Humoral immunogenicity of primary yellow fever vaccination in infants and children: a systematic review, meta-analysis and meta-regression.

BACKGROUND: Vaccination plays a critical role in mitigating the burden associated with yellow fever (YF). However, there is a lack of comprehensive evidence on the humoral response to primary vaccination in the paediatric population, with several questions debated, including the response when the vaccine is administered at early ages, the effect of co-administration with other vaccines, the duration of immunity and the use of fractional doses, among others. This study summarizes the existing evidence regarding the humoral response to primary YF vaccination in infants and children. METHODS: Studies on the humoral response to primary YF vaccination in children aged 12 years or younger were reviewed. The humoral vaccine response rate (VRR), i.e. the proportion of children who tested positive for vaccine-induced YF-specific neutralizing antibodies, was pooled through random-effects meta-analysis and categorized based on the time elapsed since vaccination. Subgroup, meta-regression and sensitivity analyses were performed. RESULTS: A total of 33 articles met the inclusion criteria, with all but one conducted in countries where YF is endemic. A total of 14 028 infants and children entered this systematic review. Within three months following vaccination, the pooled VRR was 91.9% (95% CI 89.8-93.9). A lower VRR was observed with the 17DD vaccine at the meta-regression analysis. No significant differences in immunogenicity outcomes were observed based on age, administration route, co-administration with other vaccines, or fractional dosing. Results also indicate a decline in VRR over time. CONCLUSIONS: Primary YF vaccination effectively provides humoral immunity in paediatric population. However, humoral response declines over time, and this decline is observable after the first 18 months following vaccination. A differential response according to the vaccine substrain was also observed. This research has valuable implications for stimulating further research on the primary YF vaccination in infants and children, as well as for informing future policies.

Prevention and Treatment of SARS-CoV2 Infection in People Living with HIV: The Need for Specific Data.

The HIV pandemic has led to close to 40 million people living with HIV (PLWH) worldwide. To date, SARS-CoV2 has affected > 220 million people, and unprecedented global efforts have resulted in almost 6000 million doses of SARS-CoV2 vaccines being administered. Although several specific COVID-19 antiviral and anti-inflammatory treatments and SARS-CoV2 vaccines have been approved, the data available to support their use in specific populations such as PLWH remain limited. PLWH includes a range of individuals from practically unaffected immunity to severely immunocompromised individuals, and preventive and therapeutic interventions should be tailored for these subgroups . However, in most randomized clinical trials regarding antivirals, immunomodulators and vaccines for COVID-19, PLWH have been excluded or only enrolled in small numbers leading to a paucity of data. We briefly discuss the current evidence for prevention and treatment of COVID-19 in PLWH and identify key areas where more information is required.

Gambling disorder seeking treatment patients and tobacco use in relation to clinical profiles.

OBJECTIVES: Tobacco smoking and gambling disorder (GD) often co-occur. However, few studies have assessed the extent to which cigarette smoking may serve to classify and/or better define GD behaviour profiles. METHODS: Among a large sample of n = 3,652 consecutive treatment-seeking patients with GD (91% men). Smokers were compared to non-smokers across different sociodemographic, clinical, psychopathological and personality variables. The effect sizes for the means and the proportion differences between the groups were estimated. An evaluation of the smoking changes over the last 15 years was also performed. RESULTS: From the total sample, 62.4% of gamblers reported tobacco use. A decreasing linear trend in tobacco use was observed within the studied period, women having a more irregular pattern. The use of tobacco was linked to the use of alcohol and other illegal drugs. Gamblers who smoke, as compared to those who don't, presented lower education levels, lower social position indexes and active employment. They were younger, with an earlier age of onset, shorter duration of the gambling behavior, higher GD severity, more psychological symptoms, higher scores in novelty seeking and lower scores in reward dependence, self-directedness and self-transcendence. CONCLUSIONS: Gamblers seeking treatment who smoke display particular social, clinical, psychological, temperamental and character features different from non-smoking gamblers, suggesting that the presence or absence of comorbid smoking condition in GD should always be considered when developing an optimal treatment, as gamblers who smoke might need treatment strategies different from non-smoking gamblers.

Estimates of Cancer Mortality Attributable to Carcinogenic Infections in Italy.

