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1.
Lancet HIV ; 11(5): e321-e332, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38621392

RESUMO

BACKGROUND: Integrase strand-transfer inhibitors (INSTIs) and tenofovir alafenamide have been associated with weight gain in several clinical trials and observational cohorts. However, whether weight gain associated with INSTIs and tenofovir alafenamide confers a higher risk of weight-related clinical events is unclear. We aimed to assess whether changes in BMI differentially increase hypertension or dyslipidaemia risk in people with HIV receiving INSTIs, tenofovir alafenamide, or both versus other contemporary regimens. METHODS: This multicentre, prospective observational study analysed prospective data from RESPOND, an international consortium of HIV cohorts for which recruitment began in 2017 and is still ongoing from HIV clinics and hospitals in 37 European countries and Australia. Participants were eligible if they were aged 18 years or older, receiving INSTI-containing antiretroviral therapy (ART) regimens or a contemporary non-INSTI, did not have hypertension or dyslipidaemia at baseline, and had baseline and at least two follow-up BMI, lipid, and blood pressure measurements. We excluded participants without baseline CD4 or HIV RNA results and those receiving non-ART medications associated with weight changes, including antipsychotics and mood stabilisers, corticosteroids, insulin, and insulin secretagogues. They were followed up from baseline until the earliest hypertension or dyslipidaemia event, their last visit, or Dec 31, 2021, whichever was earlier. The primary outcomes were incidence of hypertension and dyslipidaemia, for which we used multivariable Poisson regression adjusted for time-updated BMI to determine unadjusted and adjusted incidence rate ratios (IRRs) of hypertension and dyslipidaemia in people receiving INSTIs, tenofovir alafenamide, or both, and tested for interaction between time-updated ART regimen and BMI. FINDINGS: Of the 35 941 RESPOND participants, 9704 (7327 [75·5 %] male and 2377 [24·5%] female) were included in the hypertension analysis and 5231 (3796 [72·6%] male and 1435 [27·4%] female) were included in the dyslipidaemia analysis. In the univariable model, hypertension was more common in individuals receiving an INSTI with tenofovir alafenamide (IRR 1·70, 95% CI 1·54-1·88) or an INSTI without tenofovir alafenamide (1·41, 1·30-1·53) compared with those receiving neither INSTIs nor tenofovir alafenamide. Adjustment for time-updated BMI and confounders attenuated risk in participants receiving an INSTI with (IRR 1·48, 1·31-1·68) or without (1·25, 1·13-1·39) tenofovir alafenamide. Similarly, dyslipidaemia was more common in participants using tenofovir alafenamide with an INSTI (IRR 1·24, 1·10-1·40) and tenofovir alafenamide alone (1·22, 1·03-1·44) than in participants using neither INSTI nor tenofovir alafenamide. Adjustment for BMI and confounders attenuated the risk in participants receiving tenofovir alafenamide with an INSTI (adjusted IRR 1·21, 1·07-1·37), whereas the risk in those receiving tenofovir alafenamide alone became non-significant (1·15, 0·96-1·38). The associations between increasing BMI and risk of hypertension and dyslipidaemia did not differ between participants receiving different ART regimens (pinteraction=0·46 for hypertension; pinteraction=0·31 for dyslipidaemia). INTERPRETATION: Although residual confounding cannot be entirely excluded, the use of INSTIs was associated with incident hypertension, and the use of tenofovir alafenamide was associated with dyslipidaemia, with the latter association partly mediated by weight gain. These results reiterate the need for hypertension and dyslipidaemia screening in people with HIV. FUNDING: The CHU St Pierre Brussels HIV Cohort, The Austrian HIV Cohort Study, The Australian HIV Observational Database, The AIDS Therapy Evaluation in the Netherlands national observational HIV cohort, The Brighton HIV Cohort, The National Croatian HIV Cohort, The EuroSIDA cohort, The Frankfurt HIV Cohort Study, The Georgian National AIDS Health Information System, The Nice HIV Cohort, The ICONA Foundation, The Modena HIV Cohort, The PISCIS Cohort Study, The Swiss HIV Cohort Study, The Swedish InfCare HIV Cohort, The Royal Free HIV Cohort Study, The San Raffaele Scientific Institute, The University Hospital Bonn HIV Cohort, The University of Cologne HIV Cohort, Merck Life Sciences, ViiV Healthcare, and Gilead Sciences.


