Antenatal HIV-1 RNA load and timing of mother to child transmission; a nested case-control study in a resource poor setting

<p>Abstract</p> <p>Objective</p> <p>To determine HIV-1 RNA load during the third trimester of pregnancy and evaluate its effect on <it>in utero </it>and intra-partum/postpartum transmissions in a breastfeeding population.</p> <p>Design</p> <p>A nested case-control study within a PMTCT cohort of antiretroviral therapy naive pregnant women and their infants.</p> <p>Methods</p> <p>A case was a mother who transmitted HIV-1 to her infant (transmitter) who was matched to one HIV-1 positive but non-transmitting mother (control).</p> <p>Results</p> <p>From a cohort of 691 pregnant women, 177 (25.6%) were HIV-1 positive at enrolment and from these 29 (23%) transmitted HIV-1 to their infants, 10 and 19 during <it>in utero </it>and intra-partum/postpartum respectively. Twenty-four mothers sero-converted after delivery and three transmitted HIV-1 to their infants. Each unit increase in log₁₀viral load was associated with a 178 cells/mm³and 0.2 g/dL decrease in TLC and hemoglobin levels, p = 0.048 and 0.021 respectively, and a 29% increase in the risk of transmission, p = 0.023. Intra-partum/postpartum transmitters had significantly higher mean viral load relative to their matched controls, p = 0.034.</p> <p>Conclusion</p> <p>Antenatal serum HIV-1 RNA load, TLC and hemoglobin levels were significantly associated with vertical transmission but this association was independent of transmission time. This finding supports the rationale for preventive strategies designed to reduce vertical transmission by lowering maternal viral load.</p

Characteristics of hepatitis C virus resistance in an international cohort after a decade of direct-acting antivirals

Background & Aims: Direct-acting antiviral (DAA) regimens provide a cure in >95% of patients with chronic HCV infection. However, in some patients in whom therapy fails, resistance-associated substitutions (RASs) can develop, limiting retreatment options and risking onward resistant virus transmission. In this study, we evaluated RAS prevalence and distribution, including novel NS5A RASs and clinical factors associated with RAS selection, among patients who experienced DAA treatment failure. Methods: SHARED is an international consortium of clinicians and scientists studying HCV drug resistance. HCV sequence linked metadata from 3,355 patients were collected from 22 countries. NS3, NS5A, and NS5B RASs in virologic failures, including novel NS5A substitutions, were examined. Associations of clinical and demographic characteristics with RAS selection were investigated. Results: The frequency of RASs increased from its natural prevalence following DAA exposure: 37% to 60% in NS3, 29% to 80% in NS5A, 15% to 22% in NS5B for sofosbuvir, and 24% to 37% in NS5B for dasabuvir. Among 730 virologic failures, most were treated with first-generation DAAs, 94% had drug resistance in ≥1 DAA class: 31% single-class resistance, 42% dual-class resistance (predominantly against protease and NS5A inhibitors), and 21% triple-class resistance. Distinct patterns containing ≥2 highly resistant RASs were common. New potential NS5A RASs and adaptive changes were identified in genotypes 1a, 3, and 4. Following DAA failure, RAS selection was more frequent in older people with cirrhosis and those infected with genotypes 1b and 4. Conclusions: Drug resistance in HCV is frequent after DAA treatment failure. Previously unrecognized substitutions continue to emerge and remain uncharacterized. Lay summary: Although direct-acting antiviral medications effectively cure hepatitis C in most patients, sometimes treatment selects for resistant viruses, causing antiviral drugs to be either ineffective or only partially effective. Multidrug resistance is common in patients for whom DAA treatment fails. Older patients and patients with advanced liver diseases are more likely to select drug-resistant viruses. Collective efforts from international communities and governments are needed to develop an optimal approach to managing drug resistance and preventing the transmission of resistant viruses

Mother-to-child transmission of human immunodeficiency virus in aten years period

