Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.527
Filtrar
1.
N Engl J Med ; 385(27): 2531-2543, 2021 12 30.
Artigo em Inglês | MEDLINE | ID: mdl-34965338

RESUMO

BACKGROUND: Children with human immunodeficiency virus type 1 (HIV-1) infection have limited options for effective antiretroviral treatment (ART). METHODS: We conducted an open-label, randomized, noninferiority trial comparing three-drug ART based on the HIV integrase inhibitor dolutegravir with standard care (non-dolutegravir-based ART) in children and adolescents starting first- or second-line ART. The primary end point was the proportion of participants with virologic or clinical treatment failure by 96 weeks, as estimated by the Kaplan-Meier method. Safety was assessed. RESULTS: From September 2016 through June 2018, a total of 707 children and adolescents who weighed at least 14 kg were randomly assigned to receive dolutegravir-based ART (350 participants) or standard care (357). The median age was 12.2 years (range, 2.9 to 18.0), the median weight was 30.7 kg (range, 14.0 to 85.0), and 49% of the participants were girls. By design, 311 participants (44%) started first-line ART (with 92% of those in the standard-care group receiving efavirenz-based ART), and 396 (56%) started second-line ART (with 98% of those in the standard-care group receiving boosted protease inhibitor-based ART). The median follow-up was 142 weeks. By 96 weeks, 47 participants in the dolutegravir group and 75 in the standard-care group had treatment failure (estimated probability, 0.14 vs. 0.22; difference, -0.08; 95% confidence interval, -0.14 to -0.03; P = 0.004). Treatment effects were similar with first- and second-line therapies (P = 0.16 for heterogeneity). A total of 35 participants in the dolutegravir group and 40 in the standard-care group had at least one serious adverse event (P = 0.53), and 73 and 86, respectively, had at least one adverse event of grade 3 or higher (P = 0.24). At least one ART-modifying adverse event occurred in 5 participants in the dolutegravir group and in 17 in the standard-care group (P = 0.01). CONCLUSIONS: In this trial involving children and adolescents with HIV-1 infection who were starting first- or second-line treatment, dolutegravir-based ART was superior to standard care. (Funded by ViiV Healthcare; ODYSSEY ClinicalTrials.gov number, NCT02259127; EUDRACT number, 2014-002632-14; and ISRCTN number, ISRCTN91737921.).


Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Inibidores de Integrase de HIV/uso terapêutico , HIV-1 , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Oxazinas/uso terapêutico , Piperazinas/uso terapêutico , Piridonas/uso terapêutico , Administração Oral , Adolescente , Alcinos/uso terapêutico , Antirretrovirais/efeitos adversos , Benzoxazinas/uso terapêutico , Criança , Pré-Escolar , Colesterol/sangue , Ciclopropanos/uso terapêutico , Quimioterapia Combinada , Feminino , Infecções por HIV/virologia , Inibidores de Integrase de HIV/administração & dosagem , Inibidores de Integrase de HIV/efeitos adversos , Inibidores da Protease de HIV/uso terapêutico , HIV-1/isolamento & purificação , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Humanos , Masculino , Oxazinas/administração & dosagem , Oxazinas/efeitos adversos , Piperazinas/administração & dosagem , Piperazinas/efeitos adversos , Piridonas/administração & dosagem , Piridonas/efeitos adversos , Carga Viral/efeitos dos fármacos
2.
Cells ; 10(12)2021 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-34943964

RESUMO

People living with HIV (PLWH) have to take an antiretroviral therapy (ART) for life and show noncommunicable illnesses such as chronic inflammation, immune activation, and multiorgan dysregulation. Recent studies suggest that long-term use of ART induces comorbid conditions and is one of the leading causes of heart failure in PLWH. However, the molecular mechanism of antiretroviral drugs (ARVs) induced heart failure is unclear. To determine the mechanism of ARVs induced cardiac dysfunction, we performed global transcriptomic profiling of ARVs treated neonatal rat ventricular cardiomyocytes in culture. Differentially expressed genes were identified by RNA-sequencing. Our data show that ARVs treatment causes upregulation of several biological functions associated with cardiotoxicity, hypertrophy, and heart failure. Global gene expression data were validated in cardiac tissue isolated from HIV patients having a history of ART. Interestingly, we found that homeodomain-only protein homeobox (HOPX) expression was significantly increased in cardiomyocytes treated with ARVs and in the heart tissue of HIV patients. Furthermore, we found that HOPX plays a crucial role in ARVs mediated cellular hypertrophy. Mechanistically, we found that HOPX plays a critical role in epigenetic regulation, through deacetylation of histone, while the HDAC inhibitor, Trichostatin A, can restore the acetylation level of histone 3 in the presence of ARVs.


Assuntos
Cardiomegalia/genética , Infecções por HIV/tratamento farmacológico , Insuficiência Cardíaca/genética , Proteínas de Homeodomínio/genética , Proteínas Supressoras de Tumor/genética , Acetilação/efeitos dos fármacos , Animais , Antirretrovirais/efeitos adversos , Antirretrovirais/farmacologia , Cardiomegalia/induzido quimicamente , Cardiomegalia/patologia , Modelos Animais de Doenças , Epigênese Genética/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , HIV/efeitos dos fármacos , HIV/patogenicidade , Infecções por HIV/complicações , Infecções por HIV/virologia , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/patologia , Inibidores de Histona Desacetilases/farmacologia , Humanos , Ácidos Hidroxâmicos/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , RNA-Seq , Ratos , Transcriptoma/efeitos dos fármacos , Transcriptoma/genética
3.
PLoS One ; 16(12): e0261563, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34972147

