HIV-infected Patients In Spain Research Articles

Trends in hospitalizations and deaths in HIV-infected patients in Spain over two decades.

The prognosis of HIV infection dramatically improved after the introduction of triple antiretroviral therapy 25 years ago. Herein, we report the impact of further improvements in HIV management since then, looking at all hospitalizations in persons with HIV (PWH) in Spain. A retrospective study using the Spanish National Registry of Hospital Discharges. Information was retrieved since 1997-2018. From 79 647 783 nationwide hospital admissions recorded during the study period, 532 668 (0.67%) included HIV as diagnosis. The mean age of PWH hospitalized increased from 33 to 51 years (P < 0.001). The rate of HIV hospitalizations significantly declined after 2008. Comparing hospitalizations during the first (1997-2007) and last (2008-2018) decades, the rate of non-AIDS illnesses increased, mostly due to liver disease (from 35.9 to 38.3%), cardiovascular diseases (from 12.4 to 28.2%), non-AIDS cancers (from 6.4 to 15.5%), and kidney insufficiency (from 5.4 to 13%). In-hospital deaths occurred in 5.5% of PWH, declining significantly over time. Although most deaths were the result from AIDS conditions (34.8%), the most frequent non-AIDS deaths were liver disease (47.1%), cardiovascular events (29.2%), non-AIDS cancers (24.2%), and kidney insufficiency (20.7%). Hospital admissions in PWH significantly declined after 2008, following improvements in HIV management and antiretroviral therapy. Non-AIDS cancers, cardiovascular events and liver disease represent a growing proportion of hospital admissions and deaths in PWH.

Toxoplasma gondii infection in hospitalized people living with HIV in Spain, 1997 to 2015.

Toxoplasma gondii infection was one of the most frequent AIDS-defining conditions in HIV-infected individuals until the advent of combination antiretroviral therapy. We aimed to assess the clinical load, coinfection, and mortality, as well as time trends for people living with HIV and hospitalized with Toxoplasma gondii infection, in Spain from 1997 to 2015. Retrospective observational analysis using the Spanish National Registry of Hospital Discharges. Information was retrieved for the study period using the International Classification of Diseases, 9th revision. There were 66,451,094 hospital admissions in Spain from 1997 to 2015, including 472,269 (0.71%) in people living with HIV. Toxoplasma gondii infection was registered in 9006 of these (overall prevalence 1.91%), making it the fifth most common opportunistic infection in hospitalized HIV-positive patients. Prevalence of Toxoplasma gondii infection declined in this group from 4.2% in 1997 to 0.8% in 2015 (p < 0.001), while mean age increased, from 35 years in 1997 to 44 years in 2015. The overall in-hospital mortality rate declined from 13.5% in 1997 to 8.9% in 2015, and it was higher in the concomitant presence of bacterial pneumonia (28.9% vs. 10.2%, p < 0.001), cryptosporidiosis (26.9% vs. 11.5%; p = 0.03), cytomegalovirus disease (18.2% vs. 11.2%, p < 0.001), Pneumocystis jiroveci pneumonia (31.5% vs. 10.5%, p < 0.001), leukoencephalopathy (19.8% vs. 11.78% p < 0.001), and wasting syndrome (29.3% vs 10.9%; p < 0.001). Toxoplasma gondii infection prevalence has significantly declined among hospitalized HIV-infected patients in Spain during the last two decades, coinciding with the widespread use of combination antiretroviral therapy.

