The molecular epidemiology of HIV-1 in the Comunidad Valenciana (Spain): analysis of transmission clusters.

HIV infections are still a very serious concern for public heath worldwide. We have applied molecular evolution methods to study the HIV-1 epidemics in the Comunidad Valenciana (CV, Spain) from a public health surveillance perspective. For this, we analysed 1804 HIV-1 sequences comprising protease and reverse transcriptase (PR/RT) coding regions, sampled between 2004 and 2014. These sequences were subtyped and subjected to phylogenetic analyses in order to detect transmission clusters. In addition, univariate and multinomial comparisons were performed to detect epidemiological differences between HIV-1 subtypes, and risk groups. The HIV epidemic in the CV is dominated by subtype B infections among local men who have sex with men (MSM). 270 transmission clusters were identified (>57% of the dataset), 12 of which included ≥10 patients; 11 of subtype B (9 affecting MSMs) and one (n = 21) of CRF14, affecting predominately intravenous drug users (IDUs). Dated phylogenies revealed these large clusters to have originated from the mid-80s to the early 00 s. Subtype B is more likely to form transmission clusters than non-B variants and MSMs to cluster than other risk groups. Multinomial analyses revealed an association between non-B variants, which are not established in the local population yet, and different foreign groups.

Expansion of the CRF19_cpx Variant in Spain.

BACKGROUND: HIV-1 CRF19_cpx, is a recombinant variant found almost exclusively in Cuba and recently associated to a faster AIDS onset. Infection with this variant leads to higher viral loads and levels of RANTES and CXCR4 co-receptor use. OBJECTIVES: The goal of this study was to assess the presence of CRF19_cpx in the Spanish province of Valencia, given its high pathogenicity. STUDY DESIGN: 1294 HIV-1 protease-reverse transcriptase (PR/RT) sequences were obtained in Valencia (Spain), between 2005 and 2014. After subtyping, the detected CRF19_cpx sequences were aligned with 201 CRF19_cpx and 66 subtype D sequences retrieved from LANL, and subjected to maximum-likelihood phylogenetic analyses and Bayesian coalescent reconstructions. The presence of resistance mutations in the PR/RT region of these sequences was also analyzed. RESULTS: Among the 9 CRF19_cpx sequences from different patients found (prevalence <0.1%), 7 grouped in two well-supported clades (groups A, n=4, and B, n=3), suggesting the existence of at least two independent introductions which subsequently started to expand in the studied Spanish region. Unprotected sex between men was the only known transmission route. Coalescent analyses suggested that the introductions in Valencia occurred between 2008 and 2010. Resistance mutations in the RT region were found in all sequences from group A (V139D) and in two sequences from group B (E138A). CONCLUSIONS: This study reports for the first time the recent expansion of CRF19_cpx outside Cuba. Our results suggest that CRF19_cpx might become an emerging HIV variant in Spain, affecting Spanish native MSM and not only Cuban migrants.

Educational level and HIV disease progression before and after the introduction of HAART: a cohort study in 989 HIV seroconverters in Spain.

OBJECTIVES: To analyse the effect of educational level on the progression from HIV seroconversion to highly active antiretroviral therapy (HAART) requirement, HAART initiation, AIDS and death from any cause at different periods of the HIV epidemic in Spain. METHODS: Open, prospective, multicentre cohort of HIV seroconverters set up in 1983. The risk of progression was calculated by the multiple decrements method. Effect of educational level was estimated by Fine and Gray model, adjusting for sex, HIV transmission category, age and method to estimate seroconversion. Calendar period was introduced as a variable that could change over time (<1997; 1997-2003; >2003). RESULTS: Up to 2009, 989 HIV seroconverters with information on educational level were identified. Some 52% and 48% had a low and a high educational level respectively. Persons with higher education had 32% lower risk of death (HR: 0.68; 95% CI 0.45 to 1.03). Regarding progression to AIDS, educational level had no effect in the pre-HAART era (HR: 1.47; 95% CI 0.91 to 2.38), but did show an effect in the period 1997-2003 (HR: 0.58; 95% CI 0.34 to 0.99), which was accentuated after 2004 (HR: 0.26; 95% CI 0.10 to 0.68). No difference was found in time to HAART requirement or initiation. CONCLUSIONS: Results suggest that, despite similar access to HAART, persons with low educational level are at increased risk of HIV disease progression, highlighting the impact of social inequities on health. The availability of more effective treatments over time will strengthen the protective effect of higher education on the development of AIDS.

