Objectives
To describe prevalence and factors associated with unplanned pregnancies, and social and partner support during pregnancy among women from the Cohort of the Spanish HIV/AIDS Research ...Network (CoRIS).
Methods
We included all women recruited in CoRIS from 2004 to 2019, aged 18–50 years at recruitment who were pregnant during 2020. We designed a questionnaire, organized into the following domains: sociodemographic characteristics, tobacco and alcohol consumption, pregnancy and reproductive health, and social and partner support. The information was gathered via telephone interviews conducted from June to December 2021. We calculated prevalence of unplanned pregnancies as well as odds ratios (ORs) of association and 95% confidence intervals (CIs) according to sociodemographic, clinical and reproductive characteristics.
Results
Among 53 women who were pregnant during 2020, 38 (71.7%) answered the questionnaire. Median age at pregnancy was 36 years interquartile range (IQR) 31–39, 27 (71.1%) women were born outside of Spain, mainly in sub‐Saharan Africa (39.5%) and 17 (44.7%) were employed. Thirty‐four (89.5%) women had been through previous pregnancies and 32 (84.2%) had experienced previous abortions/miscarriages. Seventeen (44.7%) women had shared with their clinician their desire to get pregnant.
Thirty‐four (89.5%) pregnancies were natural and four used assisted reproductive techniques (in vitro fertilizations; one additionally used oocyte donation). Of 34 women with natural pregnancies, pregnancy was unplanned in 21 (61.8%) and 25 (73.5%) had information on how to become pregnant avoiding HIV transmission to the baby and partner. Women who did not seek advice from their physician about becoming pregnant had a significantly increased risk of unplanned pregnancy (OR = 71.25, 95% CI: 8.96–566.67).
Overall, 14 (36.8%) women reported having low social support during pregnancy and 27 (71.0%) had good/very good support by their partner.
Conclusions
Most pregnancies were natural and unplanned and very few women had talked with their clinician about their desire to become pregnant. A high proportion of women reported low social support during pregnancy.
Background
Interferon-inducible protein-10 (IP-10) and monokine induced by interferon-gamma (MIG) are chemokines recognized as inflammatory biomarkers during HIV-1 infection. We assessed their early ...and long-term dynamics after initiation of antiretroviral treatment (ART).
Methods
Persons with HIV-1 (PWH) aged>18 years starting their first ART in 2015-2021 in a prospective cohort (n=73) were included. IP-10 and MIG plasma levels were quantified using a multiplexed bead-based assay.
Results
IP-10 and MIG plasma levels showed a significant and consistent reduction following ART (80% integrase inhibitor INSTI-based) initiation, starting at day 20 and maintained throughout the study period (48 months), paralleling the HIV-1 RNA decay and CD4+ count recovery (p<0·001). At baseline, PWH≥ 50 years, CDC stage C and CD4+ count<350cells/mm
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had higher levels of IP-10 (p=0·022, p=0·001 and p=0·002, respectively) and MIG (p<0·001, p=0·024 and p=0·069, respectively). All of them matched their counterparts several months following ART initiation. MIG levels showed a greater decrease at day 10 in those treated with INSTI (p=0·038). Low-level HIV-1 viremia did not impact MIG or IP-10 levels.
Conclusion
Plasma IP-10 and MIG showed an early significant decline following ART initiation, with greater early declines in MIG levels in INSTI-based regimens. These findings suggest a strong impact of HIV-1 viremia on IP-10 and MIG levels.
Objectives
Our aim was to determine the prevalence and characteristics of people with HIV on antiretroviral therapy (ART) with multidrug resistance (MDR; confirmed resistance to three or more or ...resistance to two or more plus contraindication to one or more core ART classes) and limited treatment options (LTOs) in Spain.
Methods
This was an observational, retrospective, multicentre, cross‐sectional chart review study undertaken in five reference Spanish centres. Participants were people with HIV on ART with MDR and LTOs (detectable viral load HIV‐RNA >200 copies/mL, treatment‐limiting drug–drug interaction DDI, or intolerance precluding the use of one or more ART classes). Prevalence, demographic/clinical characteristics, and treatment options were assessed. Logistic regression analyses were used to identify MDR‐associated variables.
