Anal squamous intraepithelial lesions are frequent among young HIV-infected men who have sex with men followed up at the Spanish AIDS Research Network Cohort (CoRIS-HPV).

The aim of our study was to determine the baseline prevalence of anal squamous intraepithelial lesions (SIL) and associated risk factors in HIV-infected men who have sex with men (MSM) in a Spanish ongoing multicenter cohort. CoRIS-HPV started in 2007, nested in the Spanish AIDS Research Network Cohort (CoRIS). Anal liquid cytology testing was performed. High-risk human papillomavirus (HR-HPV) infection was determined, and positive samples were genotyped. We analyzed all subjects up to April 2011. Multivariate logistic regression analyses were performed. A total of 551 subjects with baseline anal liquid cytologies were analyzed; 37.0% negative for intraepithelial lesion, 9.0% atypical squamous cells of uncertain significance (ASCUS), 41.0% low-grade SIL, 4.0% high-grade SIL and 9.0% inadequate. Prevalence of anal SIL (excluding ASCUS) in valid samples (n = 450) was 54.7% (95% confidence interval [CI] = 49.9-59.3). Globally HR-HPV prevalence was 81.7% (95% CI = 78.0-85.2). Multiple infections (≥2 HR-HPV genotypes) were documented in 77.7% (95% CI = 73.1-82.0). The only risk factor associated with anal SIL was the number of HR-HPV types; MSM with five or more HR-HPV genotypes had an odds ratio (OR) of anal SIL seven times greater (OR = 7.4; 95% CI = 2.8-19.6) than those with one HR-HPV genotype. No associations were found for age, educational level, smoking, geographical origin, CD4 T-cell count, antiretroviral treatment or number of sexual partners. The prevalence of anal SIL in young HIV-positive MSM is high, and the main risk factor is multiple infections with HR-HPV types.

Prevalence and resistance mutations of non-B HIV-1 subtypes among immigrants in Southern Spain along the decade 2000-2010.

BACKGROUND: Most of the non-B HIV-1 subtypes are predominant in Sub-Saharan Africa and India although they have been found worldwide. In the last decade, immigration from these areas has increased considerably in Spain. The objective of this study was to evaluate the prevalence of non-B subtypes circulating in a cohort of HIV-1-infected immigrants in Seville, Southern Spain and to identify drug resistance-associated mutations. METHODS: Complete protease and first 220 codons of the reverse transcriptase coding regions were amplified and sequenced by population sequencing. HIV-1 subtypes were determined using Stanford University Drug Resistance Database, and phylogenetic analysis was performed comparing multiple reported sequences. Drug resistance mutations were defined according to the International AIDS Society-USA. RESULTS: From 2000 to 2010 a total of 1,089 newly diagnosed HIV-1-infected patients were enrolled in our cohort. Of these, 121 were immigrants, of which 98 had ethical approval and informed consent to include in our study. Twenty-nine immigrants (29/98, 29.6%) were infected with non-B subtypes, of which 15/29 (51.7%) were CRF02-AG, mostly from Sub-Saharan Africa, and 2/29 (6.9%) were CRF01-AE from Eastern Europe. A, C, F, J and G subtypes from Eastern Europe, Central-South America and Sub-Saharan Africa were also present. Some others harboured recombinant forms CRF02-AG/CRF01-AE, CRF2-AG/G and F/B, B/C, and K/G, in PR and RT-coding regions. Patients infected with non-B subtypes showed a high frequency of minor protease inhibitor resistance mutations, M36I, L63P, and K20R/I. Only one patient, CRF02_AG, showed major resistance mutation L90M. Major RT inhibitor resistance mutations K70R and A98G were present in one patient with subtype G, L100I in one patient with CRF01_AE, and K103N in another patient with CRF01_AE. Three patients had other mutations such as V118I, E138A and V90I. CONCLUSIONS: The circulation of non-B subtypes has significantly increased in Southern Spain during the last decade, with 29.6% prevalence, in association with demographic changes among immigrants. This could be an issue in the treatment and management of these patients. Resistance mutations have been detected in these patients with a prevalence of 7% among treatment-naïve patients compared with the 21% detected among patients under HAART or during treatment interruption.