Reasons for noncompliance with the national guidelines for initial antiretroviral therapy of HIV-infected patients in Spain, 2010–2015

IntroductionOur aims were to investigate the adherence to national guidelines of initial antiretroviral therapy (ART) in the Spanish multicenter CoRIS cohort during the years 2010–2015, to identify the reasons for the prescription of nonrecommended treatments, and to explore the role of institutional constraints to guideline compliance. MethodsART regimens were classified as recommended, alternative or nonrecommended according to the guidelines. Physicians were asked the reasons for prescribing nonrecommended regimens. Factors associated with the prescription of non recommended regimens were assessed using multivariable logistic regression. ResultsDuring the study period, 586 (10.7%) of 5479 patients who started ART were given a regimen not recommended in the guidelines. The most frequent reasons for prescribing nonrecommended regimens were: enrolment in clinical trials (43.3%), comorbidities and/or interactions (10.2%), pregnancy (8.7%), and cost (7.7%). Among 37 participating centers, 16 (43%), treating 3561 patients, reported limitations related with the cost of ART, and 20 (54%), treating 1365 patients, reported restrictions for prescribing at least one recommended antiretroviral. In multivariable analysis, a higher risk of receiving nonrecommended regimens was associated with male gender, HIV acquisition by heterosexual transmission, low viral loads, initiation of treatment during the years 2011 to 2015, and initiation of treatment in a center with restricted access to at least one antiretroviral drug. ConclusionsCompliance to clinical guidelines was high. A high proportion of centres reported cost limitations for ART or restricted access to at least one recommended antiretroviral drug, with a significant impact on the choice of initial regimens.

Risk of cancer in HIV-infected patients in Spain, 2004–2015. The CoRIS cohort study

IntroductionCancer is a leading cause of death in individuals with HIV. MethodsThe incidence of cancer in HIV patients of the CoRIS cohort in the 2004–2009 and 2010–2015 periods has been analysed and compared to the incidence in the Spanish general population, estimated from data of the Spanish Cancer Registry Network. ResultsBetween January 2004 and November 2015, 12,239 patients were included in CoRIS and 338 incident cancer cases were diagnosed. The overall incidence of cancer per 100,000 persons-year (95% CI) was 702.39 (629.51–781.42) with no significant differences between the 2 periods. A 38% of the incident cancer cases were AIDS defining cancers (ADC) and 62% non-AIDS defining cancers (NADC). In the period 2010–2015, there was a significant decrease in the incidence of ADC (standardised incidence ratio [SIR]); 95% CI: 0.38; 0.21–0.66) and NADC predominated. Compared to the general population, the incidence of cancer was double in men with HIV. Higher relative risks were documented (SIR; 95% CI) for Hodgkin's lymphoma in both sexes (males: 8.37, 5.13–14.17; females: 21.83, 2.66–47.79), non-Hodgkin's lymphoma in males (5.30, 2.86–8.45) and cervical cancer (7.43, 3.15–13.87) and head and neck cancer (3.28, 1.21–5.82) in women. ConclusionsThe overall incidence of cancer in individuals with HIV is higher than in the Spanish general population, and it has remained stable since 2004 with a current predominance of NADC. These data suggest that additional efforts should be made in the prevention and the early detection of cancer in these patients.

Reasons for noncompliance with the national guidelines for initial antiretroviral therapy of HIV-infected patients in Spain, 2010–2015

IntroductionOur aims were to investigate the adherence to national guidelines of initial antiretroviral therapy (ART) in the Spanish multicenter CoRIS cohort during the years 2010–2015, to identify the reasons for the prescription of nonrecommended treatments, and to explore the role of institutional constraints to guideline compliance. MethodsART regimens were classified as recommended, alternative or nonrecommended according to the guidelines. Physicians were asked the reasons for prescribing nonrecommended regimens. Factors associated with the prescription of non recommended regimens were assessed using multivariable logistic regression. ResultsDuring the study period, 586 (10.7%) of 5479 patients who started ART were given a regimen not recommended in the guidelines. The most frequent reasons for prescribing nonrecommended regimens were: enrolment in clinical trials (43.3%), comorbidities and/or interactions (10.2%), pregnancy (8.7%), and cost (7.7%). Among 37 participating centers, 16 (43%), treating 3561 patients, reported limitations related with the cost of ART, and 20 (54%), treating 1365 patients, reported restrictions for prescribing at least one recommended antiretroviral. In multivariable analysis, a higher risk of receiving nonrecommended regimens was associated with male gender, HIV acquisition by heterosexual transmission, low viral loads, initiation of treatment during the years 2011 to 2015, and initiation of treatment in a center with restricted access to at least one antiretroviral drug. ConclusionsCompliance to clinical guidelines was high. A high proportion of centres reported cost limitations for ART or restricted access to at least one recommended antiretroviral drug, with a significant impact on the choice of initial regimens.

