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1.
J Glob Health ; 10(1): 010408, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32257156

RESUMEN

Background: HIV treatment and care services were scaled up in 2007 in India with objective to increase HIV-care coverage. CD4 count based criteria was mainly used for treatment initiation with increasing threshold in later years. Therefore, this paper aimed to evaluate the survival by varying CD4 criteria for antiretroviral treatment (ART) initiation among of HIV-positive patients, and independent factors associated with the mortality. Methods: This retrospective cohort study included 127 949 HIV-positive patients aged ≥15 years, who initiated ART between 2007 and 2013 in Andhra Pradesh state, India. The patient's demographic and clinical characteristics were extracted from the patient's health records from electronic Computerized Management Information System Software (CMIS). Incidence of mortality/100 person-years was calculated for CD4 and treatment initiation categories. Kaplan-Meier and multivariable Cox-regression analyses were used to explore the association. Results: Median CD4 count was 172 (inter-quartile range (IQR) = 102-240) at the time of treatment initiation, and 19.3% of them had ≤ 100 CD4 count. Incidence of mortality for the period 2007-08 (CD4 ≤ 200 cells/mm3) was 8.5/100 person-years compared to 6.4/100 person-years at risk for the period 2012 onwards (CD4 ≤ 350 cells/mm3). Earlier thresholds for treatment initiation showed higher risk of mortality (2007-08 (CD4 ≤ 200 cells/mm3), adjusted hazard ratio (HR): 1.86, 95% confidence interval (CI): 1.68-2.07; 2009-11 (CD4 ≤ 250 cells/mm3), HR = 1.67, 95% CI = 1.51-1.85) compared to 2012 onwards (CD4 ≤ 350 cells/mm3) criteria for treatment initiation. Conclusions: Increasing CD4 threshold for treatment initiation over time was independently associated with lower risk of mortality. More efforts are required to detect and treat early, monitoring of follow-ups, promote health education to improve ART adherence, and provide supportive environment that encourages HIV-infected patients to disclose their HIV status in confidence.


Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Registros Electrónicos de Salud , Infecciones por VIH/tratamiento farmacológico , Adolescente , Adulto , Recuento de Linfocito CD4 , Femenino , Infecciones por VIH/mortalidad , Infecciones por VIH/virología , Mortalidad Hospitalaria , Humanos , Incidencia , India , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Retrospectivos
2.
Medicine (Baltimore) ; 99(11): e19140, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32176039

RESUMEN

Treatment of hepatitis C virus (HCV) infection for patients with human immunodeficiency virus (HIV) has improved with direct acting antivirals. However, outcomes among Black persons treated with ledipasvir/sofosbuvir (LDV/SOF) may be inferior to non-Blacks. We assessed responses to LDV/SOF in a cohort of Black HIV/HCV coinfected persons.Retrospective chart reviews were conducted for Black, genotype 1 (GT1), HIV/HCV coinfected patients treated with LDV/SOF at 3 hospitals in Newark, NJ between January 2014 and July 2016. Data collected included demographics, HCV treatment history, treatment duration, and response.One hundred seventeen HIV/HCV coinfected Black patients started treatment with LDV/SOF but 5 had no follow-up data and 5 prematurely discontinued treatment (1 due to side effects). We included 107 HIV/HCV coinfected patients who completed LDV/SOF at all 3 sites. The study population was 65% male, median age 58 years, 26% had cirrhosis, and 78% had GT1a. Thirty-one percent were treatment experienced but none with prior NS5a treatment. At baseline, median CD4 count was 680 cells/mm, HIV viral load (VL) was <40 copies/mL in 94% and median HCV VL was 2,257,403 IU/mL. Twenty-nine percent of patients changed antiretroviral treatment before LDV/SOF treatment due to drug interactions. Six, 89, and 12 patients completed 8, 12, and 24 weeks of LDV/SOF, respectively. Overall sustained virologic response rate was 93% with 7 relapses.In this real-world cohort of Black, GT1, HIV/HCV coinfected patients, LDV/SOF had high sustained virologic response 12 weeks post completion of treatment rate of 93%. This data supports the overall high efficacy of LDV/SOF in a historically difficult-to-treat patient population.


