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INTRODUCTION: Chronic low-grade inflammation and immune activation may persist in HIV patients despite effective antiretroviral therapy (ART). These abnormalities are associated with increased oxidative stress (OS). Bilirubin (BR) may have a beneficial role in counteracting OS. Atazanavir (ATV) inhibits UGT1A1, thus increasing unconjugated BR levels, a distinctive feature of this drug. We compared changes in OS markers in HIV patients on ATV/r versus efavirenz (EFV)-based first-line therapies. MATERIALS AND METHODS: Cohort of the Spanish Research Network (CoRIS) is a multicentre, open, prospective cohort of HIV-infected patients naïve to ART at entry and linked to a biobank. We identified hepatitis C virus/hepatitis B virus (HCV/HBV) negative patients who started first-line ART with either ATV/r or EFV, had a baseline biobank sample and a follow-up sample after at least nine months of ART while maintaining initial regimen and being virologically suppressed. Lipoprotein-associated Phospholipase A2 (Lp-PLA2), Myeloperoxidase (MPO) and Oxidized LDL (OxLDL) were measured in paired samples. Marker values at one year were interpolated from available data. Multiple imputations using chained equations were used to deal with missing values. Change in the OS markers was modelled using multiple linear regressions adjusting for baseline marker values and baseline confounders. Correlations between continuous variables were explored using Pearson's correlation tests. RESULTS: 145 patients (97 EFV; 48 ATV/r) were studied. Mean (SD) baseline values for OS markers in EFV and ATV/r groups were: Lp-PLA2 [142.2 (72.8) and 150.1 (92.8) ng/mL], MPO [74.3 (48.2) and 93.9 (64.3) µg/L] and OxLDL [76.3 (52.3) and 82.2 (54.4) µg/L]. After adjustment for baseline variables patients on ATV/r had a significant decrease in Lp-PLA2 (estimated difference -16.3 [CI 95%: -31.4, -1.25; p=0.03]) and a significantly lower increase in OxLDL (estimated difference -21.8 [-38.0, -5.6; p<0.01] relative to those on EFV, whereas no differences in MPO were found. Adjusted changes in BR were significantly higher for the ATV/r group (estimated difference 1.33 [1.03, 1.52; p<0.01]). Changes in BR and changes in OS markers were significantly correlated. CONCLUSIONS: In virologically suppressed patients on stable ART, OS was lower in ATV/r-based regimens compared to EFV. We hypothesize these changes could be in part attributable to increased BR plasma levels.
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INTRODUCTION: Emerging non-AIDS related causes of death have been observed in HIV-positive subjects in industrialized countries. We aimed to analyze overall and cause-specific excess of mortality of HIV-positive patients compared to the general population and to assess the effect of prognostic factors. MATERIAL AND METHODS: We used generalized linear models with Poisson error structure to estimate overall and cause-specific excess of mortality in HIV-positive patients from 2004 to 2012 in the cohort of the Spanish Network of HIV Research (CoRIS), compared to Spanish general population and to assess the impact of multiple risk factors. We investigated differences between short-term and long-term risk factors effects on excess of mortality. Multiple Imputation by Chained Equations was used to deal with missing data. RESULTS: In 9162 patients there were 363 deaths, 16.0% were non-AIDS malignancies, 10.5% liver and 0.3% cardiovascular related. Excess mortality was 1.20 deaths per 100 person years (py) for all-cause mortality, 0.16 for liver, 0.10 for non-AIDS malignancies and 0.03 for cardiovascular. Short-term (first-year follow-up) excess Hazard Ratio (eHR) for global mortality for baseline AIDS was 4.27 (95% CI 3.06-6.01) and 1.47 (95% CI 0.95-2.27) for HCV coinfection; long-term (subsequent follow-up) eHR for baseline AIDS was 0.88 (95% CI 0.58-1.35) and 4.48 (95% CI 2.71-7.42) for HCV coinfection. Lower CD4 count and higher viral load at entry, lower education, being male and over 50 years were predictors for overall excess mortality. Excess of liver mortality was higher in patients with CD4 counts at entry below 200 cells compared to those above 350 (eHR: 6.49, 95% CI 1.21-34.84) and in HCV-coinfected patients (eHR: 3.85, 95% CI 0.85- 17.37), although it was borderline significant. Patients over 50 years old (eHR: 5.55, 95%CI 2.4-12.85) and HCV coinfected (eHR: 5.81, 95% CI 2.6-13) showed a higher risk of non-AIDS malignancies mortality excess. Excess of cardiovascular mortality was related with HCV coinfection (eHR: 6.68, 95% CI 1.25-35.73). CONCLUSIONS: Our results show overall, liver, non-AIDS malignancies and cardiovascular excess of mortality associated with being HIV-positive, despite improvements in HIV disease management and antiretroviral therapies. Differential short-term and long-term effect of AIDS before entry and HCV coinfection was found for overall mortality.