Assuntos
Índice de Massa Corporal , Dislipidemias , Infecções por HIV , Hipertensão , Tenofovir , Tenofovir/análogos & derivados , Humanos , Feminino , Masculino , Infecções por HIV/tratamento farmacológico , Tenofovir/efeitos adversos , Tenofovir/uso terapêutico , Hipertensão/epidemiologia , Hipertensão/induzido quimicamente , Estudos Prospectivos , Dislipidemias/induzido quimicamente , Dislipidemias/epidemiologia , Pessoa de Meia-Idade , Adulto , Inibidores de Integrase de HIV/efeitos adversos , Inibidores de Integrase de HIV/uso terapêutico , Alanina/efeitos adversos , Austrália/epidemiologia , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , Aumento de Peso/efeitos dos fármacos , Europa (Continente)/epidemiologia , Fatores de Risco , Quimioterapia Combinada/efeitos adversos
3.
J Dtsch Dermatol Ges ; 22(3): 389-397, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38308171

RESUMO

BACKGROUND AND OBJECTIVES: Serovar L1-L3 of Chlamydia trachomatis (CT) causes lymphogranuloma venereum (LGV). A surge in LGV-cases has been observed among HIV-positive men who have sex with men (MSM). Discrimination between LGV and non-LGV is pivotal since it has major treatment implications. Here, we aimed to determine the prevalence and characteristics of LGV among CT-infections. PATIENTS AND METHODS: All CT-positive results from 04/2014-12/2021 at the four largest Austrian HIV and STI clinics were evaluated. Disease characteristics and patient demographics were analyzed. RESULTS: Overall, n  =  2,083 infections of CT were documented in n  =  1,479 individual patients: median age was 31.4 years, 81% were male, 59% MSM, 44% HIV-positive, 13% on HIV pre-exposure-prophylaxis. Available serovar analyses (61% [1,258/2,083]) showed L1-L3 in 15% (192/1,258). Considering only MSM with rectal CT-infection, LGV accounted for 23% (101/439). Cases of LGV vs. other CT-infections were primarily MSM (92% [177/192] vs. 62% [1,179/1,891], p < 0.001), more often HIV-positive (64% [116/180] vs. 46% [631/1,376]; p < 0.001) and had frequently concomitant syphilis infection (18% [32/180] vs. 7% [52/749]; p < 0.001). LGV commonly manifested as proctitis (38% [72/192]) whereas 45% (87/192) were asymptomatic. CONCLUSIONS: Lymphogranuloma venereum accounted for 23% of rectal CT-infections in MSM. Furthermore, 45% of all LGV-cases were asymptomatic. In the absence of CT-serovar analysis, a high LGV prevalence should be considered in risk-populations and guide empiric treatment selection.


Assuntos
Infecções por HIV , Linfogranuloma Venéreo , Minorias Sexuais e de Gênero , Humanos , Masculino , Adulto , Feminino , Linfogranuloma Venéreo/diagnóstico , Linfogranuloma Venéreo/epidemiologia , Linfogranuloma Venéreo/tratamento farmacológico , Homossexualidade Masculina , Áustria/epidemiologia , Chlamydia trachomatis , Infecções por HIV/epidemiologia
4.
Int J STD AIDS ; 35(3): 234-239, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37963428

RESUMO

Background: The incidence of pyogenic spondylodiscitis has been increasing in countries of Europe and North America, probably due to an increasing number of persons with risk factors for this infection. It is unclear whether HIV infection in the era of antiretroviral therapy (ART) increases the risk for spondylodiscitis. Method: We present 7 cases of pyogenic spondylodiscitis of the cervical, thoracic, and lumbar spine in six individuals living with HIV under ART with suppressed viral load. Results: All patients presented with severe non-radicular pain and elevated inflammatory markers. Diagnosis was confirmed by magnetic resonance imaging (MRI) scan and isolation of the pathogen. Staphylococcus aureus was the causative pathogen in five patients. One patient suffered from an infection with Klebsiella pneumoniae followed by a mixed infection with Cutibacterium acnes and Bacillus circulans 18 months later. All patients needed surgical intervention, and the mean duration of antibiotic treatment was 17 weeks (range 12-26). Five patients recovered fully, including two persons who also suffered from endocarditis. One patient died from multi-organ failure. Conclusion: Spondylodiscitis may be seen more frequently in persons living with HIV as they grow older and suffer from comorbidities which put them at risk for this infection. HIV physicians should be aware of the infection and its risk factors.


