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.
Integrase strand-transfer inhibitors (INSTIs) constitute at present one of the pillars of first-line ART.
To study the prevalence of and the trend in transmitted drug resistance (TDR) to INSTIs in ...ART-naive patients in Spain.
During the period 2012-17, 1109 patients from CoRIS were analysed. The Stanford algorithm v8.7 was used to evaluate TDR and transmission of clinically relevant resistance. To describe individual mutations/polymorphisms, the most recent IAS list (for INSTIs) and the 2009 WHO list update (for the backbone NRTIs used in combination with INSTIs in first-line treatment) were used.
Clinically relevant resistance to the INSTI class was 0.2%: T66I, 0.1%, resistance to elvitegravir and intermediate resistance to raltegravir; and G163K, 0.1%, intermediate resistance to raltegravir and elvitegravir. No clinical resistance to dolutegravir or bictegravir was observed. The prevalence of INSTI TDR following the IAS-USA INSTI mutation list was 2.6%, with no trend towards changes in the prevalence throughout the study period. The overall prevalence of NRTI WHO mutations was 4.3%, whereas clinically relevant resistance to tenofovir, abacavir and emtricitabine/lamivudine was 1.7%, 1.9% and 0.7%, respectively.
Given the low prevalence of clinically relevant resistance to INSTIs and first-line NRTIs in Spain, it is very unlikely that a newly diagnosed patient will present with clinical resistance to a first-line INSTI-based regimen. These patients may not benefit from INSTI and NRTI baseline resistance testing.
Background. The clinical relevance of ultrasensitive human immunodeficiency virus type 1 (HIV-1) genotypic resistance testing in antiretroviral treatment (ART)-experienced individuals remains ...unknown. Methods. This was a retrospective, multicentre, cohort study in ART-experienced, HIV-1-infected adults who initiated salvage ART including, at least 1 ritonavir-boosted protease inhibitor, raltegravir or etravirine. Presalvage ART Sanger and 454 sequencing of plasma HIV-1 were used to generate separate genotypic sensitivity scores (GSS) using the HIV db, ANRS, and REGA algorithms. Virological failure (VF) was defined as 2 consecutive HIV-1 RNA levels ≥200 copies/mL at least 12 weeks after salvage ART initiation, whereas subjects remained on the same ART. The ability of Sanger and 454-GSS to predict VF was assessed by receiver operating characteristic (ROC) curves and survival analyses. Results. The study included 132 evaluable subjects; 28 (21%) developed VF. Using HIVdb, 454 predicted VF better than Sanger sequencing in the ROC curve analysis (area under the curve: 0.69 vs 0.60, Delong test P = .029). Time to VF was shorter for subjects with 454-GSS < 3 vs 454-GSS ≥ 3 (Log-rank P = .003) but not significantly different between Sanger-GSS < 3 and ≥3. Factors independently associated with increased risk of VF in multivariate Cox regression were a 454-GSS < 3 (HR = 4.6, 95 CI, 1.5, 14.0, P = .007), and the number of previous antiretrovirals received (HR = 1.2 per additional drug, 95 CI, 1.1, 1.3, P= .001). Equivalent findings were obtained with the ANRS and REGA algorithms. Conclusions. Ultrasensitive HIV-1 genotyping improves GSS-based predictions of virological outcomes of salvage ART relative to Sanger sequencing. This may improve the clinical management of ART-experienced subjects living with HIV-1. Clinical Trials Registration. NCT01346878.
Introduction
Advancements in and accessibility to effective antiretroviral therapy has improved the life expectancy of people living with HIV, increasing the proportion of people living with HIV ...reaching older age (≥60 years), making this population's health‐related quality of life (HRQoL) more relevant. Our aim was to identify the determinants of poor HRQoL in people living with HIV aged ≥60 years and compare them with those of their younger counterparts.