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BACKGROUND: The wide use of lamivudine (3TC) as oral therapy for chronic HBV infection has favoured the selection and circulation of 3TC-resistant HBV strains worldwide. Although transmission of 3TC-resistant HBV variants has been reported only sporadically, few studies have been conducted in the HIV population where exposure to 3TC has been greater forming part of antiretroviral therapy (ART) regimens. METHODS: All individuals positive for serum hepatitis B surface antigen (HBsAg), newly diagnosed with HIV-1 infection, naive to ART and enrolled in the Spanish HIV cohort (CoRIS) since 2004 were identified. The HBV polymerase gene was sequenced and drug resistance mutations were characterized retrospectively in stored frozen plasma specimens. RESULTS: From 4,419 ART-naive HIV-1-infected individuals, 223 (5.1%) were positive for serum HBsAg. Baseline stored sera were available for 84 patients, of whom 73 could be characterized virologically. This population was mainly represented by men who had sex with men (52.1%), native Spaniards (65.7%) and Latin Americans (16.4%). The mean age was 36 years, mean CD4(+) T-cell count 375 cells/mm(3) and mean plasma HIV RNA 4.5 log(10) copies/ml. The HBV genotype distribution was 64% A, 20% F, 12% D and 4% others. Drug-resistant mutations in the HBV polymerase were found in four (5.5%) patients: two harboured rtL180M, one rtL80V and one rtV173L. CONCLUSIONS: The rate of primary drug resistance in HBV among newly diagnosed HIV-HBV-coinfected patients in Spain is currently low (5.5%) and restricted to 3TC. Thus, HBV drug resistance testing before prescription of oral antiviral therapy is not warranted, although periodic surveillance might be recommended.
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Farmacorresistencia Viral/genética , Infecciones por VIH/complicaciones , Virus de la Hepatitis B/efectos de los fármacos , Hepatitis B/complicaciones , Lamivudine/farmacología , Inhibidores de la Transcriptasa Inversa/farmacología , Adulto , Estudios de Cohortes , Femenino , Productos del Gen pol/genética , Infecciones por VIH/diagnóstico , Infecciones por VIH/virología , Hepatitis B/diagnóstico , Hepatitis B/virología , Antígenos de Superficie de la Hepatitis B/sangre , Virus de la Hepatitis B/enzimología , Virus de la Hepatitis B/genética , Humanos , Masculino , EspañaRESUMEN
We aimed to evaluate immunological, virological and clinical response to HAART, as well as all-cause mortality, in treatment-naive patients with a diagnosis of tuberculosis (TB) in the prior 6 months, compared to subjects with another AIDS-defining illness (ADI) or event-free individuals in an open, prospective and multicenter hospital-based cohort of HIV-infected naive adults (2004-2008). All cause mortality rates were calculated by Cox regression models. Among 4407 patients, 2400 (54.5%) started HAART: 110 (4.6%) had had previous TB and 414 (17.3%) another ADI. Median time from TB diagnosis to inititation of HAART was 53 days (IQR: 25.75-83.25), and for other ADI was 22 days (IQR: 8-42). Overall, 151 (6.3%) patients developed a new ADI during follow-up; 63% reached virological suppression and 69.4% had increases of ≥50 CD4+/µl, at 6 months. No statistically significant differences were found according to a previous history of TB or another ADI. Overall, 85 subjects died in 4031 person-years of follow-up with a mortality rate of 2.1 (95%CI: 1.7-2.6). When compared to subjects who started HAART in the absence of a previous ADI (HR 1), a prior diagnosis of an ADI other than TB was significantly associated with an increased risk of death. (HR 1.6; 95%CI: 1.1-2.3), but not a diagnosis of TB (HR 1.15; 95%CI: 0.5-2.5). In conclusion, a previous diagnosis of TB or another ADI before HAART did not compromise short-term virological and immunological response to treatment. A prior diagnosis of an ADI different to TB significantly increased all cause mortality.
