Search

BACKGROUND: The Joint United Nations Programme on HIV/AIDS launched the 90-90-90 initiative. Failure to meet the target reflects the difficulties in successfully implementing HIV treatment policy. There are research gaps in exploring personal and external factors influencing HIV treatment in Ghana. To fill this gap, we explored individual and environmental (interpersonal, community and structural) factors influencing stakeholders' HIV treatment policy implementation in Ghana.METHODS: Fifteen qualitative semi-structured in-depth interviews were conducted among representatives in different management positions at hospitals, health directorates, the Ghana AIDS Commission, the National AIDS and STI control program, and the National Association of People Living with HIV.RESULTS: Using thematic analysis, the findings suggest that individual and environmental factors such as attitude towards policy, awareness of HIV treatment policy, training received on policy implementation, difficulties related to patient factors, alternate sources of HIV care, inefficient policy decision-making, monitoring and evaluation of HIV treatment policy, lack of HIV treatment policy implementation training, poor availability of logistics, policy and guidelines, infrastructure, organization of training, and staff availability may hinder successful HIV treatment policy implementation.CONCLUSION: Several individual and environmental (interpersonal, community and structural) factors seem to influence HIV treatment policy implementation. To ensure successful policy implementation stakeholders need to receive training on new policies, availability of sufficient supplies of material resources, inclusive decision-making, receive supportive monitoring of policy implementation, and oversight.

BACKGROUND: The Joint United Nations Programme on HIV/AIDS launched the 90-90-90 initiative. Failure to meet the target reflects the difficulties in successfully implementing HIV treatment policy. There are research gaps in exploring personal and external factors influencing HIV treatment in Ghana. To fill this gap, we explored individual and environmental (interpersonal, community and structural) factors influencing stakeholders' HIV treatment policy implementation in Ghana.METHODS: Fifteen qualitative semi-structured in-depth interviews were conducted among representatives in different management positions at hospitals, health directorates, the Ghana AIDS Commission, the National AIDS and STI control program, and the National Association of People Living with HIV.RESULTS: Using thematic analysis, the findings suggest that individual and environmental factors such as attitude towards policy, awareness of HIV treatment policy, training received on policy implementation, difficulties related to patient factors, alternate sources of HIV care, inefficient policy decision-making, monitoring and evaluation of HIV treatment policy, lack of HIV treatment policy implementation training, poor availability of logistics, policy and guidelines, infrastructure, organization of training, and staff availability may hinder successful HIV treatment policy implementation.CONCLUSION: Several individual and environmental (interpersonal, community and structural) factors seem to influence HIV treatment policy implementation. To ensure successful policy implementation stakeholders need to receive training on new policies, availability of sufficient supplies of material resources, inclusive decision-making, receive supportive monitoring of policy implementation, and oversight.

Objective: In the 2020 UNAIDS HIV treatment goals, 90% of people living with HIV (PLHIV) should be diagnosed, 90% of these should receive antiretroviral treatment (ART) and 90% of these should be virally suppressed. We aimed to evaluate whether Guinea-Bissau fulfills the 2020 treatment goals for both for HIV-1 and HIV-2.Design: By combining data from a general population survey, treatment records from HIV clinics across Guinea-Bissau and a biobank from patients attending the largest HIV clinics in Bissau, we estimated each column of the 90-90-90 cascade.Method: 2601 participated in the survey and were used to estimate the proportion of PLHIV who knew their HIV status and the proportion of PLHIV on ART. Answers given in the survey was verified with treatment records from HIV clinics. We measured viral load from biobank materials from HIV patients and estimated the proportion of virally suppressed PLHIV.Result: 19.1% of PLHIV indicated to be aware of their HIV status. Of these, 48.5% received ART, and 76.4% of these were virally suppressed. For HIV-1 and HIV-1/2 the results were 21.2%, 40.9% and 75.1%. For HIV-2 the results were 15.9%, 63.6% and 80.7%. 26.9% of all HIV-1 infected in the survey were virologically suppressed, indicating that a much higher number of HIV-1 infected were aware of their status and on treatment.Conclusion: Guinea-Bissau lags severely behind both the global and regional progress. Improvement in both testing and treating HIV is necessary to improve the quality of care. Objective: In the 2020 UNAIDS HIV treatment goals, 90% of people living with HIV (PLHIV) should be diagnosed, 90% of these should receive antiretroviral treatment (ART) and 90% of these should be virally suppressed. We aimed to evaluate whether Guinea-Bissau fulfills the 2020 treatment goals for both for HIV-1 and HIV-2. Design: By combining data from a general population survey, treatment records from HIV clinics across Guinea-Bissau and a biobank from patients attending the largest HIV clinics in Bissau, we estimated each column of the 90-90-90 cascade. Method: 2601 participated in the survey and were used to estimate the proportion of PLHIV who knew their HIV status and the proportion of PLHIV on ART. Answers given in the survey was verified with treatment records from HIV clinics. We measured viral load from biobank materials from HIV patients and estimated the proportion of virally suppressed PLHIV. Result: 19.1% of PLHIV indicated to be aware of their HIV status. Of these, 48.5% received ART, and 76.4% of these were virally suppressed. For HIV-1 and HIV-1/2 the results were 21.2%, 40.9% and 75.1%. For HIV-2 the results were 15.9%, 63.6% and 80.7%. 26.9% of all HIV-1 infected in the survey were virologically suppressed, indicating that a much higher number of HIV-1 infected were aware of their status and on treatment. Conclusion: Guinea-Bissau lags severely behind both the global and regional progress. Improvement in both testing and treating HIV is necessary to improve the quality of care.

Background Identifying factors that determine the frequency of latently infected CD4+ T cells on antiretroviral therapy (ART) may inform strategies for human immunodeficiency virus (HIV) cure. We investigated the role of CD4+ count at ART initiation for HIV persistence on ART. Methods Among participants of the Strategic Timing of Antiretroviral Treatment Study, we enrolled people with HIV (PWH) who initiated ART with CD4+ T-cell counts of 500–599, 600–799, or ≥ 800 cells/mm3. After 36–44 months on ART, the levels of total HIV-DNA, cell-associated unspliced HIV-RNA (CA-US HIV-RNA), and two-long terminal repeat HIV-DNA in CD4+ T cells were quantified and plasma HIV-RNA was measured by single-copy assay. We measured T-cell expression of Human Leucocyte Antigen-DR Isotype (HLA-DR), programmed death-1, and phosphorylated signal transducer and activator of transcription-5 (pSTAT5). Virological and immunological measures were compared across CD4+ strata. Results We enrolled 146 PWH, 36 in the 500–599, 60 in the 600–799, and 50 in the ≥ 800 CD4 strata. After 36–44 months of ART, total HIV-DNA, plasma HIV-RNA, and HLA-DR expression were significantly lower in PWH with CD4+ T-cell count ≥ 800 cells/mm3 at ART initiation compared with 600–799 or 500–599 cells/mm3. The median level of HIV-DNA after 36–44 months of ART was lower by 75% in participants initiating ART with ≥ 800 vs 500–599 cells/mm3 (median [interquartile range]: 16.3 [7.0–117.6] vs 68.4 [13.7–213.1] copies/million cells, respectively). Higher pSTAT5 expression significantly correlated with lower levels of HIV-DNA and CA-US HIV-RNA. Virological measures were significantly lower in females. Conclusions Initiating ART with a CD4+ count ≥ 800 cells/mm3 compared with 600–799 or 500–599 cells/mm3 was associated with achieving a substantially smaller HIV reservoir on ART.