Methods
We used data from the ‘Vive+’ study, a cross‐sectional survey conducted between October 2019 and March 2020, nested within the PISCIS cohort of people living with HIV in Catalonia and the Balearic Islands, Spain. We used the 12‐item short‐form survey (SF‐12), divided into a physical component summary (PCS) and a mental component summary (MCS), to evaluate HRQoL. We used the least absolute shrinkage and selection operator for variable selection and used multivariable regression models to identify predictors.
Results
Of the 1060 people living with HIV (78.6% males) who participated in the study, 209 (19.7%) were aged ≥60 years. When comparing older people living with HIV (≥60 years) and their younger counterparts, older people exhibited a worse PCS (median 51.3 interquartile range {IQR} 46.0–58.1 vs. 46.43 IQR 42.5–52.7, p < 0.001) but a similar MCS (median 56.0 IQR 49.34–64.7 vs. 57.0 IQR 48.9–66.3, p = 0.476). In the multivariable analysis, cognitive function correlated with a PCS (β correlation factor β −0.18, p = 0.014), and depressive symptoms and satisfaction with social role correlated with an MCS (β 0.61 and β −0.97, respectively, p < 0.001) in people living with HIV aged ≥60 years.
Conclusion
Depressive symptoms, poor cognitive function, and lower satisfaction with social roles predict poorer HRQoL in older people living with HIV. These factors need to be considered when designing targeted interventions.
In this randomized study of 460 patients receiving effective treatment for human immunodeficiency virus type 1 (HIV-1) disease, nevirapine, efavirenz, or abacavir was substituted for the protease ...inhibitor in a regimen that also included two nucleoside reverse-transcriptase inhibitors. After 12 months, the increases in CD4 cell counts were similar in the three groups, but there was a trend toward a higher rate of treatment failure in the abacavir group.
A nonnucleoside reverse-transcriptase inhibitor may reduce the rate of adverse effects.
The use of highly active antiretroviral therapy consisting of two nucleoside reverse-transcriptase inhibitors plus a protease inhibitor led to a sharp decline in the morbidity and mortality associated with human immunodeficiency virus type 1 (HIV-1) infection.
1
,
2
Therefore, highly active antiretroviral therapy that included a protease inhibitor became the cornerstone of antiretroviral therapy.
3
,
4
However, protease-inhibitor–based regimens usually involve many pills and food or drink restrictions, may cause drug interactions, and have been associated with morphologic changes and metabolic abnormalities that could increase the risk of cardiovascular disease.
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–
9
In patients who have not previously received antiretroviral therapy, triple antiretroviral . . .
Objectives
The aim of the study was to assess the rates of discontinuation of integrase inhibitor regimens because of any neuropsychiatric adverse event (NPAE) and the factors associated with ...discontinuation.
Methods
A population‐based, prospective, multicentre cohort study was carried out. Treatment‐naïve subjects starting therapy with a regimen containing integrase inhibitors, or those switching to such a regimen, with plasma HIV‐1 RNA < 50 HIV‐1 RNA copies/mL in 14 hospitals in Catalonia or the Balearic Islands (Spain) were included in the study. Every discontinuation because of adverse events (AEs) was double‐checked directly with treating physicians. Multivariable Cox models identified factors correlated with discontinuation.
Results
A total of 4165 subjects (37% treatment‐naïve) started regimens containing dolutegravir (n = 1650; 91% with abacavir), raltegravir (n = 930) or elvitegravir/cobicistat (n = 1585). There were no significant differences among regimens in the rate of discontinuation because of any AE. Rates of discontinuation because of NPAEs were low but higher for dolutegravir/abacavir/lamivudine 2.1%; 2.9 (95% confidence interval (CI) 2.0, 4.2) discontinuations/100 patients/year versus elvitegravir/cobicistat (0.5%; 0.8 (95% CI 0.3, 1.5) discontinuations/100 patients/year, with significant differences among centres for dolutegravir/abacavir/lamivudine and NPAEs (P = 0.003). We identified an association of female gender and lower CD4 count with increased risk of discontinuation because of any AE Incidence ratio (IR) 2.3 (95% CI 1.4, 4.0) and 1.8 (95% CI 1.1, 2.8), respectively. Female gender, age > 60 years and abacavir use were not associated with NPAE discontinuations. NPAEs were commonly grade 1–2, and had been present before and improved after drug withdrawal.