Asunto(s)
Antivirales/uso terapéutico , Bencimidazoles/uso terapéutico , Coinfección/tratamiento farmacológico , Fluorenos/uso terapéutico , Infecciones por VIH/complicaciones , Hepacivirus/efectos de los fármacos , Hepatitis C/complicaciones , Uridina Monofosfato/análogos & derivados , Afroamericanos/estadística & datos numéricos , Antivirales/administración & dosificación , Bencimidazoles/administración & dosificación , Coinfección/virología , Femenino , Fluorenos/administración & dosificación , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Hepatitis C/tratamiento farmacológico , Hepatitis C/virología , Humanos , Masculino , Persona de Mediana Edad , New Jersey , Estudios Retrospectivos , Resultado del Tratamiento , Uridina Monofosfato/administración & dosificación , Uridina Monofosfato/uso terapéutico
3.
Gene ; 741: 144568, 2020 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-32165289

RESUMEN

This study was performed to assess the association of CCR5Δ32 and SDF1-3'A polymorphisms with immunological recovery failure and to investigate the influence of sociodemographic and clinical data on immune reconstitution in human immunodeficiency virus (HIV)-positive patients during antiretroviral therapy (ART). Two hundred and forty-eight HIV-positive patients under ART with undetectable plasma viral load (<40 copies/mL) were enrolled in this study and classified into two groups according to their CD4+ T-cell count changes: immunological responders (CD4+ T-cell count gain ≥ 200/µL or ≥ 30% compared with baseline) and immunological non-responders (CD4+ T-cell count gain < 200/µL or < 30% compared with baseline). DNA extraction was performed followed by CCR5Δ32 and SDF1-3'A genotyping. Sociodemographic and clinical data were evaluated from medical records. The logistic regression model showed that heterozygosity for CCR5Δ32 allele and lower pre-treatment CD4+ T-cell count (<500 cells/µL) were statistically associated with immunological recovery failure (OR = 5.873, 95%CI = 1.204-28.633, P = 0.028 and OR = 10.00, 95%CI = 3.224-31.016, P = 0.028, respectively). No association of SDF1-3'A polymorphism with immune reconstitution failure was found. Additionally, we observed that there was a statistically significant difference between lower CD4+ T-cell count and INR status than the IR group (Z = 4.687, P < 0.001). Our results demonstrated, through a logistic regression model, that CCR5Δ32 polymorphism and pre-treatment CD4+ T-cell count have significant influence on immune reconstitution of HIV-positive patients during ART. These findings highlight some immunological factors associated with poor CD4+ T-lymphocytes recovery, which affect immune response level of ART-treated HIV-positive patients.


Asunto(s)
Quimiocina CXCL12/genética , Estudios de Asociación Genética , Infecciones por VIH/genética , Receptores CCR5/genética , Adulto , Alelos , Terapia Antirretroviral Altamente Activa , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/inmunología , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , Infecciones por VIH/virología , VIH-1/efectos de los fármacos , VIH-1/patogenicidad , Heterocigoto , Humanos , Masculino , Receptores CCR5/inmunología , Carga Viral/efectos de los fármacos , Carga Viral/genética , Carga Viral/inmunología
4.
Medicine (Baltimore) ; 99(9): e19353, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32118776

RESUMEN

Pneumococcal nasopharyngeal colonization is a pre-requisite for pneumococcal disease; the risk for pneumococcal disease is high in children born to women living with human immunodeficiency virus (HIV). We investigated pneumococcal colonization, serotype distribution and antibiotic susceptibility of Streptococcus pneumoniae isolates carried by perinatal HIV-infected and HIV-exposed-uninfected (HEU) children.Serial nasopharyngeal swabs were collected from 331 HIV-infected and 491 HEU children, at up to 6 scheduled timepoints, between median ages of 25 to 181 weeks. Pneumococcus was identified by culture; serotyping and antibiotic susceptibility testing were done by conventional methods. No pneumococcal vaccine was given.HIV-infected children were less likely to be colonized with 7-valent pneumococcal conjugate vaccine 7 serotypes than HEU at a median of 25 weeks of age (23% vs 36%; P < .001); however, no differences in colonization between the 2 groups were observed at subsequent study-visits. Over the 36-months study-period pneumococcal colonization increased in both HIV-infected (from 45% to 77%) and HEU (from 57% to 61%) children. Over the study-period, pneumococcal isolates non-susceptible to cotrimoxazole decreased from 92% to 57% and had a similar trend to penicillin (from 65% to 42%) in HIV-infected children. Similarly, pneumococcal nonsusceptible to cotrimoxazole decreased from 93% to 57% and to penicillin from 69% to 37% in HEU children.Vaccine serotype colonization was common in this population and similar rates were observed in HIV-infected and HEU children. The prevalence of pneumococcal isolates non-susceptible to cotrimoxazole and penicillin decreased with age.