Trends in Epidemiology of COPD in HIV-Infected Patients in Spain (1997-2012).

PurposeThe aim of this study was to estimate trends of incidence of hospital admissions and in-hospital mortality (IHM) in HIV-infected patients with COPD in the combination antiretroviral therapy (cART) era in Spain (1997–2012).MethodsA retrospective study with data from nationwide population-based COPD diagnoses in the Spanish Minimum Basic Data Set (MBDS) was performed. We established groups according to their HIV and HCV infections: 1) HIV-uninfected patients; 2) HIV-infected patients (with or without HCV coinfection).Results1,580,207 patients discharge with a COPD diagnosis were included in the study, 8902 of them were HIV-infected patients (5000 HIV-monoinfected patients and 3902 HIV/HCV-coinfected patients). The HIV-infected patients had higher incidence rates of hospital admissions for COPD than the HIV-uninfected patients during the study period. The HIV-monoinfected patients had higher rates of hospitalizations for COPD than the HIV/HCV-coinfected patients in the early-period cART (1997–1999), but these rates decreased in the first group and increased in the second, being even similar in both groups in the late-period cART (2004–2011). On the other hand, the HIV-infected patients with COPD had higher IHM than the HIV-uninfected patients with COPD. The mortality rates were higher in the HIV-monoinfected patients with COPD than in the HIV/HCV-coinfected patients with COPD in the early-period cART; however, in the late-period cART, the mortality rates trends seems higher in the HIV/HCV group. The likelihood of death in HIV/HCV-coinfected patients with COPD was similar to than in HIV-monoinfected patients with COPD.ConclusionsIncidence of hospital admissions for COPD and IHM have decreased among HIV-monoinfected individuals but have increased steadily among HIV/HCV-coinfected individuals in the cART era.

Fifteen-Year Trends in the Prevalence of Diabetes among Hospitalized HIV-Infected Patients in Spain (1997-2012).

ObjectiveTo describe trends in the prevalence of diabetes among hospitalized HIV-infected patients between 1997 and 2012 in Spain and compare them with those of age- and sex-matched non–HIV-infected patients.MethodsThe study was based on Spanish national hospital discharge data. We performed a retrospective study for the period 1997–2012. HIV infection (HIV-infected versus non–HIV-infected [control group])and calendar period in relation to widespread use of combination antiretroviral therapy (cART) (1997–1999; 2000–2003; 2004–2007 and 2008–2012), were the exposure variables The outcome variables were diagnosis of diabetes and in-hospital mortality (IHM).ResultsFrom 1997 to 2012, we identified 91,752 cases of diabetes: 15,398 in the HIV-infected group (403,277 hospital admissions) and 76,354 in the non–HIV-infected group (1,503,467 hospital admissions). Overall, HIV-infected patients had lower prevalence values for diabetes than non–HIV-infected patients throughout the follow-up (3.8% vs. 5.1%; p<0.001). The prevalence of diabetes increased 1.56-fold among non–HIV-infected patients and 4.2-fold among HIV-infected patients. The prevalence of diabetes in females was almost twice as high in HIV-infected patients as in non–HIV-infected patients during the last study period (4.72% vs. 2.88%; p<0.001). Diabetes showed a protective effect against IHM throughout the study period (aOR = 0.70; 95%CI, 0.65–0.75).ConclusionsDuring the cART era, the prevalence of diabetes has increased sharply among HIV-infected hospitalized patients compared with matched non–HIV-infected subjects. The prevalence of diabetes is rising very fast among HIV-infected women. Diabetes has a protective effect on IHM among HIV-infected patients. Nevertheless, our study has several limitations. No information is available in the database used on important sociodemographic characteristics and relevant clinical variables including duration of the HIV infection, treatments used, drug resistance, treatment adherence or CD4 count, among others. Also, it is possible that increase of diabetes prevalence could reflect the improvement in recording habits.