Several infectious agents are ascertained causes of cancer, but the burden of cancer mortality attributable to carcinogenic infections in Italy is still unknown. To tackle this issue, we calculated the rate and regional distribution of cancer deaths due to infections sustained by seven pathogens ranked as group 1 carcinogenic agents in humans by the International Agency for Research on Cancer. Population attributable fractions related to these agents were applied to annual statistics of cancer deaths coded according to the 10th International Classification of Diseases. The estimated burden of cancer mortality attributable to carcinogenic infections in Italy during the period 2011-2015 was 8.7% of all cancer deaths registered yearly, on average. Approximately 60% of deaths occurred in men, and almost the whole burden was due to four infectious agents (Helicobacter pylori, hepatitis C virus, high-risk human papillomavirus, and hepatitis B virus). The analysis of regional distribution showed a higher number of infection-related cancer deaths in the northern regions, where the estimates reached 30 (Liguria) and 28 (Friuli Venezia Giulia) deaths per 100,000 inhabitants in 2015. Since one-twelfth of cancer deaths were attributable to these modifiable risk factors, the implementation of appropriate prevention and treatment interventions may help to reduce the impact of these infections on cancer mortality.

Burden of cancer mortality attributable to carcinogenic infections in Spain / Mortalidad por cáncer atribuible a infecciones en España

INTRODUCTION: The impact of carcinogenic infections on cancer-related mortality is unknown. METHODS: The mortality due to cancers attributable to carcinogenic infections was estimated. The attributable fraction for the infectious agents classified as group 1 carcinogenic in human beings was applied to yearly data on causes of cancer mortality over the period 2013-2017 in Spain according to the International Classification of Diseases (ICD-10). RESULTS: It was estimated that 9115 deaths (over 110,287 cancer-related deaths, 8.3%) were attributable to infections caused by carcinogenic agents. The estimated number of deaths in men was 5434 (59.6%). The estimated mortality attributable to Helicobacter pylori infection accounted for 48.3% and four agents (H. pylori, HCV, HPV, and HBV) accounted for 96.8% of all cancer deaths attributable to carcinogenic infections. The burden of cancer-related mortality attributable to carcinogenic infections in Spain during the period 2013-2017 was approximately 8%. CONCLUSIONS: In Spain, one-twelfth of cancer deaths are attributable to carcinogenic infections. Public health measures aiming to reduce the impact of carcinogenic infections are essential

INTRODUCCIÓN: El impacto de las infecciones carcinogénicas en la mortalidad por cáncer es desconocido. MÉTODOS: Se estimó la mortalidad por cáncer atribuible a infecciones carcinogénicas en España. Se aplicó la fracción atribuible de los agentes infecciosos clasificados como carcinogénicos a los datos sobre causas de muerte por cáncer anuales del período 2013-2017 según la Clasificación Internacional de Enfermedades (CIE-10). RESULTADOS: De 110.287 muertes por cáncer, se estimó que 9.115 (8,3%) fueron atribuibles a agentes infecciosos carcinogénicos en 2017. El número estimado de muertes en varones fue de 5.434 (59,6%). La mortalidad estimada por cáncer atribuible a infección por H. pylori representó el 48,3% y 4 agentes (H. pylori, VHC, VPH y VHB) registraron el 96,8% de todas las muertes por cáncer atribuible a infecciones carcinogénicas. La carga de mortalidad por cáncer atribuible a infecciones carcinogénicas en el período 2013-2017 en España fue del 8%, aproximadamente. CONCLUSIONES: Una de cada 12 muertes por cáncer son atribuibles a infecciones carcinogénicas en España. Las medidas de salud pública son esenciales para reducir el impacto de las infecciones carcinogénicas

Burden of cancer mortality attributable to carcinogenic infections in Spain.

