Aims
To compare patients who acquired HIV infection through use of injected drugs (HIV‐IDU) with patients who acquired HIV by sexual transmission (HIV‐ST) in terms of late presentation (LP), delay in ...anti‐retroviral treatment (ART) initiation, virological and immunological response to ART, mortality and progression to AIDS.
Design
Prospective multi‐centre cohort study of HIV‐infected subjects naive to ART at entry (Cohort of the Spanish HIV Research Network: CoRIS).
Setting
Thirty‐one centres from the Spanish public health‐care system.
Participants
A total of 9355 patients were included (1064 HIV‐IDU and 8291 HIV‐ST) during 2004–13.
Measurements
We compared LP (defined as presentation for care with a CD4 cell count < 350/μl and/or AIDS‐defining illness), delayed ART initiation (defined as initiating treatment more than 6 months after the date when treatment was indicated by the guidelines, or not initiating treatment at all when it was indicated), virological and immunological response to ART (defined as viral load < 50 HIV‐1 RNA copies/ml and a CD4 count increase of at least 100 cells/μl, respectively, after 1 year of treatment), mortality and progression to AIDS in HIV‐IDU and HIV‐ST.
Findings
Compared with HIV‐ST, HIV‐IDU had higher risk of LP odds ratio (OR) = 1.76; 95% confidence interval (CI) = 1.41–2.18, delayed ART initiation (OR 1.87; 95% CI = 1.46–2.40) and higher mortality hazard ratio (HR) = 1.43; 95% CI = 1.03–2.01 and risk of progression to AIDS subhazard ratio (SHR) = 1.68; 95% CI = 1.29–2.18. Virological suppression due to ART was lower in HIV‐IDU than in patients with HIV‐ST only among patients without hepatitis C virus (HCV) infection adjusted OR (aOR) = 0.59; 95% CI = 0.36–0.95; among patients with HCV infection, virological suppression due to ART did not show significant differences between HIV‐IDU and HIV‐ST. There were no significant differences in immunological response after adjusting by HCV (aOR = 0.74; 95% CI = 0.52–1.06).
Conclusions
In Spain, patients who acquire HIV infection through use of injected drugs appear to have a higher risk of late presentation, delayed initiation of anti‐retroviral treatment and progression to AIDS and death than patients who acquire HIV by sexual transmission.
Background. CD4 count at start of combination antiretroviral therapy (ART) is strongly associated with short-term survival, but its association with longer-term survival is less well characterized. ...Methods. We estimated mortality rates (MRs) by time since start of ART (<0.5, 0.5–0.9, 1–2.9, 3–4.9, 5–9.9, and ≥10 years) among patients from 18 European and North American cohorts who started ART during 1996–2001. Piecewise exponential models stratified by cohort were used to estimate crude and adjusted (for sex, age, transmission risk, period of starting ART 1996–1997, 1998–1999, 2000–2001, and AIDS and human immunodeficiency virus type 1 RNA at baseline) mortality rate ratios (MRRs) by CD4 count at start of ART (0–49, 50–99, 100–199, 200–349, 350–499, ≥500 cells/μL) overall and separately according to time since start of ART. Results. A total of 6344 of 37 496 patients died during 359 219 years of follow-up. The MR per 1000 person-years was 32.8 (95% confidence interval CI, 30.2–35.5) during the first 6 months, declining to 16.0 (95% CI, 15.4–16.8) during 5–9.9 years and 14.2 (95% CI, 13.3–15.1) after 10 years' duration of ART. During the first year of ART, there was a strong inverse association of CD4 count at start of ART with mortality. This diminished over the next 4 years. The adjusted MRR per CD4 group was 0.97 (95% CI, .94–1.00; P = .054) and 1.02 (95% CI, .98–1.07; P = .32) among patients followed for 5–9.9 and ≥10 years, respectively. Conclusions. After surviving 5 years of ART, the mortality of patients who started ART with low baseline CD4 count converged with mortality of patients with intermediate and high baseline CD4 counts.
This article describes the development of the Cohort of the Spanish Research Network (CoRIS), its methodological and organizational aspects, the demographic and clinical characteristics of the ...subjects enrolled and quantifies the losses to follow-up and associated factors.
Multicentre cohort of HIV-positive naïve subjects recruited in 28 sites of Spain from 2004-onwards. Missing and inconsistent data were submitted to internal quality controls and the datasets were externally audited. Multiple logistic regression models were used.
As of October 2009, 5,514 subjects had been recruited, representing 11,708 person-years with a median follow-up time of 1.81 years. Most are men (78.8%), infected by sexual transmission (46.1% men who have sex with men and 35.2% heterosexual persons) and Spanish (69.7%). During follow-up 64.5% have started Antiretroviral Therapy (ART) and 201 deaths have occurred. New HIV diagnoses accounted for 80.7% of the sample. Some 52% of subjects had at least one baseline sample in the BioBank while naïve to ART. Losses to follow-up (18.9%) were more frequent in younger people, in injecting drug users, in persons of non-Spanish origin, in persons with primary or lower educational level, and in those with a CD4 count over 350 cells/mm(3) at time of recruitment.