Incidence and natural history of hepatitis E virus coinfection among HIV-infected patients.

To know the prevalence, incidence and factors associated with hepatitis E virus (HEV) infection in HIV-infected individuals in Spain, as well as to provide information on the natural history of HIV/HEV coinfection. Prospective cohort study. Serum HEV IgG antibodies were tested in 613 HIV-infected patients at baseline and 2 years thereafter. Positive samples were tested for HEV-RNA. In patients with seroconversion, changes in liver function tests, serum HEV IgM antibodies and HEV RNA in samples collected between the baseline and the final time points were analyzed. One hundred and sixty-one (26%) patients tested positive for serum HEV IgG antibodies at baseline. HEV exposure was more common in men than in women (28 vs. 18%; P = 0.022) and increased linearly with age: 16, 26 and 44% in younger than 40, from 40 to 49 and older than 50 years, respectively (P = 0.000002). One patient bore the serum HEV-RNA at baseline. Eighteen (4%) HEV-seronegative patients seroconverted during the follow-up. None of the factors predicted seroconversion. One patient with seroconversion developed acute hepatitis and four mild hypertransaminasemia without another apparent cause. No case of seroconversion evolved to chronic HEV infection. Seroreversion was detected in 19% of the HEV-seropositive patients at baseline. Patients with seroreversion showed more commonly CD4 cell counts below 500 cells/μl than those who remained seropositive (77 vs. 46%; P = 0.004). Exposure to HEV among HIV-infected patients in Spain is very common, and this increases with age. Evolution to chronic infection is extremely unusual. Most cases of acute HEV infection seem to be clinically and biochemically unexpressive, therefore going unnoticed.

Impact of an adherence program to antiretroviral treatment on virologic response in a cohort of multitreated and poorly adherent HIV-infected patients in Spain.

Several studies have shown the importance of adherence to highly active antiretroviral therapy (HAART) in achieving HIV-1 suppression. However, most have focused on naïve patients and do not assess the impact of HAART on viral load (VL). Our aim was to evaluate the effectiveness of an adherence program in a cohort of multitreated and poorly adherent patients. We performed a cohort study of all adult HIV-1 infected patients with detectable VL who were treatment experienced and poorly adherent to HAART, included in an adherence program since its introduction in 2009 (n=136). The adherence program consisted of a multidisciplinary team with a nurse who specialized in behavioral intervention, counselling on substance abuse, and motivational interviewing, as well as a social worker responsible for referring patients to local healthcare centers. Effectiveness was evaluated as percentage of patients with VL <50 copies/mL at week 48 by modified intent-to-treat (mITT) analysis. Initially, 76.6% of the patients had an adherence <30% according to the Simplified Medication Adherence Questionnaire (SMAQ). At 48 weeks, 48.1% of the patients had VL <50 copies/mL, and the adherence was >90% in 71% of the patients. In multivariate analysis, a ratio of bottle refill per month >0.9 during the study [odds ratio (OR) 14.3; 95% confidence interval (CI) 4.08-50.08, p<0.001] and being on a b.i.d. regimen (OR 12.5; 95% CI 1.81-86.4, p=0.010) were associated with an undetectable VL. In conclusion, the adherence program was successful in almost half of the patients, despite their long treatment experience and prior poor adherence. This strategy may help to prevent disease progression and the risk of HIV transmission in these patients.