<p>Abstract</p> <p>Objectives</p> <p>to evaluate mother-to-child transmission (MTCT) rates and related factors in HIV-infected pregnant women from a tertiary hospital between 2000 and 2009.</p> <p>Subjects and method</p> <p>cohort of 452 HIV-infected pregnant women and their newborns. Data was collected from recorded files and undiagnosed children were enrolled for investigation. Statistical analysis: qui-square test, Fisher exact test, Student <it>t </it>test, Mann-Whitney test, ANOVA, risk ratio and confidence intervals.</p> <p>Results</p> <p>MTCT occurred in 3.74%. The study population displayed a mean age of 27 years; 86.5% were found to have acquired HIV through sexual contact; 55% were aware of the diagnosis prior to the pregnancy; 62% were not using HAART. Mean CD4 cell-count was 474 cells/ml and 70.3% had undetectable viral loads in the third trimester. HAART included nevirapine in 35% of cases and protease inhibitors in 55%; Zidovudine monotherapy was used in 7.3%. Mean gestational age at delivery was 37.2 weeks and in 92% by caesarian section; 97.2% received intravenous zidovudine. Use of AZT to newborn occurred in 100% of them. Factors identified as associated to MTCT were: low CD4 cell counts, elevated viral loads, maternal AIDS, shorter periods receiving HAART, other conditions (anemia, IUGR (intra uterine growth restriction), oligohydramnium), coinfecctions (CMV and toxoplasmosis) and the occurrence of labor. Use of HAART for longer periods, caesarian and oral zidovudine for the newborns were associated with a decreased risk. Poor adhesion to treatment was present in 13 of the 15 cases of transmission; in 7, coinfecctions were diagnosed (CMV and toxoplasmosis).</p> <p>Conclusion</p> <p>Use of HAART and caesarian delivery are protective factors for mother-to-child transmission of HIV. Maternal coinfecctions and other conditions were risk factors for MTCT.</p

Choice of the initial antiretroviral treatment for HIV-positive individuals in the era of integrase inhibitors

BACKGROUND: We aimed to describe the most frequently prescribed initial antiretroviral therapy (ART) regimens in recent years in HIV-positive persons in the Cohort of the Spanish HIV/AIDS Research Network (CoRIS) and to investigate factors associated with the choice of each regimen. METHODS: We analyzed initial ART regimens prescribed in adults participating in CoRIS from 2014 to 2017. Only regimens prescribed in >5% of patients were considered. We used multivariable multinomial regression to estimate Relative Risk Ratios (RRRs) for the association between sociodemographic and clinical characteristics and the choice of the initial regimen. RESULTS: Among 2874 participants, abacavir(ABC)/lamivudine(3TC)/dolutegavir(DTG) was the most frequently prescribed regimen (32.1%), followed by tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC)/elvitegravir(EVG)/cobicistat(COBI) (14.9%), TDF/FTC/rilpivirine (RPV) (14.0%), tenofovir alafenamide (TAF)/FTC/EVG/COBI (13.7%), TDF/FTC+DTG (10.0%), TDF/FTC+darunavir/ritonavir or darunavir/cobicistat (bDRV) (9.8%) and TDF/FTC+raltegravir (RAL) (5.6%). Compared with ABC/3TC/DTG, starting TDF/FTC/RPV was less likely in patients with CD4100.000 copies/mL. TDF/FTC+DTG was more frequent in those with CD4100.000 copies/mL. TDF/FTC+RAL and TDF/FTC+bDRV were also more frequent among patients with CD4<200 cells//muL and with transmission categories other than men who have sex with men. Compared with ABC/3TC/DTG, the prescription of other initial ART regimens decreased from 2014-2015 to 2016-2017 with the exception of TDF/FTC+DTG. Differences in the choice of the initial ART regimen were observed by hospitals' location. CONCLUSIONS: The choice of initial ART regimens is consistent with Spanish guidelines' recommendations, but is also clearly influenced by physician's perception based on patient's clinical and sociodemographic variables and by the prescribing hospital location