Results
Of 14 955 screened people with HIV, 69 (0.46%) presented with MDR and 23 (0.15%) had LTOs. The population analysed was 73.9% male with a median age of 54.0 years; the median time since HIV diagnosis was 26.5 years, and median CD4+ cell count was 511.0 cells/μL. The only factor significantly associated with MDR (univariate analysis) was CD4+ cell count. Injection drug use was the most common transmission route. Comorbidities (mainly endocrine and cardiovascular disorders; 34.8% affecting HIV management) and concomitant treatments were frequent. No recent opportunistic infections were reported. Patients had been exposed to the following ART: nucleoside analogue reverse transcriptase inhibitors (100%), protease inhibitors (95.6%), non‐nucleoside analogue reverse transcriptase inhibitors (87.0%), and integrase strand transfer inhibitors (82.6%). The available fully active drugs were dolutegravir (39.1%), bictegravir (30.4%), and raltegravir (21.7%).
Conclusions
The prevalence of people with HIV with MDR and LTOs in Spain is very low, with approximately half of those studied not exhibiting virological suppression. Low CD4+ cell counts were associated with MDR. These findings may help address the impact and treatment needs of these patients and prevent clinical progression and transmission of MDR HIV.
Objective
Late presenters (LP) for HIV care are associated with higher morbidity and mortality rates. Our aim was to describe the characteristics associated with LP among adolescents in Spain. ...Identification of particular features may help in the design of strategies for improvement.
Methods
Late‐presenting adolescents diagnosed at 12–19 years of age and enrolled in the Spanish paediatric and adult HIV/AIDS cohorts (CoRIS‐CoRISpe) from 2004 to 2019 were selected. LP were defined as those presenting with CD4 count <350 cells/mm3 or an AIDS‐defining event in the 6 months following HIV diagnosis. Confirmed low CD4 count in the next 3 months and before antiretroviral treatment initiation defined confirmed LP (cLP).
Results
Of 410 adolescents newly diagnosed with HIV, 303 (73.9%) had available data for assessing late presentation. Of these, 34.7% were LP and 23.7% were cLP. The median CD4 count for cLP was 235 cells/mm3 (interquartile range 122–285). In a multivariable analysis, adolescents at the highest risk of late presentation were early adolescents (age 12–14 years; odds ratio OR 6.50; 95% confidence interval CI 2.61–18.2), middle adolescents (age 15–17 years; OR 1.85; 95% CI 0.92–3.59), and adolescents born abroad (OR 1.71; 95% CI 0.97–3.00), particularly those of African origin (OR 3.08; 95% CI 1.38–6.79).
Conclusions
One‐quarter of adolescents presented late for HIV care in Spain. Early adolescents, middle adolescents, and those born abroad presented a sevenfold, twofold, and twofold higher risk of being cLP, respectively. Enhancing the awareness of HIV risk and the access to care, especially for younger and foreign adolescents, could help reduce late presentation and tackle the adolescent HIV epidemic.
This study aimed to analyse the long-term effect of direct-acting antivirals (DAAs) in vertically acquired HIV/HCV-coinfected youths. We performed a multicentre, longitudinal and observational study ...within the Spanish Cohort of HIV-infected children and adolescents and vertically HIV-infected patients transferred to Adult Units (CoRISpe-FARO). We included HIV/HCV-coinfected youths (n = 24) that received DAAs between 2015 and 2017 with successful sustained viral response (SVR) with a subsequent follow-up of at least three years. Long-term evolution in liver disease severity and haematologic markers, lipid and immune profiles after SVR were assessed. Study times were the start date of DAAs treatment (baseline, T0) and 1, 2, 3, 4 and 5 years after SVR (T1, T2, T3, T4 and T5, respectively). We observed global improvements in liver function data that persist over time and a favourable haematologic and immune outcome at the long-term including a constant augment in leucocytes, neutrophils, neutrophils to lymphocytes ratio (NLR) and CD4/CD8 ratio over-time. Regarding the lipid profile, we found a significant increase in total cholesterol T2, total cholesterol/high-density lipoprotein (HDL) ratio at T4, triglycerides at T5, low-density lipoprotein (LDL) over time, and a decrease in HDL in all patients but with marked higher levels in the subgroup receiving anti-HIV Protease Inhibitor (PI)-based regimens. Comparisons of vertically HIV/HCV-coinfected youths after SVR at 3-year follow-up and a control group of vertically HIV-monoinfected youths never infected by HCV showed no significant differences in most variables analysed, suggesting a possible normalization in all parameters.