RESUMO

BACKGROUND: In persons living with HIV, mitochondrial disease (MD) is difficult to diagnose, as clinical signs are non-specific with inconsistent patterns. Fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15) are mitokines elevated in MD patients without HIV, and associated with cardiometabolic comorbidities in adults living with HIV. We assessed relationships of these biomarkers with MD in children living with perinatally-acquired HIV infection (CPHIV). SETTING: Cross-sectional study of CPHIV from Pediatric ACTG 219/219C classified by Mitochondrial Disease Criteria (MDC) that defines scores 2-4 as "possible" MD. METHODS: Each case with MDC equaling 4 (MDC4; n = 23) was matched to one randomly selected control displaying no MDC (MDC0; n = 23) based on calendar date. Unmatched cases with MDC equaling 3 (MDC3; n = 71) were also assessed. Plasma samples proximal to diagnoses were assayed by ELISA. Mitokine distributions were compared using Wilcoxon tests, Spearman correlations were calculated, and associations with MD status were assessed by conditional logistic regression. RESULTS: Median FGF21 and GDF15 concentrations, respectively, were highest in MDC4 (143.9 and 1441.1 pg/mL), then MDC3 (104.0 and 726.5 pg/mL), and lowest in controls (89.4 and 484.7 pg/mL). Distributions of FGF21 (paired Wilcoxon rank sum p = 0.002) and GDF15 (paired Wilcoxon rank sum p<0.001) differed in MDC4 vs MDC0. Mitokine concentrations were correlated across all participants (r = 0.33; p<0.001). Unadjusted odds ratios of being MDC4 vs MDC0 were 5.2 [95% confidence interval (CI): 1.06-25.92] for FGF21 and 3.5 (95%CI: 1.19-10.25) for GDF15. Relationships persisted after covariate adjustments. CONCLUSION: FGF21 and GDF15 levels may be useful biomarkers to screen for CPHIV with mitochondrial dysfunction.


Assuntos
Fatores de Crescimento de Fibroblastos/biossíntese , Fator 15 de Diferenciação de Crescimento/biossíntese , Infecções por HIV/etiologia , Doenças Mitocondriais/diagnóstico , Adolescente , Antirretrovirais/efeitos adversos , Antirretrovirais/uso terapêutico , Biomarcadores/metabolismo , Criança , Pré-Escolar , Estudos Transversais , Citocinas/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Fatores de Crescimento de Fibroblastos/genética , Seguimentos , Fator 15 de Diferenciação de Crescimento/genética , Infecções por HIV/complicações , Infecções por HIV/metabolismo , Humanos , Lactente , Masculino , Mitocôndrias/metabolismo , Doenças Mitocondriais/complicações , Doenças Mitocondriais/metabolismo , Análise de Regressão , Risco , Adulto Jovem
4.
Curr Opin HIV AIDS ; 16(6): 286-291, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34545036

RESUMO

PURPOSE OF REVIEW: HIV treatment has evolved since the introduction of antiretroviral therapy (ART) in the 1990s. Earlier treatment strategies, and the introduction of integrase inhibitors in preferred first-line ART have fundamentally changed cardiovascular side effects due to HIV infection and ART. This review provides an update on cardiovascular toxicity of contemporary ART. RECENT FINDINGS: Cardiovascular disease (CVD) risk, including heart failure, is still increased in people living with HIV (PLWH). Exposure to older antiretrovirals, including stavudine and zidovudine, still impact on CVD risk through persistent changes in body fat distribution years after discontinuation. Protease inhibitors (PI) and efavirenz have associated metabolic disturbances and increased risk of CVD, although use is decreasing worldwide. Integrase inhibitors and CCR5 antagonists seem to have negligible immediate CVD toxicity. Weight gain on newer antiretrovirals including integrase inhibitors is a reason for concern. SUMMARY: CVD risk should be monitored carefully in PLWH who were exposed to first generation ART, efavirenz or to PIs. Registries should capture ART use and CVD events to stay informed on actual clinical risk in the current era of rapid initiation on integrase inhibitor-based ART.


Assuntos
Infecções por HIV , Antirretrovirais/efeitos adversos , Infecções por HIV/tratamento farmacológico , Humanos , Inibidores de Proteases/uso terapêutico
5.
PLoS Med ; 18(9): e1003738, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34520459

RESUMO

BACKGROUND: Tuberculosis (TB) preventive therapy (TPT) is an essential component of care for people living with HIV (PLHIV). We compared efficacy, safety, completion, and drug-resistant TB risk for currently recommended TPT regimens through a systematic review and network meta-analysis (NMA) of randomized trials. METHODS AND FINDINGS: We searched MEDLINE, Embase, and the Cochrane Library from inception through June 9, 2020 for randomized controlled trials (RCTs) comparing 2 or more TPT regimens (or placebo/no treatment) in PLHIV. Two independent reviewers evaluated eligibility, extracted data, and assessed the risk of bias. We grouped TPT strategies as follows: placebo/no treatment, 6 to 12 months of isoniazid, 24 to 72 months of isoniazid, and rifamycin-containing regimens. A frequentist NMA (using graph theory) was carried out for the outcomes of development of TB disease, all-cause mortality, and grade 3 or worse hepatotoxicity. For other outcomes, graphical descriptions or traditional pairwise meta-analyses were carried out as appropriate. The potential role of confounding variables for TB disease and all-cause mortality was assessed through stratified analyses. A total of 6,466 unique studies were screened, and 157 full texts were assessed for eligibility. Of these, 20 studies (reporting 16 randomized trials) were included. The median sample size was 616 (interquartile range [IQR], 317 to 1,892). Eight were conducted in Africa, 3 in Europe, 3 in the Americas, and 2 included sites in multiple continents. According to the NMA, 6 to 12 months of isoniazid were no more efficacious in preventing microbiologically confirmed TB than rifamycin-containing regimens (incidence rate ratio [IRR] 1.0, 95% CI 0.8 to 1.4, p = 0.8); however, 6 to 12 months of isoniazid were associated with a higher incidence of all-cause mortality (IRR 1.6, 95% CI 1.2 to 2.0, p = 0.02) and a higher risk of grade 3 or higher hepatotoxicity (risk difference [RD] 8.9, 95% CI 2.8 to 14.9, p = 0.004). Finally, shorter regimens were associated with higher completion rates relative to longer regimens, and we did not find statistically significant differences in the risk of drug-resistant TB between regimens. Study limitations include potential confounding due to differences in posttreatment follow-up time and TB incidence in the study setting on the estimates of incidence of TB or all-cause mortality, as well as an underrepresentation of pregnant women and children. CONCLUSIONS: Rifamycin-containing regimens appear safer and at least as effective as isoniazid regimens in preventing TB and death and should be considered part of routine care in PLHIV. Knowledge gaps remain as to which specific rifamycin-containing regimen provides the optimal balance of efficacy, completion, and safety.