Una sostenibilidad social para la regeneración urbana de la ciudad inteligente

Today the concept of “Smart City” is usual in the new urban and globalized vocabulary. Despite, the power of its modernity can conceal a insufficient reflection about the scope of its capacity to transform the urban and contemporary paradigm. This research offers a reflection regard what since the euro Mediterranean contest, the concept of “smart city”, can contribute to the international debate, and alerts about the importance to know the deliberation of the urban transformations through the history and also the contemporary age.Actualmente el concepto “Smart City” es habitual en el nuevo vocabulario urbano globalizado. Sin embargo, la potencia de su modernidad puede estar ocultando una reflexión insuficiente sobre el alcance de su capacidad de transformar del paradigma urbano contemporáneo. Nuestra investigación propone una reflexión sobre lo que desde el contexto euro mediterráneo, el concepto “ciudad inteligente” puede aportar al debate internacional, y alerta sobre la importancia de conocer la deliberación de las transformaciones urbanas a través de la historia y también en este momento

Frequent de novo generation of HCV3a resistance-associated substitutions in Spain

Background: HCV subtype 3a, responsible for approximately 17% of HCV infections in Spain, remains a difficult-to-treat genotype despite the availability of highly effective treatments based on direct-acting antivirals. Current treatment regimens often combine a NS5A inhibitor with NS5B inhibitor (sofosbuvir). Resistance-associated substitutions (RASs) can have a profound impact on treatment response, especially in cirrhotic patients, with NS5A variant Y93H of particular interest due to its substantial fold-decrease in susceptibility to all NS5A inhibitors. For this reason, it is of interest to evaluate the virus epidemic history for patterns that can be of public health relevance. Methods: We combine publicly available with newly generated HCV3a NS5A and NS5B sequence data to elucidate the international HCV3a migration network with a focus on the role of Spain. Bayesian phylogenetic inference methods were used to estimate the epidemiological relations between the sampled virus lineages and to reconstruct the historical transmission patterns. Migration rates between locations were inferred using a discrete phylogeographic model in which rates from and to locations can differ. Results: There were no clear associations between the sample’s origin and amino acid usage patterns for NS5B RASs S282T, C316N/Y and V321A and for NS5A RASs M28T/V and L31M/V, while Q30L and Y93H appear overrepresented in Pakistanian (p=0.009) and Spanish strains respectively (p=0.052). Reconstruction of ancestral sequences shows that the Y93H RAS is usually de novo generated on external branches, dispersed over the whole phylogeny. Thus there is no founder effect for Y93H, as opposed to what is seen for HCV1a NS3 variant Q80K. The strengths and intensities of migration links between locations vary between the NS5A and NS5B datasets. Spain acts as a sink for HCV3a in both datasets but while most HCV3a import into Spain originates from Germany according to the NS5A data, the NS5B data point towards UK as the main source. Virus movements from Spain are usually towards other European countries (in particular to Portugal and Germany) and English-speaking countries (the so-called Anglosphere, which encompasses the Australia, Canada, India, Pakistan, the UK and the USA). The inconsistencies in the dominant origin location of HCV3a migration into Spain across datasets point out that each genomic region represents a different sample from the epidemic, and its combined phylogeographical analyses create a complementary picture of relevant migration patterns. This illustrates the usefulness of incorporating data from multiple genomic regions, the added value of longer genomic regions, and the need for broader sampling strategies. Conclusions: Spain can become an important 'host-spot' region of Y93H dissemination in the future, due to frequent de novo generation of this NS5A variant. Furthermore, while the inferred higher-level migration patterns are robust to the available sampling for a genomic sub-region, the details of the migration links between Spain and other locations vary by dataset. Our results indicate a need for the analyses of larger genomic regions, and a worldwide sampling of the HCV3a epidemic to more reliably infer the most important sources of HCV3a in Spain.status: publishe