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•DAAs in vertically HIV/HCV-youths implies a long-term reduction in liver damage biomarkers.•Successful DAAs is accompanied by a constant immune profile recovery.•Pro-atherogenic lipid pattern increases with marked higher levels in the group receiving Protease Inhibitor-based ART.•At 3-year follow-up after SVR, there were no differences compared to vertically HIV-monoinfected youths.
We have detected two mutations in the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at amino acid positions 1163 and 1167 that appeared independently in multiple ...transmission clusters and different genetic backgrounds. Furthermore, both mutations appeared together in a cluster of 1,627 sequences belonging to clade 20E. This cluster is characterized by 12 additional single nucleotide polymorphisms but no deletions. The available structural information on the S protein in the pre- and postfusion conformations predicts that both mutations confer rigidity, which could potentially decrease viral fitness. Accordingly, we observed reduced infectivity of this spike genotype relative to the ancestral 20E sequence
, and the levels of viral RNA in nasopharyngeal swabs were not significantly higher. Furthermore, the mutations did not impact thermal stability or antibody neutralization by sera from vaccinated individuals but moderately reduce neutralization by convalescent-phase sera from the early stages of the pandemic. Despite multiple successful appearances of the two spike mutations during the first year of SARS-CoV-2 evolution, the genotype with both mutations was displaced upon the expansion of the 20I (Alpha) variant. The midterm fate of the genotype investigated was consistent with the lack of advantage observed in the clinical and experimental data.
We observed repeated, independent emergence of mutations in the SARS-CoV-2 spike involving amino acids 1163 and 1167, within the HR2 functional motif. Conclusions derived from evolutionary and genomic diversity analysis suggest that the co-occurrence of both mutations might pose an advantage for the virus and therefore a threat to effective control of the epidemic. However, biological characterization, including
experiments and analysis of clinical data, indicated no clear benefit in terms of stability or infectivity. In agreement with this, continuous epidemiological surveillance conducted months after the first observations revealed that both mutations did not successfully outcompete other variants and stopped circulating 9 months after their initial detection. Additionally, we evaluated the potential of both mutations to escape neutralizing antibodies, finding that the presence of these two mutations on their own is not likely to confer antibody escape. Our results provide an example of how newly emerged spike mutations can be assessed to better understand the risk posed by new variants and indicate that some spike mutations confer no clear advantage to the virus despite independently emerging multiple times and are eventually displaced by fitter variants.
We investigated whether blood telomere length (TL), epigenetic age acceleration (EAA), and soluble inflammatory monocyte cytokines are associated with cardiovascular events or diabetes (DM) in people ...living with HIV (PLHIV). This was a case-control study nested in the Spanish HIV/AIDS Cohort (CoRIS). Cases with myocardial infarction, stroke, sudden death, or diabetes after starting antiretroviral therapy were included with the available samples and controls matched for sex, age, tobacco use, pre-ART CD4 cell count, viral load, and sample time-point. TL (T/S ratio) was analysed by quantitative PCR and EAA with DNA methylation changes by next-generation sequencing using the Weidner formula. Conditional logistic regression was used to explore the association with cardiometabolic events. In total, 180 participants (94 cases (22 myocardial infarction/sudden death, 12 strokes, and 60 DM) and 94 controls) were included. Of these, 84% were male, median (IQR) age 46 years (40-56), 53% were current smokers, and 22% had CD4 count ≤ 200 cells/mm
and a median (IQR) log viral load of 4.52 (3.77-5.09). TL and EAA were similar in the cases and controls. There were no significant associations between TL, EAA, and monocyte cytokines with cardiometabolic events. TL and EAA were mildly negatively correlated with sCD14 (rho = -0.23;
= 0.01) and CCL2/MCP-1 (rho = -0.17;
= 0.02). We found no associations between TL, EAA, and monocyte cytokines with cardiovascular events or diabetes. Further studies are needed to elucidate the clinical value of epigenetic biomarkers and TL in PLHIV.
Exosome-derived miR-21 was independently associated with CD4 T cell decline in HIV-1-infected elite controllers (OR 0.369, 95% CI 0.137–0.994, p = 0.049). Also, a negative correlation between miR-21 ...expression and MCP-1 level was found (r = −0.649, p = 0.020), while no correlation between soluble biomarkers or cellular immune activation was found.