Asunto(s)
Infecciones por VIH/virología , Infecciones Neumocócicas/diagnóstico , Streptococcus pneumoniae/patogenicidad , Adolescente , Distribución de Chi-Cuadrado , Niño , Preescolar , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Humanos , Lactante , Vacunas contra la Influenza/uso terapéutico , Masculino , Líquido del Lavado Nasal/microbiología , Infecciones Neumocócicas/epidemiología , Prevalencia , Sudáfrica/epidemiología
5.
Mem Inst Oswaldo Cruz ; 115: e190461, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32187328

RESUMEN

Phylogenetic analyses were crucial to elucidate the origin and spread of the pandemic human immunodeficiency virus type 1 (HIV-1) group M virus, both during the pre-epidemic period of cryptic dissemination in human populations as well as during the epidemic phase of spread. The use of phylogenetics and phylodynamics approaches has provided important insights to track the founder events that resulted in the spread of HIV-1 strains across vast geographic areas, specific countries and within geographically restricted communities. In the recent years, the use of phylogenetic analysis combined with the huge availability of HIV sequences has become an increasingly important approach to reconstruct HIV transmission networks and understand transmission dynamics in concentrated and generalised epidemics. Significant efforts to obtain viral sequences from newly HIV-infected individuals could certainly contribute to detect rapidly expanding HIV-1 lineages, identify key populations at high-risk and understand what public health interventions should be prioritised in different scenarios.


Asunto(s)
Infecciones por VIH/transmisión , VIH-1/genética , Filogeografía , Animales , Análisis por Conglomerados , Gorilla gorilla , Infecciones por VIH/virología , Humanos , Filogenia
6.
Mem Inst Oswaldo Cruz ; 114: e190350, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32022169

RESUMEN

BACKGROUND: Iron homeostasis contribute for the human immunodeficiency virus (HIV) pathogenesis. OBJECTIVES: We assessed the iron intake pattern in antiretroviral naïve Brazilian men living with HIV correlating with clinical and nutritional parameters. METHODS: The iron consumption mean was estimated according to a food frequency questionnaire (FFQ), and a 3-day food record (3dFR) submitted to the patients. HIV viral load, CD4+ T cell counts, serum iron, haematological and anthropometrics parameters were recorded. FINDINGS: Fifty-one HIV-infected adult men naïve for antiretroviral therapy (ART) were enrolled. The mean age of participants was 35 (SEM ± 1.28) years old, with mean time of HIV-1 infection of 1.78 (0-16.36, min-max) years. Majority (41.18%) had complete secondary, and 21.57% had tertiary educational level. The income was around 1x (54.90%) to 2x (41.18%) minimum wage. Fifty-four percent showed normal weight, while 40% were overweight. The patients showed normal mean values of haematological parameters, and mean serum iron was 14.40 µM (SEM ± 0.83). The FFQ showed moderate correlation with the 3dFR (ρ = 0.5436, p = 0.0009), and the mean values of iron intake were 10.55(± 0.92) mg/day, recorded by FFQ, and 15.75(± 1.51) mg/day, recorded by 3dFR. The iron intake, recorded by FFQ, negatively correlated with serum iron (ρ = -0.3448, p = 0.0132), and did not have influence in the CD4+ T cell counts [e.B 0.99 (0.97-1.01, 95% confidence interval (CI), p = 0.2]. However, the iron intake showed a positive effect in HIV viral load [e.B 1.12 (1.02-1.25, 95%CI), p < 0.01]. MAIN CONCLUSIONS: This study draws attention for the importance of iron intake nutritional counseling in people living with HIV. However, more studies are required to clarify the association between high iron intake and HIV infection and outcome.