Our objective is to improve local decision-making for strategies to end the HIV epidemic using the newly developed Levers of HIV agent-based model (ABM). Agent-based models use computer simulations that incorporate heterogeneity in individual behaviors and interactions, allow emergence of systemic behaviors, and extrapolate into the future. The Levers of HIV model (LHM) uses Chicago neighborhood demographics, data on sex-risk behaviors and sexual networks, and data on the prevention and care cascades, to model local dynamics. It models the impact of changes in local preexposure prophylaxis (PrEP) and antiretroviral treatment (ART) (ie, levers) for meeting Illinois’ goal of “Getting to Zero” (GTZ) —reducing by 90% new HIV infections among men who have sex with men (MSM) by 2030. We simulate a 15-year period (2016-2030) for 2304 distinct scenarios based on 6 levers related to HIV treatment and prevention: (1) linkage to PrEP for those testing negative, (2) linkage to ART for those living with HIV, (3) adherence to PrEP, (4) viral suppression by means of ART, (5) PrEP retention, and (6) ART retention. Using tree-based methods, we identify the best scenarios at achieving a 90% HIV infection reduction by 2030. The optimal scenario consisted of the highest levels of ART retention and PrEP adherence, next to highest levels of PrEP retention, and moderate levels of PrEP linkage, achieved 90% reduction by 2030 in 58% of simulations. We used Bayesian posterior predictive distributions based on our simulated results to determine the likelihood of attaining 90% HIV infection reduction using the most recent Chicago Department of Public Health surveillance data and found that projections of the current rate of decline (2016-2019) would not achieve the 90% (p = 0.0006) reduction target for 2030. Our results suggest that increases are needed at all steps of the PrEP cascade, combined with increases in retention in HIV care, to approach 90% reduction in new HIV diagnoses by 2030. These findings show how simulation modeling with local data can guide policy makers to identify and invest in efficient care models to achieve long-term local goals of ending the HIV epidemic.

Background Analytical treatment interruptions (ATI) are pauses of antiretroviral therapy (ART) in the context of human immunodeficiency virus (HIV) cure trials. They are the gold standard in determining if interventions being tested can achieve sustained virological control in the absence of ART. However, withholding ART comes with risks and discomforts to trial participant. We used mathematical models to explore how ATI study design can be improved to maximize statistical power, while minimizing risks to participants. Methods Using previously observed dynamics of time to viral rebound (TVR) post-ATI, we modelled estimates for optimal sample size, frequency, and ATI duration required to detect a significant difference in the TVR between control and intervention groups. Groups were compared using a log-rank test, and analytical and stochastic techniques. Results In placebo-controlled TVR studies, 120 participants are required in each arm to detect 30% difference in frequency of viral reactivation at 80% power. There was little statistical advantage to measuring viral load more frequently than weekly, or interrupting ART beyond 5 weeks in a TVR study. Conclusions Current TVR HIV cure studies are underpowered to detect statistically significant changes in frequency of viral reactivation. Alternate study designs can improve the statistical power of ATI trials.

Attempts to reduce the human immunodeficiency virus type 1 (HIV-1) reservoir and induce antiretroviral therapy (ART)-free virologic control have largely been unsuccessful. In this phase 1b/2a, open-label, randomized controlled trial using a four-group factorial design, we investigated whether early intervention in newly diagnosed people with HIV-1 with a monoclonal anti-HIV-1 antibody with a CD4-binding site, 3BNC117, followed by a histone deacetylase inhibitor, romidepsin, shortly after ART initiation altered the course of HIV-1 infection (NCT03041012). The trial was undertaken in five hospitals in Denmark and two hospitals in the United Kingdom. The coprimary endpoints were analysis of initial virus decay kinetics and changes in the frequency of CD4+ T cells containing intact HIV-1 provirus from baseline to day 365. Secondary endpoints included changes in the frequency of infected CD4+ T cells and virus-specific CD8+ T cell immunity from baseline to day 365, pre-ART plasma HIV-1 3BNC117 sensitivity, safety and tolerability, and time to loss of virologic control during a 12-week analytical ART interruption that started at day 400. In 55 newly diagnosed people (5 females and 50 males) with HIV-1 who received random allocation treatment, we found that early 3BNC117 treatment with or without romidepsin enhanced plasma HIV-1 RNA decay rates compared to ART only. Furthermore, 3BNC117 treatment accelerated clearance of infected cells compared to ART only. All groups had significant reductions in the frequency of CD4+ T cells containing intact HIV-1 provirus. At day 365, early 3BNC117 + romidepsin was associated with enhanced HIV-1 Gag-specific CD8+ T cell immunity compared to ART only. The observed virological and immunological effects of 3BNC117 were most pronounced in individuals whose pre-ART plasma HIV-1 envelope sequences were antibody sensitive. The results were not disaggregated by sex. Adverse events were mild to moderate and similar between the groups. During a 12-week analytical ART interruption among 20 participants, 3BNC117-treated individuals harboring sensitive viruses were significantly more likely to maintain ART-free virologic control than other participants. We conclude that 3BNC117 at ART initiation enhanced elimination of plasma viruses and infected cells, enhanced HIV-1-specific CD8+ immunity and was associated with sustained ART-free virologic control among persons with 3BNC117-sensitive virus. These findings strongly support interventions administered at the time of ART initiation as a strategy to limit long-term HIV-1 persistence. Attempts to reduce the human immunodeficiency virus type 1 (HIV-1) reservoir and induce antiretroviral therapy (ART)-free virologic control have largely been unsuccessful. In this phase 1b/2a, open-label, randomized controlled trial using a four-group factorial design, we investigated whether early intervention in newly diagnosed people with HIV-1 with a monoclonal anti-HIV-1 antibody with a CD4-binding site, 3BNC117, followed by a histone deacetylase inhibitor, romidepsin, shortly after ART initiation altered the course of HIV-1 infection (NCT03041012). The trial was undertaken in five hospitals in Denmark and two hospitals in the United Kingdom. The coprimary endpoints were analysis of initial virus decay kinetics and changes in the frequency of CD4+ T cells containing intact HIV-1 provirus from baseline to day 365. Secondary endpoints included changes in the frequency of infected CD4+ T cells and virus-specific CD8+ T cell immunity from baseline to day 365, pre-ART plasma HIV-1 3BNC117 sensitivity, safety and tolerability, and time to loss of virologic control during a 12-week analytical ART interruption that started at day 400. In 55 newly diagnosed people (5 females and 50 males) with HIV-1 who received random allocation treatment, we found that early 3BNC117 treatment with or without romidepsin enhanced plasma HIV-1 RNA decay rates compared to ART only. Furthermore, 3BNC117 treatment accelerated clearance of infected cells compared to ART only. All groups had significant reductions in the frequency of CD4+ T cells containing intact HIV-1 provirus. At day 365, early 3BNC117 + romidepsin was associated with enhanced HIV-1 Gag-specific CD8+ T cell immunity compared to ART only. The observed virological and immunological effects of 3BNC117 were most pronounced in individuals whose pre-ART plasma HIV-1 envelope sequences were antibody sensitive. The results were not disaggregated by sex. Adverse events were mild to moderate and similar between the groups. During a 12-week analytical ART interruption among 20 participants, 3BNC117-treated individuals harboring sensitive viruses were significantly more likely to maintain ART-free virologic control than other participants. We conclude that 3BNC117 at ART initiation enhanced elimination of plasma viruses and infected cells, enhanced HIV-1-specific CD8+ immunity and was associated with sustained ART-free virologic control among persons with 3BNC117-sensitive virus. These findings strongly support interventions administered at the time of ART initiation as a strategy to limit long-term HIV-1 persistence.