INTRODUCTION: The impact of carcinogenic infections on cancer-related mortality is unknown. METHODS: The mortality due to cancers attributable to carcinogenic infections was estimated. The attributable fraction for the infectious agents classified as group 1 carcinogenic in human beings was applied to yearly data on causes of cancer mortality over the period 2013-2017 in Spain according to the International Classification of Diseases (ICD-10). RESULTS: It was estimated that 9115 deaths (over 110,287 cancer-related deaths, 8.3%) were attributable to infections caused by carcinogenic agents. The estimated number of deaths in men was 5434 (59.6%). The estimated mortality attributable to Helicobacter pylori infection accounted for 48.3% and four agents (H. pylori, HCV, HPV, and HBV) accounted for 96.8% of all cancer deaths attributable to carcinogenic infections. The burden of cancer-related mortality attributable to carcinogenic infections in Spain during the period 2013-2017 was approximately 8%. CONCLUSIONS: In Spain, one-twelfth of cancer deaths are attributable to carcinogenic infections. Public health measures aiming to reduce the impact of carcinogenic infections are essential.

The use of stand-by emergency treatment (SBET) for malaria in travellers: A systematic review and meta-analysis of observational studies.

BACKGROUND: Since SBET is a controversial strategy for malaria self-treatment, this study aims to systematically review primary studies on its use amongst travellers. METHODS: Once studies were independently selected and data extracted, the pooled effect estimates (ES) were calculated through meta-analysis. Number of SBET users, of travellers carrying medications abroad, of subjects experiencing fever, of users complying with correct dosage, of those experiencing adverse effects, of those seeking medical care following SBET use, and those with positive malaria diagnostic test were collected and analysed. Subgroup and sensitive analyses were also performed. RESULTS: Of 935 titles and abstracts screened, 9 articles were included in the qualitative synthesis and 7 in the meta-analysis for the main outcome, with a pooled ES of the overall use of SBET in the studied population of 2%. There was significant heterogeneity for all studies. The pooled ES of travellers who carried SBET medications abroad and of SBET users seeking medical care after self-administration was 65% and 52%, respectively. CONCLUSIONS: This meta-analysis indicated that the vast majority of travellers prescribed with SBET did not use it and the adherence to pre-travel recommendations on SBET use is suboptimal. Further studies to assess SBET cost-effectiveness and safety are needed.

Stand-by emergency treatment (SBET) of malaria in Spanish travellers: a cohort study.

BACKGROUND: Among strategies for malaria prevention, stand-by emergency treatment (SBET) is a possible approach, but scarce evidences exists investigating travellers' adherence and behaviours toward its use; therefore, the presented study aimed to determine travellers' compliance toward the SBET when prescribed in travel clinics. METHODS: A prospective cohort study was performed at the Travel Health Clinic of the Hospital Universitari de Bellvitge, Barcelona, Spain, during 2017. The research was planned on survey-based design, using pre- and post-travel questionnaires. RESULTS: In the study period, of 5436 subjects who attended the HUB Travel Medicine Clinic, 145 travellers to malaria-endemic areas were prescribed SBET, and all patients agreed to participate in the study by completing the pre-travel questionnaire. Approximately half the participants were women (n = 75, 51.7%), and the median age of all travellers was 29 years (range 13-57), mainly travelling to South-East Asia (n = 69, 47.6%), with Indonesia and the Philippines as the most popular destinations. The length of travels had a median duration of 29 days (range 10-213). Of the recruited participants, 98 replied to the online post-travel survey, reaching a response rate of 67.6%. A total of 62.2% of travellers to which SBET was prescribed did not buy and carry drugs while travelling abroad. No participants' baseline or travel characteristic was shown to be significantly associated (p > 0.05) with this behaviour. Four women (4.1%) experienced fever and self-administered SBET, without seeking medical attention. No malaria cases were observed. CONCLUSIONS: This cohort study addressed travellers' adherence and behaviour toward SBET, highlighting an incorrect use of the emergency treatment in case of presumptive malaria symptoms. This should be taken into account during pre-travel consultation, since the success of this strategy for malaria prevention depends on travellers' strong adherence to it.

Neurological involvement in patients with acute/recent HIV-1 infection. A case-control study.

