Early Detection of Cancer and Precancerous Lesions in Persons with HIV through a Comprehensive Cancer Screening Protocol.

BACKGROUND: Non-AIDS defining malignancies present a growing challenge for persons with HIV (PWH), yet tailored interventions for timely cancer diagnosis are lacking. The Spanish IMPAC-Neo protocol was designed to compare two comprehensive cancer screening strategies integrated into routine HIV care. This study reports baseline data on the prevalence and types of precancerous lesions and early-stage cancer among participants at enrolment. Acceptability of the procedure was additionally assessed. METHODS: Cross-sectional analysis of a comprehensive screening protocol to detect precancer and cancer. The readiness of healthcare providers to implement the protocol was evaluated using a validated 4-item survey. RESULTS: Among the 1430 enrolled PWH, 1172 underwent 3181 screening tests, with positive findings in 29.4% of cases, leading to further investigation in 20.7%. Adherence to the protocol was 84%, with HIV providers expressing high acceptability (97.1%), appropriateness (91.4%), and feasibility (77.1%). A total of 145 lesions were identified in 109 participants, including 60 precancerous lesions in 35 patients (3.0%), 9 early-stage cancers in 9 patients (0.8%), and 76 low-risk lesions in 65 subjects (5.5%). Adverse events related to screening occurred in 0.8% of participants, all mild. The overall prevalence of cancer precursors or early-stage cancer was 3.8% (95% CI, 2.74%-5.01%), with highest rates observed in individuals screened for anal and colorectal cancers. CONCLUSIONS: The baseline comprehensive cancer screening protocol of the IMPAC-Neo study successfully identified a significant proportion of PWH with precancerous lesions and early-stage cancer. High adherence rates and positive feedback from providers suggest effective implementation potential in real-world healthcare settings.

Experience with tocilizumab in severe COVID-19 pneumonia after 80 days of follow-up: A retrospective cohort study.

OBJECTIVES: To describe the clinical characteristics and predictors of major outcomes in patients treated with tocilizumab (TCZ) for severe COVID-19 pneumonia. PATIENTS AND METHODS: Case series of all sequential patients with severe COVID-19 pneumonia treated with TCZ at an Academic Spanish hospital (March 12 - May 2, 2020). Clinical outcomes: death, length of hospital stay. An early clinical response to TCZ (48-72 h after the administration) was assessed by variations in respiratory function markers, Brescia COVID Respiratory Severity Scale (BCRSS), inflammatory parameters, and patients' and physicians' opinion. Associations were tested by multiple logistic regression. RESULTS: From a cohort of 236 patients, 77 patients treated with TCZ were included (median age 62 years (IQR 53.0-72.0), 64.9% were males), 42.9% had Charlson index ≥3; hypertension (41.6%), obesity (34.7%), and diabetes (20.8%). Median follow-up was 83.0 days (78.0-86.5), no patient was readmitted. ICU admission was required for 42 (54.5%), invasive mechanical ventilation in 38 (49.4%) and 10 patients died (12.9% global, 23.8% at ICU admitted). After multivariate adjustment, TCZ response by BCRSS (OR 0.03 (0.01-0.68), p = 0.028), and Charlson index (OR 3.54 (1.20-10.44), p = 0.022) has been identified as independent factors associated with mortality. Median of hospital stay was 16.0 days (11.0-23.0); BCRSS, physician subjective and D-dimer response were associated with shorter hospitalization stay. CONCLUSIONS: In a Mediterranean cohort, use of tocilizumab for severe COVID-19 show 12.9% of mortality. Early TCZ-response by BCRSS and low comorbidity were associated with increased survival. Early TCZ-response was related to shorter median hospital stay.

Neurocognitive Impairment in Well-Controlled HIV-Infected Patients: A Cross-Sectional Study.