International audience; Human immunodeficiency virus (HIV) infection is associated with an increased risk of non-Hodgkin lymphoma (NHL). Even in the era of suppressive antiretroviral treatment, HIV-infected individuals remain at higher risk of developing NHL compared to the general population. To identify potential genetic risk loci, we performed case-control genome-wide association studies and a meta-analysis across three cohorts of HIV+ patients of European ancestry, including a total of 278 cases and 1924 matched controls. We observed a significant association with NHL susceptibility in the C-X-C motif chemokine ligand 12 (CXCL12) region on chromosome 10. A fine mapping analysis identified rs7919208 as the most likely causal variant (P = 4.77e-11), with the G>A polymorphism creating a new transcription factor binding site for BATF and JUND. These results suggest a modulatory role of CXCL12 regulation in the increased susceptibility to NHL observed in the HIV-infected population.

This retrospective study evaluated the reactivity of 3 human immunodeficiency virus (HIV) confirmatory assays (INNO-LIA, Geenius, and MP) and 7 HIV rapid tests on samples from 2 different study populations in Belgium. For the early-treated cohort (83 HIV-1 adult patients treated within 3 months after infection), HIV-1 diagnosis was not obtained in at least 1 confirmatory assay in 12.0% (10/83) and in an HIV rapid test in 31.3% (26/83). Confirmation assay sensitivities ranged from 87.5% to 95.2%, whereas rapid test assay sensitivities ranged from 75.9% to 100%. The time to treatment initiation or the length of time on treatment did not have a statistical influence on the probability to obtain a false-negative test result. The fastest reversion was demonstrated after 4 months of treatment. Among the long-term treated cohort (390 HIV-1 patients with ≥ 9 years of undetectable viral load), false-negative test results were found in at least 1 HIV confirmatory assay for 2.1% (8/390) of the patients and in a HIV rapid test for 4.9% (19/390). Confirmation assay sensitivities ranged from 98.1% to 99.5%, whereas rapid test sensitivities ranged from 96.2% to 100%. Longer treatment increased nonreactivity of the HIV rapid tests (P = .033). Undetectable viral load decreases the sensitivities of HIV diagnostic tests, and further monitoring of the performance of serological assays is advised. ispartof: JOURNAL OF INFECTIOUS DISEASES vol:222 issue:10 pages:1660-1669 ispartof: location:United States status: published

Cet article aborde les aspects préventifs, thérapeutiques et les perspectives de « guérison » du VIH. La PrEP se positionne comme un pilier essentiel pour contrôler l'épidémie. La bithérapie antirétrovirale visant à diminuer les toxicités médicamenteuses n'est pas qu'un sujet de recherche, mais aussi une réalité. Les molécules de longue durée d'action injectables sont prometteuses et très attendues par les patients fatigués de leurs prises quotidiennes. Sur le plan des effets secondaires, la prise pondérale avec les inhibiteurs d'intégrase et la sécurité du dolutégravir chez les femmes enceintes ont fait couler beaucoup d'encre. Enfin, la suppression virologique soutenue après transplantation allogénique de cellules souches hématopoïétiques mutées sur le corécepteur CCR5 provoque de nouvelles vagues d'optimisme face à une cure par thérapie génique.

The long-acting antiretroviral cabotegravir and rilpivirine combination has just received FDA, EMA and Health Canada approval. This novel drug delivery approach is about to revolutionize the therapy of people living with HIV, decreasing the 365 daily pill burden to only six intramuscular injections per year. In addition, islatravir, a first-in-class nucleoside reverse transcriptase translocation inhibitor, is intended to be formulated as an implant with a dosing interval of 1 year or more. At present, long-acting antiretroviral therapies (LA-ARTs) are given at fixed standard doses, irrespectively of the patient's weight and BMI, and without consideration for host genetic and non-genetic factors likely influencing their systemic disposition. Despite a few remaining challenges related to administration (e.g. pain, dedicated medical procedure), the development and implementation of LA-ARTs can overcome long-term adherence issues by improving patients' privacy and reducing social stigma associated with the daily oral intake of anti-HIV treatments. Yet, the current 'one-size-fits-all' approach does not account for the recognized significant inter-individual variability in LA-ART pharmacokinetics. Therapeutic drug monitoring (TDM), an important tool for precision medicine, may provide physicians with valuable information on actual drug exposure in patients, contributing to improve their management in real life. The present review aims to update the current state of knowledge on these novel promising LA-ARTs and discusses their implications, particularly from a clinical pharmacokinetics perspective, for the future management and prevention of HIV infection, issues of ongoing importance in the absence of curative treatment or an effective vaccine.

Current antiretroviral therapy (ART) guidelines recommend treating all children with HIV-1 infection. This has changed from the broader use of ART to treat children to improve morbidity and minimise mortality. However, prior to current recommendations, not everyone with HIV-1 received timely treatment. What happens to the paediatric immune system when HIV-1 replication is not appropriately supressed remains unclear. 11 samples from adolescents with HIV-1 on ART and uninfected controls in the UK, aged 12–25 years, were examined; overall, adolescents with CD4+counts > 500/μl and a viral load < 50 copies/ml were compared with adolescents with CD4+counts < 500/μl and a viral load > 50 copies/ml at time of sampling. Measurements of thymic output were combined with high throughput next generation sequencing and bioinformatics to systematically organize CD4+and CD8+T cell receptor (TCR) repertoires. TCR repertoire diversity, clonal expansions, TCR sequence sharing, and formation of TCR clusters in HIV-1 infected adolescents with successful HIV-1 suppression were compared to adolescents with ineffective HIV-1 suppression. Thymic output and CD4+T cell numbers were decreased in HIV-1 infected adolescents with poor HIV-1 suppression. A strong homeostatic TCR response, driven by the decreased CD4+T cell compartment and reduced thymic output was observed in the virally uncontrolled HIV-1-infected adolescents. Formation of abundant robust TCR clusters and structurally related TCRs were found in the adolescents with effective HIV-1 suppression. Numerous CD4+T cell numbers in the virally controlled adolescents emphasize the importance of high thymic output and formation of robust TCR clusters in the maintenance of HIV-1 suppression. While the profound capacity for immune recovery in children may allow better opportunity to deal with immunological stress, when ART is taken appropriately, this study demonstrates new insights into the unique paediatric immune system and the immunological changes when HIV-1 replication is ongoing.

Women are underrepresented in most HIV clinical trials in Western countries, but their participation remains crucial as the lack of information on sex- and gender-specific effects may hinder the safety and efficacy of antiretroviral treatments. The aim of this study was to identify barriers to and facilitators of women's participation in HIV clinical trials in Switzerland. We conducted semi-structured interviews among 20 women with HIV to explore factors associated with non-participation in clinical trials. The interviewer presented to participants a clinical trial's description and discussed it with them. Lexicometric analysis on transcribed interviews identified three themes and eight sub-themes related to the pros and cons of participation in HIV clinical trials. Participants evoked mainly decision-making drivers, concerns for women living with HIV and treatment side-effects. They highlighted the need for extensive information provided by trusted healthcare professionals on the research process as central to the decision to enrol in HIV clinical trials. Familial responsibilities were clearly identified as barriers to their participation, but not pregnancy. Additional preoccupations were other health concerns and comorbidities and the consequences of stopping ongoing antiretroviral treatments. To overcome the barriers to the participation of women living with HIV in clinical research in Western countries, healthcare professionals and researchers should increase women's research literacy by involving them in the study design and by tailoring clinical trials to their social roles and health concerns. Trust in professionals is a facilitator of enrolment of women living with HIV that should be maintained.