Efectividad del tratamiento antirretroviral combinado de gran actividad en eventos recurrentes de sida en una cohorte de seroconvertores al virus de la inmunodeficiencia humana / Effectiveness of combined antiretroviral therapy on multiple aids-defining illnesses in an hiv seroconverter cohort

Introducción La efectividad del tratamiento antirretroviral de gran actividad (TARGA) en la reducción del tiempo al primer evento definitorio de sida ha sido demostrada por diversos estudios observacionales, pero el efecto en eventos recurrentes de sida no es tan evidente. Material y métodos Se dispone de 1.938 sujetos seroconvertores al VIH de la cohorte GEMES. Se ha utilizado una extensión del modelo de Cox para analizar el tiempo desde la seroconversión a cada evento sida, que tiene en cuenta el tiempo entre sucesivos eventos y que permite que el riesgo de referencia cambie con el número de paciente con sida previos. El calendario se dividió en tres períodos coincidiendo con la disponibilidad de diferentes regímenes de terapia antirretroviral. Resultados Durante el seguimiento 1.524 (78,6%), 259(13,4%), 83 (4,3%) y 72 (3,7%) sujetos desarrollaron 0, 1, 2 y 3 o más eventos definitorios de sida, respectivamente. Después de ajustar por sexo, edad a la seroconversión y categoría de exposición, el riesgo de sida para el período TARGA fue RR=0,38 (IC del 95%, 0,30-0,48) en comparación con el período 1992–1995.Teniendo en cuenta el número de sujetos con sida previos, se observó un RR de 0,40 (IC del95%, 0,32-0,50) para el primer evento sida, RR=0,27 (IC del 95%, 0,15-0,50) para el segundo y 0,41 (IC del 95%, 0,18-0,96) para el tercero. Considerando todos los eventos de sida, se obtiene un riesgo RR=0,32 (IC del 95%, 0,125-0,40). Los usuarios de drogas por vía parenteral tienen un riesgo mayor de desarrollar un primer episodio de sida que los homosexuales, RR=2,14 (IC del 95%, 1,48-3,10).Conclusiones Los resultados obtenidos muestran un efecto protector de la terapia al primer sida, manteniéndose el efecto para posteriores eventos. La inclusión en el análisis de todos los eventos recurrentes de sida permite obtener estimaciones del riesgo más precisas (AU)

Introduction: Several observational studies support the protective effect of combined antiretroviral therapy (cART) on time to first AIDS-defining event, but the effect on multiple AIDS defining illnesses remains unclear. The aim of this study is to analyse whether the protective effect of cART persists beyond the first AIDS-defining illness. Material and methods: A total of 1938 subjects from GEMES seroconverter cohort have been included. Toanalyse cART effectiveness, calendar time has been divided into three periods according to antiretroviral availability. A population-averaged proportional hazard model with staggered entries that counted the gap time, and had event-specific baseline risks, was fitted. Results: During follow-up, 1524 (78.6%), 259 (13.4%), 83 (4.3%) and 72 (3.7%) subjects incurred 0, 1, 2,and 3 or more AIDS-defining illnesses, respectively. After adjustment for sex, age at seroconversion and exposure category, the Relative Risk (RR) of AIDS in the cART period was 0.38 (95%CI 0.30-0.48) compared with the 1992-95 period. The RR of the first, second and third AIDS-defining illness in the cART period were0.40 (95% CI: 0.32-0.50), 0.27 (95% CI: 0.15-0.50) and 0.41 (95% CI: 0.18-0.96) respectively, relative to the reference calendar period when we allowed the odds ratios to vary by the number of prior AIDS-defining events. The relative risk of AIDS, taking all events into account, was 0.32 (95% CI: 0.25-0.40). Intravenous drug users have a higher risk of developing a first episode of AIDS than homosexuals, RR: 2.14 (95% CI:1.48-3.10).Conclusions: Results indicate that the relative effect of cART appears to be both protective and stable over multiple AIDS-defining illnesses. Analysis of multiple AIDS-defining illnesses improves the precision of the estimated relative risk (AU)

[Effectiveness of combined antiretroviral therapy on multiple AIDS-defining illnesses in an HIV seroconverter cohort]. / Efectividad del tratamiento antirretroviral combinado de gran actividad en eventos recurrentes de sida en una cohorte de seroconvertores al virus de la inmunodeficiencia humana.

