RESUMO
Importance: Data on the use of antiretroviral drugs, including new drugs and formulations, for the treatment and prevention of HIV infection continue to guide optimal practices. Objective: To evaluate new data and incorporate them into current recommendations for initiating HIV therapy, monitoring individuals starting on therapy, changing regimens, preventing HIV infection for those at risk, and special considerations for older people with HIV. Evidence Review: New evidence was collected since the previous International Antiviral (formerly AIDS) Society-USA recommendations in 2018, including data published or presented at peer-reviewed scientific conferences through August 22, 2020. A volunteer panel of 15 experts in HIV research and patient care considered these data and updated previous recommendations. Findings: From 5316 citations about antiretroviral drugs identified, 549 were included to form the evidence basis for these recommendations. Antiretroviral therapy is recommended as soon as possible for all individuals with HIV who have detectable viremia. Most patients can start with a 3-drug regimen or now a 2-drug regimen, which includes an integrase strand transfer inhibitor. Effective options are available for patients who may be pregnant, those who have specific clinical conditions, such as kidney, liver, or cardiovascular disease, those who have opportunistic diseases, or those who have health care access issues. Recommended for the first time, a long-acting antiretroviral regimen injected once every 4 weeks for treatment or every 8 weeks pending approval by regulatory bodies and availability. For individuals at risk for HIV, preexposure prophylaxis with an oral regimen is recommended or, pending approval by regulatory bodies and availability, with a long-acting injection given every 8 weeks. Monitoring before and during therapy for effectiveness and safety is recommended. Switching therapy for virological failure is relatively rare at this time, and the recommendations for switching therapies for convenience and for other reasons are included. With the survival benefits provided by therapy, recommendations are made for older individuals with HIV. The current coronavirus disease 2019 pandemic poses particular challenges for HIV research, care, and efforts to end the HIV epidemic. Conclusion and Relevance: Advances in HIV prevention and management with antiretroviral drugs continue to improve clinical care and outcomes among individuals at risk for and with HIV.
Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/prevenção & controle , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Fatores Etários , Antirretrovirais/economia , Betacoronavirus , COVID-19 , Comorbidade , Infecções por Coronavirus/epidemiologia , Esquema de Medicação , Custos de Medicamentos , Farmacorresistência Viral/genética , Substituição de Medicamentos/normas , Quimioterapia Combinada/métodos , Feminino , Infecções por HIV/sangue , Infecções por HIV/diagnóstico , Humanos , Agências Internacionais , Masculino , Pandemias , Pneumonia Viral/epidemiologia , Polimedicação , Profilaxia Pré-Exposição/métodos , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , RNA Viral/sangue , SARS-CoV-2 , Sociedades Médicas , Estados Unidos , Carga Viral/genéticaRESUMO
The integration of HIV DNA into the host genome contributes to lifelong infection in most individuals. Few studies have examined integration in lymphoid tissue, where HIV predominantly persists before and after antiretroviral treatment (ART). Of particular interest is whether integration site distributions differ between infection stages with paired blood and tissue comparisons. Here, we profiled HIV integration site distributions in sorted memory, tissue-resident, and/or follicular helper CD4+ T cell subsets from paired blood and lymphoid tissue samples from acute, chronic, and ART-treated individuals. We observed minor differences in the frequency of nonintronic and nondistal intergenic sites, varying with tissue and residency phenotypes during ART. Genomic and epigenetic annotations were generally similar. Clonal expansion of cells marked by identical integration sites was detected, with increased detection in chronic and ART-treated individuals. However, overlap between or within CD4+ T cell subsets or tissue compartments was only observed in 8 unique sites of the 3540 sites studied. Together, these findings suggest that shared integration sites between blood and tissue may, depending on the tissue site, be the exception rather than the rule and indicate that additional studies are necessary to fully understand the heterogeneity of tissue-sequestered HIV reservoirs.
Assuntos
DNA Viral/genética , Infecções por HIV/genética , Interações Hospedeiro-Patógeno/genética , Integração Viral/genética , Adulto , Antirretrovirais/administração & dosagem , Linfócitos T CD4-Positivos/virologia , Genoma Humano/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/patologia , Infecções por HIV/virologia , HIV-1/genética , HIV-1/patogenicidade , Humanos , Tecido Linfoide/virologia , Masculino , Subpopulações de Linfócitos T/virologia , Carga Viral/genética , Adulto JovemRESUMO
The aim of this study is to test a pooling approach for the RT-PCR test to detect low viral loads of SARS-CoV-2. We found that a single positive specimen can still be detected in pools of up to 10. Each laboratory should conduct its own evaluation and validation of pooling protocols according to its specific context.