The reported prevalence of HIV-associated neurocognitive disorders in HIV people depends on the population studied and the methodology used. We analyze the prevalence of neurocognitive impairment (NCI) and associated factors in patients on successful antiretroviral therapy (ART), without comorbidities. Cross-sectional observational study in HIV subjects, ≥18 years old, on stable ART, and HIV viral load of <50 copies/mL. Patients with medical or psychiatric comorbidities and substance abuse were excluded. NCI was diagnosed using Frascati criteria, examining seven neurocognitive domains (NDs). We analyzed the association between NCI and HIV-related clinical variables, carotid intima-media thickness, bacterial translocation, and plasma inflammatory biomarkers [soluble CD14, interleukin-6 (IL-6), and tumor necrosis factor-α]. The prevalence of NCI was calculated with a 95% confidence interval (CI). We fitted a logistic regression model to assess the strength of the associations. Eighty-four patients were included with an observed NCI prevalence of 29.8% (95% CI: 21.0-40.2): 19% had asymptomatic NCI, 8.3% had mild neurocognitive disorder, and 2.4% had HIV-associated dementia. Delayed recall was the most commonly affected ND (27.4%). People diagnosed at least 10 years ago (odds ratio [OR]: 6.5, 95% CI: 1.6-21.7) and those with IL-6 levels above 1.8 pg/mL (OR: 6.0, 95% CI: 1.1-31.3) showed higher odds of NCI in adjusted analyses. Participants with carotid plaques had lower scores for delayed recall: -0.9 ± 1.1 versus -0.2 ± 1.1 (p = .04). Prevalence of NCI is high in otherwise healthy adults with HIV-infection. In this population, more than 10 years since HIV diagnosis and high IL-6 levels are associated with NCI. Delayed recall ND is worse in patients with subclinical atherosclerosis.

Role of HIV in the desire of procreation and motherhood in women living with HIV in Spain: a qualitative approach.

BACKGROUND: Improved antiretroviral treatments and decrease in vertical transmission of HIV have led to a higher number of women living with HIV to consider childbearing. However, stigma and social rejection result in specific challenges that HIV positive women with procreation intentions have to face with. Our objective was to in depth analyse elements shaping their desire for procreation and specifically investigate the impact of HIV. METHODS: A qualitative study was conducted through open interviews with 20 women living with HIV between 18 and 45 years of age, from the Spanish AIDS Research Network Cohort (CoRIS). Interviews were audio-recorded and transcribed. A content analysis was performed. RESULTS: HIV diagnosis is a turning point in women's sexual and emotional life that is experienced traumatically. HIV diagnosis is usually associated with the fear of an immediate death and the idea of social isolation. At this moment, women temporarily reject future motherhood or having a sexual life. HIV status is only disclosed to the closed social circle and partner support is essential in HIV diagnosis assimilation process. Health professionals provide information on assisted reproductive technology and on how to minimize risk of partner HIV transmission. Most of barriers for procreation acknowledged by women are not related to HIV. However, women fear vertical transmission and experience other barriers derived from HIV infection. In this context, pregnancy makes women feel themselves as "normal women" despite HIV. Motherhood is considered an element of compensation that helps them to cope with HIV diagnosis. All these elements make health professionals key actors: they provide information and support after HIV diagnosis. CONCLUSIONS: Barriers and drivers for procreation are similar among HIV positive women and general population. However, stigma and discrimination linked with HIV weigh in HIV positive women decision of motherhood. In this context, it is necessary to provide these women with the necessary counselling, guidance and resources to take decisions about procreation properly informed.

Subclinical atherosclerosis in low Framingham risk HIV patients.

BACKGROUND: Pathogenesis of atherosclerosis is complex, and differences between HIV-infected patients and general population cannot be completely explained by the higher prevalence of traditional cardiovascular risk factors. We aimed to analyse the association between inflammation and subclinical atherosclerosis in HIV patients with low Framingham risk score. MATERIALS AND METHODS: Case-control study. SETTING: Outpatient Infectious Diseases clinic in a university hospital. SUBJECTS: HIV-1-infected patients aged > 35 years receiving antiretroviral treatment with viral load < 50 copies/mL and Framingham risk score < 10%. EXCLUSION CRITERIA: inflammatory diseases; dyslipidaemia requiring statins; smoking > 5 cigarettes/day; diabetes; hypertension; vascular diseases. MAIN OUTCOME: subclinical atherosclerosis determined by ultrasonography: common carotid intima-media thickness greater than 0·8 mm or carotid plaque presence. Explanatory variables: ribosomal bacterial DNA (rDNA), sCD14, interleukin-6 (IL-6) and TNF-α. RESULTS: Eighty-four patients were included, 75% male, mean age 42 years and mean CD4+ cells 657 ± 215/mm3 . Median Framingham risk score was 1% at 10 years (percentile 25-75: 0·5-4%). Eighteen patients (21%) had subclinical atherosclerosis; the associated factors were older age (P = 0·001), waist-hip ratio (P = 0·01), time from HIV diagnosis (P = 0·02), rDNA (P = 0·04) and IL-6 (P = 0·01). In multivariate analysis, OR for subclinical atherosclerosis was 7 (95% CI, 1.3-40, P = 0.02) and 9 (95% CI, 1.0-85, P = 0.04) for patients older than 44 years and IL-6 > 6·6 pg/mL, respectively. CONCLUSIONS: Well-controlled HIV patients with low Framingham risk score have a high prevalence of subclinical carotid atherosclerosis, and the main risk factors are age and inflammation. These patients are not receiving primary prophylaxis for cardiovascular events according to current guidelines.