Incidence of tuberculosis in HIV-infected patients in Spain: the impact of treatment for LTBI

Twenty hospitals in Spain. To describe the incidence of active tuberculosis (TB) and factors related to TB development after treatment for latent tuberculous infection (TLTBI) in human immunodeficiency virus-1 (HIV-1) infected patients in the highly active antiretroviral therapy era. In a multicentre cohort of HIV-1-infected patients, we calculated TB incidence by tuberculin skin test (TST) results and TLTBI, and factors associated with a positive TST and the development of TB after TLTBI. Of 7902 patients, 6.5% had a history of TB at enrolment: 168 patients developed TB during 10,889 person-years (py) of follow-up, corresponding to an incidence rate of 1.54 cases per 100 py (95%CI 1.33-1.80). TB incidence in TST-positive patients who did not receive TLTBI was three times higher (6 cases/100 py) than in those who did (1.75 cases/100 py). In patients who received TLTBI, risk of development of TB was higher among cases aged <35 years (HR 6.14, 95%CI 1.12-33.73) and in those with a nadir CD4(+) cell count of <200 cells/μl (HR 5.64, 95%CI 1.34-23.70). TLTBI is effective in preventing the development of TB in HIV-infected patients, particularly in those who were TST-positive.

Increasing Incidence of Hepatocellular Carcinoma in HIV-Infected Patients in Spain

To report the clinical and epidemiological characteristics of hepatocellular carcinoma (HCC) diagnosed in a cohort of human immunodeficiency virus (HIV)-infected patients in Spain. All HIV-infected patients diagnosed of HCC in 18 hospitals in Spain before 31 December 2010 were included. The main characteristics of HCC cases are described and comparisons between cases according to the year of diagnosis are presented. Eighty-two cases of HCC in HIV-infected patients were included, all of them related to viral hepatitis coinfection: hepatitis C virus (HCV) in 66 (81%), hepatitis B virus (HBV) in 6 (7%), and HBV/HCV in 10 (12%). From 1999, when the first case of HCC was diagnosed, a progressive increment in the incidence of HCC in the cohort has occurred. In patients coinfected with HIV/HCV-coinfected patients, the incidence HCC increased from 0.2 to 2.8 cases per 1000 person-years between 2000 and 2009. Death occurred in 65 patients (79%), with a median survival of 91 days (interquartile range, 31-227 days). Three of 11 patients (28%) who received potentially curative therapy died, compared with 62 of 71 patients (87%) who did not receive curative therapy (P = .0001). Compared with cases of HCC diagnosed before 2005, cases diagnosed later did not show a higher survival rate. HCC is an emerging complication of cirrhosis in HIV-infected patients. A sharp increase in its incidence has occurred in those also infected by HCV in the recent years. Unfortunately, HCC is frequently diagnosed at an advanced stage, and mortality continues to be very high, with no significant changes in recent years. Earlier diagnosis, which may allow potentially curative therapy, is necessary.

Riesgo cardiovascular en pacientes con infección por el virus de la inmunodeficiencia humana en España. Cohorte CoRIS, 2011

Current information on cardiovascular risk (CVR) in HIV-infected patients in Spain is limited. An analysis was made of a prospective multicentre cohort of Spanish HIV-infected patients (CoRIS) between January-2010 and July-2011. CVR was evaluated using Framingham, REGICOR and SCORE equations. The study included 1019 patients (76% males, mean age 40 years) recruited from 13 hospitals belonging to 10 autonomous communities in Spain. Almost two-thirds (65.4%) of patients were on antiretroviral therapy (ART), 36.7% with non-nucleoside analogs, 24% with protease inhibitors (PIs) (52% with atazanavir/r or darunavir/r) and 4,6% with raltegravir. More than half (56.2%) of the patients had an HIV viral load <50 copies/ml. Smoking prevalence was 46%, HDL cholesterol (HDL-C) <40mg/dl 36.1%, total cholesterol (total-C) >200mg/dl 27.8%, age >45years 27.2%, metabolic syndrome 11.5%, hypertension 9.4%, cocaine use 7%, and diabetes 2.9%. ART was associated with higher total-C and LDL-C concentrations, although also higher HDL-C and lower total-C/HDL-C ratio; patients receiving PIs boosted with a high ritonavir dose showed higher total-C levels and higher total-C/HDL-C ratio. According to Framingham cardiovascular, and coronary, REGICOR, and SCORE equations, 15.2%, 6.4%, 4.2% and 3.9% of patients, respectively, were classified as having moderate or high CVR. In HIV-infected patients from CoRIS, prevalence of modifiable CVR factors is still high. Commonly used scores identify a relatively low number of patients with high CVR.