Assuntos
Betacoronavirus/genética , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Programas de Rastreamento/métodos , Pneumonia Viral/diagnóstico , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , COVID-19 , Teste para COVID-19 , Humanos , Pandemias , RNA Viral/genética , SARS-CoV-2 , Manejo de Espécimes , Tunísia , Carga Viral/genéticaRESUMO
Chronic hepatitis C virus (HCV) infection can lead to liver cirrhosis and hepatocellular carcinoma. To eliminate HCV infection in an endemic area, an epidemiological baseline of the current HCV infection in the population is required. We therefore aimed to evaluate the HCV burden in the Thai Province of Phetchabun, which has the highest HCV infection rate in the country. Toward this, a province-wide district-based representative sampling of 4,769 individuals ages 35-64 years previously shown to represent high-risk age-groups were tested for anti-HCV antibodies using the automated chemiluminescent microparticle assays. Active HCV infection and subsequent genotyping were determined from serologically reactive samples by amplification of the HCV core gene. We found that 6.9% (327/4,769) were anti-HCV positive, of which 75.8% (248/327) had detectable HCV RNA and 5.8% (19/327) were in the presence of hepatitis B virus coinfection. Nucleotide sequencing and phylogenetic analysis revealed that HCV genotype 6 was the most prevalent (41%, 101/248), followed by genotype 3 (31%, 78/248), and genotype 1 (28%, 69/248). Socioeconomic and demographic factors including male gender, education, and agricultural work were associated with HCV seropositivity. From these results, we defined the regional HCV genotypes and estimated the HCV burden necessary toward the implementation of pan-genotypic direct-acting antivirals, which may be appropriate and effective toward the diversity of genotypes identified in this study. Micro-elimination of HCV in Phetchabun may serve as a model for a more comprehensive coverage of HCV treatment in Thailand.
Assuntos
Doenças Endêmicas/estatística & dados numéricos , Hepacivirus/genética , Hepatite B/epidemiologia , Hepatite C Crônica/epidemiologia , RNA Viral/genética , Adulto , Anticorpos Antivirais/sangue , Doença Crônica , Coinfecção , Erradicação de Doenças/organização & administração , Monitoramento Epidemiológico , Feminino , Genótipo , Hepacivirus/classificação , Hepatite B/diagnóstico , Hepatite B/patologia , Hepatite B/virologia , Vírus da Hepatite B/classificação , Vírus da Hepatite B/genética , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/patologia , Hepatite C Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Tipagem Molecular , Filogenia , Prevalência , Tailândia/epidemiologia , Carga Viral/genéticaRESUMO
BACKGROUND: Coinfection of Hepatitis C virus (HCV) with human immunodeficiency virus (HIV) has a higher risk of mortality than HCV or HIV monoinfection. HCV and HIV infections are specified by systemic inflammation, but the inflammation process in HCV/HIV coinfection is much complicated and is not well characterized. OBJECTIVE: The aim of this study was to analyze the expression of TLR-3, TLR-7, IL-10, IFN-1 (IFN-α, IFN-ß), and TNF-α in HIV, HCV and HIV/HCV co-infected patients. METHODS: Forty-five patients including HIV group (n=15), HCV group (n=15), HIV/HCV coinfection group (n=15) and healthy control group (n=15) participated. Peripheral blood mononuclear cells (PBMCs) were obtained. PBMC-RNA, HCV and HIV RNA were extracted from all subjects and cDNA was synthesized. The viral load analyzed by reverse transcription-quantitative PCR (RT-qPCR), and the expression levels of IFN-α, IFN-ß, TLR-3, TLR-7, TNF, and IL-10 mRNA were quantified in PBMCs. RESULTS: The levels of IFN-I, IL-10, and TNF-α were overexpressed in all patients' groups (p<0.05), TLR-7 was upregulated in all groups, but this upregulation was not statistically significant (p>0.05). TLR-3 showed a decrease in all patient groups (p<0.05). The statistical analysis demonstrated that TLR-3 has a negative correlation with HIV load, whereas other genes positively correlated with HIV load. In addition, TLR-3, TNF-α, and IFN-I were negatively correlated with HCV load, whereas TLR-7 and IL-10 s were positively correlated with HCV load. CONCLUSION: Our results showed a significant relationship between the expression level of innate immunity genes and inflammation in HCV, HIV, and HIV/HCV coinfected patients.