Primary HIV-1 infection is a relevant period for its virological and epidemiological consequences. Most patients present a symptomatic disease that can be potentially serious, but neurological involvement during primary HIV-1 infection has been poorly studied. The aim of this study was to describe the characteristics and outcomes of primary HIV-1 infection patients presenting neurological symptoms and to compare them with primary HIV-1 infection patients without neurological involvement. Retrospective case-control study (1:3) comparing primary HIV-1 infection patients with and without neurological involvement enrolled in the Acute/Recent Hospital Clinic PHI Cohort between 1997 and 2016. Matching criteria included age (±10 years), gender, year of diagnosis (±4 years), and Fiebig stage. The conditional logit model was used for comparisons. Fourteen out of 463 patients (3.02%) enrolled in the Acute/Recent Hospital Clinic PHI Cohort between 1997 and 2016 presented neurological symptoms. 28.5% of cases presented as meningitis and 71.5% as meningoencephalitis. Cerebrospinal fluid showed non-specific findings, including pleocytosis with lymphocyte predominance and increased protein levels. All cases required hospitalisation, whereas only 19% of the controls did. No other pathogen was identified in any case, but five patients initiated empirically antimicrobial treatment for other aetiologies until diagnosis was confirmed. CD4/CD8 ratio was significantly lower (p = 0.039) and plasmatic viral load significantly higher in the case group, compared to controls (p = 0.028). Risk factors, HIV-1 tropism, subtype distribution, and prescribed ART regimens were comparable between cases and controls. After 6 months on ART, 92% of cases had undetectable viral load, similar to controls, and CD4/CD8 ratio became also comparable between groups. All cases recovered rapidly with ART and were discharged without sequels. Neurological involvement during primary HIV-1 infection is unusual but serious, always requiring hospitalisation. Diagnosis is difficult because of the wide range of symptoms and similarities with other viral aetiologies. Neurological manifestations during primary HIV-1 infection are associated with a lower CD4/CD8 ratio and with a higher viral load than controls. Immediate ART initiation and rapid viral load decrease are required, allowing complete clinical recovery.

Regional differences in the management and outcome of kidney transplantation in patients with human immunodeficiency virus infection: A 3-year retrospective cohort study.

BACKGROUND: In the developed world, kidney transplantation (KT) in patients with human immunodeficiency virus (HIV) infection is well established. Developing countries concentrate 90% of the people living with HIV, but their experience is underreported. Regional differences may affect outcomes. OBJECTIVES: We compared the 3-year outcomes of patients with HIV infection receiving a KT in two different countries, in terms of incomes and development. METHODS: This was an observational, retrospective, double-center study, including all HIV-infected patients >18 years old undergoing KT. RESULTS: Between 2005 and 2015, 54 KTs were performed (39 in a Brazilian center, and 15 in a Spanish center). Brazilians had less hepatitis C virus co-infection (5% vs 27%, P=.024). Median cold ischemia time was higher in Brazil (25 vs 18 hours, P=.001). Biopsy-proven acute rejection (AR) was higher in Brazil (33% vs 13%, P=.187), as were the number of AR episodes (22 vs 4, P=.063). Patient survival at 3 years was 91.3% in Brazil and 100% in Spain; P=.663. All three cases of death in Brazil were a result of bacterial infections within the first year post transplant. At 3 years, survival free from immunosuppressive changes was lower in Brazil (56% vs 90.9%, P=.036). Raltegravir-based treatment to avoid interaction with calcineurin inhibitor was more prevalent in Spain (80% vs 3%; P<.001). HIV infection remained under control in all patients, with undetectable viral load and no opportunistic infections. CONCLUSION: Important regional differences exist in the demographics and management of immunosuppression and antiretroviral therapy. These details may influence AR and infectious complications. Non-AIDS infections leading to early mortality in Brazil deserve special attention.

Human immunodeficiency virus-infected liver transplant recipients with incidental hepatocellular carcinoma: A prospective multicenter nationwide cohort study.