Assuntos
Antirretrovirais/uso terapêutico , Antituberculosos/uso terapêutico , Coinfecção , Infecções por HIV/tratamento farmacológico , Sobreviventes de Longo Prazo ao HIV , Serviços Preventivos de Saúde , Tuberculose/prevenção & controle , Adolescente , Adulto , Idoso , Antirretrovirais/efeitos adversos , Antituberculosos/efeitos adversos , Criança , Pré-Escolar , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Humanos , Lactente , Isoniazida/uso terapêutico , Masculino , Pessoa de Meia-Idade , Rifamicinas/uso terapêutico , Medição de Risco , Fatores de Risco , Resultado do Tratamento , Tuberculose/diagnóstico , Tuberculose/epidemiologia , Tuberculose/microbiologia , Adulto Jovem
6.
PLoS Med ; 18(9): e1003712, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34520463

RESUMO

BACKGROUND: Human immunodeficiency virus (HIV) is the strongest known risk factor for tuberculosis (TB) through its impairment of T-cell immunity. Tuberculosis preventive treatment (TPT) is recommended for people living with HIV (PLHIV) by the World Health Organization, as it significantly reduces the risk of developing TB disease. We conducted a systematic review and meta-analysis of modeling studies to summarize projected costs, risks, benefits, and impacts of TPT use among PLHIV on TB-related outcomes. METHODS AND FINDINGS: We searched MEDLINE, Embase, and Web of Science from inception until December 31, 2020. Two reviewers independently screened titles, abstracts, and full texts; extracted data; and assessed quality. Extracted data were summarized using descriptive analysis. We performed quantile regression and random effects meta-analysis to describe trends in cost, effectiveness, and cost-effectiveness outcomes across studies and identified key determinants of these outcomes. Our search identified 6,615 titles; 61 full texts were included in the final review. Of the 61 included studies, 31 reported both cost and effectiveness outcomes. A total of 41 were set in low- and middle-income countries (LMICs), while 12 were set in high-income countries (HICs); 2 were set in both. Most studies considered isoniazid (INH)-based regimens 6 to 2 months long (n = 45), or longer than 12 months (n = 11). Model parameters and assumptions varied widely between studies. Despite this, all studies found that providing TPT to PLHIV was predicted to be effective at averting TB disease. No TPT regimen was substantially more effective at averting TB disease than any other. The cost of providing TPT and subsequent downstream costs (e.g. post-TPT health systems costs) were estimated to be less than $1,500 (2020 USD) per person in 85% of studies that reported cost outcomes (n = 36), regardless of study setting. All cost-effectiveness analyses concluded that providing TPT to PLHIV was potentially cost-effective compared to not providing TPT. In quantitative analyses, country income classification, consideration of antiretroviral therapy (ART) use, and TPT regimen use significantly impacted cost-effectiveness. Studies evaluating TPT in HICs suggested that TPT may be more effective at preventing TB disease than studies evaluating TPT in LMICs; pooled incremental net monetary benefit, given a willingness-to-pay threshold of country-level per capita gross domestic product (GDP), was $271 in LMICs (95% confidence interval [CI] -$81 to $622, p = 0.12) and was $2,568 in HICs (-$32,115 to $37,251, p = 0.52). Similarly, TPT appeared to be more effective at averting TB disease in HICs; pooled percent reduction in active TB incidence was 20% (13% to 27%, p < 0.001) in LMICs and 37% (-34% to 100%, p = 0.13) in HICs. Key limitations of this review included the heterogeneity of input parameters and assumptions from included studies, which limited pooling of effect estimates, inconsistent reporting of model parameters, which limited sample sizes of quantitative analyses, and database bias toward English publications. CONCLUSIONS: The body of literature related to modeling TPT among PLHIV is large and heterogeneous, making comparisons across studies difficult. Despite this variability, all studies in all settings concluded that providing TPT to PLHIV is potentially effective and cost-effective for preventing TB disease.


Assuntos
Antirretrovirais/uso terapêutico , Antituberculosos/economia , Antituberculosos/uso terapêutico , Coinfecção , Custos de Medicamentos , Infecções por HIV/tratamento farmacológico , Sobreviventes de Longo Prazo ao HIV , Serviços Preventivos de Saúde/economia , Tuberculose/prevenção & controle , Antirretrovirais/efeitos adversos , Antirretrovirais/economia , Antituberculosos/efeitos adversos , Análise Custo-Benefício , Infecções por HIV/diagnóstico , Infecções por HIV/economia , Infecções por HIV/epidemiologia , Humanos , Incidência , Modelos Econômicos , Medição de Risco , Fatores de Risco , Resultado do Tratamento , Tuberculose/diagnóstico , Tuberculose/economia , Tuberculose/epidemiologia
7.
PLoS Med ; 18(9): e1003739, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34491987

RESUMO

BACKGROUND: Among people living with HIV (PLHIV), more flexible and sensitive tuberculosis (TB) screening tools capable of detecting both symptomatic and subclinical active TB are needed to (1) reduce morbidity and mortality from undiagnosed TB; (2) facilitate scale-up of tuberculosis preventive therapy (TPT) while reducing inappropriate prescription of TPT to PLHIV with subclinical active TB; and (3) allow for differentiated HIV-TB care. METHODS AND FINDINGS: We used Botswana XPRES trial data for adult HIV clinic enrollees collected during 2012 to 2015 to develop a parsimonious multivariable prognostic model for active prevalent TB using both logistic regression and random forest machine learning approaches. A clinical score was derived by rescaling final model coefficients. The clinical score was developed using southern Botswana XPRES data and its accuracy validated internally, using northern Botswana data, and externally using 3 diverse cohorts of antiretroviral therapy (ART)-naive and ART-experienced PLHIV enrolled in XPHACTOR, TB Fast Track (TBFT), and Gugulethu studies from South Africa (SA). Predictive accuracy of the clinical score was compared with the World Health Organization (WHO) 4-symptom TB screen. Among 5,418 XPRES enrollees, 2,771 were included in the derivation dataset; 67% were female, median age was 34 years, median CD4 was 240 cells/µL, 189 (7%) had undiagnosed prevalent TB, and characteristics were similar between internal derivation and validation datasets. Among XPHACTOR, TBFT, and Gugulethu cohorts, median CD4 was 400, 73, and 167 cells/µL, and prevalence of TB was 5%, 10%, and 18%, respectively. Factors predictive of TB in the derivation dataset and selected for the clinical score included male sex (1 point), ≥1 WHO TB symptom (7 points), smoking history (1 point), temperature >37.5°C (6 points), body mass index (BMI) <18.5kg/m2 (2 points), and severe anemia (hemoglobin <8g/dL) (3 points). Sensitivity using WHO 4-symptom TB screen was 73%, 80%, 94%, and 94% in XPRES, XPHACTOR, TBFT, and Gugulethu cohorts, respectively, but increased to 88%, 87%, 97%, and 97%, when a clinical score of ≥2 was used. Negative predictive value (NPV) also increased 1%, 0.3%, 1.6%, and 1.7% in XPRES, XPHACTOR, TBFT, and Gugulethu cohorts, respectively, when the clinical score of ≥2 replaced WHO 4-symptom TB screen. Categorizing risk scores into low (<2), moderate (2 to 10), and high-risk categories (>10) yielded TB prevalence of 1%, 1%, 2%, and 6% in the lowest risk group and 33%, 22%, 26%, and 32% in the highest risk group for XPRES, XPHACTOR, TBFT, and Gugulethu cohorts, respectively. At clinical score ≥2, the number needed to screen (NNS) ranged from 5.0 in Gugulethu to 11.0 in XPHACTOR. Limitations include that the risk score has not been validated in resource-rich settings and needs further evaluation and validation in contemporary cohorts in Africa and other resource-constrained settings. CONCLUSIONS: The simple and feasible clinical score allowed for prioritization of sensitivity and NPV, which could facilitate reductions in mortality from undiagnosed TB and safer administration of TPT during proposed global scale-up efforts. Differentiation of risk by clinical score cutoff allows flexibility in designing differentiated HIV-TB care to maximize impact of available resources.