Eligibility for and outcome of treatment of latent tuberculosis infection in a cohort of HIV-infected people in Spain.

BACKGROUND: Previous studies have demonstrated the efficacy of treatment for latent tuberculosis infection (TLTBI) in persons infected with the human immunodeficiency virus, but few studies have investigated the operational aspects of implementing TLTBI in the co-infected population.The study objectives were to describe eligibility for TLTBI as well as treatment prescription, initiation and completion in an HIV-infected Spanish cohort and to investigate factors associated with treatment completion. METHODS: Subjects were prospectively identified between 2000 and 2003 at ten HIV hospital-based clinics in Spain. Data were obtained from clinical records. Associations were measured using the odds ratio (OR) and its 95% confidence interval (95% CI). RESULTS: A total of 1242 subjects were recruited and 846 (68.1%) were evaluated for TLTBI. Of these, 181 (21.4%) were eligible for TLTBI either because they were tuberculin skin test (TST) positive (121) or because their TST was negative/unknown but they were known contacts of a TB case or had impaired immunity (60). Of the patients eligible for TLTBI, 122 (67.4%) initiated TLTBI: 99 (81.1%) were treated with isoniazid for 6, 9 or 12 months; and 23 (18.9%) with short-course regimens including rifampin plus isoniazid and/or pyrazinamide. In total, 70 patients (57.4%) completed treatment, 39 (32.0%) defaulted, 7 (5.7%) interrupted treatment due to adverse effects, 2 developed TB, 2 died, and 2 moved away. Treatment completion was associated with having acquired HIV infection through heterosexual sex as compared to intravenous drug use (OR:4.6; 95% CI:1.4-14.7) and with having taken rifampin and pyrazinamide for 2 months as compared to isoniazid for 9 months (OR:8.3; 95% CI:2.7-24.9). CONCLUSIONS: A minority of HIV-infected patients eligible for TLTBI actually starts and completes a course of treatment. Obstacles to successful implementation of this intervention need to be addressed.

Factores asociados con la no realizacion de la prueba de la tuberculina en una cohorte de pacientes VIH positivos / Factors related to non-prescription of tuberculin skin testing in a cohort of HIV-infected people

Introduccion Dada la asociacion entre tuberculosis (TB) e infeccion por VIH, la realizacion del Mantoux esta indicada en todo paciente infectado con VIH. Este articulo analiza la frecuencia de no realizacion de la prueba de la tuberculina y sus factores asociados en una cohorte de infectados con VIH. Pacientes y metodos Entre 2000-C2002 se identifico en 10 hospitales a todos los pacientes infectados con VIH y no seguidos previamente, de forma regular, en consultas especificas. Se recogio informacion de la historia clinica sobre realizacion del Mantoux y otras variables. Se calculo el porcentaje de no realizacion del Mantoux y los factores asociados mediante la utilizacion como medida de asociacion de la odds ratio (OR) y su intervalo de confianza (IC) del 95%. Para el analisis multivariante se ajusto un modelo de regresion logistica. Resultados Mil doscientos cuarenta y dos pacientes cumplieron criterios de inclusion y a 185 pacientes no se les realizo el Mantoux (el 17,6% de aquellos en los que estaba indicado). La probabilidad de no realizacion del Mantoux fue mayor en usuarios de drogas (OR: 2,6; IC del 95%: 1,1¨C6,5) y menor entre los desempleados (OR: 0,6; IC del 95%: 0,3¨C1,0), aquellos con mas de 200 CD4 (CD4 200¨C499: OR: 0,5; IC del 95%: 0,3¨C0,9; CD4 ¡Ý500: OR: 0,3; IC del 95%: 0,2¨C0,6) y los contactos con enfermos tuberculosos (OR: 0,2; IC del 95%: 0,1¨C0,5).ConclusionesEl porcentaje de no realizacion del Mantoux es bastante elevado. La no realizacion del Mantoux parece asociarse con las expectativas del medico, tanto sobre el resultado de la prueba como sobre la correcta cumplimentacion del tratamiento preventivo anti-TB por el paciente ( AU)