There is a lack of data on incidental hepatocellular carcinoma (iHCC) in the setting of liver transplantation (LT) in human immunodeficiency virus (HIV)-infected patients. This study aims to describe the frequency, histopathological characteristics, and outcomes of HIV+ LT recipients with iHCC from a Spanish multicenter cohort in comparison with a matched cohort of LT patients without HIV infection. A total of 15 (6%) out of 271 patients with HIV infection who received LT in Spain from 2002 to 2012 and 38 (5%) out of the 811 HIV- counterparts presented iHCC in liver explants (P = 0.58). Patients with iHCC constitute the present study population. All patients also had hepatitis C virus (HCV)-related cirrhosis. There were no significant differences in histopathological features of iHCC between the 2 groups. Most patients showed a small number and size of tumoral nodules, and few patients had satellite nodules, microvascular invasion, or poorly differentiated tumors. After a median follow-up of 49 months, no patient developed hepatocellular carcinoma (HCC) recurrence after LT. HIV+ LT recipients tended to have lower survival than their HIV- counterparts at 1 (73% versus 92%), 3 (67% versus 84%), and 5 years (50% versus 80%; P = 0.06). There was also a trend to a higher frequency of HCV recurrence as a cause of death in the former (33% versus 10%; P = 0.097). In conclusion, among LT recipients for HCV-related cirrhosis, the incidence and histopathological features of iHCC in HIV+ and HIV- patients were similar. However, post-LT survival was lower in HIV+ patients probably because of a more aggressive HCV recurrence. Liver Transplantation 23 645-651 2017 AASLD.

Cyclosporine A in addition to standard ART during primary HIV-1 infection: pilot randomized clinical trial.

Background: Initiating ART during acute/recent HIV-1 infection reduces viral reservoir formation. It has been proposed that, during this phase, the size of the viral reservoir could be further reduced by the association of immunomodulatory therapy with ART. Contradictory results have emerged, however, from two trials evaluating the impact on immune recovery and the viral reservoir of adding cyclosporine A to ART during primary HIV-1 infection. Patients and methods: Twenty patients with acute/recent HIV-1 infection were randomized to receive ART alone (tenofovir, emtricitabine and lopinavir/ritonavir) or associated with 8 weeks of cyclosporine A (0.3-0.6 mg/kg twice daily). The impact on viral load, immune response and integrated and non-integrated DNA viral reservoir at 0, 8 and 36 weeks of treatment was evaluated. Results: The estimated median time from HIV-1 infection to ART onset was 63 days (IQR 53; 79.5) with 90% of patients at Fiebig V stage. No significant differences were observed in viral load decay, CD4 T cell recovery, immune response markers or the evolution of integrated DNA at week 8 (end of cyclosporine A) and week 36 between groups. However, non-integrated DNA significantly increased in the cyclosporine A arm between weeks 0 and 36. Cyclosporine A was well tolerated. Conclusions: Adding cyclosporine A to ART during acute/recent infection did not improve immune recovery. However, unintegrated DNA increased in the cyclosporine A group, suggesting an anti-integration effect, a point warranting further research (ClinicalTrials.gov Identifier: NCT00979706).

IFN-free therapy for HIV/HCV-coinfected patients within the liver transplant setting.

OBJECTIVES: IFN-based therapy against hepatitis C recurrence after liver transplantation (LT) has poor effectiveness and tolerability. In HIV/HCV-coinfected liver transplant recipients, the results are even poorer. Here, we report our experience using direct antiviral agents (DAAs) in 11 consecutive coinfected patients within the LT setting. METHODS: Four patients with compensated cirrhosis and hepatocellular carcinoma were treated while awaiting LT and seven patients received antiviral therapy due to severe hepatitis C recurrence after LT [fibrosing cholestatic hepatitis (n = 1), fibrosis stage ≥F3 (n = 2) and decompensated cirrhosis (n = 4)]. Patients were treated with different sofosbuvir-based regimens with or without ribavirin for 12 or 24 weeks. RESULTS: Sustained virological response (SVR) was achieved in all patients. Two of the four patients treated while awaiting LT reached the time of transplant with undetectable HCV-RNA that remained undetectable 12 weeks after LT, one patient had detectable HCV-RNA at the time of transplant but achieved SVR after completing 12 weeks of therapy after LT and the last patient is still on the waiting list. Seven patients with severe post-LT hepatitis C recurrence were treated within 11-120 months after LT. In these patients, viral eradication was associated with an improvement in liver function and clinical decompensation. Tolerance to antiviral therapy was good and only four patients reported mild adverse events. CONCLUSIONS: IFN-free regimens are effective and well tolerated in HIV/HCV-coinfected patients within the LT setting, but more data are needed to confirm our promising results and to establish the best treatment option in this population.

Pregnancy in a renal transplant recipient with HIV-1 infection: a case report.