Asunto(s)
Antirretrovirales/administración & dosificación , Infecciones por VIH/virología , Hierro en la Dieta/efectos adversos , Carga Viral/efectos de los fármacos , Adulto , Recuento de Linfocito CD4 , Estudios Transversales , Femenino , Infecciones por VIH/sangre , Infecciones por VIH/tratamiento farmacológico , Homeostasis , Humanos , Hierro en la Dieta/análisis , Masculino , Estado Nutricional , Factores Socioeconómicos , Encuestas y Cuestionarios
7.
West Afr J Med ; 37(1): 1-6, 2020.
Artículo en Inglés, Francés | MEDLINE | ID: mdl-32030704

RESUMEN

BACKGROUND: Pregnant women with asymptomatic bacteriuria are at increased risk of developing symptomatic urinary tract infections. HIV infection may modify the acquisition of bacteriuria in pregnancy. OBJECTIVE: To identify the determinants of asymptomatic bacteriuria in HIV-positive and HIV-negative pregnant women in Olabisi Onabanjo University Teaching Hospital, Sagamu, Nigeria. METHODS: A cross-sectional study involving 211 HIV-positive pregnant women and 422 HIV-negative pregnant women attending their first antenatal clinic between October 2017 and March 2018. Information on socio-demographic characteristics and risk factors for asymptomatic bacteriuria in study participants was recorded. Microbial culture was carried out on aseptically collected urine samples. RESULTS: Asymptomatic bacteriuria was found in 66(31.3%) and 118(28.0%) in HIV-positive and negative women respectively. Advanced maternal age, gestational age above 20 weeks, low socioeconomic status, history of urinary tract infections in previous pregnancies and low CD4 cell count had statistically significant association with increased prevalence of asymptomatic bacteriuria among HIV positive women. Binary logistic regression analysis showed that low socioeconomic status and history of urinary tract infections in previous pregnancies were strong determinants of asymptomatic bacteriuria among HIV positive women (AOR 4.1, CI 1.9-8.7, P < 0.001; AOR 5.8, CI 2.5-13.6, P < 0.001 respectively). In HIV negative women, gestational age above 20 weeks had statistically significant association with increased prevalence of asymptomatic bacteriuria (AOR= 2.34, CI 1.3-4.1, P= 0.002). CONCLUSION: Low socioeconomic status and previous history of urinary tract infections are determinants of asymptomatic bacteriuria in HIV positive women while gestational age above 20 weeks is a determinant in HIV negative women. These determinants could be used to identify women at high risk of asymptomatic bacteriuria for targeted screening.


Asunto(s)
Bacterias/aislamiento & purificación , Bacteriuria/microbiología , Bacteriuria/orina , Infecciones por VIH/complicaciones , Seronegatividad para VIH , Complicaciones Infecciosas del Embarazo/microbiología , Complicaciones Infecciosas del Embarazo/orina , Orina/microbiología , Adulto , Bacteriuria/epidemiología , Estudios Transversales , Femenino , Infecciones por VIH/virología , Humanos , Nigeria/epidemiología , Embarazo , Complicaciones Infecciosas del Embarazo/epidemiología , Prevalencia , Infecciones Urinarias/epidemiología , Infecciones Urinarias/microbiología , Infecciones Urinarias/orina
8.
PLoS One ; 15(2): e0227763, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32049963