Executive summary of the GESIDA/National AIDS Plan Consensus Document on antiretroviral therapy in adults infected by the human immunodeficiency virus (updated January 2015).

In this update, antiretroviral therapy (ART) is recommended for all patients infected by type 1 human immunodeficiency virus (HIV-1). The strength and grade of the recommendation vary depending on the CD4+ T-lymphocyte count, the presence of opportunistic infections or comorbid conditions, age, and the efforts to prevent the transmission of HIV. The objective of ART is to achieve an undetectable plasma viral load (PVL). Initial ART should comprise three drugs, namely, two nucleoside reverse transcriptase inhibitors (NRTI) and one drug from another family. Three of the recommended regimens, all of which have an integrase strand transfer inhibitor (INSTI) as the third drug, are considered a preferred regimen; a further seven regimens, which are based on an INSTI, an non-nucleoside reverse transcriptase inhibitor (NNRTI), or a protease inhibitor boosted with ritonavir (PI/r), are considered alternatives. The reasons and criteria for switching ART are presented both for patients with an undetectable PVL and for patients who experience virological failure, in which case the rescue regimen should include three (or at least two) drugs that are fully active against HIV. The specific criteria for ART in special situations (acute infection, HIV-2 infection, pregnancy) and comorbid conditions (tuberculosis and other opportunistic infections, kidney disease, liver disease, and cancer) are updated.

Vitamin D insufficiency and subclinical atherosclerosis in non-diabetic males living with HIV.

INTRODUCTION: Vitamin D insufficiency (VDI) has been associated with increased cardiovascular risk in the non-HIV population. This study evaluates the relationship among serum 25-hydroxyvitamin D [25(OH)D] levels, cardiovascular risk factors, adipokines, antiviral therapy (ART) and subclinical atherosclerosis in HIV-infected males. METHODS: A cross-sectional study in ambulatory care was made in non-diabetic patients living with HIV. VDI was defined as 25(OH)D serum levels <75 nmol/L. Fasting lipids, glucose, inflammatory markers (tumour necrosis factor-α, interleukin-6, high-sensitivity C-reactive protein) and endothelial markers (plasminogen activator inhibitor-1, or PAI-I) were measured. The common carotid artery intima-media thickness (C-IMT) was determined. A multivariate logistic regression analysis was made to identify factors associated with the presence of VDI, while multivariate linear regression analysis was used to identify factors associated with common C-IMT. RESULTS: Eighty-nine patients were included (age 42 ± 8 years), 18.9% were in CDC (US Centers for Disease Control and Prevention) stage C and 75 were on ART. VDI was associated with ART exposure, sedentary lifestyle, higher triglycerides levels and PAI-I. In univariate analysis, VDI was associated with greater common C-IMT. The multivariate linear regression model, adjusted by confounding factors, revealed an independent association between common C-IMT and patient age, time of exposure to protease inhibitors (PIs) and impaired fasting glucose (IFG). In contrast, there were no independent associations between common C-IMT and VDI or inflammatory and endothelial markers. CONCLUSIONS: VDI was not independently associated with subclinical atherosclerosis in non-diabetic males living with HIV. Older age, a longer exposure to PIs, and IFG were independent factors associated with common C-IMT in this population.

Low-level HIV viremia is associated with microbial translocation and inflammation.