Prevalence of Vitamin D Deficiency and Its Related Risk Factor in a Spanish Cohort of Adult HIV-Infected Patients: Effects of Antiretroviral Therapy

We analyzed serum 25(OH) cholecalciferol [25(OH)D] levels and factors related to deficiency (<20 ng/ml) or insufficiency (<30 ng/ml) in a cohort of Spanish HIV-infected patients and compared them with an age- and latitude-matched population from another study. We prospectively assessed 25(OH)D deficiency/insufficiency in a cohort of 352 HIV patients during 2009-2010. Predisposing factors were recorded and their relationship to low levels was assessed by logistic regression; a nutritional survey examined intake, nutritional status, and sunlight exposure in a subgroup of 92 patients. We studied the correlation of 25(OH)D with parathyroid hormone (PTH) and alkaline phosphatase. Age-, sex-, and race/ethnicity-adjusted vitamin D deficiency (<20 ng/ml) was 44.0% (95% CI, 38.8-49.4%) and insufficiency (<30 ng/ml) was 71.6% (95% CI, 66.9-76.3). Deficiency was 16.4% more prevalent in our sample than in non-HIV-infected Spaniards. Lower sunlight exposure was the only factor related to lower levels in the lifestyle and nutritional survey (p=0.045). In multiple logistic regression, higher body mass index (BMI), black race/ethnicity, lower seasonal sunlight exposure, men who have sex with men (MSM), and heterosexual transmission categories, efavirenz exposure and lack of HIV viral suppression were independently associated with deficiency/insufficiency. These variables predicted 79% of cases [AUC=0.872 (95% CI, 0.83-0.91)]. Patients receiving protease inhibitors (PIs) [OR 4.0 (95% CI, 1.3-12.3); p=0.014] or NNRTI [OR 3.6 (95% CI, 1.7-11.2); p=0.025] had higher odds of increased PTH levels; this was significant only in 25(OH)D-deficient patients (p=0.004). As in less insolated areas, the prevalence of vitamin D deficiency/insufficiency was high in HIV-infected patients in Spain; among treated patients, levels were higher with PIs than with efavirenz.

Increase of Transmitted Drug Resistance among HIV-Infected Sub-Saharan Africans Residing in Spain in Contrast to the Native Population

BackgroundThe prevalence of transmitted HIV drug resistance (TDR) is stabilizing or decreasing in developed countries. However, this trend is not specifically evaluated among immigrants from regions without well-implemented antiretroviral strategies.MethodsTDR trends during 1996–2010 were analyzed among naïve HIV-infected patients in Spain, considering their origin and other factors. TDR mutations were defined according to the World Health Organization list.Results Pol sequence was available for 732 HIV-infected patients: 292 native Spanish, 226 sub-Saharan Africans (SSA), 114 Central-South Americans (CSA) and 100 from other regions. Global TDR prevalence was 9.7% (10.6% for Spanish, 8.4% for SSA and 7.9% for CSA). The highest prevalences were found for protease inhibitors (PI) in Spanish (3.1%), for non-nucleoside reverse transcriptase inhibitors (NNRTI) in SSA (6.5%) and for nucleoside reverse transcriptase inhibitors (NRTI) in both Spanish and SSA (6.5%). The global TDR rate decreased from 11.3% in 2004–2006 to 8.4% in 2007–2010. Characteristics related to a decreasing TDR trend in 2007-10 were Spanish and CSA origin, NRTI- and NNRTI-resistance, HIV-1 subtype B, male sex and infection through injection drug use. TDR remained stable for PI-resistance, in patients infected through sexual intercourse and in those carrying non-B variants. However, TDR increased among SSA and females. K103N was the predominant mutation in all groups and periods.ConclusionTDR prevalence tended to decrease among HIV-infected native Spanish and Central-South Americans, but it increased up to 13% in sub-Saharan immigrants in 2007–2010. These results highlight the importance of a specific TDR surveillance among immigrants to prevent future therapeutic failures, especially when administering NNRTIs.