Assuntos
Antirretrovirais/uso terapêutico , Antituberculosos/uso terapêutico , Coinfecção , Infecções por HIV/tratamento farmacológico , Sobreviventes de Longo Prazo ao HIV , Programas de Rastreamento , Serviços Preventivos de Saúde , Tuberculose/prevenção & controle , Adulto , Antirretrovirais/efeitos adversos , Antituberculosos/efeitos adversos , Botsuana/epidemiologia , Ensaios Clínicos como Assunto , Diagnóstico Precoce , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prevalência , Prognóstico , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco , Tuberculose/diagnóstico , Tuberculose/epidemiologia , Tuberculose/microbiologia
8.
PLoS Med ; 18(9): e1003703, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34492003

RESUMO

BACKGROUND: Tuberculosis preventive therapy (TPT) reduces TB-related morbidity and mortality in people living with HIV (PLHIV). Cascade-of-care analyses help identify gaps and barriers in care and develop targeted solutions. A previous latent tuberculosis infection (LTBI) cascade-of-care analysis showed only 18% of persons in at-risk populations complete TPT, but a similar analysis for TPT among PLHIV has not been completed. We conducted a meta-analysis to provide this evidence. METHODS AND FINDINGS: We first screened potential articles from a LTBI cascade-of-care systematic review published in 2016. From this study, we included cohorts that reported a minimum of 25 PLHIV. To identify new cohorts, we used a similar search strategy restricted to PLHIV. The search was conducted in Medline, Embase, Health Star, and LILACS, from January 2014 to February 2021. Two authors independently screened titles and full text and assessed risk of bias using the Newcastle-Ottawa Scale for cohorts and Cochrane Risk of Bias for cluster randomized trials. We meta-analyzed the proportion of PLHIV completing each step of the LTBI cascade-of-care and estimated the cumulative proportion retained. These results were stratified based on cascades-of-care that used or did not use LTBI testing to determine eligibility for TPT. We also performed a narrative synthesis of enablers and barriers of the cascade-of-care identified at different steps of the cascade. A total of 71 cohorts were included, and 70 were meta-analyzed, comprising 94,011 PLHIV. Among the PLHIV included, 35.3% (33,139/94,011) were from the Americas and 29.2% (27,460/94,011) from Africa. Overall, 49.9% (46,903/94,011) from low- and middle-income countries, median age was 38.0 [interquartile range (IQR) 34.0;43.6], and 65.9% (46,328/70,297) were men, 43.6% (29,629/67,947) were treated with antiretroviral therapy (ART), and the median CD4 count was 390 cell/mm3 (IQR 312;458). Among the cohorts that did not use LTBI tests, the cumulative proportion of PLHIV starting and completing TPT were 40.9% (95% CI: 39.3% to 42.7%) and 33.2% (95% CI: 31.6% to 34.9%). Among cohorts that used LTBI tests, the cumulative proportions of PLHIV starting and completing TPT were 60.4% (95% CI: 58.1% to 62.6%) and 41.9% (95% CI:39.6% to 44.2%), respectively. Completion of TPT was not significantly different in high- compared to low- and middle-income countries. Regardless of LTBI test use, substantial losses in the cascade-of-care occurred before treatment initiation. The integration of HIV and TB care was considered an enabler of the cascade-of-care in multiple cohorts. Key limitations of this systematic review are the observational nature of the included studies, potential selection bias in the population selection, only 14 cohorts reported all steps of the cascade-of-care, and barriers/facilitators were not systematically reported in all cohorts. CONCLUSIONS: Although substantial losses were seen in multiple stages of the cascade-of-care, the cumulative proportion of PLHIV completing TPT was higher than previously reported among other at-risk populations. The use of LTBI testing in PLHIV in low- and middle-income countries was associated with higher proportion of the cohorts initiating TPT and with similar rates of completion of TPT.


Assuntos
Antirretrovirais/uso terapêutico , Antituberculosos/uso terapêutico , Coinfecção , Infecções por HIV/tratamento farmacológico , Sobreviventes de Longo Prazo ao HIV , Tuberculose Latente/prevenção & controle , Serviços Preventivos de Saúde , Adulto , Antirretrovirais/efeitos adversos , Antituberculosos/efeitos adversos , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Humanos , Tuberculose Latente/diagnóstico , Tuberculose Latente/epidemiologia , Tuberculose Latente/microbiologia , Masculino , Medição de Risco , Fatores de Risco , Resultado do Tratamento
9.
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 , Ganho 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
10.
Medicine (Baltimore) ; 100(35): e26817, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34477118