Assuntos
Discite , Infecções por HIV , Infecções Estafilocócicas , Humanos , Discite/tratamento farmacológico , Discite/diagnóstico , Discite/microbiologia , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções Estafilocócicas/diagnóstico , Antibacterianos/uso terapêutico , Dor
5.
BMC Infect Dis ; 22(1): 770, 2022 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-36192705

RESUMO

BACKGROUND: Sarcoidosis is a systemic inflammatory disease that is characterized by non-caseating epithelioid-cell granulomas upon histology. However, similar histological findings may also be seen with certain infections. Thus, differentiation from infection is pivotal to ensure appropriate treatment. Here, we present a case of a disseminated infection with Mycobacterium genavense owing to an interleukin 12 receptor subunit beta 1 (IL-12Rß1) associated immunodeficiency in a previously healthy female who was initially misdiagnosed with sarcoidosis. M. genavense is a nontuberculous mycobacterium which can cause lymphadenopathy, gastrointestinal and bone marrow infiltration in immunocompromised patients. With this case report we aim to highlight that an infection with M. genavense on the ground of a genetic defect of mycobacterial immune control may represent a rare differential diagnosis of sarcoidosis. CASE PRESENTATION: A 31-year-old female was referred to our hospital with progressive lymphadenopathy, hepatosplenomegaly, pancytopenia and systemic inflammation. She had previously been evaluated for generalized lymphadenopathy in another hospital. At that time, lymph node biopsies had revealed sarcoid-like lesions and a systemic corticosteroid treatment was initiated based on a putative diagnosis of sarcoidosis. When her condition worsened, she was transferred to our university clinic, where the diagnosis of disseminated M. genavense infection owing to an inborn interferonopathy was made. Her family history revealed that her brother had also suffered from IL-12Rß1 deficiency and had died from a systemic infection with M. genavense at the age of 21. The patient received antimycobacterial treatment combined with subcutaneous type I interferon, which eventually led to a gradual improvement over the next months. CONCLUSIONS: Differentiating between sarcoidosis and sarcoid-like lesions secondary to infections may be challenging, especially when pathogens are difficult to detect or not expected in an apparently immunocompetent patient. Patients with IL-12Rß1-associated immunodeficiency may be asymptomatic until adulthood, and disseminated M. genavense infection on the grounds of an IL-12Rß1-associated immunodeficiency may represent a rare differential diagnosis of sarcoidosis.


Assuntos
Síndromes de Imunodeficiência , Interferon Tipo I , Linfadenopatia , Infecções por Mycobacterium não Tuberculosas , Infecções por Mycobacterium , Sarcoidose , Adulto , Feminino , Humanos , Síndromes de Imunodeficiência/complicações , Linfadenopatia/complicações , Masculino , Mycobacterium , Infecções por Mycobacterium/complicações , Infecções por Mycobacterium/diagnóstico , Infecções por Mycobacterium/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/complicações , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Micobactérias não Tuberculosas/genética , Receptores de Interleucina-12/genética , Sarcoidose/diagnóstico
6.
Vaccine ; 40(29): 3948-3953, 2022 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-35606234

RESUMO

INTRODUCTION: Vaccination against seasonal influenza is recommended for all HIV-infected persons. Few data have been reported on the effect of repeated annual vaccination in this population. METHODS: We measured haemagglutination inhibition antibody responses and investigated seroprotection rates in 344 HIV-infected adults before and 12 weeks after influenza vaccination with a trivalent subunit vaccine. RESULTS: 68.3% of patients were male, the median age was 45 years. 83.7% had a viral load < 50 copies/mL. The median CD4 count was 604/µL. 304 patients (88.4%) had received influenza vaccinations in previous years. Seroprotection rates for A/H1N1 and B were over 90% in all age groups before vaccination and close to 100% after vaccination. For A/H3N2, seroprotection rates were lowest in individuals below 30 years both before and after vaccination (22.2% and 50.0%) and higher in older age groups (48.4% and 83.9% in people over 60 years). GMT fold increases were not significantly different across the age groups (3.0 to 4.2, p = 0.425). Previous influenza vaccinations were associated with higher seroprotection rates before and after vaccination (62.2% and 84.2% in patients with 8 or more previous vaccinations vs. 15.0% and 57.5% without previous vaccinations, respectively). Individuals with detectable viral load, elevated immune activation (urine neopterin ≥ 250 µmol/mol creatinine), and higher CD4 nadir (≥200 cells/µL) showed a trend towards inferior immune responses to vaccination, whereas gender and CD4 count did not have an effect. CONCLUSION: The lower seroprotection rates observed in younger individuals may be explained by the higher proportion of patients without HIV treatment and with fewer previous encounters with influenza strains. Good seroprotection rates can be achieved in elderly HIV-infected patients and after repeated annual vaccinations.