BACKGROUND: Decrease in HIV viral load (VL) is accompanied by decrease in microbial translocation (MT) and chronic inflammation, but the behavior of these markers in patients with HIV-VL <20 copies per milliliter is unknown. The aim of this study was to determine whether strict control of HIV-VL is associated with MT and chronic inflammation. METHODS: Observational cross-sectional study. INCLUSION CRITERIA: HIV patients receiving antiretroviral therapy and HIV-VL <200 copies per milliliter for more than 6 months. EXCLUSION CRITERIA: chronic liver disease, active infection, or antibiotic consumption. Recruitment: patients who consecutively visited the outpatient clinic in November 2011. Primary endpoint: molecular MT as determined by detection in plasma of 16S ribosomal DNA. Secondary variables: lipopolysaccharide, soluble CD14, tumor necrosis factor α, and interleukin 6. Primary explanatory variable: HIV-VL (COBAS AmpliPrep/COBAS TaqMan HIV-1 test, version 2.0) with a detection limit of 20 copies per milliliter. RESULTS: Fifty-two patients were included: 65% men, median age 45 years, HIV acquired predominantly through sex (75%), 40% Centers for Disease Control and Prevention stage C, and median CD4 lymphocyte count 552 cells per cubic millimeter (range, 126-1640 cells/mm). Molecular MT was observed in 46% and 18% of patients with low-level (20-200 copies/mL) and negative (<20 copies/mL) HIV-VL, respectively (P < 0.05). Plasma levels of inflammatory markers (tumor necrosis factor α and interleukin 6) were higher in patients with molecular MT (P < 0.01) and were not influenced for HIV-VL. CONCLUSIONS: Patients with HIV infection receiving treatment and negative HIV-VL (<20 copies/mL) present less frequently MT than patients with low-level HIV viremias (20-200 copies/mL). MT is associated with higher levels of inflammation markers, independent of HIV-VL.

[Costs and cost-efficacy analysis of the preferred treatments by GESIDA/National Plan for AIDS for the initial antiretroviral therapy in adult human immunodeficiency virus (HIV) infected patients in 2012]. / Análisis de costes y de coste/eficacia de las pautas preferentes de GESIDA/Plan Nacional sobre el Sida en 2012 para el tratamiento antirretroviral inicial en adultos infectados por el virus de la inmunodeficiencia humana (VIH).

INTRODUCTION: The GESIDA and National AIDS Plan panel of experts propose «preferred regimens¼ of antiretroviral treatment (ART) as initial therapy in HIV infected patients for 2012. The objective of this study is to evaluate the costs and the efficiency of initiating treatment with these «preferred regimens¼. METHODS: Economic assessment of costs and efficiency (cost/efficacy) using decision tree analysis model. Efficacy was defined as the probability of having a viral load <50 copies/ml at week 48, in an intention-to-treat analysis. Cost of initiating treatment with an ART regime was defined as the costs of ART and all its consequences (adverse effects, changes of ART regime, and drug resistance analyses) during the first 48 weeks. The perspective of the analysis is that of the National Health System, considering only differential direct costs: ART (official prices), management of adverse effects, studies of resistance and determination of HLA B 5701. The setting is Spain and the costs are those of 2012. A sensitivity deterministic analysis was conducted, building three scenarios for each regime: baseline, most favourable, and most unfavourable cases. RESULTS: In the baseline case scenario, the cost of initiating treatment ranges from 6,895 euros for TDF/FTC+NVP to 12,067 euros for TDF/FTC+RAL. The efficacy ranges between 0.66 for ABC/3TC+LPV/r and 0.87 for TDF/FTC+RAL. Efficiency, in terms of cost/efficacy, varies between 9,387 and 13,823 euros per responder at 48 weeks, for TDF/FTC/EFV and TDF/FTC+RAL, respectively. In the most unfavourable scenario, the most efficient regime is TDF/FTC+NVP (9,742 per responder). CONCLUSION: Considering the official prices of ART, the most efficient regimens are TDF/FTC/EFV (baseline case and most favourable scenarios), and TDF/FTC+NVP (most unfavourable scenario).

[Reproducibility of a method to quantify vaginal human immunodeficiency virus viral load]. / Estudio de consistencia de una metodología para cuantificar la carga viral vaginal del virus de la inmunodeficiencia humana.