RESUMO

ABSTRACT: In order to design effective strategies to eradicate the HIV, an understanding of persistent viral reservoirs is needed. Many studies have demonstrated HIV residual viremia prevalence in high income countries, data from low- and middle-income countries (LMIC) are limited. We assessed the prevalence, and factors associated with residual viremia in people with HIV (PWH), who were virally-suppressed on antiretroviral therapy (ART) in LMIC. We also compared residual viremia prevalence between the LMIC and US.This is a cross-sectional, retrospective study that utilized stored specimen samples from the AIDS clinical trials group (ACTG) studies A5175 and A5208. The last available sample among participants with plasma HIV RNA < 400 copies/mL for ≥3 years were tested by the HIV molecular and monitoring core gag (HMMCgag) single copy assay (SCA). Residual viremia was defined as detectable if ≥1 copy/mL. Spearman's correlation and multivariable stepwise logistic regression were used to assess associations of various factors with SCA.A total of 320 participants, 246 (77%) from LMIC and 74 (23%) from US, were analyzed. Median (IQR) age was 33 (2840) years; baseline CD4 166 (88,230) cells/mm3; HIV RNA 5.0 (4.5, 5.3) log10 copies/mL; duration of viral suppression 3.4 (3.1, 4.0) years and 48% were male. In 85 participants with information available, 53% were subtype C, 42% subtype B and 5% other subtypes. Overall prevalence of residual viremia was 57% [95% CI, 52-63] with 51% [40-63] in US and 59% [53-65] in LMIC. Among participants with detectable SCA, the median (IQR) HIV RNA was 3.8 (2.2, 8.1) copies/mL. The multivariable model conducted in LMIC participants showed that higher baseline HIV RNA was associated with detectable residual RNA (OR 2.9, 95% CI 1.8, 4.6 for every log10 increase, P < .001). After including both US and LMIC in the final model, baseline HIV RNA remained significant. No difference in SCA detestability was found between US and LMIC sites (OR 1.1 [0.6, 2.0], P = .72) after adjusting for baseline RNA and parent study.The prevalence of residual viremia between both groups were not different and more than half of the participants had detectable viremia. Higher baseline HIV RNA was independently associated with residual viremia.


Assuntos
Antirretrovirais/efeitos adversos , Países em Desenvolvimento/estatística & dados numéricos , Viremia/etiologia , Adulto , Antirretrovirais/uso terapêutico , Estudos Transversais , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Modelos Logísticos , Masculino , Prevalência , Estudos Retrospectivos , Viremia/epidemiologia
11.
Medicine (Baltimore) ; 100(30): e26588, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34397689

RESUMO

ABSTRACT: High cardiovascular disease risk in people living with HIV is partly attributed to antiretroviral therapy (ART). Lipid response to ART has been extensively studied, yet, little is known how small molecule lipids respond to Integrase inhibitor-based (INSTI-based) compared to Protease inhibitor-based (PI-based) ART regimens.Ancillary study to a phase 3, randomized, open-label trial [AIDS Clinical Trial Group A5257 Study] in treatment-naive HIV-infected patients randomized in a 1:1:1 ratio to receive ritonavir-boosted atazanavir (ATV/r), ritonavir-boosted darunavir (DRV/r) (both PI-based), or raltegravir with Tenofovir Disoproxil Fumarate-TDF plus emtricitabine (RAL, INSTI-based).We examined small molecule lipid response in a subcohort of 75 participants. Lipidomic assays of plasma samples collected pre- and post-ART treatment (48 weeks) were conducted using ultra-performance liquid chromatography coupled to time-of-flight mass spectrometry. The effect of ART regimens was regressed on lipid species response adjusting for the baseline covariates (lipids, age, sex, race, CD4 level, BMI, and smoking). Results were validated in the Centers for AIDS Research Network of Integrated Clinical Systems study (N = 16).Out of 417 annotated lipids, glycerophospholipids (P = .007) and sphingolipids (P = .028) had a higher response to ATV/r and DRV/r compared to RAL. The lysophosphatidylcholine (LPCs(16:1),(17:1),(20:3)) and phosphophatidylcholine species (PCs(40:7),(38:4)) had an opposite response to RAL versus ATV/r in the discovery and validation cohort. The INSTI-based regimen had an opposite response of ceramide species ((d38:1), (d42:2)), PCs((35:2), (38:4)), phosphatidylethanolamines (PEs(38:4), (38:6)), and sphingomyelin(SMd38:1) species compared with the PI-based regimens. There were no differences observed between 2 PI-based regimens.We observed differences in response of small molecule lipid species by ART regimens in treatment-naive people living with HIV.


Assuntos
Antirretrovirais/efeitos adversos , Lipidômica/métodos , Adulto , Antirretrovirais/uso terapêutico , Sulfato de Atazanavir/efeitos adversos , Sulfato de Atazanavir/uso terapêutico , Distribuição de Qui-Quadrado , Darunavir/efeitos adversos , Darunavir/uso terapêutico , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/fisiopatologia , Humanos , Lipidômica/estatística & dados numéricos , Lipídeos , Masculino , Espectrometria de Massas/métodos , Pessoa de Meia-Idade , Plasma/efeitos dos fármacos , Raltegravir Potássico/efeitos adversos , Raltegravir Potássico/uso terapêutico , Tenofovir/efeitos adversos , Tenofovir/uso terapêutico
12.
Curr Opin HIV AIDS ; 16(6): 303-308, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34459469

RESUMO

PURPOSE OF REVIEW: Chronic kidney disease (CKD) is common in people living with HIV (PLWH) and is related to a multitude of factors. The aim of this review is to provide an overview of the most recent evidence of renal adverse effects of antiretroviral drugs, predictors of CKD risk and areas for future research. RECENT FINDINGS: Advancing age, cardiometabolic risk factors and adverse effects of antiretroviral drugs contribute to the higher prevalence of CKD in PLWH. Genetic factors and baseline clinical CKD risk are strongly correlated to risk of incident CKD, although it is unclear to what extent gene polymorphisms explain renal adverse effects related to tenofovir disoproxil fumarate (TDF). Switching from TDF to tenofovir alafenamide (TAF) in people with baseline renal dysfunction improves renal parameters; however, the long-term safety and benefit of TAF in individuals at low risk of CKD is an area of ongoing research. SUMMARY: Several factors contribute to estimated glomerular function decline and CKD in PLWH. Clinical risk scores for CKD may be useful to inform selection of ART in an ageing population. In people with baseline renal dysfunction, potentially nephrotoxic antiretroviral drugs should be avoided.