We report the first case of a pregnancy in a renal transplant recipient with HIV infection. She underwent renal transplantation in 2005 and became pregnant in 2009. The patient underwent vaginal delivery and a healthy full-term, female baby was born. Almost 6 years after delivery, both mother and child were doing well. The management of concurrent renal transplantation, HIV infection and pregnancy was extremely challenging. Women with HIV infection who have undergone renal transplantation should be accurately informed of the potential health risks for them and their offspring. Multidisciplinary teams are mandatory in order to properly manage these patients.

Human immunodeficiency virus infection does not worsen prognosis of liver transplantation for hepatocellular carcinoma.

UNLABELLED: The impact of human immunodeficiency virus (HIV) infection on patients undergoing liver transplantation (LT) for hepatocellular carcinoma (HCC) is uncertain. This study aimed to assess the outcome of a prospective Spanish nationwide cohort of HIV-infected patients undergoing LT for HCC (2002-2014). These patients were matched (age, gender, year of LT, center, and hepatitis C virus (HCV) or hepatitis B virus infection) with non-HIV-infected controls (1:3 ratio). Patients with incidental HCC were excluded. Seventy-four HIV-infected patients and 222 non-HIV-infected patients were included. All patients had cirrhosis, mostly due to HCV infection (92%). HIV-infected patients were younger (47 versus 51 years) and had undetectable HCV RNA at LT (19% versus 9%) more frequently than non-HIV-infected patients. No significant differences were detected between HIV-infected and non-HIV-infected recipients in the radiological characteristics of HCC at enlisting or in the histopathological findings for HCC in the explanted liver. Survival at 1, 3, and 5 years for HIV-infected versus non-HIV-infected patients was 88% versus 90%, 78% versus 78%, and 67% versus 73% (P = 0.779), respectively. HCV infection (hazard ratio = 7.90, 95% confidence interval 1.07-56.82) and maximum nodule diameter >3 cm in the explanted liver (hazard ratio = 1.72, 95% confidence interval 1.02-2.89) were independently associated with mortality in the whole series. HCC recurred in 12 HIV-infected patients (16%) and 32 non-HIV-infected patients (14%), with a probability of 4% versus 5% at 1 year, 18% versus 12% at 3 years, and 20% versus 19% at 5 years (P = 0.904). Microscopic vascular invasion (hazard ratio = 3.40, 95% confidence interval 1.34-8.64) was the only factor independently associated with HCC recurrence. CONCLUSIONS: HIV infection had no impact on recurrence of HCC or survival after LT. Our results support the indication of LT in HIV-infected patients with HCC.

Prevalence of lower extremity peripheral arterial disease in individuals with chronic immune mediated inflammatory disorders.

OBJECTIVE: To compare the prevalence of lower extremity peripheral artery disease (PAD) and to assess whether age-associated progression in ankle-brachial index (ABI) differs between individuals with chronic immune-mediated inflammatory diseases (CIID) and the general population. METHODS: Pooled analysis with data from individuals aged 50 years and older with ABI measurements, obtained from population-based cross-sectional studies conducted in Catalonia (Spain). Information on three CIID diagnoses (i.e., inflammatory bowel disease, systemic connective tissue disorders, and inflammatory polyarthropathies and spondylopathies, considered as one entity for purposes of analysis) was obtained from electronic medical records. To ascertain the statistical association between PAD and CIID, logistic regression models were fitted and adjusted for age, sex, and cardiovascular risk factors. We tested the interaction between age and CIID diagnosis for ABI values. RESULTS: We included 8799 individuals, 312 (3.6%) with CIID. The age-standardized prevalence of PAD was higher in the CIID group (12% vs. 6% in general population, p = 0.001), and the model adjusted for age, sex, and cardiovascular risk factors also showed higher risk in individuals with CIID [Odds Ratio (95% confidence interval) = 1.65 (1.15-2.38); p = 0.007]. The inflammatory polyarthropathies/spondylopathies diagnosis was significantly associated with PAD in the fully adjusted model [1.80 (1.18-2.75); p = 0.006]. The atherosclerotic process was accelerated in individuals with CIID, compared to the general population (p for interaction<0.001). CONCLUSION: In individuals with CIID, age-standardized prevalence of PAD was significantly higher than in the general population and the atherosclerotic process was accelerated. However, only inflammatory polyarthropathies/spondylopathies was associated with significant risk of PAD.