INTRODUCTION: Several observational studies support the protective effect of combined antiretroviral therapy (cART) on time to first AIDS-defining event, but the effect on multiple AIDS defining illnesses remains unclear.The aim of this study is to analyse whether the protective effect of cART persists beyond the first AIDS-defining illness. MATERIAL AND METHODS: A total of 1938 subjects from GEMES seroconverter cohort have been included. To analyse cART effectiveness, calendar time has been divided into three periods according to antiretroviral availability. A population-averaged proportional hazard model with staggered entries that counted the gap time, and had event-specific baseline risks, was fitted. RESULTS: During follow-up, 1524 (78.6%), 259 (13.4%), 83 (4.3%) and 72 (3.7%) subjects incurred 0, 1, 2, and 3 or more AIDS-defining illnesses, respectively. After adjustment for sex, age at seroconversion and exposure category, the Relative Risk (RR) of AIDS in the cART period was 0.38 (95%CI 0.30-0.48) compared with the 1992-95 period. The RR of the first, second and third AIDS-defining illness in the cART period were 0.40 (95% CI: 0.32-0.50), 0.27 (95% CI: 0.15-0.50) and 0.41 (95% CI: 0.18-0.96) respectively, relative to the reference calendar period when we allowed the odds ratios to vary by the number of prior AIDS-defining events. The relative risk of AIDS, taking all events into account, was 0.32 (95% CI: 0.25-0.40). Intravenous drug users have a higher risk of developing a first episode of AIDS than homosexuals, RR: 2.14 (95% CI: 1.48-3.10). CONCLUSIONS: Results indicate that the relative effect of cART appears to be both protective and stable over multiple AIDS-defining illnesses. Analysis of multiple AIDS-defining illnesses improves the precision of the estimated relative risk.

Prevalence and risk factors of high-risk human papillomavirus in female sex workers in Spain: differences by geographical origin.

OBJECTIVE: To study the influence of socioeconomic variables, lifestyles, and sexual behaviors on the prevalence of high-risk human papillomavirus (HR-HPV) infection in female sex worker (FSW) according to their geographic origin in Alicante, Spain. METHODS: This is a cross-sectional study of 549 FSW attending an AIDS information and prevention center from May 2003 to December 2004. Face-to-face interviews were carried out. HR-HPV was determined through Digene HR-HPV Test. Hybrid Capture II-positive samples (Digene Corp., Gaithersburg, MD) for PCR were directly sequenced. Data were analyzed using multiple logistic regression. RESULTS: HR-HPV prevalence was 28% in Spaniards, 32% in Latin Americans, 32% in Eastern Europeans, 16% in sub-Saharan Africans, and 65% in North Africans (p=0.04). Lower HR-HPV prevalence was associated with higher age, higher education, and higher body mass index (BMI) (p values for trend<0.05). In multivariate analyses, the effects of geographical origin, age, and education were maintained, together with time in sex work; women engaged for >1 year had a lower HR-HPV prevalence (OR 0.57, 95% CI 0.36-0.91) compared with those engaged <1 year. HR-HPV-16 was the most common type (n=23, 24%), followed by HR-HPV-18 and HR-HPV-31, (n=11, 11%), respectively. CONCLUSIONS: HR-HPV prevalence is very high in FSW and varies by geographic origin. Women of younger age and lower education level and those engaged in sex work for <1 year showed the highest prevalence, making them a priority group for cervical cancer prevention programs.

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.

Prevalencia de infecciones crónicas ocultas en una cohorte de pacientes en tratamiento sustitutivo con metadona / Prevalence of chronic hidden infections in a cohort of patients in sustitutive treatment with methadone

FUNDAMENTO: Analizar la prevalencia de infección oculta por los virus de la hepatis B (VHB) y C (VHC), de la inmunodeficiencia humana (VIH) e infección tuberculosa en usuarios de drogas en tratamiento sustitutivo con metadona (TSM). PACIENTES Y MÉTODO: Se realizó serología VHB, VHC, VIH y prueba de Mantoux a 189 usuarios de drogas. Se recogieron antecedentes de drogadicción y vía de consumo. RESULTADOS: Los datos de la prevalencia observada fueron: VIH, 29,2 por ciento; VHC, 75,9 por ciento; infección tuberculosa, 59,3 por ciento. La vía parenteral, una inclusión tardía en el TSM y un inicio temprano en el consumo de heroína se asociaron a infección por el VIH y VHC. CONCLUSIONES: Existe una alta prevalencia de infección tuberculosa y VHC en usuarios de drogas. Un acceso temprano al TSM podría disminuir esta prevalencia (AU)