Assuntos
Fármacos Anti-HIV , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Infecções por HIV , Fármacos Anti-HIV/efeitos adversos , Antirretrovirais/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Tenofovir/efeitos adversos
13.
Curr Opin HIV AIDS ; 16(6): 292-302, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34459470

RESUMO

PURPOSE OF REVIEW: Advances in antiretroviral therapy (ART) have transformed HIV infection into a chronic and manageable condition. The introduction of potent and more tolerable antiretrovirals (ARVs) with favorable pharmacokinetic profiles has changed the prevalence and nature of drug-drug interactions (DDIs). Here, we review the relevance of DDIs in the era of contemporary ART. RECENT FINDINGS: Management of DDIs remains an important challenge with modern ART, primarily due to increased polypharmacy in older persons living with HIV. Significant DDIs exist between boosted ARVs or older nonnucleoside reverse transcriptase inhibitors and comedications for chronic comorbidities (e.g., anticoagulants, antiplatelets, statins) or complex conditions (e.g., anticancer agents, immunosuppressants). Newer ARVs such as unboosted integrase inhibitors, doravirine, and fostemsavir have reduced DDI potential, but there are clinically relevant DDIs that warrant consideration. Potential consequences of DDIs include increased toxicity and/or reduced efficacy of ARVs and/or comedications. Management approaches include switching to an ARV with less DDI potential, changing comedications, or altering medication dosage or dosing frequency. Deprescribing strategies can reduce DDIs and polypharmacy, improve adherence, minimize unnecessary adverse effects, and prevent medication-related errors. SUMMARY: Management of DDIs requires close interdisciplinary collaboration from multiple healthcare disciplines (medicine, nursing, pharmacy) across a spectrum of care (community, outpatient, inpatient).


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Infecções por HIV , Idoso , Idoso de 80 Anos ou mais , Antirretrovirais/efeitos adversos , Interações Medicamentosas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Infecções por HIV/tratamento farmacológico , Humanos , Prevalência
14.
PLoS One ; 16(7): e0254767, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34280229

RESUMO

INTRODUCTION: The postpartum period can be challenging for women living with HIV. Understanding how the postpartum period impacts ART adherence and condomless sex could inform the development of comprehensive sexual and reproductive health and HIV services tailored to the needs of women living with HIV during this critical interval. METHODS: In a longitudinal cohort study of HIV-seropositive Kenyan women, late ART refills and self-reported condomless sex were compared between the woman's pregnancy and the postpartum period. Analyses were conducted using generalized estimating equations and adjusted for alcohol use, depressive symptoms, intimate partner violence (IPV), and having a recent regular partner. Effect modification was explored for selected variables. RESULTS AND DISCUSSION: 151 women contributed visits. Late ART refills occurred at 7% (32/439) of pregnancy visits compared to 18% (178/1016) during the postpartum period (adjusted relative risk [aRR] 2.44, 95% confidence interval [CI] 1.62-3.67). This association differed by women's education level. Women with ≥8 years of education had late ART refills more during the postpartum period than pregnancy (aRR 3.00, 95%CI 1.95-4.62). In contrast, in women with <8 years of education, late ART refills occurred similarly during pregnancy and the postpartum period (aRR 0.88, 95%CI 0.18-4.35). Women reported condomless sex at 10% (60/600) of pregnancy visits compared to 7% (72/1081) of postpartum visits (aRR 0.76, 95%CI 0.45-1.27). This association differed by whether women had experienced recent IPV. Women without recent IPV had a significant decline in condomless sex from pregnancy to postpartum (aRR 0.53, 95%CI 0.30-0.95) while women with recent IPV had no significant change in condomless sex from pregnancy to postpartum (aRR 1.76, 95%CI 0.87-3.55). CONCLUSION: Improved support for ART adherence during the postpartum period and addressing IPV to limit condomless sex could improve HIV treatment and prevention outcomes for HIV-seropositive women as well as their infants and sexual partners.


Assuntos
Terapia Antirretroviral de Alta Atividade , Infecções por HIV/epidemiologia , Soropositividade para HIV/epidemiologia , Comportamento Sexual/psicologia , Adolescente , Adulto , Antirretrovirais/efeitos adversos , Antirretrovirais/uso terapêutico , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/transmissão , Infecções por HIV/virologia , Humanos , Violência por Parceiro Íntimo , Quênia/epidemiologia , Estudos Longitudinais , Masculino , Gravidez , Fatores de Risco , Parceiros Sexuais , Sexo sem Proteção , Adulto Jovem
15.
Lancet Child Adolesc Health ; 5(9): 642-651, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34302760

RESUMO

BACKGROUND: Bictegravir is a potent integrase strand-transfer inhibitor (INSTI) with a high genetic barrier to resistance. Bictegravir, coformulated with emtricitabine and tenofovir alafenamide, is recommended by key European and US HIV treatment guidelines as the preferred single-tablet regimen for adults and adolescents. The aim of this study was to assess the pharmacokinetics, safety, and efficacy of switching to this regimen in virologically suppressed children and adolescents with HIV. METHODS: In this single-arm, open-label trial, we enrolled virologically suppressed children and adolescents (aged 6 to <18 years) with HIV at 22 hospital clinics in South Africa, Thailand, Uganda, and the USA. Eligible participants had a bodyweight of at least 25 kg, were virologically suppressed (HIV-1 RNA <50 copies per mL) on a stable ART regimen for at least 6 months before screening, had a CD4 count of at least 200 cells per µL, and an estimated glomerular filtration rate of at least 90 mL/min per 1·73 m2 by the Schwartz formula at screening. All participants received the fixed-dose regimen of coformulated bictegravir 50 mg, emtricitabine 200 mg, and tenofovir alafenamide 25 mg once daily. Pharmacokinetic analysis was used for dosing confirmation, and results compared with adult values. The primary outcomes were area under the curve at the end of the dosing interval (AUCtau) and concentration at the end of the dosing interval (Ctau) of bictegravir, and incidence of treatment-emergent adverse events and laboratory abnormalities at week 24. Efficacy and safety analyses included all participants who received at least one dose of study drug. We report the 48-week results. This study is registered with ClinicalTrials.gov, NCT02881320. FINDINGS: Between Sept 29, 2016 and Feb 16, 2018, we enrolled 102 participants. 100 participants received bictegravir, emtricitabine, and tenofovir alafenamide (cohort 1 [adolescents aged 12 to <18 years], n=50; cohort 2 [children aged 6 to <12 years], n=50). The mean bictegravir AUCtau was 89 100 ng × h/mL (coefficient of variation 31·0%) in adolescents (cohort 1) and 128 000 ng × h/mL (27·8%) in children (cohort 2). Compared with adults, bictegravir Ctau was 35% lower in adolescents and 11% lower in children. The 90% CIs of both parameters were within the predefined pharmacokinetic equivalence boundary and within overall range of exposures observed in adults and deemed to be safe and efficacious (geometric least-squares mean ratio [GLSM] 86·3% [90% CI 80·0-93·0] for AUCtau and 65·4% [58·3-73·3] for Ctau in adolescents; GLSM 125% [90% CI 117-134] for AUCtau and 88·9% [80·6-98·0] for Ctau for children). Bictegravir, emtricitabine, and tenofovir alafenamide was well tolerated; most adverse events were grade 2 or less in severity and no study drug-related serious adverse events were reported. One participant discontinued study drug due to adverse events (grade 2 insomnia and anxiety). Virological suppression (HIV-1 RNA <50 copies per mL) was maintained by all 100 participants at week 24 and by 98 (98%) of 100 at week 48; no participants had treatment-emergent resistance. INTERPRETATION: In adolescents and children with HIV, the bictegravir, emtricitabine, and tenofovir alafenamide single-tablet regimen was well tolerated and maintained virological suppression. Our data support the treatment of HIV in adolescents and children with this single-tablet regimen. At present, the single-tablet regimen is recommended as first-line treatment in the USA for adolescents and as an alternative regimen in children and has the potential to represent an important regimen in the paediatric population. FUNDING: Gilead Sciences.


