model with robust variance. RESULTS: The sensitivity of HIV self-report was 78.5% (75.2%-81.5%) and of HCV was 81.2% (79.1%-83.2%), being lower in younger and foreign-born PWID. Specificity for HCV was 55.9% (51.6%-60.1%). PWID who engaged in infection risk behaviors had lower risk of being undiagnosed. Being foreign-born and younger increased the risk of undiagnosed infection. PWID who had not accessed medical care in the last 6months had 1.46 (1.10-1.93) times more risk of undiagnosed HIV and 1.37 (1.11-1.70) times more risk of undiagnosed HCV. CONCLUSION: Outreach programmes are essential to provide PWID, specially foreign-born and younger PIWD, access to HIV and HCV test.

Level of impact on the public health of universal human immunodeficiency virus screening in an Emergency Department. / Estudio del impacto a nivel de salud pública del cribado universal del virus de la inmunodeficiencia humana en un servicio de Urgencias.

INTRODUCTION: The aim of this study was to determine the prevalence of HIV and the acceptability of rapid testing in an emergency department (ED), Barcelona (6/07/2011 to 8/03/2013). METHOD: A convenience sample was used, depending on nurse availability in the ED. Participants signed an informed consent. Results were confirmed by conventional methods. RESULT: A total of 2,140 individuals were offered testing, and 5% rejected taking part (107/2,140). Three subjects (3/2,033 [0.15%]) had confirmed reactive test. Individuals with a higher education were more likely to perform a rapid HIV test in ED (P<.005). CONCLUSION: A low prevalence of new HIV diagnoses was found among participants, although there was a high acceptability rate to perform rapid testing in the ED.

Heterogeneity of community-based voluntary, counselling and testing services for HIV in Europe: the HIV-COBATEST survey.

This study reports the first EU-wide survey of community-based voluntary counselling and testing services (CBVCTs), with the following aims: to assess the current availability of CBVCTs and how the concept of CBVCT is understood; to describe CBVCT modalities and strategies; and to measure the use of rapid tests within CBVCTs. A cross-sectional survey was conducted in two different key informant groups: HIV/AIDS National Focal Points (NFPs) and CBVCTs from the EU and European Free Trade Association (EFTA) countries. A definition of CBVCTs was reached. Descriptive and correspondence analyses were performed. The COBATEST survey was answered by NFPs from 25 of the 32 EU/EFTA countries (response rate of 78.1%), and by 55 CBVCTs in 22 different countries. CBVCTs were functioning in nearly all the responding countries, but only 56% explicitly included them in their national strategic plans. In those that had CBVCTs, the NFPs often lacked reliable information on CBVCTs. In general, CBVCTs in Europe are focused mainly on men who have sex with men, are primarily peer-driven and highly communitarised, whereas CBVCTs targeting other at-risk populations are more medicalised. In addition, the oral test is under-used and in general test performance is highly medicalised. Results show that there is a wide heterogeneity of CBVCTs in Europe, which is varied and highly medicalised. The data provided in this study in conjunction with other deliverables produced by the COBATEST project should contribute to the development of standardised indicators to enable comparisons over time and eventually improve the effectiveness of CBVCTs across Europe.

Economic evaluation of HIV testing for men who have sex with men in community-based organizations - results from six European cities.