Assuntos
Infecções por HIV/imunologia , HIV/imunologia , Hepacivirus/imunologia , Hepatite C Crônica/imunologia , Imunidade Inata , RNA Viral/imunologia , Adulto , Estudos de Casos e Controles , Coinfecção , Feminino , Regulação da Expressão Gênica , HIV/genética , Infecções por HIV/genética , Infecções por HIV/patologia , Infecções por HIV/virologia , Hepacivirus/genética , Hepatite C Crônica/genética , Hepatite C Crônica/patologia , Hepatite C Crônica/virologia , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Inflamação , Interferon-alfa/genética , Interferon-alfa/imunologia , Interferon beta/genética , Interferon beta/imunologia , Interleucina-10/genética , Interleucina-10/imunologia , Masculino , Pessoa de Meia-Idade , RNA Viral/genética , Receptor 3 Toll-Like/genética , Receptor 3 Toll-Like/imunologia , Receptor 7 Toll-Like/genética , Receptor 7 Toll-Like/imunologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia , Carga Viral/genética , Carga Viral/imunologiaRESUMO
BACKGROUND: Viral load (VL) testing is being scaled up in resource-limited settings. However, not all commercially available VL testing methods have been evaluated under field conditions. This study is one of a few to evaluate the Biocentric platform for VL quantification in routine practice in Sub-Saharan Africa. METHODS: Venous blood specimens were obtained from patients eligible for VL testing at two health facilities in Swaziland from October 2016 to March 2017. Samples were centrifuged at two laboratories (LAB-1, LAB-2) to obtain paired plasma specimens for VL quantification with the national reference method and on the Biocentric platform. Agreement (correlation, Bland-Altman) and accuracy (sensitivity, specificity) indicators were calculated at the VL thresholds of 416 (2.62 log10) and 1000 (3.0 log10) copies/mL. Leftover samples from patients with discordant VL results were re-quantified and accuracy indicators recalculated. Logistic regression was used to compare laboratory performance. RESULTS: A total of 364 paired plasma samples (LAB-1: n = 198; LAB-2: n = 166) were successfully tested using both methods. The correlation was high (R = 0.82, p < 0.01), and the Bland-Altman analysis showed a minimal mean difference (- 0.03 log10 copies/mL; 95% CI: -1.15 to 1.08). At the clinical threshold level of 3.0 log10 copies/mL, the sensitivity was 88.6% (95% CI: 78.7 to 94.9) and the specificity was 98.3% (95% CI: 96.1 to 99.4). Sensitivity was higher in LAB-1 (100%; 95% CI: 71.5 to 100) than in LAB-2 (86.4%; 95% CI: 75.0 to 94.0). Most upward (n = 8, 2.2%) and downward (n = 11, 3.0%) misclassifications occurred at the 2.62 log threshold, with LAB-2 having a 16 (95% CI: 2.26 to 113.27; p = 0.006) times higher odds of downward misclassification. After retesting of discordant leftover samples (n = 17), overall sensitivity increased to 93.5% (95% CI: 85.5 to 97.9) and 97.1% (95% CI: 90.1 to 99.7) at the 2.62 and 3.0 thresholds, and specificity increased to 98.6% (95% CI: 96.5 to 99.6) and 99.0% (95% CI: 97.0 to 99.8) respectively. CONCLUSIONS: The test characteristics of the Biocentric platform were overall comparable to the national reference method for VL quantification. One laboratory tended to misclassify VL results downwards, likely owing to unmet training needs and lack of previous hands-on practice.