Assuntos
Alanina , Antirretrovirais , Monitoramento de Medicamentos/métodos , Emtricitabina , Infecções por HIV , Tenofovir/análogos & derivados , Adolescente , Alanina/administração & dosagem , Alanina/efeitos adversos , Alanina/farmacocinética , Amidas/administração & dosagem , Amidas/efeitos adversos , Amidas/farmacocinética , Antirretrovirais/administração & dosagem , Antirretrovirais/efeitos adversos , Antirretrovirais/farmacocinética , Contagem de Linfócito CD4/métodos , Criança , Cálculos da Dosagem de Medicamento , Quimioterapia Combinada/métodos , Emtricitabina/administração & dosagem , Emtricitabina/efeitos adversos , Emtricitabina/farmacocinética , Feminino , Infecções por HIV/sangue , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Compostos Heterocíclicos com 3 Anéis/farmacocinética , Humanos , Masculino , Piperazinas/administração & dosagem , Piperazinas/efeitos adversos , Piperazinas/farmacocinética , Piridonas/administração & dosagem , Piridonas/efeitos adversos , Piridonas/farmacocinética , Tenofovir/administração & dosagem , Tenofovir/efeitos adversos , Tenofovir/farmacocinética , Resultado do Tratamento , Carga Viral/métodos
16.
Cells ; 10(5)2021 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-34065305

RESUMO

Contemporary antiretroviral agents afford enhanced potency and safety for patients living with HIV. Newer antiretroviral drugs are often better tolerated than those initially approved in the early stages of the HIV epidemic. While the safety profile has improved, adverse drug reactions still occur. We have segregated the antiretroviral agents used in contemporary practice into class groupings based on their mechanism of antiviral activity (non-nucleoside reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors, integrase inhibitors, protease inhibitors, and entry inhibitors) while providing a review and discussion of the hepatoxicity seen in the most relevant clinical literature published to date. Clinical literature for individual agents is discussed and agent comparisons afforded within each group in tabular format. Our review will provide a summative overview of the incidence and medications associated with hepatic adverse reactions linked to the use of contemporary antiretroviral drugs.


Assuntos
Antirretrovirais/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/patologia , Ensaios Clínicos como Assunto/estatística & dados numéricos , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Infecções por HIV/virologia , Humanos
17.
Biochem Pharmacol ; 192: 114666, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34186065

RESUMO

The latent viral reservoir formed by HIV-1, mainly in CD4 + T cells, is responsible for the failure of antiretroviral therapy (ART) to achieve a complete elimination of the virus in infected individuals. We previously determined that CD4 + T cells from individuals with chronic myeloid leukemia (CML) on treatment with dasatinib are resistant to HIV-1 infection ex vivo. The main mechanism for this antiviral effect is the preservation of SAMHD1 activity. In this study, we aimed to evaluate the impact of dasatinib on the viral reservoir of HIV-infected individuals with CML who were on simultaneous treatment with ART and dasatinib. Due to the low estimated incidence of HIV-1 infection and CML (1:65,000), three male individuals were recruited in Spain and Germany. These individuals had been on treatment with standard ART and dasatinib for median 1.3 years (IQR 1.3-5.3 years). Reservoir size and composition in PBMCs from these individuals was analyzed in comparison with HIV-infected individuals on triple ART regimen and undetectable viremia. The frequency of latently infected cells was reduced more than 5-fold in these individuals. The reactivation of proviruses from these cells was reduced more than 4-fold and, upon activation, SAMHD1 phosphorylation was reduced 40-fold. Plasma levels of the homeostatic cytokine IL-7 and CD4 effector subpopulations TEM and TEMRA in peripheral blood were also reduced. Therefore, treatment of HIV-infected individuals with dasatinib as adjuvant of ART could disturb the reservoir reactivation and reseeding, which might have a beneficial impact to reduce its size.


Assuntos
Antirretrovirais/administração & dosagem , Dasatinibe/administração & dosagem , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Provírus/efeitos dos fármacos , Reinfecção/prevenção & controle , Adulto , Antirretrovirais/efeitos adversos , Estudos Transversais , Dasatinibe/efeitos adversos , Quimioterapia Combinada , Feminino , Infecções por HIV/diagnóstico , HIV-1/fisiologia , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/induzido quimicamente , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Masculino , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Provírus/fisiologia , Reinfecção/diagnóstico , Resultado do Tratamento
18.
BMC Pregnancy Childbirth ; 21(1): 453, 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34182944

RESUMO

BACKGROUND: Multi-drug resistant and rifampicin-resistant tuberculosis (MDR/RR-TB) in pregnant women is a cause for concern globally; few data have described the safety of second-line anti-TB medications during pregnancy. We aim to describe TB treatment and pregnancy outcomes among pregnant women receiving second-line anti-tuberculosis treatment for MDR/RR-TB in Johannesburg, South Africa. METHODS: We conducted a retrospective record review of pregnant women (≥ 18 years) who received treatment for MDR/RR-TB between 01/2010-08/2016 at three outpatient treatment sites in Johannesburg, South Africa. Demographic, treatment and pregnancy outcome data were collected from available medical records. Preterm birth (< 37 weeks), and miscarriage were categorized as adverse pregnancy outcomes. RESULTS: Out of 720 women of child-bearing age who received MDR/RR-TB treatment at the three study sites, 35 (4.4%) pregnancies were identified. Overall, 68.7% (24/35) were HIV infected, 83.3% (20/24) were on antiretroviral therapy (ART). Most women, 88.6% (31/35), were pregnant at the time of MDR/RR-TB diagnosis and four women became pregnant during treatment. Pregnancy outcomes were available for 20/35 (57.1%) women, which included 15 live births (11 occurred prior to 37 weeks), 1 neonatal death, 1 miscarriage and 3 pregnancy terminations. Overall, 13/20 (65.0%) women with known pregnancy outcomes had an adverse pregnancy outcome. Of the 28 women with known TB treatment outcomes 17 (60.7%) completed treatment successfully (4 were cured and 13 completed treatment), 3 (10.7%) died and 8 (28.6%) were lost-to-follow-up. CONCLUSIONS: Pregnant women with MDR/RR-TB suffer from high rates of adverse pregnancy outcomes and about 60% achieve a successful TB treatment outcome. These vulnerable patients require close monitoring and coordinated obstetric, HIV and TB care.