OBJECTIVE: To assess the reproducibility of a method to collect and quantify HIV nucleic acids in vaginal secretions. METHODS: We analysed two consecutive vaginal samples collected by direct aspiration from 52 HIV infected women. Nucleic acids were extracted by QIAamp RNA-viral and quantified with a modified Cobas Amplicor HIV-1 Monitor. RESULTS: Intra-class correlation coefficient between matched samples: 0.99. Differences of pooled HIV DNA+RNa and RNA were <0.40 uLog for 95% of all samples (Bland-Altman plots). CONCLUSIONS: This method is a standard and reproducible assay to detect and measure HIV vaginal viral load.

Microbiology and outcome of iliopsoas abscess in 124 patients.

To describe the microbiology and outcome of iliopsoas abscess (IPA) in a large case series, we analyzed 124 cases of IPA collected from 1990 through 2004 in 11 hospitals in Spain. Twenty-seven (21.8%) patients had primary and 97 (78.2%) had secondary IPA. The main sources of infection were bone (50.5%), gastrointestinal tract (24.7%), and urinary tract (17.5%). A definitive microbial diagnosis was achieved in 93 (75%) cases. Abscess culture was the most frequent procedure leading to microbial diagnosis, followed by blood cultures. Staphylococcus aureus, Escherichia coli, and Bacteroides species were the most frequent microbial causes: S. aureus was the most common organism in patients with primary abscesses (42.9%) and with abscesses of skeletal origin (35.2%), whereas E. coli was the leading organism in those with abscesses of urinary (61.5%) and gastrointestinal (42.1%) tracts. Mycobacterium tuberculosis was found in 15 patients, 4 of them associated with human immunodeficiency virus (HIV) infection. Twenty (21.5%) cases had polymicrobial infections; these were more common among patients with abscesses of gastrointestinal origin. Information on clinical outcome was available for 120 patients; 19 (15.8%) had a relapse and 6 (5%) died due to complications related to the IPA. Patients who died were older and more likely to have bacteremia and E. coli isolated from cultures. In conclusion, secondary IPA is more prevalent than primary IPA. Among those with secondary IPA, most abscesses are secondary to a skeletal source. A bacterial etiology can be identified in most cases. The overall prognosis of patients with this condition is good.

[Chronic hepatitis C virus infection and associated liver disease among the inmates of a Spanish prison]. / Infección crónica por el virus de la hepatitis C y enfermedad hepática asociada en una prisión española.

OBJECTIVE: The objective of this study was to determine the prevalence and genotype distribution of chronic hepatitis C virus (HCV) infection in a penitentiary population. The secondary objective was to describe histological findings in liver of the biopsied population, and identify risk factors associated with liver fibrosis and inflammatory activity. METHODS: Among 800 inmates, 730 accepted HCV antibody screening and PCR confirmation. Sociodemographic, behavioral, and incarceration-related variables were analyzed. Liver biopsy was offered to individuals with chronic HCV infection. Advanced liver disease was defined as fibrosis 3 and/or an inflammatory activity index score 8). RESULTS: HCV antibodies were found in 279 inmates. PCR confirmed HCV infection in 250 inmates, yielding a prevalence of 34.2% (95% confidence interval [CI]: 30.8-37.8). Intravenous drug use was independently associated with HCV infection, odds ratio (OR) 51.7 (95% CI: 31-86). Genotypes were 1a 32.9%, 3 29.7%, 1b 18.4% and 4 17.1%. Fifty-one liver biopsies were performed; advanced liver disease was found in 7 patients (13.7%) based on fibrosis and in 31 patients (60.7%) based on the inflammatory activity index. High AST and ALT levels were associated with advanced liver disease established on both fibrosis and inflammatory activity (P<.05). Lengthy intravenous drug use was associated with inflammatory activity (P=.02; OR 1.2; 95% CI: 1.03-1.7). CONCLUSIONS: Persistent HCV infection is highly prevalent among prison inmates and is associated with intravenous drug abuse. HCV genotype diversity is higher in prison inmates than in the general population. Higher transaminase levels are associated with advanced liver disease.

Characteristics and outcome of AIDS-related Hodgkin lymphoma before and after the introduction of highly active antiretroviral therapy.