Assuntos
Infecções por HIV , Vírus da Influenza A Subtipo H1N1 , Vacinas contra Influenza , Influenza Humana , Adulto , Idoso , Anticorpos Antivirais , Áustria , Feminino , Testes de Inibição da Hemaglutinação , Humanos , Vírus da Influenza A Subtipo H3N2 , Masculino , Pessoa de Meia-Idade , Vacinação
7.
J Acquir Immune Defic Syndr ; 90(4): e4-e12, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35298446

RESUMO

OBJECTIVES: Phylogenetic analyses of 2 or more countries allow to detect differences in transmission dynamics of local HIV-1 epidemics beyond differences in demographic characteristics. METHODS: A maximum-likelihood phylogenetic tree was built using pol -sequences of the Swiss HIV Cohort Study (SHCS) and the Austrian HIV Cohort Study (AHIVCOS), with international background sequences. Three types of phylogenetic cherries (clusters of size 2) were analyzed further: (1) domestic cherries; (2) international cherries; and (3) SHCS/AHIVCOS-cherries. Transmission group and ethnicities observed within the cherries were compared with the respective distribution expected from a random distribution of patients on the phylogeny. RESULTS: The demographic characteristics of the AHIVCOS (included patients: 3'141) and the SHCS (included patients: 12'902) are very similar. In the AHIVCOS, 36.5% of the patients were in domestic cherries, 8.3% in international cherries, and 7.0% in SHCS/AHIVCOS cherries. Similarly, in the SHCS, 43.0% of the patients were in domestic cherries, 8.2% in international cherries, and 1.7% in SHCS/AHIVCOS cherries. Although international cherries in the SHCS were dominated by heterosexuals with men who have sex with men being underrepresented, the opposite was the case for the AHIVCOS. In both cohorts, cherries with one patient belonging to the transmission group intravenous drug user and the other one non-intravenous drug user were underrepresented. CONCLUSIONS: In both cohorts, international HIV transmission plays a major role in the local epidemics, mostly driven by men who have sex with men in the AHIVOS, and by heterosexuals in the SHCS, highlighting the importance of international collaborations to understand global HIV transmission links on the way to eliminate HIV.


Assuntos
Epidemias , Infecções por HIV , Soropositividade para HIV , HIV-1 , Minorias Sexuais e de Gênero , Abuso de Substâncias por Via Intravenosa , Áustria/epidemiologia , Análise por Conglomerados , Estudos de Coortes , Infecções por HIV/tratamento farmacológico , Soropositividade para HIV/epidemiologia , HIV-1/genética , Homossexualidade Masculina , Humanos , Masculino , Filogenia , Abuso de Substâncias por Via Intravenosa/epidemiologia , Suíça/epidemiologia
8.
HIV Med ; 23(8): 895-910, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35233903

RESUMO

OBJECTIVE: To compare the incidence of hypertension in people living with HIV receiving integrase strand transfer inhibitor (INSTI)-based antiretroviral therapy (ART) versus non-nucleoside reverse transcriptase inhibitors (NNRTIs) or boosted protease inhibitors (PIs) in the RESPOND consortium of HIV cohorts. METHODS: Eligible people with HIV were aged ≥18 years who initiated a new three-drug ART regimen for the first time (baseline), did not have hypertension, and had at least two follow-up blood pressure (BP) measurements. Hypertension was defined as two consecutive systolic BP measurements ≥140 mmHg and/or diastolic BP ≥90 mmHg or initiation of antihypertensives. Multivariable Poisson regression was used to determine adjusted incidence rate ratios (aIRRs) of hypertension, overall and in those who were ART naïve or experienced at baseline. RESULTS: Overall, 4606 people living with HIV were eligible (INSTIs 3164, NNRTIs 807, PIs 635). The median baseline systolic BP, diastolic BP, and age were 120 (interquartile range [IQR] 113-130) mmHg, 78 (70-82) mmHg, and 43 (34-50) years, respectively. Over 8380.4 person-years (median follow-up 1.5 [IQR 1.0-2.7] years), 1058 (23.0%) participants developed hypertension (incidence rate 126.2/1000 person-years, 95% confidence interval [CI] 118.9-134.1). Participants receiving INSTIs had a higher incidence of hypertension than those receiving NNRTIs (aIRR 1.76; 95% CI 1.47-2.11), whereas the incidence was no different in those receiving PIs (aIRR 1.07; 95% CI 0.89-1.29). The results were similar when the analysis was stratified by ART status at baseline. CONCLUSION: Although unmeasured confounding and channelling bias cannot be excluded, INSTIs were associated with a higher incidence of hypertension than were NNRTIs, but rates were similar to those of PIs overall, in ART-naïve and ART-experienced participants within RESPOND.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Inibidores de Integrase de HIV , Hipertensão , Adolescente , Adulto , Idoso de 80 Anos ou mais , Fármacos Anti-HIV/efeitos adversos , Antirretrovirais/uso terapêutico , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Inibidores de Integrase de HIV/efeitos adversos , Humanos , Hipertensão/induzido quimicamente , Hipertensão/epidemiologia , Incidência , Inibidores de Integrase/uso terapêutico , Inibidores da Transcriptase Reversa/efeitos adversos
9.
Artigo em Inglês | MEDLINE | ID: mdl-34886257