Conclusions
In this large prospective cohort study, patients receiving dolutegravir, raltegravir or elvitegravir/cobicistat did not show significant differences in the rate of discontinuation because of any toxicity. The rate of discontinuations because of NPAEs was low, but was significantly higher for dolutegravir than for elvitegravir/cobicistat, with significant differences among centres, suggesting that greater predisposition to believe that a given adverse event is caused by a given drug of some treating physicians might play a role in the discordance seen between cohorts.
Although the attainment of Millennium Development Goal 4 (MDG 4), reducing under-five mortality by two-thirds by the year 2015, depends on optimizing breast-feeding practices in resource-limited ...settings, there are some conditions in which breast-feeding is impossible, contraindicated, or not recommended. The overall impact of involuntary nonbreast-feeding on the attainment of MDG 4 has not been documented. In industrialized and many middle-income countries replacement feeding is affordable, feasible, acceptable, sustainable, and safe and complete avoidance of breast-feeding is the norm to prevent postnatal transmission of HIV. The situation is very different in many low-income countries affected by the HIV epidemic where infants are exposed to HIV and antiretroviral (ARV) mediation through breast milk for long periods with risk of acquiring HIV infection, development of multidrug resistant HIV and short and long term toxicity associated to ARV medications. Despite the obvious needs, there is no specific research on how to make replacement feeding safer for infants with no access to breast-feeding and for whom replacement feeding is justified. Orphans, abandoned and infants of severely ill mothers unable to breast-feed, won't benefit from the research done on making breast-feeding safer for HIV exposed infants. A child rights perspective illuminates societal obligations to provide replacement feeding with infant formula milk to such infants, and to support research to make it safer at the same time that breast-feeding is promoted and protected for the general population.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Next Generation Sequencing (NGS) and Sanger-based technologies are used for HIV drug resistance genotyping. Here we describe DeepChek(R)-HIV (DC) and ViroScore-HIV (VS), the first CE-IVD marked ...medical devices for NGS and Sanger, respectively. DC and VS perform automated analysis and HIV resistance interpretation of both Sanger and NGS sequences in a matter of minutes. DC accepts raw sequences (FASTQ) or alignment files (BAM, FASTA) from any type of sequencing platform (MiSeq, 454horizontal ellipsis) and includes several clinical guidelines for drug resistance assessments. Specific bioinformatics pipelines were developed to address major issues influencing treatment decision (insertions, deletions and homopolymer corrections). Both DC and VS are secured applications following good practices for software development and were validated for safety and efficacy in several research and diagnostic laboratories. We analyzed in 6 months more than 3300 samples from various cohorts worldwide with both DC and VS. On average, DC identified over 40% new variants missed by Sanger sequencing while also detecting the majority (94%) of the substitutions identified by Sanger. Usually, additional mutations found by Sanger corresponded to artefact information coming from chromatogram interpretations. The variant calling component of the algorithm demonstrated both accurate classification of low-frequency variants and the efficient handling of homopolymer sequencing errors. In a specific panel of 170 samples, DC identified new insertions (prevalence >=1%), in 7% of the samples all of which missed by alternative technologies. DeepChek-HIV and ViroScore-HIV are downstream analysis platforms for HIV genotyping and drug resistance testing. It optimally managed the end to end analysis and comparison of NGS and Sanger data. It should provide additional reliable guidance to ARV treatment choices for research and clinical uses.
Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening ...coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-ω (IFN-ω) (13 patients), against the 13 types of IFN-α (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men.
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