In people with HIV (PWH) on antiretroviral therapy (ART), immune dysfunction persists, including elevated expression of immune checkpoint (IC) proteins on total and HIV-specific T-cells. Reversing immune exhaustion is one strategy to enhance the elimination of HIV-infected cells that persist in PWH on ART. We aimed to evaluate whether blocking cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), T cell immunoglobulin domain and mucin domain 3 (TIM-3), T cell immunoglobulin and ITIM domain (TIGIT) and lymphocyte activation gene-3 (LAG-3) alone or in combination would enhance HIV-specific CD4(+) and CD8(+) T cell function ex vivo. Intracellular cytokine staining was performed using human peripheral blood mononuclear cells (PBMCs) from PWH on ART (n=11) and expression of CD107a, IFNγ, TNFα and IL-2 quantified with HIV peptides and antibodies to IC. We found that i) IC blockade enhanced the induction of CD107a and IL-2, but not IFNγ and TNFα, in response to Gag and Nef peptides, ii) the induction of CD107a and IL-2 was greatest with multiple combinations of two antibodies, and iii) antibodies to LAG-3, CTLA-4 and TIGIT in combinations showed synergistic induction of IL-2 in HIV-specific CD8(+) and CD107a and IL-2 production in HIV-specific CD4(+) and CD8(+) T cells. These results demonstrate that the combination of antibodies to LAG-3, CTLA-4 or TIGIT can increase the frequency of cells expressing CD107a and IL-2 that associated with cytotoxicity and survival of HIV-specific CD4(+) and CD8(+) T cells in PWH on ART. These combinations should be further explored for an HIV cure.

A majority of people living with HIV (PLWH) now have access to HIV treatment with high antiviral potency and favorable tolerability profile. However, in some treatment experienced PLWH viral strains resistant to major current classes of antiretrovirals have emerged, usually due to periods with continued virus replication in the presence of failing drug regimens and thus selection pressure. In such context, new treatment options are therefore needed. Fostemsavir (RUKOBIA®) is the prodrug of temsavir, a first-in-class oral attachment inhibitor approved for the treatment of heavily treatment-experienced adults with multidrug-resistant HIV-1 infection. In this case RUKOBIA® is part of a complex regimen of antiretroviral drugs, often in addition to other drugs for chronic co-morbidities (e.g., heart disease, diabetes mellitus, hepatic and renal impairment, etc). In such a multi-drug regimen context, therapeutic drug monitoring (TDM) of temsavir can be necessary to exclude or adjust for relevant drug-drug interactions. A highly selective assay by liquid chromatography method coupled to tandem mass spectrometry (LC-MS/MS) was therefore developed for the quantification of temsavir in human plasma. A convenient sample preparation using protein precipitation with acetonitrile followed by supernatant dilution was carried out. Temsavir and fostemsavir were separated in less than 2 min using a multi-step UPLC gradient, thus ensuring adequate quantification of temsavir. The assay for the quantification of temsavir was extensively validated over the large range of clinically relevant concentrations from 1 to 10,000 ng/mL, in accordance with international bioanalytical method guidelines. The method achieves excellent performance in terms of trueness (99.7 - 105.3%), repeatability and intermediate precision (both from 1.6% to 5.8%). This LC-MS/MS method is now part of the routine analyses of the Laboratory of the Service of Clinical Pharmacology of Lausanne (CHUV), Switzerland, as an integrated part of our general TDM Service for antiretrovirals.

Introduction: The ability of the human immunodeficiency virus (HIV) of invading immune system cells, especially CD4+ to multiply and stay alive, when not reversed, has as inevitable outcome the acquired immunodeficiency syndrome (AIDS), an event in which patients start to develop secondary diseases such as opportunistic infections and cancer. Objective: To identify cases of Hodgkin’s lymphoma in HIV+ patients using highly effective antiretrovirals. Method: Cross-sectional observational study with exploratory and descriptive design and qualitative and quantitative approach, carried out during the month of October 2018 based on the analysis of 57 HIV-infected patients’ charts diagnosed with cancer and admitted to a hospital located in Fortaleza, CE. Results: A total of 21 non-AIDS-defining cancers were detected. Of these, skin cancer, with 14.3% (3) followed by breast cancer, with 9.5% (2), Hodgkin’s lymphoma, 9.5% (2) and stomach cancer, with 9.5% (2) were the most common cases. Conclusion: The data obtained in the present study rank Hodgkin’s lymphoma in second place among the non-AIDS-defining cancers encountered. However, while considering the small number of cases, due to the study limitations, these data are scanty to conclude the actual quantity of Hodgkin’s lymphoma among the non-AIDS-defining cancers occurred in HIV-positive patients locally or to estimate the participation of HIV, viral load, immune condition and co-infection as risk factors. Introducción: La capacidad del virus de inmunodeficiencia humana (VIH) para invadir las células del sistema inmunitario, especialmente las células T CD4 + para multiplicarse y mantenerse con vida, cuando no se revierte, tiene el resultado inevitable del síndrome de inmunodeficiencia adquirida (SIDA), evento en el que los pacientes comienzan a presentar enfermedades secundarias como infecciones oportunistas y cáncer. Objetivo: Identificar los casos de linfoma de Hodgkin en pacientes VIH+ utilizando los antirretrovirales de alta eficacia. Método: Este es un estudio observacional transversal con diseño exploratorio y descriptivo y enfoque cualitativo, realizado durante octubre de 2018 a partir del análisis de 57 registros médicos de pacientes VIH + diagnosticados con cáncer y hospitalizados en un hospital ubicado en Fortaleza, CE. Resultados: Se identificaron un total de 21 cánceres que no definen el SIDA. De estos, los más comunes fueron cáncer de piel con 14,3% (3), seguido de cáncer de seno con 9,5% (2), linfoma de Hodgkin 9,5% (2) y cáncer de estómago con 9,5% (2) de los casos. Conclusión: Los datos obtenidos en el presente estudio colocan al linfoma de Hodgkin en segundo lugar entre los cánceres no definitorios de SIDA encontrados. Sin embargo, considerando el bajo número de casos resultantes de las limitaciones de la investigación, esta información no nos permite concluir acerca de la cantidad real de linfoma de Hodgkin entre los otros cánceres no definitorios de SIDA en pacientes VIH + en la localidad, ni estimar la participación del VIH, la carga viral, la condición inmune y las coinfecciones como factores de riesgo. Introdução: A capacidade do vírus da imunodeficiência humana (HIV) de invadir células do sistema imunológico, principalmente células T CD4+, para se multiplicar e manter-se vivo, quando não revertido, possui, como desfecho inevitável, a síndrome da imunodeficiência adquirida (SIDA), evento no qual os pacientes começam a apresentar doenças secundárias como infecções oportunistas e câncer. Objetivo: Identificar casos de linfoma de Hodgkin em pacientes HIV+ em uso dos antirretrovirais de alta efetividade. Método: Estudo do tipo observacional transversal com delineamento exploratório e descritivo e abordagem quali-quantitativa, realizado durante o mês de outubro de 2018, a partir da análise de 57 prontuários de pacientes HIV+ diagnosticados com câncer e internados em um hospital localizado em Fortaleza, CE. Resultados: Foi identificado um total de 21 cânceres não definidores de SIDA. Destes, os mais comuns foram o câncer de pele com 14,3% (3); seguido do câncer de mama com 9,5% (2); linfoma de Hodgkin com 9,5% (2); e o câncer de estômago com 9,5% (2) dos casos. Conclusão: Os dados obtidos no presente estudo colocam o linfoma de Hodgkin em segundo lugar entre os cânceres não definidores de SIDA encontrados. Contudo, ao considerar o baixo número de casos, resultante das limitações da pesquisa, essas informações não permitem concluir sobre a real quantidade de linfomas de Hodgkin entre os demais cânceres não definidores de SIDA ocorridos em pacientes HIV+ na localidade, tampouco estimar a participação do HIV, carga viral, condição imunológica e coinfecções como fatores de risco.