RESUMO

(1) Objective: To investigate changes in mortality rates and predictors of all-cause mortality as well as specific causes of death over time among HIV-positive individuals in the combination antiretroviral therapy (cART) era. (2) Methods: We analyzed all-cause as well as cause-specific mortality among the Austrian HIV Cohort Study between 1997 and 2014. Observation time was divided into five periods: Period 1: 1997-2000; period 2: 2001-2004; period 3: 2005-2008; period 4: 2009-2011; and period 5: 2012-2014. Mortality rates are presented as deaths per 100 person-years (d/100py). Potential risk factors associated with all-cause mortality and specific causes of death were identified by using multivariable Cox proportional hazard models. Models were adjusted for time-updated CD4, age and cART, HIV transmission category, population size of residence area and country of birth. To assess potential nonlinear associations, we fitted all CD4 counts per patient using restricted cubic splines with truncation at 1000 cells/mm3. Vital status of patients was cross-checked with death registry data. (3) Results: Of 6848 patients (59,704 person-years of observation), 1192 died: 380 (31.9%) from AIDS-related diseases. All-cause mortality rates decreased continuously from 3.49 d/100py in period 1 to 1.40 d/100py in period 5. Death due to AIDS-related diseases, liver-related diseases and non-AIDS infections declined, whereas cardiovascular diseases as cause of death remained stable (0.27 d/100py in period 1, 0.10 d/100py in period 2, 0.16 d/100py in period 3, 0.09 d/100py in period 4 and 0.14 d/100py in period 5) and deaths due to non-AIDS-defining malignancies increased. Compared to latest CD4 counts of 500 cells/mm3, lower CD4 counts conferred a higher risk of deaths due to AIDS-related diseases, liver-related diseases, non-AIDS infections and non-AIDS-defining malignancies, whereas no significant association was observed for cardiovascular mortality. Results were similar in sensitivity analyses where observation time was divided into two periods: 1997-2004 and 2005-2014. (4) Conclusions: Since the introduction of cART, risk of death decreased and causes of death changed. We do not find evidence that HIV-positive individuals with a low CD4 count are more likely to die from cardiovascular diseases.


Assuntos
Infecções por HIV , Áustria , Contagem de Linfócito CD4 , Causas de Morte , Estudos de Coortes , Humanos , Fatores de Risco
10.
Lancet HIV ; 8(11): e711-e722, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34555326