Assuntos
Aborto Espontâneo/epidemiologia , Antituberculosos/efeitos adversos , Complicações Infecciosas na Gravidez/tratamento farmacológico , Nascimento Prematuro/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Aborto Espontâneo/induzido quimicamente , Aborto Espontâneo/microbiologia , Adulto , Antirretrovirais/efeitos adversos , Coinfecção/complicações , Coinfecção/tratamento farmacológico , Coinfecção/microbiologia , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Gravidez , Complicações Infecciosas na Gravidez/microbiologia , Resultado da Gravidez , Nascimento Prematuro/induzido quimicamente , Nascimento Prematuro/microbiologia , Estudos Retrospectivos , África do Sul/epidemiologia , Resultado do Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/complicações
19.
PLoS One ; 16(5): e0251763, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34043687

RESUMO

BACKGROUND: Besides its contribution in the treatment of Human Immunodeficiency Virus-infected patients, anti-retroviral drugs may also cause mild to serious adverse effects. It is the main causes for poor drug adherence, treatment discontinuation and changes in Anti-Retroviral Treatment (ART) regimens. Thus, the aim of this study was to assess the incidence and predictors of adverse drug reaction among adult Human Immunodeficiency Virus positive patients on anti-retroviral treatment from January 1, 2013 up to December 30, 2018 at Arba Minch town public health facilities, Southern Ethiopia. METHODS: An institution based retrospective cohort study was conducted on 456 charts. Secondary data was collected by structured questionnaire. Data were entered in Epi-data version 4.4.2 software and exported to STATA Version 14 for analysis. The Kaplan-Meier survival curve with Log-rank was used to estimate survival time. Bi-variable and multivariable Cox proportional hazard regression models were fitted to identify predictors of adverse drug reaction. In the bi-variable analysis, the variables with p-value < 0.25 were eligible for multivariable analysis. Finally, variables with p-values less than 0.05 in the multivariable Cox regression were considered as independent predictors. The statistical significance was declared at p-value<0.05. RESULTS: Out of 456 patients observed for 14,903 person-months (pm), 79 experienced adverse drug reactions and the overall incidence density rate was 0.53/100 pm, CI: 0.42-0.66/100 person's month or 6.36 per 100 Pearson year of observation. Females were at higher risk of experiencing adverse drug reactions (ADRs) compared to males [AHR = 2.35; CI (1.18, 4.69)]. The risk of experiencing ADRs among patient with advanced WHO clinical stage (stage III and IV) was higher compared to stage I and II [AHR = 3.0, CI (1.22, 7.37)]. The risk of experiencing an ADR was at any given time higher among AZT and NVP containing regimens compared to TDF and EFV containing regimens. Finally, the risk of ADR among those patients from the health center was reduced by 59% compared to hospital patients, [AHR = 0.41, CI (0.17, 0.97)]. CONCLUSION AND RECOMMENDATION: The incidence rate of ADRs was reduced among patients on ARVs compared to previous studies and it was high during the early years of ART initiation. HIV patients should be closely followed in the early years of ART initiation, since this is the time of highest risk ADRs and emphasis should be given for female and clinically advanced patients.


Assuntos
Antirretrovirais/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Infecções por HIV/tratamento farmacológico , Adulto , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Etiópia , Feminino , Infecções por HIV/diagnóstico , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco/métodos , Medição de Risco/estatística & dados numéricos , Fatores de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Fatores de Tempo
20.
Ital J Pediatr ; 47(1): 84, 2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33823890

RESUMO

BACKGROUND: Despite the rapid scale-up of antiretroviral therapy, virologic failure has become global public health concern and challenge, especially in developing countries. Viral load monitoring is an important approach to identify treatment failure and develop public health interventions in children receiving antiretroviral therapy. Thus, this study aims to assess the magnitude and associated factors of virological failure among children on antiretroviral therapy. METHODS: A facility-based cross-sectional study was conducted among 399 HIV-positive children on antiretroviral therapy from 2016 to 2019 in Bahir Dar Town public health facilities. Data were extracted from children's charts using a standardized data extraction tool, adapted from ART intake and follow-up forms. Data were entered using Epi-Data Version 3.1, and analyzed using SPSS Version 25. Bivariable and multivariable binary logistic regression models were done to identify factors associated with virological failure. Variables with p-values < 0.25 were fitted into the multivariable analysis. Finally, variables with p-values <0.05 were considered as statistically significant factors. RESULTS: The period prevalence of virological failure was found to be 14.8% (95% CI: 11.5-19.3%). Opportunistic infections (AOR = 2.19, CI: 1.13-4.25), history of treatment interruption and restart (AOR = 2.21, CI: 1.09-4.54), younger age (AOR = 2.42, CI: 1.02-5.74), poor/fair ART adherence (AOR = 2.19, CI: 1.05-4.57), and advanced baseline WHO clinical staging (AOR = 2.32, CI: 1.14-4.74) were found to be factors significantly associated with virological failure. CONCLUSION: The magnitude of virological failure among HIV-infected children remained high. Children with poor/fair ART adherence, history of treatment interruption, advanced baseline WHO clinical staging, younger age, and opportunistic infections were significantly associated with virologic failure. Thus, special attention should be given to children who had poor/fair ART adherence and presenting with opportunistic infections.


Assuntos
Antirretrovirais/efeitos adversos , Infecções por HIV/tratamento farmacológico , Carga Viral , Adolescente , Fatores Etários , Criança , Pré-Escolar , Estudos Transversais , Etiópia/epidemiologia , Feminino , Infecções por HIV/epidemiologia , Humanos , Lactente , Recém-Nascido , Masculino , Adesão à Medicação , Infecções Oportunistas/epidemiologia , Falha de Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...