The implementation of CoRIS has been successful; the cohort has wide representation at national level, is actively recruiting new members and blood samples, and has excellent data quality. Losses to follow-up are of similar magnitude to other cohort studies, as are the factors associated with them.
To estimate incidence and clearance of high-risk human papillomavirus (HR-HPV), and their risk factors, in men who have sex with men (MSM) recently infected by HIV in Spain; 2007-2013.
Multicenter ...cohort. HR-HPV infection was determined and genotyped with linear array. Two-state Markov models and Poisson regression were used.
We analysed 1570 HR-HPV measurements of 612 MSM over 13 608 person-months (p-m) of follow-up. Median (mean) number of measurements was 2 (2.6), median time interval between measurements was 1.1 years (interquartile range: 0.89-1.4). Incidence ranged from 9.0 95% confidence interval (CI) 6.8-11.8 per 1000 p-m for HPV59 to 15.9 (11.7-21.8) per 1000 p-m for HPV51. HPV16 and HPV18 had slightly above average incidence: 11.9/1000 p-m and 12.8/1000 p-m. HPV16 showed the lowest clearance for both 'prevalent positive' (15.7/1000 p-m; 95% CI 12.0-20.5) and 'incident positive' infections (22.1/1000 p-m; 95% CI 11.8-41.1). More sexual partners increased HR-HPV incidence, although it was not statistically significant. Age had a strong effect on clearance (P-value < 0.001) due to the elevated rate in MSM under age 25; the effect of HIV-RNA viral load was more gradual, with clearance rate decreasing at higher HIV-RNA viral load (P-value 0.008).
No large variation in incidence by HR-HPV type was seen. The most common incident types were HPV51, HPV52, HPV31, HPV18 and HPV16. No major variation in clearance by type was observed, with the exception of HPV16 which had the highest persistence and potentially, the strongest oncogenic capacity. Those aged below 25 or with low HIV-RNA- viral load had the highest clearance.
To compare causes of death (CoDs) from two independent sources: National Basic Death File (NBDF) and deaths reported to the Spanish HIV Research cohort Cohort de adultos con infección por VIH de la ...Red de Investigación en SIDA CoRIS) and compare the two coding algorithms: International Classification of Diseases, 10th revision (ICD-10) and revised version of Coding Causes of Death in HIV (revised CoDe).
Between 2004 and 2008, CoDs were obtained from the cohort records (free text, multiple causes) and also from NBDF (ICD-10). CoDs from CoRIS were coded according to ICD-10 and revised CoDe by a panel. Deaths were compared by 13 disease groups: HIV/AIDS, liver diseases, malignancies, infections, cardiovascular, blood disorders, pulmonary, central nervous system, drug use, external, suicide, other causes and ill defined.
There were 160 deaths. Concordance for the 13 groups was observed in 111 (69%) cases for the two sources and in 115 (72%) cases for the two coding algorithms. According to revised CoDe, the commonest CoDs were HIV/AIDS (53%), non-AIDS malignancies (11%) and liver related (9%), these percentages were similar, 57, 10 and 8%, respectively, for NBDF (coded as ICD-10). When using ICD-10 to code deaths in CoRIS, wherein HIV infection was known in everyone, the proportion of non-AIDS malignancies was 13%, liver-related accounted for 3%, while HIV/AIDS reached 70% due to liver-related, infections and ill-defined causes being coded as HIV/AIDS.
There is substantial variation in CoDs in HIV-infected persons according to sources and algorithms. ICD-10 in patients known to be HIV-positive overestimates HIV/AIDS-related deaths at the expense of underestimating liver-related diseases, infections and ill defined causes. CoDe seems as the best option for cohort studies.
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.
The aim of this study was to analyse associations between educational level and delayed HIV diagnosis (DD), late initiation of combined antiretroviral therapy (cART), overall and in subjects with ...timely HIV diagnosis, virological and immunological responses to cART, and mortality from HIV diagnosis and cART initiation.
This was a multicentre cohort study of HIV-positive treatment-naive subjects in Spain between 2004-2009. Logistic and Cox regression analyses were used.
Of 4,549 subjects, 44.5% had low education level (LOW), 34.4% medium education level (MED) and 21.1% high education level (HIG). In men, DD was more common in MED (OR 1.3 95% CI 1.0, 1.7) or LOW OR 1.8 (95% CI 1.4, 2.3) compared to HIG. In women, the opposite was observed; women with HIG were 40% more likely to have DD than those with LOW (OR 1.4 95% CI 0.8, 2.5). In individuals with timely HIV diagnoses, percentages of late cART initiators were similar (LOW 9.5%, MED 11.4% and HIG 7.0%; P=0.114). Immunological (LOW 68%, MED 76% and HIG 84%) and virological (LOW 76%, MED 83% and HIG 86%) responses to cART increased significantly with educational level; these increases remained significant in multivariate analyses. Mortality for LOW subjects was higher than for HIG, from HIV diagnosis (hazard ratio HR 2.3 95% CI 1.1, 4.9) and from cART initiation (HR 1.8 95% CI 0.8, 3.9).