RESUMO

BACKGROUND: Weight gain effects of individual antiretroviral drugs are not fully understood. We investigated associations between a prespecified clinically significant increase (>7%) in body-mass index (BMI) and contemporary antiretroviral use. METHODS: The International Cohort Consortium of Infectious Diseases (RESPOND) is a prospective, multicohort collaboration, including data from 17 well established cohorts and over 29 000 people living with HIV. People with HIV under prospective follow-up from Jan 1, 2012, and older than 18 years were eligible for inclusion. Each cohort contributed a predefined minimum number of participants related to the size of the specific cohort (with a minimum of 1000 participants). Participants were required to have CD4 cell counts and HIV viral load measurement in the 12 months before or within 3 months after baseline. For all antiretroviral drugs received at or after RESPOND entry, changes from pre-antiretroviral BMI levels (baseline) were considered at each BMI measurement during antiretroviral treatment. We used logistic regression to identify individual antiretrovirals that were associated with first occurrence of a more than 7% increase in BMI from pre-antiretroviral BMI. We adjusted analyses for time on antiretrovirals, pre-antiretroviral BMI, demographics, geographical region, CD4 cell count, viral load, smoking status, and AIDS at baseline. RESULTS: 14 703 people were included in this study, of whom 7863 (53·5%) had a more than 7% increase in BMI. Compared with lamivudine, use of dolutegravir (odds ratio [OR] 1·27, 95% CI 1·17-1·38), raltegravir (1·37, 1·20-1·56), and tenofovir alafenamide (1·38, 1·22-1·35) was significantly associated with a more than 7% BMI increase, as was low pre-antiretroviral BMI (2·10, 1·91-2·31 for underweight vs healthy weight) and Black ethnicity (1·61, 1·47-1·76 vs White ethnicity). Higher CD4 count was associated with a reduced risk of BMI increase (0·97, 0·96-0·98 per 100 cells per µL increase). Relative to lamivudine, dolutegravir without tenofovir alafenamide (OR 1·21, 95% CI 1·19-1·32) and tenofovir alafenamide without dolutegravir (1·33, 1·15-1·53) remained independently associated with a more than 7% increase in BMI; the associations were higher when dolutegravir and tenofovir alafenamide were used concomitantly (1·79, 1·52-2·11, and 1·70, 1·44-2·01, respectively). INTERPRETATION: Clinicians and people with HIV should be aware of associations between weight gain and use of dolutegravir, tenofovir alafenamide, and raltegravir, particularly given the potential consequences of weight gain, such as insulin resistance, dyslipidaemia, and hypertension. FUNDING: The CHU St Pierre Brussels HIV Cohort, The Austrian HIV Cohort Study, The Australian HIV Observational Database, The AIDS Therapy Evaluation in the Netherlands national observational HIV cohort, The EuroSIDA cohort, The Frankfurt HIV Cohort Study, The Georgian National AIDS Health Information System, The Nice HIV Cohort, The ICONA Foundation, The Modena HIV Cohort, The PISCIS Cohort Study, The Swiss HIV Cohort Study, The Swedish InfCare HIV Cohort, The Royal Free HIV Cohort Study, The San Raffaele Scientific Institute, The University Hospital Bonn HIV Cohort and The University of Cologne HIV Cohorts, ViiV Healthcare, and Gilead Sciences.


Assuntos
Antirretrovirais/efeitos adversos , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Aumento de Peso , Adulto , Antirretrovirais/uso terapêutico , Austrália/epidemiologia , Índice de Massa Corporal , Estudos de Coortes , Europa (Continente)/epidemiologia , Feminino , Infecções por HIV/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
11.
J Acquir Immune Defic Syndr ; 86(2): 248-257, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33079903

RESUMO

OBJECTIVES: To investigate the effectiveness, safety, and reasons for premature discontinuation of direct-acting antivirals (DAAs) in a diverse population of HIV/hepatitis C virus (HCV) coinfected individuals in Europe. METHODS: All HIV/HCV coinfected individuals in the EuroSIDA study that started interferon free DAA treatment between January 6, 2014, and January 3, 2018, with ≥12 weeks of follow-up after treatment stop were included in this analysis. Sustained virological response (SVR) was defined as a negative HCV-RNA result ≥12 weeks after stopping treatment (SVR12). Logistic regression was used to explore factors associated with SVR12. RESULTS: 1042 individuals started interferon-free DAA treatment after 1/6/2014 and were included, 862 (82.2%) had a known response to treatment, and 789 [91.5%, 95% confidence interval (CI): 89.7 to 93.4] of which achieved SVR12. There were no differences in SVR12 across regions of Europe (P = 0.84). After adjustment, the odds of achieving SVR12 was lower in individuals that received sofosbuvir/simeprevir ± ribavirin (RBV) [adjusted odds ratio 0.21 (95% CI: 0.08 to 0.53)] or ombitasvir/paritaprevir/dasabuvir ± RBV [adjusted odds ratio 0.46 (95% CI: 0.22 to 1.00)] compared with sofosbuvir/ledipasvir ± RBV. Forty-three (4.6%) individuals had one or more components of their HCV regimen stopped early, most commonly because of toxicity (n = 14); of these 14, 11 were treated with ribavirin. Increased bilirubin was the most common grade 3 or 4 laboratory adverse event (n = 15.3%) and was related to treatment with atazanavir and ribavirin. CONCLUSIONS: Our findings from real-world data on HIV/HCV coinfected individuals across Europe show DAA treatment is well tolerated and that high rates of SVR12 can be achieved in all regions of Europe.


