Development of nevirapine resistance in children exposed to the prevention of mother-to-child HIV-1 transmission programme in Maputo, Mozambique

Background: Single-dose nevirapine (sd-NVP) has been the main option for prevention of mother-to-child transmission (PMTCT) of HIV-1 in low-resource settings. However, sd-NVP can induce the selection of HIV-1 resistant mutations in mothers and infants. In Mozambique, there are limited data regarding the profile of NVP resistance associated mutations (RAM) in the context of PMTCT. Objectives: To assess the prevalence and the factors associated with NVP RAM among children born to HIV-1 infected mothers enrolled in the PMTCT programme adopted in Mozambique. Methods: One hundred and fifty seven children aged 6 to 48 weeks were sequentially included (July 2011 to March 2012) at four centres in Maputo. Genotyping of RAM was performed in samples with HIV-1 RNA≥ 100 copies/μL (Viroseq). Sequencing was performed with ABI 3100 (Applied Biosystems). Logistic regression modelling was undertaken to identify the factors associated with NVP RAM. Results: Seventy-nine children had their samples genotyped. Their median age was 7.0 (3–12) months and 92.4% received prophylaxis with sd-NVP at birth plus daily NVP. 35.4% of mothers received antiretrovirals (ARVs) for PMTCT. ARV RAM were detected in 43 (54.4%) of the children. 45.6% of these children had at least one NVP RAM. The most common mutations associated with NVP resistance were K103N (n = 16) and Y181C (n = 15). NVP RAM was significantly associated with mother exposure to PMTCT (crude odds ratio [OR] 30.3, 95% CI 4.93–186.34) and with mother’s CD4 count < 350 cells/mm3 (crude OR 3.08, 95% CI 1.02–9.32). In the multivariable analysis the mother’s exposure to PMTCT was the only variable significantly associated with NVP RAM (adjusted OR 48.65, 95% CI 9.33–253.66). Conclusions: We found a high prevalence of NVP RAM among children who were exposed to the drug regimen for PMTCT in Mozambique. The mothers’ exposure to PMTCT significantly increased the risk of NVP RAM.This study was funded by the Associação para a Investigação e Desenvolvimento da Faculdade de Medicina (AIDFM). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.info:eu-repo/semantics/publishedVersio

Potency of HIV-2-specific antibodies increase in direct association with loss of memory B cells

Potent HIV-neutralizing antibodies are critical for vaccination and viral reservoir control. High levels of neutralizing antibodies characterize HIV-2 infection, a naturally occurring model of attenuated HIV disease with low-to-undectable viremia. We found that HIV-2-specific antibody potency increased in direct association with the loss of both switched and unswitched memory B cells in untreated HIV-2 infection. Thus, HIV antibody affinity maturation is linked to memory B-cell exhaustion even in reduced viremia settings.info:eu-repo/semantics/publishedVersio

Antibody response against selected epitopes in the HIV-1 envelope gp41 ectodomain contributes to reduce viral burden in HIV-1 infected patients

The ectodomain of gp41 is the target of potent binding and neutralizing antibodies (NAbs) and is being explored in new strategies for antibody-based HIV vaccines. Previous studies have suggested that the W164A-3S (3S) and EC26-2A4 (EC26) peptides located in the gp41 ectodomain may be potential HIV vaccine candidates. We assessed 3S- and EC26-specific binding antibody responses and related neutralizing activity in a large panel of chronic HIV-1-infected Portuguese individuals on ART. A similar proportion of participants had antibodies binding to 3S (9.6%) and EC26 (9.9%) peptides but the level of reactivity against 3S was significantly higher compared to EC26, except in the rare patients with double peptide reactivity. The higher antigenicity of 3S was unrelated with disease stage, as assessed by CD4+ T cell counts, but it was directly related with plasma viral load. Most patients that were tested (89.9%, N = 268) showed tier 1 neutralizing activity, the potency being inversely associated with plasma viral load. In the subset of patients that were tested for neutralization of tier 2 isolates, neutralization breadth was inversely correlated with plasma viral load and directly correlated with CD4+ T cell counts. These results are consistent with a role for neutralizing antibodies in controlling viral replication and preventing the decline of CD4+ T lymphocytes. Importantly, in patients with 3S-specific antibodies, neutralizing titers were inversely correlated with viral RNA levels and proviral DNA levels. Moreover, patients with 3S and/or EC26-specific antibodies showed a 1.9-fold higher tier 2 neutralization score than patients without antibodies suggesting that 3S and/or EC26-specific antibodies contribute to neutralization breadth and potency in HIV-1 infected patients. Overall, these results suggest that antibodies targeting the S3 and EC26 epitopes may contribute to reduce viral burden and provide further support for the inclusion of 3S and EC26 epitopes in HIV-1 vaccine candidates.publishersversionpublishe