Introduction Tuberculin skin testing (TST) for tuberculosis (TB) is recommended for all patients with HIV infection because of the known relationship between these two conditions. In this report we analyze the incidence and variables associated with non-prescription of TST in a cohort of HIV-infected people. Patients and methods Longitudinal study conducted between 2000 and 2002 at 10 HIV hospital-based clinics. All HIV-infected patients who had not been regularly followed-up previously in dedicated clinics were identified. Data about TST and other variables related to TB were obtained from the clinical records. We calculated the percentage of patients who did not undergo TST and the associated factors, using odds ratios (ORs) and the 95% CI to investigate associations. A multivariate logistic regression analysis was performed. Results A total of 1242 patients met the inclusion criteria. TST was not performed in 185 patients (17.6% of those eligible). The fact of being an intravenous drug abuser was associated with a higher probability of TST non-prescription (OR: 2.6, 95% CI 1.1¨C6.5), whereas being unemployed (OR: 0.6, 95% CI 0.3¨C1.0), having a CD4 cell count >200 (CD4 200¨C499: OR 0.5, 95% CI 0.3¨C0.9. CD4¡Ý500: OR 0.3, 95% CI 0.2¨C0.6), and contact with persons with TB (OR 0.2, 95% CI 0.1¨C0.5) were associated with a lower probability. ConclusionsIn this study, the percentage of TST non-prescription was quite high. The results suggest that TST non-prescription in this population is related to the clinicians¡¯ expectations regarding the results of the test and the patients¡¯ adherence to treatment for latent TB infection(AU)

[Factors related to non-prescription of tuberculin skin testing in a cohort of HIV-infected people]. / Factores asociados con la no realización de la prueba de la tuberculina en una cohorte de pacientes VIH positivos.

INTRODUCTION: Tuberculin skin testing (TST) for tuberculosis (TB) is recommended for all patients with HIV infection because of the known relationship between these two conditions. In this report we analyze the incidence and variables associated with non-prescription of TST in a cohort of HIV-infected people. PATIENTS AND METHODS: Longitudinal study conducted between 2000 and 2002 at 10 HIV hospital-based clinics. All HIV-infected patients who had not been regularly followed-up previously in dedicated clinics were identified. Data about TST and other variables related to TB were obtained from the clinical records. We calculated the percentage of patients who did not undergo TST and the associated factors, using odds ratios (ORs) and the 95% CI to investigate associations. A multivariate logistic regression analysis was performed. RESULTS: A total of 1242 patients met the inclusion criteria. TST was not performed in 185 patients (17.6% of those eligible). The fact of being an intravenous drug abuser was associated with a higher probability of TST non-prescription (OR: 2.6, 95% CI 1.1-6.5), whereas being unemployed (OR: 0.6, 95% CI 0.3-1.0), having a CD4 cell count >200 (CD4 200-499: OR 0.5, 95% CI 0.3-0.9. CD4> or =500: OR 0.3, 95% CI 0.2-0.6), and contact with persons with TB (OR 0.2, 95% CI 0.1-0.5) were associated with a lower probability. CONCLUSIONS: In this study, the percentage of TST non-prescription was quite high. The results suggest that TST non-prescription in this population is related to the clinicians' expectations regarding the results of the test and the patients' adherence to treatment for latent TB infection.

Molecular epidemiology of HIV type 1 in newly diagnosed patients in southern Spain.