RESUMEN

INTRODUCTION: Aging and chronic HIV infection are clinical conditions that share the states of inflammation and hypercoagulability. The life expectancy of the world population has increased in the last decades, bringing as complications the occurrence of diseases that undergoing metabolic, bone, cardiological, vascular and neurological alterations. HIV-infected patients experience these changes early and are living longer due to the success of antiretroviral therapy. The objectives of this study was to evaluate some changes in the plasma hemostatic profile of 115 HIV-reactive elderly individuals over 60 years old in the chronic phase of infection, and compare with 88 healthy uninfected elderly individuals. Plasma determinations of D-dimers, Fibrinogen, von Willebrand Factor, Antithrombin, Prothrombin Time, Activated Partial Thromboplastin Time, and platelet count were performed. In the HIV-reactive group, these variables were analyzed according to viral load, protease inhibitor use and CD4+ T lymphocyte values. After adjusted values for age and sex, the results showed higher levels of Antithrombin (103%; 88%, p = 0.0001) and Prothrombin Time activities (92.4%; 88.2%, p = 0.019) in the HIV group compared to the control group. We observed higher values of Fibrinogen in protease inhibitor users in both the male (p = 0.043) and female (p = 0.004) groups, and in the female HIV group with detected viral load (p = 0.015). The male HIV group with a CD4+ count> 400 cells / mm3 presented higher von Willebrand Factor values (p = 0.036). D-Dimers had higher values in the older age groups (p = 0.003; p = 0.042, respectively). CONCLUSION: Our results suggest that the elderly with chronic HIV infection with few comorbidities had a better hemostatic profile than negative control group, reflecting the success of treatment. Protease inhibitor use and age punctually altered this profile.


Asunto(s)
Infecciones por VIH/sangre , Infecciones por VIH/virología , VIH/fisiología , Hemostasis , Anciano , Anciano de 80 o más Años , Recuento de Linfocito CD4 , Estudios de Casos y Controles , Comorbilidad , Estudios Transversales , Femenino , Infecciones por VIH/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Inhibidores de Proteasas/farmacología , Carga Viral
9.
PLoS One ; 15(2): e0228036, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32015565

RESUMEN

Atomic Force Microscopy was utilized to study the morphology of Gag, ΨRNA, and their binding complexes with lipids in a solution environment with 0.1Å vertical and 1nm lateral resolution. TARpolyA RNA was used as a RNA control. The lipid used was phospha-tidylinositol-(4,5)-bisphosphate (PI(4,5)P2). The morphology of specific complexes Gag-ΨRNA, Gag-TARpolyA RNA, Gag-PI(4,5)P2 and PI(4,5)P2-ΨRNA-Gag were studied. They were imaged on either positively or negatively charged mica substrates depending on the net charges carried. Gag and its complexes consist of monomers, dimers and tetramers, which was confirmed by gel electrophoresis. The addition of specific ΨRNA to Gag is found to increase Gag multimerization. Non-specific TARpolyA RNA was found not to lead to an increase in Gag multimerization. The addition PI(4,5)P2 to Gag increases Gag multimerization, but to a lesser extent than ΨRNA. When both ΨRNA and PI(4,5)P2 are present Gag undergoes comformational changes and an even higher degree of multimerization.


Asunto(s)
Infecciones por VIH/genética , VIH-1/genética , ARN Viral/genética , Productos del Gen gag del Virus de la Inmunodeficiencia Humana/ultraestructura , Membrana Celular/química , Membrana Celular/genética , Infecciones por VIH/virología , Seropositividad para VIH , VIH-1/química , VIH-1/patogenicidad , Humanos , Lípidos/química , Microscopía de Fuerza Atómica , Complejos Multiproteicos/química , Complejos Multiproteicos/genética , Fosfatidilinositol 4,5-Difosfato/química , Unión Proteica , Multimerización de Proteína/genética , ARN Viral/química , Proteínas de Unión al ARN/química , Proteínas de Unión al ARN/genética , Productos del Gen gag del Virus de la Inmunodeficiencia Humana/química , Productos del Gen gag del Virus de la Inmunodeficiencia Humana/genética
10.
BMC Infect Dis ; 20(1): 123, 2020 Feb 11.
Artículo en Inglés | MEDLINE | ID: mdl-32046664