Structured Treatment Interruptions and Low Doses of IL-2 in Patients with Primary HIV Infection. Inflammatory, Virological and Immunological Outcomes.

BACKGROUND: Interventions during primary HIV infection (PHI) can modify the clinical course during the chronic phase. The long-term effect of structured treatment interruptions (STI) followed by low doses of interleukin-2 (IL-2) in treated PHI patients is unknown. METHODS: Twelve PHI patients with viral load (VL) <20 copies/mL, CD4 cells >500 cells/mm3, and CD4/CD8 ratio >1, on antiretroviral therapy (ART) initiated within the first 90 days of infection and continued for at least 12 months were included. They underwent four STI and were then allocated (week 0 of the study) to ART alone or ART plus low doses of IL-2. ART was stopped once VL <20 copies/mL ('final stop'). Primary endpoints were VL<3000 copies/mL and CD4 cells >500 cells/mm3 at 48 weeks; secondary endpoints were immune activation, inflammatory markers until 48 weeks and the time before resuming ART (CD4 <350 cells/mm3 or AIDS) after 'final stop', compared between groups. RESULTS: Ten out of 12 patients were males, median age was 35 years and the main risk was men-who-have-sex-with-men. Only one out of 12 patients (in the STI group) maintained VL<3000 copies/mL and CD4 cells >500 cells/mm3 without ART at 48 weeks. All other virological and immunological parameters were comparable between groups at week 0, 'final stop' and week 48. However, the proportion of CD8-CD38+ cells, tumor necrosis factor and srIL-2 were higher in the IL-2 group at 'final stop' and week 24. All these differences vanished during follow-up. At 5 years after the final stop 3 out of 6 patients in the IL-2 group and 6 out of 6 patients in the STI group have resumed ART (P = 0.19). CONCLUSIONS: STI and IL-2 failed to achieve virological control after ART interruption. STI were not deleterious in long-term follow-up, an important issue for eradication and functional cure trials. TRIAL REGISTRATION: ClinicalTrials.gov NCT02300623.

Trends in Transmission of Drug Resistance and Prevalence of Non-B Subtypes in Patients with Acute or Recent HIV-1 Infection in Barcelona in the Last 16 Years (1997-2012).

OBJECTIVES: To evaluate the prevalence of transmitted drug resistance (TDR) and non-B subtypes in patients with acute/recent HIV-1 infection in Barcelona during the period 1997-2012. METHODS: Patients from the "Hospital Clínic Primary HIV-1 Infection Cohort" with a genotyping test performed within 180 days of infection were included. The 2009 WHO List of Mutations for Surveillance of Transmitted HIV-1 Drug Resistance was used for estimating the prevalence of TDR and phylogenetic analysis for subtype determination. RESULTS: 189 patients with acute/recent HIV-1 infection were analyzed in 4 time periods (1997-2000, n=28; 2001-4, n=42; 2005-8, n=55 and 2009-12, n=64). The proportion of patients with acute/recent HIV-1 infection with respect to the total of newly HIV-diagnosed patients in our center increased over the time and was 2.18%, 3.82%, 4.15% and 4.55% for the 4 periods, respectively (p=0.005). The global prevalence of TDR was 9%, or 17.9%, 9.5%, 3.6% and 9.4% by study period (p=0.2). The increase in the last period was driven by protease-inhibitor and nucleoside-reverse-transcriptase-inhibitor resistance mutations while non-nucleoside-reverse-transcriptase inhibitor TDR and TDR of more than one family decreased. The overall prevalence of non-B subtypes was 11.1%, or 0%, 4.8%, 9.1% and 20.3 by study period (p=0.01). B/F recombinants, B/G recombinants and subtype F emerged in the last period. We also noticed an increase in the number of immigrant patients (p=0.052). The proportion of men-who-have-sex-with-men (MSM) among patients with acute/recent HIV-1 infection increased over the time (p=0.04). CONCLUSIONS: The overall prevalence of TDR in patients with acute/recent HIV-1 infection in Barcelona was 9%, and it has stayed relatively stable in recent years. Non-B subtypes and immigrants proportions progressively increased.