OBJECTIVES: We analyzed survival, therapeutic response, and prognostic factors in patients with HIV-related Hodgkin lymphoma (HL) treated or not with highly active antiretroviral therapy (HAART). METHODS: This study included 104 patients with HL, treated (n = 83) or not (n = 21) with HAART. Outcomes and prognostic factors of complete remission (CR), overall survival (OS), and disease-free survival (DFS) were assessed by an intention-to-treat analysis of all patients who received at least 1 chemotherapy course. RESULTS: No differences were found between groups at baseline in the specific characteristics of HIV and HL. The proportion of patients receiving appropriate-for-stage therapy for HL was similar for both groups. The CR rates in the HAART (-) and HAART (+) groups were 14 (70%) of 20 versus 71 (91%) of 78 (P = 0.023). The median OS in the HAART (-) group was 39 months (95% confidence interval [CI]: 0 to 89) and was not reached in the HAART (+) group (P = 0.0089). The median DFS in the HAART (-) group was 85 months (95% CI: 73 to 97) and was not reached in the HAART (+) group (P = 0.129). Factors independently associated with CR by logistic regression analysis were appropriate-for-stage therapy of HL, HAART, and baseline CD4 count > or =100 cells/microL. CR was the only factor independently associated with OS by Cox regression analysis. CONCLUSIONS: The achievement of CR was independently associated with appropriate-for-stage therapy for HL, with HAART, and with a baseline CD4 count > or =100 cells/microL. The only variable independently associated with OS was the achievement of CR.

Immunovirologic consequences and safety of short, non-structured interruptions of successful antiretroviral treatment.

OBJECTIVES: The aim was to evaluate the safety of short antiretroviral treatment interruptions and their virologic and immunologic consequences in HIV-infected adults on highly active antiretroviral treatment (HAART) with suppressed viral replication. The viral efficacy upon reintroduction was also evaluated. PATIENTS AND METHODS: All patients with undetectable viral load while on HAART were prospectively followed to detect any treatment interruption. We analysed viral and cellular kinetics, incidence of resistance mutations, clinical outcome and results after therapy resumption. RESULTS: Twenty patients were included, mean time since HIV diagnosis was 95 months and time with undetectable viral load 16 months. Treatment was interrupted because of adverse effects, cancer, tuberculosis or patient will. Treatment was reintroduced after 4 weeks using, if possible, the same combination. HIV viral load was detectable on day 28 after interruption in 18 patients (90%). Median of CD4 cell count (p25-p75) decreased from 478/mm3 (96-716) to 257/mm3 (118-663) (p=0.5). Resistance mutations were found in 9 patients (45%) after interruptions. Treatment was reintroduced in 14 patients; all of them achieved viral suppression. CONCLUSIONS: In patients receiving HAART who have undetectable viral load, an interruption, no longer than 4 weeks, due to any intercurrent problem seems to be safe. Response to resumption can usually be achieved. Due to the frequent development of resistance, a genotypic test during interruption might be helpful.

Osteonecrosis in patients infected with HIV: clinical epidemiology and natural history in a large case series from Spain.

BACKGROUND: There is a paucity of data on clinical epidemiology of osteonecrosis in HIV-infected patients. We aimed to describe patients' characteristics and natural history of this poorly known condition. METHODS: All cases of symptomatic HIV-related osteonecrosis diagnosed from 1990 through 2003 in 19 Spanish clinics were reviewed. Functional status at the last visit was assessed with the validated Western Ontario and McMaster Universities Index questionnaire. RESULTS: Of 54 patients analyzed, 29 (53.7%) had a single bone necrosis, and 25 (46.3%) had 2 or more sites involved. Progression of symptoms happened more often in patients with hip involvement (17/39 vs 0/8 patients; P = 0.019). Twenty patients (37%) required surgical intervention. Male sex and higher CD4 cell count were associated with surgery on multivariable analysis. Overall, at the end of the follow-up period, half of the patients had moderate to severe disability (Western Ontario and McMaster Universities Index score > or =60). During a follow-up period of 137 person-years, only 2 new episodes of osteonecrosis were observed (rate of recurrences, 1.5/100 person-years; 95% confidence interval, 0.4-5.1). CONCLUSIONS: HIV-related osteonecrosis is associated with significant disability over time. Location of bone necrosis, sex, and CD4 cell count may influence the outcome. The risk for recurrences for patients who have experienced 1 episode is low.