Tuberculosis, a re-emergent disease

© 2005 Elsevier Ireland Ltd. All rights reserved.Tuberculosis (TB) remains a major cause of morbidity and mortality worldwide. In Western Europe, regions with a high incidence of TB usually also have a high incidence of HIV infection; TB and HIV co-infection have increased over the past decade and among HIV infected patients, nearly half also develop TB. In settings where HIV is prevalent, TB drug resistance has also increased and several reports of TB and multi-drug resistant TB outbreaks, especially in health care settings, raise serious concerns about nosocomial transmission. Further research and new developments into more rapid diagnostic methods and sensitivity testing as well as the development of new anti-TB drugs are important to fight the disease. In addition, public health infrastructures have to be strengthened in order to increase adherence to TB treatment, where directly observed treatment strategy is the cornerstone for a successful outcome.info:eu-repo/semantics/publishedVersio

Coronavirus 2019-nCoV: Is the genie already out of the bottle?

© 2020 Elsevier Ltd. All rights reserved.Once again, a virus has jumped the species barrier. Coronavirus 2019-nCoV emerged apparently in a wet market in China, and after a few weeks the number of cases already exceeds those of SARS in 2002/03 (Fig. 1) in terms of both morbidity and mortality. Excellent publications have addressed many aspects of a possible novel endemic/pandemic zoonosis, often with a focus on MERS-CoV (2–4), includingprevention, drug and vaccine-development for coronaviruses, or the importance of “a ‘One Health’ approach to control … …zoonotic pathogens with epidemic potential”. The hugely increased appetite for meat-products worldwide, but also in China, is likely to increase livestock production and sale, as well as scavenging of remaining wildlife resources, primarily the latter with consequent increases in the risk of exposure to novel infectious agents.info:eu-repo/semantics/publishedVersio

Adherence to Mediterranean diet in HIV infected patients: relation with nutritional status and cardiovascular risk

Background & aims: The Mediterranean diet (MedDiet) has been associated to a lower prevalence of metabolic syndrome (MS) and a lower cardiovascular risk (CVR). Our aim was to assess HIV infected individual's adherence to the MedDiet and its relationship with nutritional status and CVR. Methods: Clinical and anthropometric data were collected and a nutritional assessment was performed. Adherence to the MedDiet was assessed using the questionnaire MedDietScore, ranging from 0 to 55, where higher scores indicated a higher adherence. CVR was estimated for each patient using the Framingham Risk Score (FRSs-CVD). Results: We included 571 individuals, mostly males (67.1%; n = 383). MedDiet adherence score was 27.5 ± 5.5 points. The proportion of overweight/obese individuals was 40.3% (n = 230) and MS 33.9% (n = 179); CVD estimation showed that 53.2% (n = 304), 30.1% (n = 172) and 16.6% (n = 95) of patients had a low, moderate and very high CVR, respectively. The group with BMI below 25 kg/m2 presented lower adherence to MedDiet and patients within moderate CVR category and with MS presented a higher adherence to MedDiet. Conclusions: Overall we found a moderate adherence to the Mediterranean diet. A higher adherence was associated to individuals with a BMI ≥ 25 kg/m2, those with MS and to patients with moderate to high cardiovascular risk, suggesting the adoption of this food pattern in the presence of comorbidities.info:eu-repo/semantics/publishedVersio

Cardiovascular risk in HIV-infected individuals: a comparison of three risk prediction algorithms