The non-decreasing incidence of HIV among men who have sex with men (MSM) has motivated the emergence of Community Based Voluntary Counselling and Testing (CBVCT) services specifically addressed to MSM. The CBVCT services are characterized by facilitated access and linkage to care, a staff largely constituted by voluntary peers, and private not-for-profit structures outside the formal health system institutions. Encouraging results have been measured about their effectiveness, but these favourable results may have been obtained at high costs, questioning the opportunity to expand the experience. We performed an economic evaluation of HIV testing for MSM at CBVCT services, and compared them across six European cities. We collected retrospective data for six CBVCT services from six cities (Copenhagen, Paris, Lyon, Athens, Lisbon, and Ljubljana), for the year 2014, on the number of HIV tests and HIV reactive tests, and on all expenditures to perform the testing activities. The total costs of CBVCTs varied from 54,390€ per year (Ljubljana) to 245,803€ per year (Athens). The cost per HIV test varied from to 41€ (Athens) to 113€ (Ljubljana). The cost per HIV reactive test varied from 1966€ (Athens) to 9065€ (Ljubljana). Our results show that the benefits of CBVCT services are obtained at an acceptable cost, in comparison with the literature (values, mostly from the USA, range from 1600$ to 16,985$ per HIV reactive test in clinical and non-clinical settings). This result was transversal to several European cities, highlighting that there is a common CBVCT model, the cost of which is comparable regardless of the epidemiological context and prices. The CBVCT services represent an effective and "worth it" experience, to be continued and expanded in future public health strategies towards HIV.

[General characteristics of the original articles included in the scoping review on health and immigration in Spain]. / Características generales de los artículos originales incluidos en las revisiones bibliográficas sobre salud e inmigración en España.

BACKGROUND: The new socio-demographic reality that came about with the incorporation of the immigrant population in Spain requires an analysis of the needs and priorities generated by this situation in all areas, including research in health. The objective of this study is to determine the general characteristics of a group of articles included in a literature review on the subject, carried out within the framework of the CIBERSP Subprogram on Migration and Health. METHODS: Scoping Review of the literature published in the period 1998-2012. Articles in Spanish or English developed in Spain and that fulfil the definition of immigrant from the International Organization for Migration were selected. The literature search was performed in Medline and MEDES. The temporal distribution of the production and main characteristics of the articles are described trough absolute and relative frequencies. RESULTS: The initial search identified 2.625 articles (Medline 2434; 191 Medes-MEDicina) 311 were including finally. Most epidemiological studies are cross-sectional design with primary data. 69% compared with native population. The main theme has been associated with infectious diseases (n=217, 70%). The period of maximum production is between 2004 and 2011(n=256, 82%). The country of origin is the most common way of classifying immigrants (n=220, 71%). CONCLUSIONS: The epidemiology of infectious prevails as the main theme of the studies performed in Spain about the health of the immigrant population. Most of the studies include native population as a comparison group.

[Partner notification in sexually transmitted infections. A neglected activity?]. / Estudios de contactos para infecciones de transmisión sexual. ¿Una actividad descuidada?

OBJECTIVES: To undertake a critical literature review of published evidence on the effectiveness of contact tracing in sexually transmitted infections, mechanisms of referral, and the criteria for initiating this activity. To describe how these factors vary by causative agent and to characterize the current state of contact tracing in sexually transmitted infections in developed countries. METHODS: A systematic literature review was undertaken using online databases and scientific publications, as well as guidelines and documents pertaining to the legal framework within which contact tracing takes place. RESULTS: Contact tracing is specifically recommended for infections caused by Neisseria gonorrhoeae, Chlamydia trachomatis, syphilis and HIV. The principal approaches to contact tracing reported were patient referral, provider referral or conditional patient referral. In addition, patient-dispensed partner treatment and the use of new technologies were reported. Numerous studies have evaluated the efficacy, effectiveness and social and legal context of contact tracing in different countries and populations. This situation contrasts with that in Spain, where there is a notable absence of guidelines, legal framework and formal studies dealing with contact tracing in sexually transmitted infections. CONCLUSIONS: Contact tracing is an increasingly important tool in the public health management of sexually transmitted infections and should be valued as such. This activity should be an integral and effective component of the control and prevention of sexually transmitted infection programmes in all autonomous regions in Spain. Research in this field is required to develop the legal framework and practice guidelines appropriate to the local context.

The potential contribution of small-scale intervention projects in the field to the national health information system for HIV and sexually transmitted infections: a case study of a multilevel intervention in Guatemala.