Assuntos
Infecções por HIV/diagnóstico , HIV-1/genética , RNA Viral/sangue , Reação em Cadeia da Polimerase em Tempo Real/métodos , Carga Viral/métodos , Adolescente , Adulto , Testes Diagnósticos de Rotina/economia , Testes Diagnósticos de Rotina/métodos , Testes Diagnósticos de Rotina/normas , Essuatíni , Feminino , Infecções por HIV/sangue , Infecções por HIV/virologia , HIV-1/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Sistemas Automatizados de Assistência Junto ao Leito/economia , Sistemas Automatizados de Assistência Junto ao Leito/normas , Valor Preditivo dos Testes , RNA Viral/análise , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Testes Sorológicos , Manejo de Espécimes/métodos , Carga Viral/genética , Adulto JovemRESUMO
UNLABELLED: Expression of the programmed death 1 (PD-1) receptor and its ligands are implicated in the T cell exhaustion phenotype which contributes to the persistence of several chronic viral infections, including human hepatitis C virus (HCV). The antiviral potential of BMS-936558 (MDX-1106) - a fully human anti-PD-1 monoclonal immunoglobulin-G4 that blocks ligand binding - was explored in a proof-of-concept, placebo-controlled single-ascending-dose study in patients (Nâ=â54) with chronic HCV infection. Interferon-alfa treatment-experienced patients (nâ=â42) were randomized 5â¶1 to receive a single infusion of BMS-936558 (0.03, 0.1, 0.3, 1.0, 3.0 mg/kg [nâ=â5 each] or 10 mg/kg [nâ=â10]) or of placebo (nâ=â7). An additional 12 HCV treatment-naïve patients were randomized to receive 10 mg/kg BMS-936558 (nâ=â10) or placebo (nâ=â2). Patients were followed for 85 days post-dose. Five patients who received BMS-936558 (0.1 [nâ=â1] or 10 mg/kg) and one placebo patient achieved the primary study endpoint of a reduction in HCV RNA ≥0.5 log10 IU/mL on at least 2 consecutive visits; 3 (10 mg/kg) achieved a >4 log10 reduction. Two patients (10 mg/kg) achieved HCV RNA below the lower limit of quantitation (25 IU/mL), one of whom (a prior null-responder) remained RNA-undetectable 1 year post-study. Transient reductions in CD4(+), CD8(+) and CD19(+) cells, including both naïve and memory CD4(+) and CD8(+) subsets, were observed at Day 2 without evidence of immune deficit. No clinically relevant changes in immunoglobulin subsets or treatment-related trends in circulating cytokines were noted. BMS-936558 exhibited dose-related exposure increases, with a half-life of 20-24 days. BMS-936558 was mostly well tolerated. One patient (10 mg/kg) experienced an asymptomatic grade 4 ALT elevation coincident with the onset of a 4-log viral load reduction. Six patients exhibited immune-related adverse events of mild-to-moderate intensity, including two cases of hyperthyroidism consistent with autoimmune thyroiditis. Further investigation of PD-1 pathway blockade in chronic viral disease is warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT00703469.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Antivirais/uso terapêutico , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/tratamento farmacológico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Adulto , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/farmacocinética , Antivirais/efeitos adversos , Método Duplo-Cego , Feminino , Meia-Vida , Hepacivirus/genética , Humanos , Interferon-alfa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Nivolumabe , Receptor de Morte Celular Programada 1/metabolismo , RNA Viral/genética , Carga Viral/efeitos dos fármacos , Carga Viral/genéticaRESUMO
BACKGROUND: The blood HIV RNA viral load is the best-defined predictor of HIV transmission, in part due to ease of measurement and the correlation of blood and genital tract (semen or cervico-vaginal) viral load, although recent studies found semen HIV RNA concentration to be a stronger predictor of HIV transmission. There is currently no standardized method for semen collection when measuring HIV RNA concentration. Therefore, we compared two collection techniques in order to study of the impact of antiretroviral therapy on the semen viral load. METHODOLOGY/PRINCIPAL FINDINGS: Semen was collected by masturbation from HIV-infected, therapy-naïve men who have sex with men (MSM) either undiluted (Visit 1) or directly into transport medium (Visit 2). Seminal plasma was then isolated, and the HIV RNA concentration obtained with each collection technique was measured and corrected for dilution if necessary. Collection of semen directly into transport medium resulted in a median HIV RNA viral load that was 0.4 log10 higher than undiluted samples. CONCLUSIONS/SIGNIFICANCE: The method of semen collection is an important consideration when quantifying the HIV RNA viral load in this compartment.
Assuntos
HIV-1/genética , RNA Viral/análise , Sêmen/virologia , Manejo de Espécimes/métodos , Carga Viral/genética , Humanos , Masculino , RNA Viral/sangueRESUMO
Increasing evidence shows that genes have a pivotal role in affecting the dynamic pattern of viral loads in the body of a host. By reviewing the biochemical interactions between a virus and host cells as a dynamic system, we outline a computational approach for mapping the genetic control of virus dynamics. The approach integrates differential equations (DEs) to quantify the dynamic origin and behavior of a viral infection system. It enables geneticists to generate various testable hypotheses about the genetic control mechanisms for virus dynamics and infection. The experiment designed according to this approach will also enable researchers to gain insight into the role of genes in limiting virus abundance and the dynamics of viral drug resistance, facilitating the development of personalized medicines to eliminate viral infections.