The prevalence of different HIV-1 subtypes in Spain varies by geographic region. In the present study isolates were collected from 72 newly diagnosed individuals in western Andalucia from 2004 to 2006. Viral sequences were amplified and the subtype diversity and prevalence of resistance mutations in the reverse transcriptase and protease genes were determined. The results presented here demonstrate that subtype B virus predominates in this region (88.9%), with the non-B subtypes CRF02_AG (9.7%) and B/G (1.4%) also present. Only two isolates (2.9%) carried resistance mutations in the reverse transcriptase gene and none of the isolates had major resistance mutations in the protease gene. Minor mutations in the protease gene were more prevalent with 86.1% of isolates containing at least one minor mutation. These results elucidate the subtype diversity present in this region and suggest that the transmission of highly resistant virus variants does not occur at a high frequency in this population.

Antiretroviral therapy based on protease inhibitors as a protective factor against liver fibrosis progression in patients with chronic hepatitis C.

Cohort studies have shown that highly active antiretroviral therapy (HAART) can improve liver-related mortality in HIV/hepatitis C virus (HCV)-coinfected patients. A reduction in the accelerated liver fibrosis progression observed in HIV infection induced by HAART could explain these findings. A few studies have assessed the impact of HAART on liver fibrosis, but with contradictory results. Therefore, we evaluated the associations between the use of different antiretroviral drug classes and HAART combinations, and liver fibrosis in HIV-infected patients with chronic hepatitis C. Six hundred and eighty-three HIV/HCV-coinfected patients, who underwent a liver biopsy and who had not received anti-HCV treatment were included. Age at HCV infection < 23years (adjusted odds ratio [AOR] = 0.7, 95% confidence interval [95% CI] = 0.3-0.9, P = 0.05) and protease inhibitor (PI)-based HAART versus no use of HAART (AOR = 0.5, 95% CI = 0.3-0.9, P = 0.01) were negatively associated with advanced fibrosis (> or = F3). PI-based HAART versus no use of HAART (AOR = 0.4, 95% CI = 0.2-0.7, P = 0.001) was negatively associated with fibrosis progression rate > or = 0.2 units/year and independently of age at HCV infection and CD4+ T-cell counts. Fifteen (17%) patients treated only with PIs and zidovudine plus lamivudine showed > or = F3, compared with 65 (37%) patients without HAART (P = 0.001). Forty (31%) patients on PI and stavudine plus lamivudine showed > or = F3 (P = 0.3, when compared with patients with no HAART). The use of PI-based HAART in HIV/HCV-coinfected patients is associated with less severe fibrosis and slower progression of fibrosis. The nucleoside analogue backbone in a HAART regimen may influence this association.

Discontinuation of antiretroviral therapy in patients with chronic HIV infection: clinical, virologic, and immunologic consequences.

To investigate the clinical, virologic and immunologic consequences of planned treatment interruptions in chronically HIV-infected patients. One hundred forty-one patients with undetectable viral load for at least 6 months and CD4+ T cells count greater than 500 per microliter were recruited. Their antiretroviral therapy was stopped and clinical, analytic, virologic, and immunologic data were recorded at baseline, during discontinuation, and after restarting treatment. Viral load rebound after discontinuation in 137 (97%) patients, and was similar to prehighly active antiretroviral therapy (HAART) levels. A rapid decrease in CD4+ T-cell count (median, 240 cells per microliter), was observed in the first 3 months in all patients, with pronounced differences between them. After a median follow-up of 36 months, 45.5% patients were still without therapy. Factors related to a more severe decline were a prior lower CD4+ T nadir (<200 cells per microliter) before starting HAART, a greater increase (>500 cells per microliter) with it, a higher CD4+ T-cell count before interruption (>800 cells per microliter) and a higher viral load rebound after it. The increase in CD4+ T-cell counts after reinitiation was slower than the decline and only 55% of patients have regained the preinterruption levels at 12 months of follow- up. Twelve infectious events were registered. Treatment failure related to drug resistance was observed in two patients. Planned treatment interruptions may be safe in selected patients with previous CD4+ T cell nadir greater than 200 cells per microliter and pre-HAART VL less than 55.000 copies per milliliter, but should be not recommended in patients with the prognostic factors related to a rapid decline described in this study. Furthermore, there is a considerable concern about the development of drug resistance and the possibility of an incomplete immune reconstitution after the treatment interruption in some patients.