Background: Considering the remaining threat of drug-resistantmutations (DRMs) to antiretroviral treatment (ART) efficacy, we investigated how the selective pressure of human leukocyte antigen (HLA)-restricted cytotoxic T lymphocytes drives certain DRMs’ emergence and retention. Methods: We systematically screened DRM:HLA class I allele combinations in 3997 ART-naïve Swiss HIV Cohort Study (SHCS) patients. For each pair, a logistic regression model preliminarily tested for an association with the DRM as the outcome. The three HLA:DRM pairs remaining after multiple testing adjustment were analyzed in three ways: cross-sectional logistic regression models to determine any HLA/infection time interaction, survival analyses to examine if HLA type correlated with developing specific DRMs, and via NetMHCpan to find epitope binding evidence of immune escape. Results: Only one pair, RT-E138:HLA-B18, exhibited a significant interaction between infection duration and HLA. The survival analyses predicted two pairs with an increased hazard of developing DRMs: RT-E138:HLA-B18 and RT-V179:HLA-B35. RT-E138:HLA-B18 exhibited the greatest significance in both analyses (interaction term odds ratio [OR] 1.169 [95% confidence interval (CI) 1.075–1.273]; p-value

OBJECTIVE To describe effects of HAART on high-risk human papillomavirus (HPV) antibody response in HIV-positive MSM and the meaning of this response for subsequent HPV-related cancer risk. DESIGN Prospective seroepidemiological study of 281 HIV-positive MSM initiating HAART between 1995 and 2004 in the Swiss HIV Cohort Study. METHODS For each individual, two serum samples, one at HAART initiation (pre-HAART) and another 24 months later (post-HAART), were tested for L1 antibodies to HPV6, 11, 16, 18, 31, 33, 35, 45, 52 and 58, as well as HPV16-E6 antibodies, using a multiplex serology assay. Identification of HPV-related cancer included data linkage with Swiss cancer registries. RESULTS Pre-HAART, 45.2% were seropositive for any high-risk HPV-L1 and 32.4% for HPV16-L1. Sexual intercourse during the last 6 months was the only evaluated factor associated with L1 seropositivity pre-HAART. Seropositivity increased post-HAART to 60.5% for any high-risk HPV-L1 [prevalence ratio versus pre-HAART = 1.34, 95% confidence interval (CI) 1.14-1.57] and 48.0% for HPV16-L1 (prevalence ratio versus pre-HAART = 1.48, 95% CI 1.20-1.83), and seroconversion was significantly associated with both lower CD4 cell count and CD4/CD8 ratio (P

Objectives: The aim of the study was to determine the time to, and risk factors for, triple-class virological failure (TCVF) across age groups for children and adolescents with perinatally acquired HIV infection and older adolescents and adults with heterosexually acquired HIV infection. Methods: We analysed individual patient data from cohorts in the Collaboration of Observational HIV Epidemiological Research Europe (COHERE). A total of 5972 participants starting antiretroviral therapy (ART) from 1998, aged < 20 years at the start of ART for those with perinatal infection and 15–29 years for those with heterosexual infection, with ART containing at least two nucleoside reverse transcriptase inhibitors (NRTIs) and a nonnucleoside reverse transcriptase inhibitor (NNRTI) or a boosted protease inhibitor (bPI), were followed from ART initiation until the most recent viral load (VL) measurement. Virological failure of a drug was defined as VL > 500 HIV-1 RNA copies/mL despite ≥ 4 months of use. TCVF was defined as cumulative failure of two NRTIs, an NNRTI and a bPI. Results: The median number of weeks between diagnosis and the start of ART was higher in participants with perinatal HIV infection compared with participants with heterosexually acquired HIV infection overall [17 (interquartile range (IQR) 4–111) vs. 8 (IQR 2–38) weeks, respectively], and highest in perinatally infected participants aged 10–14 years [49 (IQR 9–267) weeks]. The cumulative proportion with TCVF 5 years after starting ART was 9.6% [95% confidence interval (CI) 7.0−12.3%] in participants with perinatally acquired infection and 4.7% (95% CI 3.9−5.5%) in participants with heterosexually acquired infection, and highest in perinatally infected participants aged 10–14 years when starting ART (27.7%; 95% CI 13.2−42.1%). Across all participants, significant predictors of TCVF were those with perinatal HIV aged 10–14 years, African origin, pre-ART AIDS, NNRTI-based initial regimens, higher pre-ART viral load and lower pre-ART CD4. Conclusions: The results suggest a beneficial effect of starting ART before adolescence, and starting young people on boosted PIs, to maximize treatment response during this transitional stage of development., 0, SCOPUS: ar.j, FLWOA, info:eu-repo/semantics/published

Introduction In many countries, mortality due to suicide is higher among people living with HIV than in the general population. We aimed to analyse trends in suicide mortality before and after the introduction of triple combination antiretroviral therapy (cART), and to identify risk factors associated with death from suicide in Switzerland. Methods We analysed data from the Swiss HIV Cohort Study from the pre‐cART (1988‐1995), earlier cART (1996‐2008) and later cART (2009‐2017) eras. We used multivariable Cox regression to assess risk factors for death due to suicide in the ART era and computed standardized mortality ratios (SMRs) to compare mortality rates due to suicide among persons living with HIV with the general population living in Switzerland, using data from the Swiss National Cohort. Results and Discussion We included 20,136 persons living with HIV, of whom 204 (1.0%) died by suicide. In men, SMRs for suicide declined from 12.9 (95% CI 10.4‐16.0) in the pre‐cART era to 2.4 (95% CI 1.2‐5.1) in the earlier cART and 3.1 (95% CI 2.3‐4.3) in the later cART era. In women, the corresponding ratios declined from 14.2 (95% CI 7.9‐25.7) to 10.2 (3.8‐27.1) and to 3.3 (95% CI 1.5‐7.4). Factors associated with death due to suicide included gender (adjusted hazard ratio 0.58 (95% CI 0.38‐0.87) comparing women with men), nationality (1.95 (95% CI 1.34‐2.83) comparing Swiss with other), Centers for Disease Control and Prevention clinical stage (0.33 (95% CI 0.24‐0.46) comparing stage A with C), transmission group (2.64 (95% CI 1.71‐4.09) for injection drug use and 2.10 (95% CI 1.36‐3.24) for sex between men compared to other), and mental health (2.32 (95% CI 1.71‐3.14) for a history of psychiatric treatment vs. no history). There was no association with age. Conclusions Suicide rates have decreased substantially among people living with HIV in the last three decades but have remained about three times higher than in the general population since the introduction of cART. Continued emphasis on suicide prevention among men and women living with HIV is important.

Introduction: As the relative burden of community-acquired bacterial pneumonia among HIV-positive patients increases, adequate prediction of case severity on presentation is crucial. We sought to determine what characteristics measurable on presentation are predictive of worse outcomes. Methods: We studied all admissions for community-acquired bacterial pneumonia over 1 year at a tertiary centre. Patient demographics, comorbidities, HIV-specific markers and CURB-65 scores on Emergency Department presentation were reviewed. Outcomes of interest included mortality, bacteraemia, intensive care unit admission and orotracheal intubation. Results: A total of 396 patients were included, 49 HIV positive and 347 HIV negative. Mean CURB-65 score was 1.3 for HIV-positive and 2.2 for HIV-negative patients (p200 CD4 cells/mL subgroup (adjusted odds ratio 2.2 CI 95% [0.7–7.6] and adjusted odds ratio 0.8 CI 95% [0.1–6.5] respectively). Antiretroviral therapy and viral load suppression were not associated with different outcomes (p>0.05). Conclusions: High CURB-65 scores and CD4 counts