Assuntos
Antivirais/uso terapêutico , Coinfecção/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , Hepatite C/tratamento farmacológico , Interferons/uso terapêutico , Anilidas , Antivirais/administração & dosagem , Benzimidazóis , Ciclopropanos , Feminino , Fluorenos , Hepacivirus , Hepatite C/complicações , Hepatite C Crônica/tratamento farmacológico , Humanos , Interferons/administração & dosagem , Lactamas Macrocíclicas , Masculino , Pessoa de Meia-Idade , Prolina/análogos & derivados , Ribavirina/administração & dosagem , Ribavirina/uso terapêutico , Simeprevir/administração & dosagem , Simeprevir/uso terapêutico , Sofosbuvir/administração & dosagem , Sofosbuvir/uso terapêutico , Sulfonamidas , Resposta Viral Sustentada , Valina
15.
AIDS ; 33(12): 1853-1862, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31259763

RESUMO

OBJECTIVE: The aim of the study was to assess coronary artery disease (CAD) characteristics by coronary computed tomography-angiography (CCTA) in individuals with HIV infection on long-term antiretroviral therapy (ART) DESIGN:: Retrospective case-controlled matched cohort study. METHODS: Sixty-nine HIV-positive patients who underwent 128-slice dual source CCTA (mean age 54.9 years, 26.1% women) with mean 17.8 ±â€Š9.4 years of HIV infection and a mean duration on ART of 13 ±â€Š7.3 years were propensity score-matched (1 : 1) for age, sex, BMI, and five cardiovascular risk factors with 69 controls. CCTA was evaluated for stenosis severity [according to Coronary Artery Disease - Reporting and Data System (CAD-RADS)], total plaque burden [segment involvement score (SIS) and mixed-noncalcified plaque burden (G-score)]. As inflammatory biomarkers, high-risk plaque (HRP) features (napkin-ring sign, low-attenuation plaque, spotty calcification, positive remodeling), perivascular fat attenuation index (FAI), and ectatic coronary arteries were assessed. RESULTS: CAD-RADS was higher in HIV-positive participants as compared with controls (2.21 ±â€Š1.4 vs. 1.69 ±â€Š1.5, P = 0.031). A higher prevalence of CAD and G-score (P = 0.043 and P = 0.003) was found. HRP prevalence [23 (34.3%) vs. 8 (12.1%); P = 0.002] and the number of HRP (36 vs. 10, P < 0.001) were higher in HIV-positive individuals. A perivascular FAI greater than -70 Hounsfield units was present in 27.8% of HRP. Ectatic coronary arteries were found in 10 (14.5%) HIV-positive persons vs. 0% in controls (P = 0.003). CONCLUSION: Noncalcified and HRP burden in HIV-infected individuals on long-term ART is higher and associated with higher cardiovascular risk. Moreover, HIV-positive individuals displayed a higher stenosis severity (CAD-RADS) and more ectatic coronary arteries compared with the control group.


Assuntos
Antirretrovirais/uso terapêutico , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/patologia , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Adulto , Estudos de Casos e Controles , Angiografia por Tomografia Computadorizada , Doença da Artéria Coronariana/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Medição de Risco
17.
Int J Infect Dis ; 84: 75-79, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31054966

RESUMO

OBJECTIVE: HIV positive individuals, particularly men having sex with men (MSM), are at increased risk of sexually transmitted infections (STIs) at genital and extra-genital sites. Data on anorectal Ureaplasma infections are lacking. The aim of our study was to characterize anal Ureaplasma positivity among a cohort of HIV positive MSM and evaluate possible association with papillomavirus infection at the same site. METHODS: Anal swab samples, collected as part of routine screening for Chlamydia trachomatis and Neisseria gonorrhea, were additionally tested for HPV genotypes as well as for Ureaplasma and Mycoplasma using nucleic acid amplification method. RESULTS: Out of a total of 222 study participants, 195 (89%, 95% CI (84.9-93.2)) were positive for HPV, approximately three quarter being high-risk genotypes. Forty three individuals (19.4%, 95% CI (14.4-24.3)) harbored Ureaplasma spp. Infection with high-risk HPV types was significantly associated with co-presence of Ureaplasma with an odds ratio (95% confidence-interval) of 2.59 (1.03-6.54), P = 0.04. CONCLUSION: Besides a high predominance of HPV infection, asymptomatic HIV positive MSM had a high prevalence of anal Ureaplasma positivity. Concomitant infections with high-risk HPV genotypes were common and statistically significant. The role of this co-existence as a potential risk factor for anal carcinogenesis needs further elucidation.