Late Initiation of HAART Among HIV-Infected Patients in Spain Is Frequent and Related to a Higher Rate of Virological Failure but not to Immigrant Status

Purpose: To determine whether immigrant status is associated with late initiation of highly active antiretroviral treatment (HAART) and/or poor response to antiretrovirals. Methods: GESIDA 5808 is a multicenter, retrospective cohort study (inclusion period January 2005 through December 2006) of treatment-naïve patients initiating HAART that compares HIV-infected patients who are immigrants with Spanish-born patients. A late starter (LS) was defined as any patient starting HAART with a CD4+ lymphocyte count <200 cells/μL and/or diagnosis of an AIDS-defining illness before or at the start of therapy. The primary endpoint was time to treatment failure (TTF), defined as virological failure (VF), death, opportunistic infection, treatment discontinuation/switch (D/S), or missing patient. Secondary endpoints were time to treatment failure as observed data (TTO; censoring missing patients) and time to virological failure (TVF; censoring missing patients and D/S not due to VF). Results: LS accounted for 56% of the patients. Lower educational and socioeconomic level and intravenous drug use (IVDU) were associated with categorization as LS, but immigrant status was not. Cox regression analysis (hazard ratio [HR]; 95% CI) between LS and non-LS patients showed no differences in TTF (0.97; 0.78–1.20) or TTO (1.18; 0.88–1.58), although it did reveal a difference in TVF (1.97; 1.18–3.29). CD4+ lymphocyte recovery was equivalent for both LS and non-LS patients (159 vs 173). Conclusions: In our cohort, immigrant status was not shown to be related to late initiation of HAART. Although LS patients did not have a longer TTF for any reason, TVF was significantly shorter. Despite universal free access to HAART in Spain, measures to ensure early diagnosis and treatment of HIV infection are necessary.

Prevalence of HLA-B*5701 in HIV-Infected Patients in Spain (Results of the EPI Study)

A hypersensitivity reaction (HSR) is associated with abacavir (ABC), a nucleoside reverse transcriptase inhibitor. Genetic association of ABC HSR with the presence of HLA-B*5701 has been demonstrated in PREDICT-1 study, showing a prevalence of 5.6% in HIV-infected population. However the prevalence of this allele in HIV-infected patients in Spain has not been established yet. This is a cross-sectional epidemiological study that included 1,198 patients in 74 centers that serve the HIV-infected population of Spain. HLA-B*5701 was checked both in the hospital lab and one central lab, showing an overall prevalence of this allele of 6%. HLA-B*5701 was most prevalent in Caucasian population (6.5%). Concordance between the local and central lab was very high for positive and negative results (95.7% and 99.3%, respectively). These aspects define this test as a useful tool for the management of HIV-infected patients.

Diagnóstico microbiológico de la infección por el VIH

Currently, there are around 150,000 HIV-infected patients in Spain. This number, together with the fact that this disease is now a chronic condition since the introduction of antiretroviral therapy, has generated an increasing demand on the clinical microbiology laboratories in our hospitals. This increase has occurred not only in the diagnosis and treatment of opportunistic diseases, but also in tests related to the diagnosis and therapeutic management of HIV infection. To meet this demand, the Sociedad de Enfermedades Infecciosas y Microbiología Clinica (Spanish Society of Infectious Diseases and Clinical Microbiology) has updated its standard Procedure for the microbiological diagnosis of HIV infection. The main advances related to serological diagnosis, plasma viral load, and detection of resistance to antiretroviral drugs are reviewed in this version of the Procedure.