Objectives: We assessed differences in antiretroviral treatment (ART) coverage and virological suppression across three HIV key populations, as defined by self-reported HIV transmission category: sex between men, injection drug use (IDU) and heterosexual transmission. Design: A multinational cohort study. Methods: Within the EuroSIDA study, we assessed region-specific percentages of ART coverage among those in care and virological suppression (

A recent study conducted in blood has proposed CD32 as the marker identifying the "elusive" HIV reservoir. We have investigated the distribution of CD32 + CD4 T cells in blood and lymph nodes (LNs) of HIV-1-uninfected subjects and viremic untreated and long-term-treated HIV-1-infected individuals and their relationship with PD-1 + CD4 T cells. The frequency of CD32 + CD4 T cells was increased in viremic compared to treated individuals in LNs, and a large proportion (up to 50%) of CD32 + cells coexpressed PD-1 and were enriched within T follicular helper (Tfh) cells. We next investigated the role of LN CD32 + CD4 T cells in the HIV reservoir. Total HIV DNA was enriched in CD32 + and PD-1 + CD4 T cells compared to CD32 - and PD-1 - cells in both viremic and treated individuals, but there was no difference between CD32 + and PD-1 + cells. There was no enrichment of latently infected cells with inducible HIV-1 in CD32 + versus PD-1 + cells in antiretroviral therapy (ART)-treated individuals. HIV-1 transcription was then analyzed in LN memory CD4 T cell populations sorted on the basis of CD32 and PD-1 expression. CD32 + PD-1 + CD4 T cells were significantly enriched in cell-associated HIV RNA compared to CD32 - PD-1 - (averages of 5.2-fold in treated individuals and 86.6-fold in viremics), CD32 + PD-1 - (2.2-fold in treated individuals and 4.3-fold in viremics), and CD32 - PD-1 + (2.2-fold in ART-treated individuals and 4.6-fold in viremics) cell populations. Similar levels of HIV-1 transcription were found in CD32 + PD-1 - and CD32 - PD-1 + CD4 T cells. Interestingly, the proportion of CD32 + and PD-1 + CD4 T cells negatively correlated with CD4 T cell counts and length of therapy. Therefore, the expression of CD32 identifies, independently of PD-1, a CD4 T cell population with persistent HIV-1 transcription and coexpression of CD32 and PD-1, the CD4 T cell population with the highest levels of HIV-1 transcription in both viremic and treated individuals.IMPORTANCE The existence of long-lived latently infected resting memory CD4 T cells represents a major obstacle to the eradication of HIV infection. Identifying cell markers defining latently infected cells containing replication-competent virus is important in order to determine the mechanisms of HIV persistence and to develop novel therapeutic strategies to cure HIV infection. We provide evidence that PD-1 and CD32 may have a complementary role in better defining CD4 T cell populations infected with HIV-1. Furthermore, CD4 T cells coexpressing CD32 and PD-1 identify a CD4 T cell population with high levels of persistent HIV-1 transcription.

Supplemental Digital Content is available in the text, Prevalence and risk factors for hepatic steatosis (HS) in the human immunodeficiency virus (HIV)-positive population of western countries are controversially discussed and potentially confounded by coinfection with viral hepatitis. Significant HS (more than 10% of hepatocytes) can be accurately assessed using controlled attenuation parameter (CAP) determination. Aim of this study was to assess prevalence and factors associated with significant HS in HIV monoinfected patients. A total of 364 HIV-infected patients (289 monoinfected) were included in this prospective, cross-sectional study. All patients underwent CAP determination. Steatosis was classified as S1 (significant steatosis) with CAP > 238 dB/m, S2 with CAP > 260 dB/m, and S3 with CAP > 292 dB/m. Multivariable logistic regression analyses were performed to assess the factors associated with HS in this cohort. Significant HS was detected in 118 monoinfected patients (149 in the total cohort). In the total cohort as well as in the monoinfected patients alone, HS grade distribution showed a similar pattern (S1:29%, S2:34%, and S3:37%). Interestingly, patients with HS had a longer history of HIV infection and combined antiretroviral therapy (cART). Interalia, age, gender, ethnicity, and metabolic factors were strongly associated with HS, while body mass index (BMI), triglyceride, and glycated hemoglobin (HbA1c) levels were independently associated with significant HS. HS is highly prevalent among HIV monoinfected patients. Although metabolic risk factors, such as obesity and poorly controlled diabetes, are independently associated with HS in HIV monoinfected patients, cART and control of HIV seem to play an indirect role in the development of HS, probably through the return-to-health effect.

Objectives: The aim of the study was to evaluate differences in immunovirological response to combination antiretroviral therapy (cART) in migrant and native men and women within a European collaboration of HIV cohorts Collaboration of Observational HIV Epidemiological Research in Europ (COHERE) in EuroCoord, 2004-2013. Methods: Migrants were defined as those with geographical origin (GO) different from the reporting country and were grouped as originating from Western Europe and Western Countries (WEWC), Eastern Europe (EE), North Africa and the Middle East (NAME), sub-Saharan Africa (SSA), Latin America (LA), Caribbean (CRB) and Asia/Oceania (ASIA/OCE). Native (NAT) individuals were defined as those originating from the reporting country. CD4 cell counts were modelled using piecewise linear mixed-effects models with two slopes, whereas models to estimate subdistribution hazard ratios (sHRs) were used for time to virological response (VR) (i.e. time from cART initiation to the first of two successive HIV RNA measurements < 400 HIV-1 RNA copies/ml). Results: Of 32 817 individuals, 25 799 (78.6%) were men. The percentage of migrants was higher in women (48.9%) than in men (21.2%) and migrants from SSA accounted for the largest migrant group (29.9% in men and 63.3% in women). Migrant men and women from SSA started at lower CD4 cell counts than NAT individuals, which remained lower over time. VR was ≥ 85% at 12 months for all groups except CRB women (77.7%). Compared with NAT men and women, lower VR was experienced by NAME [sHR 0.91; 95% confidence interval (CI) 0.86-0.97] and SSA (sHR 0.88; 95% CI 0.82-0.95) men and CRB (sHR 0.77; 85% CI 0.67-0.89) women, respectively. Conclusions: Immunovirological response to cART in Western Europe varies by GO and sex of patients. ART benefits are not equal for all, underlining the point that efforts need to prioritize those most in need.

OBJECTIVE: Model trajectories of CD4 and CD8 cell counts after starting combination antiretroviral therapy (ART), and use the model to predict trends in these counts and the CD4:CD8 ratio. DESIGN: Cohort study of antiretroviral-naive HIV-positive adults who started ART after 1997 (ART Cohort Collaboration) with >6 months of follow-up data. METHODS: We jointly estimated CD4 and CD8 count trends and their correlation using a bivariate random effects model, with linear splines describing their population trends, and predicted the CD4:CD8 ratio trend from this model. We assessed whether CD4 and CD8 count trends and the CD4:CD8 ratio trend varied according to CD4 count at start of ART (baseline), and, whether these trends differed in patients with and without virological failure more than 6 months after starting ART. RESULTS: A total of 39,979 patients were included (median follow-up was 53 months). Among patients with baseline CD4 count >/=50 cells/mm, predicted mean CD8 counts continued to decrease between 3 and 15 years post-ART, partly driving increases in the predicted mean CD4:CD8 ratio. During 15 years of follow-up, normalisation of the predicted mean CD4:CD8 ratio (to >1) was only observed among patients with baseline CD4 count >/=200 cells/mm. A higher baseline CD4 count predicted a shorter time to normalisation. CONCLUSIONS: Declines in CD8 count and increases in CD4:CD8 ratio occurred up to 15 years after starting ART. The likelihood of normalisation of the CD4:CD8 ratio is strongly related to baseline CD4 count.This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0.