ABSTRACT - Introduction: Cardiovascular (CV) risk is known to be increased in HIV-infected individuals. Our aim was to assess CV risk in HIV-infected adults. Methods: CV risk was estimated for each patient using three different risk algorithms: SCORE, the Framingham risk score (FRS), and DAD. Patients were classified as at low, moderate or high CV risk. Clinical and anthropometric data were collected. Results: We included 571 HIV-infected individuals, mostly male (67.1%; n=383). Patients were divided into two groups according to antiretroviral therapy (ART): naïve (7.5%; n=43) or under ART (92.5%; n=528). The mean time since HIV diagnosis was 6.7±6.5 years in the naive group and 13.3±6.1 years in the ART group. Metabolic syndrome (MS) was identified in 33.9% (n=179) and 16.3% (n=7) of participants in the ART and naïve groups, respectively. MS was associated with ART (OR=2.7; p=0.018). Triglycerides ≥150 mg/dl (OR=13.643, p<0.001) was one of the major factors contributing to MS. Overall, high CV risk was found in 4.4% (n=23) of patients when the SCORE tool was used, in 20.5% (n=117) using the FRS, and in 10.3% (n=59) using the DAD score. The observed agreement between the FRS and SCORE was 55.4% (k=0.183, p<0.001), between the FRS and DAD 70.5% (k=0.465, p<0.001), and between SCORE and DAD 72.3% (k=0.347, p<0.001). Conclusion: On the basis of the three algorithms, we detected a high rate of high CV risk, particularly in patients under ART. The FRS was the algorithm that classified most patients in the high CV risk category (20.5%). In addition, a high prevalence of MS was identified in this patient group.RESUMO - Introdução: O risco cardiovascular (RCV) pode estar aumentado em indivíduos com infeção por Vírus Imunodeficiência Humana (VIH). O objetivo deste trabalho foi avaliar o RCV em adultos infetados por VIH. Métodos: O RCV foi estimado utilizando três algoritmos diferentes, Score, Framingham Risk Score (FRSs-CVD) e DAD; os participantes foram classificados apresentando RCV baixo, moderado ou elevado. Recolheram-se dados clínicos e antropométricos. Resultados: Incluíram-se 571 indivíduos, maioritariamente do género masculino (67,1%; n=383). Dividiram-se os participantes em dois grupos, com e sem terapêutica antirretroviral (cTAR): naïve (7,5%; n=43) versus cTAR (92,5%; n=528). O tempo médio desde o diagnóstico da infeção por VIH foi 6,7±6,5 anos no grupo naïve e 13,3±6,1 anos no grupo cART. A síndrome metabólica (SM) foi identificada em 33,9% (n=179) e em 16,3% (n=7) dos participantes, respetivamente no grupo cART e no grupo naïve. Verificou-se um RCV elevado em 4,4% (n=23) dos participantes, com recurso à ferramenta Score, em 20,5% (n=117) utilizando a FRSs e em 10,3% dos participantes (n=59) utilizando a ferramenta DAD. A concordância observada entre FRSs e Score foi 55,4% (k=0,183; p<0,001), entre FRSs e DAD 70,5% (k=0,465; p<0,001) e entre Score e DAD 72,3% (k=0,347; p<0,001). Conclusão: Com recurso aos algoritmos utilizados, identificou-se uma presença significativa de elevado RCV, sendo a ferramenta FRSs-CVD a que classificou mais indivíduos na categoria de RCV elevado (20,5%), e simultaneamente verificou-se uma prevalência elevada de SM.info:eu-repo/semantics/publishedVersio

Genetic diversity and drug resistance profiles in HIV type 1- and HIV type 2-infected patients from Cape Verde Islands

Our aim was to characterize for the first time the genetic diversity of HIV in Cape Verde Islands as well as the drug resistance profiles in treated and untreated patients. Blood specimens were collected from 41 HIV-1 and 14 HIV-2 patients living in Santiago Island. Half of the patients were on antiretroviral treatment (ART). Pol and env gene sequences were obtained using in-house methods. Phylogenetic analysis was used for viral subtyping and the Stanford Algorithm was used for resistance genotyping. For HIV-1, the amplification of pol and env was possible in 27 patients (66%). HIV-1 patients were infected with subtypes G (13, 48%), B (2, 7%), F1 (2, 7%), and CRF02_AG (2, 7%), and complex recombinant forms including a new C/G variant (n=8, 30%). Drug resistance mutations were detected in the PR and RT of three (10%) treated patients. M41L and K103N transmitted drug resistance mutations were found in 2 of 17 (12%) untreated patients. All 14 HIV-2 isolates belonged to group A. The origin of 12 strains was impossible to determine whereas two strains were closely related to the historic ROD strain. In conclusion, in Cape Verde there is a long-standing HIV-2 epidemic rooted in ROD-like strains and a more recent epidemic of unknown origin. The HIV-1 epidemic is caused by multiple subtypes and complex recombinant forms. Drug resistance HIV-1 strains are present at moderate levels in both treated and untreated patients. Close surveillance in these two populations is crucial to prevent further transmission of drug-resistant strains.This work was supported by Fundação GlaxoSmithKline para as Ciências da Saúde, Portugal, Fundação para a Ciência e Tecnologia (project PTDCSAU-FCF6767/2006), Portugal, and CHAIN (Collaborative HIV and Anti-HIV Drug Resistance Network), European Union. Pedro Borrego, Cheila Rocha, and Inês Bártolo are supported by Ph.D. grants from Fundação para a Ciência e Tecnologia, Portugal.info:eu-repo/semantics/publishedVersio