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Infecciones Oportunistas Relacionadas con el SIDA/diagnóstico , Terapia Antirretroviral Altamente Activa , Infecciones por VIH/tratamiento farmacológico , Tuberculosis Pulmonar/diagnóstico , Infecciones Oportunistas Relacionadas con el SIDA/inmunología , Infecciones Oportunistas Relacionadas con el SIDA/mortalidad , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Recuento de Linfocito CD4 , Estudios de Cohortes , Femenino , Infecciones por VIH/inmunología , Infecciones por VIH/mortalidad , Infecciones por VIH/virología , Humanos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Tuberculosis Pulmonar/inmunología , Tuberculosis Pulmonar/mortalidad , Carga Viral , Adulto JovenRESUMEN
Introducción En España, la proporción de inmigrantes en los servicios clínicos de infección por virus de la inmunodeficiencia humana (VIH) es creciente. El objetivo del presente artículo es describir las características sociodemográficas, epidemiológicas y clínicas de una cohorte de personas con infección por VIH de la Red de Investigación en Sida (CoRIS) según su lugar de origen. Métodos CoRIS es una cohorte abierta, prospectiva y multicéntrica de adultos con infección por VIH sin tratamiento antirretrovírico previo, que se atendieron en 19 hospitales de 9 Comunidades Autónomas españolas entre enero de 2004 y octubre de 2006. Se describen las características por región de origen y se comparan con los casos españoles Resultados Se incluyeron 2.507 pacientes: el 76,3% fueron varones, con una mediana de edad de 36 años. Por el lugar de origen, el 71,5% fueron españoles; el 16,0% fueron latinoamericanos; el 5,8% fueron de África Subsahariana; el 3,7% fueron de Europa occidental; el 1,7% fueron de Europa del este, y el 1,4% fueron de África del norte. En comparación con los españoles, hubo diferencias significativas en sexo, edad y categoría de transmisión. La mediana de linfocitos CD4 al ingreso a la cohorte fue de 352×106/l, sin que hubiera diferencias según el origen. La mediana de carga vírica fue de 48,962 copias/ml, significativamente menor en el grupo de África subsahariana. Tras 11,4 meses de seguimiento, el 57,9% había iniciado tratamiento, sin que hubiera diferencias por origen. La prevalencia de coinfección con hepatitis C fue del 29,9% en españoles, del 7,3% en latinoamericanos, del 11,7% en los sujetos de África subsahariana y del 45,7% en los sujetos de Europa del este (p-60;0,05). El 13,4% tuvo prueba de tuberculina positiva; el 28,6% en los sujetos del África subsahariana y el 30,8% en los sujetos de África del norte. La tuberculosis fue más frecuente entre los sujetos de Europa del este (9,5%) y del África subsahariana (8,3%) que en españoles (4,8%) (p-60;0,05). Conclusiones Casi un tercio de las personas con infección por VIH que se atendieron recientemente en España fueron extranjeros. Sus características sociodemográficas, epidemiológicas y clínicas reflejan la epidemia en sus lugares de origen. Sin embargo, su situación inmunológica cuando acceden al hospital y en el inicio del tratamiento no difiere de la de los pacientes españoles (AU)