Co-trimoxazole reduces mortality in HIV-infected adults with tuberculosis (TB), and in vitro data suggest potential antimycobacterial activity of co-trimoxazole. We aimed to evaluate whether prophylaxis with co-trimoxazole is associated with a decreased risk of incident TB in Swiss HIV Cohort Study (SHCS) participants. We determined the incidence of TB per 1,000 person-years from January 1992 to December 2012. Rates were analyzed separately in participants with current or no previous antiretroviral treatment (ART) using Poisson regression adjusted for CD4 cell count, sex, region of origin, injection drug use, and age. A total of 13,431 cohort participants contributed 107,549 person-years of follow-up: 182 patients had incident TB—132 (73%) before and 50 (27%) after ART initiation. The multivariable incidence rate ratios for cumulative co-trimoxazole exposure per year for persons with no previous ART and current ART were 0.70 (95% confidence interval [CI], 0.55 to 0.89) and 0.87 (95% CI, 0.74 to 1.0), respectively. Co-trimoxazole may prevent the development of TB among HIV-positive persons, especially among those with no previous ART.

Thwarting HIV Multiple genome-wide association studies have revealed that human leukocyte antigen (HLA) genes of the major histocompatibility complex locus have the strongest impact on HIV. In particular, a single-nucleotide polymorphism 35 base pairs upstream of HLA-C shows significant association with viral load and protection against HIV. How HLA-C mediates these effects is unknown. Apps et al. (p. 87 ) now demonstrate that increasing surface expression of HLA-C is associated with reduced viral load and reduced rate of progression to low CD4 + T cell counts in African and European Americans. High HLA-C expression likely promoted improved HIV control through a more effective cytotoxic CD8 + T cell response. In contrast to HIV infection, high HLA-C expression was associated with a higher risk of the inflammatory bowel disease, Crohn's disease.

Background & aims To report the association of lymphoepithelial cysts (LEC) of the pancreas with Human Immunodeficiency Virus (HIV) infection. An association between LEC and HIV infection is already established in the parotid gland (PG). Methods Report of the first two cases of LEC of the pancreas associated with HIV infection and comparison of the clinical and histopathological aspects of LECs of the pancreas and of the PG. Results LECs of the pancreas were discovered by CT imaging in 2 patients with a history of HIV infection. Notably, LEC completely resolved in one patient after initiation of antiretroviral therapy. Conclusion This is the first report of an association of LEC of the pancreas and HIV infection. In the presence of LEC of the pancreas, we propose a systematic screening for HIV infection and associated lesions in the PG. Antiretroviral therapy should be initiated in untreated patients. Surgery should be reserved for symptomatic patients in whom medical therapy has failed.

BACKGROUND Human systemic antibody responses to commensal microbiota are not well characterised during health and disease. Of particular interest is the analysis of their potential modulation caused by chronic HIV 1 infection which is associated with sustained enteropathy and systemic B cell disturbances reflected by impaired B cell responses and chronic B cell hyperactivity. The mechanisms underlying B cell hyperactivation and the specificities of the resulting hypergammaglobulinaemia are only poorly understood. METHODS By a technique referred to as live bacterial FACS (fluorescence activated cell sorting) the present study investigated systemic antibody responses to several gut and skin commensal bacteria as well as Candida albicans in longitudinal plasma and serum samples from healthy donors chronic HIV 1 infected individuals with or without diarrhoea and patients with inflammatory bowel disease (IBD). RESULTS The data show that systemic antibody responses to the commensal microbiota were abundantly present in humans and remained remarkably stable over years. Overall systemic antibody responses to gut commensal bacteria were not affected during chronic HIV 1 infection with titres decreasing when normalised to elevated plasma immunoglobulin G (IgG) levels found in patients with HIV. In contrast increases in the titres of high affinity antimicrobiota antibodies were detected in patients with IBD demonstrating that conditions with known increased intestinal permeability and aberrant mutualism can induce changes in antibody titres observed in these assays. CONCLUSION Neither HIV associated enteropathy nor B cell dysfunction impact on the high affinity systemic antibody responses to gut commensal bacteria. HIV associated hypergammaglobulinaemia is therefore unlikely to be driven by induction of antimicrobiota antibodies.

INTRODUCTION: Migrants are overrepresented in the European HIV epidemic. We aimed to understand the barriers and facilitators to HIV testing and current treatment and healthcare needs of migrants living with HIV in Europe. METHODS: A cross-sectional study was conducted in 57 HIV clinics in nine countries (Belgium, Germany, Greece, Italy, The Netherlands, Portugal, Spain, Switzerland and United Kingdom), July 2013 to July 2015. HIV-positive patients were eligible for inclusion if they were as follows: 18 years or older; foreign-born residents and diagnosed within five years of recruitment. Questionnaires were completed electronically in one of 15 languages and linked to clinical records. Primary outcomes were access to primary care and previous negative HIV test. Data were analysed using random effects logistic regression. Outcomes of interest are presented for women, heterosexual men and gay/bisexual men. RESULTS: A total of 2093 respondents (658 women, 446 heterosexual men and 989 gay/bisexual men) were included. The prevalence of a previous negative HIV test was 46.7%, 43.4% and 82.0% for women, heterosexual and gay/bisexual men respectively. In multivariable analysis previous testing was positively associated with: receipt of post-migration antenatal care among women, permanent residency among heterosexual men and identifying as gay rather than bisexual among gay/bisexual men. Access to primary care was found to be high (>83%) in all groups and was strongly associated with country of residence. Late diagnosis was common for women and heterosexual men (60.8% and 67.1%, respectively) despite utilization of health services prior to diagnosis. Across all groups almost three-quarters of people on antiretrovirals had an HIV viral load

Objectives: In the context of HIV clinical care, open discussion regarding sexual health and reproductiveplans has become increasingly relevant. The aim of this paper is to explore barriers to communicationbetween providers and women living with HIV regarding childbearing.Methods: In-depth interviews (IDIs) were conducted with 48 HIV infected women receiving ART at 7different HIV clinics providing comprehensive HIV care services in four districts in Uganda, between Julyand August 2012. All women were aware of their HIV diagnosis prior to pregnancy or had given birthwhile living with HIV.Results: Four themes emerged describing barriers to communication, from the HIV-positive women’spoint of view: (i) provider indifference or opposition to childbearing post HIV diagnosis, (ii) anticipationof negative response from provider, (iii) provider’s emphasis on ‘scientific’ facts, (iv) ‘accidentalpregnancy’.Conclusion: Existing evidence regarding effective provider-patient communication should be consideredfor its application for reproductive counseling among HIV infected women.Practice implications: These data demonstrate the need for current counseling guidelines to exploreapproaches that encourage open, non-judgmental, non-directive discussions with HIV positiveindividuals around their reproductive desires and intentions in a health care setting

BACKGROUND: Natural killer (NK) cell phenotype and function have recently gained much attention as playing crucial roles in antibody-dependent cellular cytotoxicity (ADCC). We investigated NK cell function, as measured by ADCC, in HIV-1-positive individuals before and 6 months after highly active antiretroviral therapy (HAART) initiation.METHOD: The ability of antibodies and NK cells to mediate ADCC was investigated separately and in combination in an autologous model. The NK cell subset distribution and NK cell phenotype (ie, expression of maturation and activation markers within NK cell subsets) were analyzed.RESULTS: The ability of NK cells to mediate ADCC was significantly increased after only 6 months of HAART and was not explained by a normalization of NK cell subsets (CD56 CD16 and CD56 CD16 NK cells) but rather by normalization in the frequency of NK cells expressing CCR7 and CD27. For individuals with no increase in ADCC after 6 months of HAART, the frequency of NK cells expressing NKp46 was downregulated. The ability of antibodies to mediate ADCC alone and in combination in an autologous model was not improved.CONCLUSIONS: HAART improves the ability of NK cells to mediate ADCC after 6 months. This improvement does not correlate with general immune restoration, as measured by CD4 T-cell counts, but rather to a decrease in the frequency of NK cells expressing CCR7 and CD27.