We found important differences by educational level in diagnosis delay, virological and immunological responses to cART and mortality in a country with universal health care. Women with high educational level are at higher risk of having delayed HIV diagnoses. Educational level should be taken into account when designing HIV testing and clinical management strategies.
Objectives
The aim of the study was to assess the adequacy of initial antiretroviral therapy (ART), in terms of its timing and the choice of regimens, according to the Spanish national treatment ...guidelines Spanish AIDS Study Group−National Plan for AIDS (GeSIDA‐PNS) Guidelines for treatment‐naïve HIV‐infected patients.
Methods
A prospective cohort study of HIV‐positive ART‐naïve subjects attending 27 centres in Spain from 2004 to 2010 was carried out. Regimens were classified as recommended, alternative or nonrecommended according to the guidelines. Delayed start of treatment was defined as starting treatment later than 12 months after the patient had fulfilled the treatment criteria. Multivariate logistic and Cox regression analyses were performed.
Results
A total of 6225 ART‐naïve patients were included in the study. Of 4516 patients who started treatment, 91.5% started with a recommended or alternative treatment. The use of a nonrecommended treatment was associated with a CD4 count > 500 cells/μL odds ratio (OR) 2.03; 95% confidence interval (CI) 1.14–3.59, hepatitis B (OR 2.23; 95% CI 1.50–3.33), treatment in a hospital with < 500 beds, and starting treatment in the years 2004–2006. Fourteen per cent of the patients had a delayed initiation of treatment. Delayed initiation of treatment was more likely in injecting drug users, patients with hepatitis C, patients with higher CD4 counts and during the years 2004–2006, and it was less likely in patients with viral loads > 5 log HIV‐1 RNA copies/ml. The use of a nonrecommended regimen was significantly associated with mortality hazard ratio (HR) 1.61; 95% CI 1.03–2.52; P = 0.035 and lack of virological response.
Conclusions
Compliance with the recommendations of Spanish national guidelines was high with respect to the timing and choice of initial ART. The use of nonrecommended regimens was associated with a lack of virological response and higher mortality.
Objectives. Since subjects may have been diagnosed before cohort entry, analysis of late HIV diagnosis (LD) is usually restricted to the newly diagnosed. We estimate the magnitude and risk factors of ...LD in a cohort of seroprevalent individuals by imputing seroconversion dates. Methods. Multicenter cohort of HIV-positive subjects who were treatment naive at entry, in Spain, 2004–2008. Multiple-imputation techniques were used. Subjects with times to HIV diagnosis longer than 4.19 years were considered LD. Results. Median time to HIV diagnosis was 2.8 years in the whole cohort of 3,667 subjects. Factors significantly associated with LD were: male sex; Sub-Saharan African, Latin-American origin compared to Spaniards; and older age. In 2,928 newly diagnosed subjects, median time to diagnosis was 3.3 years, and LD was more common in injecting drug users. Conclusions. Estimates of the magnitude and risk factors of LD for the whole cohort differ from those obtained for new HIV diagnoses.
HIV cohort collaborations, which pool data from diverse patient cohorts, have provided key insights into outcomes of antiretroviral therapy (ART). However, the extent of, and reasons for, ...between-cohort heterogeneity in rates of AIDS and mortality are unclear.
We obtained data on adult HIV-positive patients who started ART from 1998 without a previous AIDS diagnosis from 17 cohorts in North America and Europe. Patients were followed up from 1 month to 2 years after starting ART. We examined between-cohort heterogeneity in crude and adjusted (age, sex, HIV transmission risk, year, CD4 count and HIV-1 RNA at start of ART) rates of AIDS and mortality using random-effects meta-analysis and meta-regression.
During 61 520 person-years, 754/38 706 (1.9%) patients died and 1890 (4.9%) progressed to AIDS. Between-cohort variance in mortality rates was reduced from 0.84 to 0.24 (0.73 to 0.28 for AIDS rates) after adjustment for patient characteristics. Adjusted mortality rates were inversely associated with cohorts' estimated completeness of death ascertainment excellent: 96-100%, good: 90-95%, average: 75-89%; mortality rate ratio 0.66 (95% confidence interval 0.46-0.94) per category. Mortality rate ratios comparing Europe with North America were 0.42 (0.31-0.57) before and 0.47 (0.30-0.73) after adjusting for completeness of ascertainment.
Heterogeneity between settings in outcomes of HIV treatment has implications for collaborative analyses, policy and clinical care. Estimated mortality rates may require adjustment for completeness of ascertainment. Higher mortality rate in North American, compared with European, cohorts was not fully explained by completeness of ascertainment and may be because of the inclusion of more socially marginalized patients with higher mortality risk.
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