Introduction A growing number of immigrants are using the public health services for HIV in Spain. We describe the sociodemographic, epidemiological, and clinical characteristics of a cohort of naïve HIV-infected subjects (CoRIS cohort) according to their place of origin. Methods CoRIS is an open, hospital-based cohort of naïve, HIV-infected persons attended in 19 hospitals from 9 of the 19 autonomous regions in Spain. We describe the characteristics of the cohort members by place of origin, and compare them with the Spanish cases identified from January 2004 to October 2006, using the chi-square and Fisher exact tests. Results Of 2507 patients, 76.3% were men and median age was 36 years. By origin, 71.5% were Spanish, 16.0% Latin Americans (LA), 5.8% sub-Saharan Africans (SSA), 3.7% Western Europeans (WE), 1.7% Eastern Europeans (EE) and 1.4% North Africans (NA). Compared to Spaniards, there were significant differences by origin in sex, age, and transmission category. Median CD4 count at cohort entry was 352 cell/μL, with no differences according to origin. Median viral load was 48 962 copies/mL and was significantly lower for SSA. Over 11.4 months of follow-up, 57.9% initiated HAART with no differences by origin. Hepatitis C prevalence was 29.9% in Spaniards, 7.3% in Latin Americans, 11.7% in SSA, and 45.7% in EE (P-60;0.05). Overall, 13.4% were Mantoux-positive (28.6% in SSA and 30.8% in NA). Tuberculosis was more common among cases from EE (9.5%) and SSA (8.3%) compared to Spaniards (4.8%) (P-60;0.05).ConclusionsAlmost one third of naïve HIV-infected patients in CoRIS are foreign-born. Their sociodemographic, epidemiological and clinical characteristics reflect the epidemic in their places of origin. However, their immunological status at cohort entry and initiation of HAART is no different from that of Spaniards(AU)
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Humanos , Infecciones por VIH/epidemiología , VIH/patogenicidad , Serodiagnóstico del SIDA , Seroprevalencia de VIH/tendencias , Seropositividad para VIH/epidemiología , Emigrantes e Inmigrantes/estadística & datos numéricos , España/epidemiología , Etnicidad , Estudios ProspectivosRESUMEN
INTRODUCTION: A growing number of immigrants are using the public health services for HIV in Spain. We describe the sociodemographic, epidemiological, and clinical characteristics of a cohort of naïve HIV-infected subjects (CoRIS cohort) according to their place of origin. METHODS: CoRIS is an open, hospital-based cohort of naïve, HIV-infected persons attended in 19 hospitals from 9 of the 19 autonomous regions in Spain. We describe the characteristics of the cohort members by place of origin, and compare them with the Spanish cases identified from January 2004 to October 2006, using the chi-square and Fisher exact tests. RESULTS: Of 2507 patients, 76.3% were men and median age was 36 years. By origin, 71.5% were Spanish, 16.0% Latin Americans (LA), 5.8% sub-Saharan Africans (SSA), 3.7% Western Europeans (WE), 1.7% Eastern Europeans (EE) and 1.4% North Africans (NA). Compared to Spaniards, there were significant differences by origin in sex, age, and transmission category. Median CD4 count at cohort entry was 352 cell/microL, with no differences according to origin. Median viral load was 48 962 copies/mL and was significantly lower for SSA. Over 11.4 months of follow-up, 57.9% initiated HAART with no differences by origin. Hepatitis C prevalence was 29.9% in Spaniards, 7.3% in Latin Americans, 11.7% in SSA, and 45.7% in EE (P<0.05). Overall, 13.4% were Mantoux-positive (28.6% in SSA and 30.8% in NA). Tuberculosis was more common among cases from EE (9.5%) and SSA (8.3%) compared to Spaniards (4.8%) (P<0.05). CONCLUSIONS: Almost one third of naïve HIV-infected patients in CoRIS are foreign-born. Their sociodemographic, epidemiological and clinical characteristics reflect the epidemic in their places of origin. However, their immunological status at cohort entry and initiation of HAART is no different from that of Spaniards.