Estudio multicéntrico sobre prevalencia de las coinfecciones por virus de hepatitis, indicación de tratamiento de hepatitis crónica C y necesidad de trasplante hepático en pacientes infectados por el VIH en España. Estudio GESIDA 29/02-FIPSE 12185/01

The aims of this study were to estimate the prevalence of HIV and hepatitis virus coinfection in the Spanish population and to determine the percentage of patients who are candidates for chronic hepatitis C virus (HCV) treatment and liver transplantation within this population. A cross-sectional study was performed in 2002 in two Spanish populations of HIV-infected patients: 1,260 patients from 39 centers throughout Spain (P1) and 1,560 patients from three tertiary teaching hospitals in Madrid (P2). The following hepatitis A virus (HAV), hepatitis B virus (HBV) and HCV serological prevalence were found in the P1 and P2 groups, respectively: HAV-IgG antibodies: 74% and 78%; HBsAg1: 4.9% and 4.8%; HBsAg-, anti-HBc1, anti-HBs1: 39% and 39%; HBsAg-, anti-HBc1, anti-HBs-: 25% and 31%; HBsAg-, anti-HBc-, anti-HBs1: 7% and 8%; HBsAg-, anti-HBc-, anti-HBs-: 22% and 16%. Anti-HCV1: 61% and 65%, respectively. Of the patients with positive HCV serology, 88.8% and 84.6% of each group were positive for HCV-RNA by polymerase chain reaction. Multiple coinfections with hepatitis viruses were found in 3.2% and 2.8%, respectively; of these, 70% and 78% had coinfection with HBV, HCV and HDV. Liver cirrhosis was found in 5.8% and 9.6% of the patients coinfected with HIV and HCV, respectively. Liver transplant was indicated in approximately one out of every six coinfected patients with liver cirrhosis. The 43 and 37% of the HCV coinfected patients were good candidates for anti-HCV treatment, but only 14% and 15% of patients had initiated it. A high percentage of HIV-infected patients in Spain were coinfected with hepatitis viruses, especially HCV. The number of possible candidates for liver transplantation is rising and could increase in the next few years. In the future, greater efforts to treat HIV-and hepatitis virus-coinfected patients will be required.

Epidemiological trends of HIV infection in Spain

Epidemiological trends of HIV infection in Spain

Prevalence of genotypic resistance to nucleoside analogues in antiretroviral-naive and antiretroviral-experienced HIV-infected patients in Spain

To determine the prevalence of genotypic resistance to nucleoside analogues (NA) in a large group of HIV-infected individuals in Spain, some of whom had no previous treatment with antiretroviral drugs (antiretroviral-naive) and some of whom had such experience (antiretroviral-experienced). Cross-sectional study in out-patient clinics in three reference hospitals for HIV/AIDS located in Barcelona, Madrid and Seville, Spain. Primary mutant genotypes were examined in plasma HIV RNA collected from 150 antiretroviral-naive subjects, half in 1993 and the other half in 1997. Furthermore, drug resistance mutations were analysed in plasma collected from another 150 antiretroviral-experienced patients who had received 2 NA for longer than 1 year, either in sequence as monotherapy or as combination therapy. A line probe assay was used for recognizing mutations conferring resistance to zidovudine (ZDV), didanosine (ddI), zalcitabine (ddC), and lamivudine (3TC). A point-mutation nested-PCR assay was used for examining a codon 151 mutation associated with multiple drug resistance. One or more mutations associated with primary resistance to NA were seen in 10 antiretroviral-naive (13.3%) patients in 1993 and in nine (12%) in 1997. In all but two cases, they were associated with ZDV resistance. In contrast, all but six (96%) of the antiretroviral-experienced subjects harboured drug-resistant mutant viruses. The codon 184 mutation (associated with resistance to 3TC) was detected in 92% of patients treated with 3TC, but also in 18% of those treated with only ddI or ddC. The codon 215 mutation was found in 67.3% of patients who had been exposed to ZDV; the codon 69 mutation was found in 15% of patients treated with ddC; and the codon 74 mutation was found in only 7.2% of patients treated with ddI. Finally, the codon 151 multidrug resistant mutation was found in four (2.7%) of 150 patients with a long-term exposure to NA. Overall, the prevalence of drug-resistant HIV-1 genotypes was 12.7% in antiretroviral-naive patients, most of whom had ZDV-resistant mutants. There is no evidence of an increase during the last 5 years. However, multidrug-resistant HIV genotypes are currently circulating in Spain.