Assuntos
Canal Anal/microbiologia , Soropositividade para HIV/complicações , Homossexualidade Masculina , Infecções por Papillomavirus/etiologia , Ureaplasma/isolamento & purificação , Adulto , Soropositividade para HIV/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade
19.
PLoS One ; 13(7): e0200750, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30001427

RESUMO

BACKGROUND: In 2016, the World Health Organization (WHO) and 69th World Health Assembly approved the first global health sector strategy (GHSS) on viral hepatitis with the goal to eliminate hepatitis C virus (HCV) infections worldwide. The aim is a 90% reduction of new infections and 65% reduction of HCV-related deaths by 2030. AIM: This study reports on the epidemiology of HCV infections in the Austrian state of Tyrol (total population 750,000) and uses a predictive model to identify how the WHO strategy for elimination of HCV can be achieved. METHODS: We developed a regional disease burden model based on observed local diagnosis data from 2001 to 2016. Scenarios were developed to evaluate the impact of diagnosis and treatment on HCV-related outcomes (viremic prevalence, decompensated cirrhosis, hepatocellular carcinoma, and liver-related deaths) from 2015 through 2030. RESULTS: In the last 15 years, 1,721 patients living in Tyrol have been diagnosed with chronic HCV infection. When ageing, mortality and treatment were factored in, there were an estimated 2,043 viremic HCV infections in 2016, of which 1,136 cases had been diagnosed. A baseline model predicts a decrease of 588 HCV cases from 2015 to 2030, which would not translate into the significant reduction of infections needed to achieve WHO global health recommendations. A total of 1,843 infected individuals need to be identified and treated to achieve the WHO goals by 2030 (1,254 averted cases as compared to baseline model). Implementation of this strategy would avoid 523 new HCV infections and decreases HCV-related mortality by 73%. CONCLUSION: HCV elimination and >65% reduction of associated mortality are possible for Tyrol, but requires a significant increase in new diagnoses and treatment rate. The model presented in this study could serve as an example for other regions to reliably predict regional disease burden and estimate how WHO goals can be met in the future.


Assuntos
Hepatite C Crônica/epidemiologia , Hepatite C Crônica/prevenção & controle , Hepatite C Crônica/terapia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Áustria/epidemiologia , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/virologia , Efeitos Psicossociais da Doença , Feminino , Genótipo , Hepacivirus , Hepatite C Crônica/complicações , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/virologia , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Prevalência , Viremia/complicações , Organização Mundial da Saúde , Adulto Jovem
20.
Open Forum Infect Dis ; 3(2): ofw089, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27419163

RESUMO

Background. Viral loads (VLs) detectable at low levels are not uncommon in patients on combination antiretroviral therapy (cART). We investigated whether a single quantifiable VL predicted virological failure (VF). Methods. We analyzed patients receiving standard regimens with at least 1 VL measurement below the limit of quantification (BLQ) in their treatment history. The first VL measurement after 6 months of unmodified cART served as baseline VL for the subsequent analyses of the time to reach single VL levels of ≥200, ≥400, and ≥1000 copies/mL. Roche TaqMan 2.0 was used to quantify human immunodeficiency virus-1 ribonucleic acid. Factors associated with VF were determined by Cox proportional hazards models. Results. Of 1614 patients included in the study, 68, 44, and 34 experienced VF ≥200, ≥400, and ≥1000 copies/mL, respectively. In multivariable analyses, compared with patients who were BLQ, a detectable VL ≤ 50 and VL 51-199 copies/mL predicted VF ≥ 200 copies/mL (hazards ratio [HR] = 2.19, 95% confidence interval [CI] = 1.06-4.55 and HR = 4.21, 95% CI = 2.15-8.22, respectively). In those with VL 51-199 copies/mL, a trend for an increased risk of VF ≥400 and VF ≥1000 copies/mL could be found (HR = 2.13, 95% CI = 0.84-5.39 and HR = 2.52, 95% CI = 0.96-6.60, respectively). Conclusions. These findings support closer monitoring and adherence counseling for patients with a single measurement of quantifiable VL <200 copies/mL.

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