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Emigrantes e Inmigrantes/estadística & datos numéricos , Infecciones por VIH/epidemiología , Infecciones Oportunistas Relacionadas con el SIDA/epidemiología , Adolescente , Adulto , África del Sur del Sahara/etnología , Anciano , Anciano de 80 o más Años , Recuento de Linfocito CD4 , Estudios de Cohortes , Comorbilidad , Europa (Continente)/etnología , Femenino , Estudios de Seguimiento , Infecciones por VIH/transmisión , Hepatitis B/epidemiología , Hepatitis C/epidemiología , Histoplasmosis/epidemiología , Humanos , América Latina/etnología , Masculino , Persona de Mediana Edad , América del Norte/etnología , Factores de Riesgo , España/epidemiología , Tuberculosis/epidemiología , Carga Viral , Adulto JovenRESUMEN
OBJECTIVE: To assess the repercussion of late diagnosis of HIV infection on AIDS incidence in the era of highly active antiretroviral therapy. DESIGN: Analysis of AIDS surveillance data. SETTING: Spain. PATIENTS: AIDS cases reported from 1994 though 2000. MAIN OUTCOME MEASURES: Late testers were defined as persons who had a first positive HIV test in the month of or immediately preceding AIDS diagnosis. Their incidence trend was compared against that for the remaining cases, and the influence of demographic factors evaluated. RESULTS: Of 30 778 AIDS cases, 8499 (28%) were late testers, and of these, 1061 (12%) died within 3 months of diagnosis of HIV infection. From 1995 to 2000, AIDS diagnoses declined by 36% among late testers versus 67% for the remainder (P < 0.001). The percentage of late testers increased from 24% in 1994-1996 to 35% in 1998-2000 (P < 0.001). Among the 7825 AIDS cases diagnosed in 1998-2000, late testing was independently associated (P < 0.01) with male sex, age over 44 years, residence in provinces with a lower AIDS incidence, foreign origin, and no record of injecting drug use or prison stay. CONCLUSIONS: A growing proportion of AIDS cases involves late diagnosis of HIV infection. Persons who are unaware of their HIV infection cannot benefit from antiretroviral therapy and, hence, early diagnosis would strengthen the impact of such therapy and so reduce AIDS incidence.
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Síndrome de Inmunodeficiencia Adquirida/diagnóstico , Terapia Antirretroviral Altamente Activa/tendencias , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida/epidemiología , Síndrome de Inmunodeficiencia Adquirida/psicología , Adulto , Terapia Antirretroviral Altamente Activa/psicología , Actitud Frente a la Salud , Femenino , Humanos , Incidencia , Masculino , Factores de TiempoRESUMEN
OBJECTIVES: To describe exposure categories and HIV prevalence among subjects voluntarily tested in Spain by country of origin. METHODS: HIV prevalence and exposure categories were compared between national and non-Spanish subjects voluntarily tested in 18 sexually transmitted disease/HIV testing clinics from 16 Spanish cities in 2000. RESULTS: Of 8861 testers, 2810 (31.7%) came from foreign countries; 73.1% from Latin America, 9.1% from western Europe, 6.2% from central/eastern Europe, 4.4% from northern Africa, and 4.2% from sub-Sahara Africa. Among women from Latin America, 78% were sex workers compared to 5.5% Spanish women. HIV infection was diagnosed in 170 persons, 34.7% from foreign countries. HIV prevalence for Spanish subjects (23% for men and 1.0% for women) was significantly different from men and women from Latin America (11.3% and 0.3% respectively), Sub-Saharan Africa (9.1% and 7.5% respectively), and women from the north of Africa (11.8%). Compared with Spaniards, analyses of persons of the same exposure category showed higher HIV prevalence in men who had sex with men from Latin America (odds ratio: 4.1; 95% CI: 2.4-6.9), heterosexual men from sub-Sahara Africa (OR: 19.3; 95% CI: 6.4-58.0), and Latin America (OR: 9.4; 95% CI: 3.4-25.9), heterosexual women from sub-Sahara Africa (OR: 16.9; 95% CI: 3.5-82.4) and from northern Africa (OR: 15.3; 95% CI: 3.2-73.2). CONCLUSIONS: An important proportion of HIV testers from these clinics came from foreign countries and some groups showed a high prevalence of HIV infection. Specific prevention and testing programmes adapted to the needs of migrants in Spain should be developed.