OBJECTIVE: Guatemala's efforts to fight sexually transmitted infections and HIV/AIDS are compromised by the lack of timely and accurate data. The strengthening of the national Monitoring and Evaluation system is key for a better understanding of the epidemics and the formulation of effective public health responses. This study assessed how health service providers in resource-poor countries can contribute indicators to national health authorities. METHODS: Review of data sources produced by projects of a NGO harmonizing the identified indicators with national and international standards. During a field visit, they were validated with key stakeholders. RESULTS: Study results are 19 original and 13 harmonized indicators. CONCLUSIONS: Findings suggest that small-scale projects can contribute to the strengthening of national health information systems.

[Diagnostic resources for sexually transmitted infections in laboratories in Catalonia (Spain)]. / Recursos diagnósticos para las infecciones de transmisión sexual en los laboratorios de Cataluña (España).

OBJECTIVE: With the aim of describing both the capacity and organization of the laboratories in Catalonia to diagnose sexually transmitted infections, a cross-sectional study was performed between November 2005 and March 2006, which included 140 laboratories. RESULTS: Ninety-eight laboratories performed some STI tests, 45 received more than 50 vaginal swabs per month, 42 diagnosed Chlamydia trachomatis, but only six used polymerase chain reaction techniques. None diagnosed venereal lymphogranuloma. Eighty were able to detect Neisseria gonorrhoeae, 76 by means of culture and 63 analyzed its antibiotic resistance. A total of 23, 22, 22 and 14 laboratories received more than 500 blood samples for hepatitis B, hepatitis C, HIV and syphilis, respectively. Non-treponemic and treponemic tests were available in 84 and 52 laboratories, respectively. CONCLUSIONS: In Catalonia, most STIs can be diagnosed but new technologies need to be introduced. Moreover, the efficiency of biological sample circuits should be improved.

Determinants of HIV progression and assessment of the optimal time to initiate highly active antiretroviral therapy: PISCIS Cohort (Spain).

OBJECTIVE: We analyze the factors related to progression to AIDS or death in HIV-infected patients from the Proyecto para la Informatización del Seguimiento Clínico epidemiológico de los pacientes con Infección por VIH/SIDA (PISCIS) Cohort and we assess the optimal time to initiate highly active antiretroviral therapy (HAART) taking lead time into account. METHODS: We selected naive patients who were AIDS-free and initiated HAART after January 1998. Statistical analyses were performed using Cox proportional hazards models. Lead time was defined as the time it took the deferred group with an early disease stage to reach the later stage. The analysis accounting for lead time was performed using multiple imputation methods based on estimates from the pre-HAART period as described elsewhere. RESULTS: Multivariate analysis on 2035 patients (median follow-up = 34.3 months) showed significantly higher hazard ratios (HRs) for a CD4 count <200 cells/microL (HR = 3.79, 95% confidence interval [CI]: 2.18 to 6.57), HIV-1 RNA level >100,000 copies/mL (HR = 1.84, 95% CI: 1.26 to 2.69), and hepatitis C virus (HCV) coinfection (HR = 2.40, 95% CI: 1.65 to 3.49), whereas a lower risk was found for those who started HAART between January 2001 and June 2004 (HR = 0.55, 95% CI: 0.30 to 0.90). When lead time and unseen events were included, we found a higher risk of progression to AIDS among patients who deferred treatment when the CD4 count reached <200 cells/microL (HR = 2.97, 95% CI: 1.91 to 4.63) and 200 to 350 cells/microL (HR = 1.85, 95% CI: 1.03 to 3.33) compared with those who started treatment with CD4 counts from 200 to 350 cells/microL and >350 cells/microL, respectively. CONCLUSIONS: Advanced HIV disease, HCV coinfection, and early HAART period were determinants of AIDS progression or death. Lead-time analysis in asymptomatic HIV-infected patients suggests that the best time to start HAART is before the CD4 count falls to lower than 350 cells/microL.