The Belgian HIV epidemic is largely concentrated among men who have sex with men and Sub-Saharan Africans. We studied the continuum of HIV care of those diagnosed with HIV living in Belgium and its associated factors., SCOPUS: ar.j, info:eu-repo/semantics/published

For more than two decades, CD4 cell count measurements have been central to understanding HIV disease progression, making important clinical decisions, and monitoring the response to antiretroviral therapy (ART). In well resourced settings, the monitoring of patients on ART has been supported by routine virological monitoring. Viral load monitoring was recommended by WHO in 2013 guidelines as the preferred way to monitor people on ART, and efforts are underway to scale up access in resource-limited settings. Recent studies suggest that in situations where viral load is available and patients are virologically suppressed, long-term CD4 monitoring adds little value and stopping CD4 monitoring will have major cost savings. CD4 cell counts will continue to play an important part in initial decisions around ART initiation and clinical management, particularly for patients presenting late to care, and for treatment monitoring where viral load monitoring is restricted. However, in settings where both CD4 cell counts and viral load testing are routinely available, countries should consider reducing the frequency of CD4 cell counts or not doing routine CD4 monitoring for patients who are stable on ART.

Die HIV-Infektion, welche sich als fieberhafte, der Mononukleose ähnliche Krankheit präsentieren kann, wird als Diagnose im Akutstadium häufig verpasst. Da es während der HIV-Primoinfektion zu einer hohen Viruslast kommt, ist es sehr wichtig, Patienten in diesem Stadium zu diagnostizieren, denn durch die hohe Viruskonzentration sind die Patienten sehr ansteckend. Es wird angenommen, dass > 50% der Patienten Symptome einer akuten HIV-Infektion durchmachen, welche vor allem durch Fieber, Müdigkeit, einem Exanthem, Myalgien und Kopfschmerzen gekennzeichnet sind. Die Frühtherapie einer HIV-Infektion ist kontrovers. Insbesondere fehlen prospektive vergleichende Studien, die beweisen, dass eine Frühtherapie während der Serokonversionsphase den Verlauf der HIV-Infektion beeinflusst.

Well preserved spirometry but evidence of small-airway dysfunction in never-smoking HIV-infected individualshttp://ow.ly/oZCC308iUpo

BACKGROUND: Invasive pneumococcal disease (IPD) is an important cause of morbidity among individuals infected with human immunodeficiency virus (HIV). We described incidence and risk factors for IPD in HIV-infected and uninfected individuals.METHODS: Nationwide population-based cohort study of HIV-infected adults treated at all Danish HIV treatment centers during 1995-2012. Nineteen population-matched controls per HIV-infected individual were retrieved. The risk of IPD was assessed using Poisson regression.RESULTS: The incidence of IPD was 304.7 cases per 100 000 person-years of follow-up (PYFU) in HIV-infected and 12.8 per 100 000 PYFU in HIV-uninfected individuals. After adjusting for confounders, HIV infection (relative risk [RR], 24.4 [95% confidence interval [CI], 23.7-25.1]), male sex (RR, 1.20 [95% CI, 1.16-1.24]), increasing age (per year) (RR, 1.03 [95% CI, 1.03-1.04]), and calendar period (pre-cART RR, 2.80 [95% CI, 2.70-2.91] compared with late cART) were significantly associated with an increased risk of IPD. Among HIV-infected individuals, male sex (RR, 1.57 [95% CI, 1.49-1.66]), smoking (RR, 1.34 [95% CI, 1.26-1.42]), and injecting drug use (RR, 2.51 [95% CI, 2.26-2.67]) were associated with an increased risk of IPD. Detectable viral loads (RR, 1.88 [95% CI, 1.79-1.98]) and a relative fall in CD4 T-cell counts were also associated with an increased risk (≥500 to 350-500 CD4 T cells/µL: RR, 1.29 [95% CI, 1.21-1.37] and CONCLUSIONS: The incidence of IPD in HIV-infected individuals remained significantly higher than the incidence observed in non-HIV-infected subjects, despite the widespread use of cART. IDUs have a persistently high risk of IPD. Injecting drug use, smoking, and the receipt of cART are suitable targets for preventive measures in the future.

OBJECTIVE: The presence of minority nonnucleoside reverse transcriptase inhibitor (NNRTI)-resistant HIV-1 variants prior to antiretroviral therapy (ART) has been linked to virologic failure in treatment-naive patients. DESIGN: We performed a large retrospective study to determine the number of treatment failures that could have been prevented by implementing minority drug-resistant HIV-1 variant analyses in ART-naïve patients in whom no NNRTI resistance mutations were detected by routine resistance testing. METHODS: Of 1608 patients in the Swiss HIV Cohort Study, who have initiated first-line ART with two nucleoside reverse transcriptase inhibitors (NRTIs) and one NNRTI before July 2008, 519 patients were eligible by means of HIV-1 subtype, viral load and sample availability. Key NNRTI drug resistance mutations K103N and Y181C were measured by allele-specific PCR in 208 of 519 randomly chosen patients. RESULTS: Minority K103N and Y181C drug resistance mutations were detected in five out of 190 (2.6%) and 10 out of 201 (5%) patients, respectively. Focusing on 183 patients for whom virologic success or failure could be examined, virologic failure occurred in seven out of 183 (3.8%) patients; minority K103N and/or Y181C variants were present prior to ART initiation in only two of those patients. The NNRTI-containing, first-line ART was effective in 10 patients with preexisting minority NNRTI-resistant HIV-1 variant. CONCLUSION: As revealed in settings of case-control studies, minority NNRTI-resistant HIV-1 variants can have an impact on ART. However, the sole implementation of minority NNRTI-resistant HIV-1 variant analysis in addition to genotypic resistance testing (GRT) cannot be recommended in routine clinical settings. Additional associated risk factors need to be discovered.

Item does not contain fulltext This study examines a proposed theoretical model examining the interrelationships between stigma, disclosure, coping, and medication adherence among 158 HIV-infected patients on antiretroviral therapy (ART) in northern Tanzania. Perceived and self-stigma, voluntary and involuntary disclosure, positive and negative coping, and demographics were assessed by trained interviewers, and self-reported adherence was collected during 5 months follow-up. Data were examined using correlation and regression analyses. The analyses showed that perceived stigma is primarily related to involuntary disclosure, whereas self-stigma is related to voluntary disclosure. Religious coping positively relates to acceptance, whereas perceived stigma explains higher levels of denial of HIV status. Lastly, adherence was negatively affected by alcohol use, self-stigma, and denial. We conclude that adherence is predominantly predicted by negative rather than positive coping mechanisms. Therefore, substituting maladaptive coping mechanisms like denial and alcohol use with a more adaptive coping style may be an important strategy to improve long-term ART adherence and well-being of patients. Moreover, this study showed that it is useful to examine both involuntary and voluntary disclosure when studying its relation with stigma.

Various neurological and neuropsychological manifestations are still relatively frequently reported in HIV infected patients in the highly active antiretroviral therapy era. A fraction of them could be related to HIV replication in the central nervous system (CNS) despite adequate peripheral viral suppression. This hypothesis is supported by numerous reports of detectable HIV RNA in the cerebrospinal fluid in the context of a low or undetectable viremia in association with neurological or neuropsychological complaints. In addition, some antiviral molecules may not achieve adequate levels in the CNS, thus potentially favoring intracerebral HIV replication and even antiretroviral resistance. Neurologic manifestations in the presence of CNS HIV replication often decrease after antiretroviral treatment CNS penetration optimization.