RESUMEN

BACKGROUND: The rate of S68G mutation in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase has increased and is closely related to the K65R mutation among CRF01_AE-infected patients who failed treatment. We aimed to explore the temporal association of S68G and K65R mutations and disclose the role of the former on susceptibility to nucleotide/nucleoside reverse transcriptase inhibitor (NRTI) and viral replication with the K65R double mutations among CRF01_AE-infected patients who failed treatment. METHODS: The occurrence of S68G and K65R mutations was evaluated among HIV-1 of various subtypes in the global HIV Drug Resistance Database. The temporal association of S68G and K65R mutations was analyzed through next-generation sequencing in four CRF01_AE-infected patients who failed treatment with tenofovir/lamivudine/efavirenz. The impact of the S68G mutation on susceptibility to NRTI and replication fitness was analyzed using pseudovirus phenotypic resistance assays and growth competition assays, respectively. RESULTS: The frequency of the S68G mutation increased by 1.4-9.7% in almost all HIV subtypes and circulating recombinant forms in treatment-experienced patients, except subtype F. The S68G mutation often occurred in conjunction with the K65R mutation among RTI-treated patients, with frequencies ranging 21.1-61.7% in various subtypes. Next-generation sequencing revealed that the S68G mutation occurred following the K65R mutation in three of the four CRF01_AE-infected patients. In these three patients, there was no significant change detected in the half maximal inhibitory concentration for zidovudine, tenofovir, or lamivudine between the K65R and K65R/S68G mutations, as demonstrated by the phenotypic resistance assays. Virus stocks of the K65R and K65R/S68G mutations were mixed with 4:6, 1:1, and 9:1 and cultured for 13 days, the K65R/S68G mutants outgrew those of the K65R mutants irrespective of the input ratio. CONCLUSIONS: S68G may be a natural polymorphism and compensatory mutation of K65R selected by NRTIs in the CRF01_AE strain of HIV-1. This mutation does not affect susceptibility to NRTI; however, it improves the replication fitness of K65R mutants. This study deciphers the role of the S68G mutation in the HIV reverse transcriptase of the CRF01_AE strain and provides new evidence for the interpretation of drug-resistant mutations in non-B subtypes of HIV-1.


Asunto(s)
Farmacorresistencia Viral/genética , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Transcriptasa Inversa del VIH/genética , VIH-1/genética , Mutación , Fármacos Anti-VIH/uso terapéutico , VIH-1/efectos de los fármacos , Humanos , Lamivudine/uso terapéutico , Tasa de Mutación , Polimorfismo Genético , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Tenofovir/uso terapéutico , Insuficiencia del Tratamiento , Replicación Viral/efectos de los fármacos , Zidovudina/uso terapéutico
11.
Nat Immunol ; 21(3): 274-286, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-32066947

RESUMEN

Human immunodeficiency virus 1 (HIV-1) infection is associated with heightened inflammation and excess risk of cardiovascular disease, cancer and other complications. These pathologies persist despite antiretroviral therapy. In two independent cohorts, we found that innate lymphoid cells (ILCs) were depleted in the blood and gut of people with HIV-1, even with effective antiretroviral therapy. ILC depletion was associated with neutrophil infiltration of the gut lamina propria, type 1 interferon activation, increased microbial translocation and natural killer (NK) cell skewing towards an inflammatory state, with chromatin structure and phenotype typical of WNT transcription factor TCF7-dependent memory T cells. Cytokines that are elevated during acute HIV-1 infection reproduced the ILC and NK cell abnormalities ex vivo. These results show that inflammatory cytokines associated with HIV-1 infection irreversibly disrupt ILCs. This results in loss of gut epithelial integrity, microbial translocation and memory NK cells with heightened inflammatory potential, and explains the chronic inflammation in people with HIV-1.


Asunto(s)
Citocinas/sangre , VIH-1/inmunología , VIH-1/patogenicidad , Inmunidad Innata , Células Asesinas Naturales/inmunología , Linfocitos/inmunología , Factor 1 de Transcripción de Linfocitos T/inmunología , Regulación de la Expresión Génica , Infecciones por VIH/genética , Infecciones por VIH/inmunología , Infecciones por VIH/virología , Homeostasis/inmunología , Humanos , Memoria Inmunológica , Técnicas In Vitro , Inflamación/genética , Inflamación/inmunología , Inflamación/virología , Factor 1 de Transcripción de Linfocitos T/genética , Vía de Señalización Wnt/inmunología
12.
BMC Bioinformatics ; 21(1): 52, 2020 Feb 11.
Artículo en Inglés | MEDLINE | ID: mdl-32046642

RESUMEN

BACKGROUND: HIV/AIDS is responsible for the deaths of one million people every year. Although mathematical modeling has provided many insights into the dynamics of HIV infection, there is still a lack of accessible tools for researchers unfamiliar with modeling techniques to apply them to their own clinical data. RESULTS: Here we present ushr, a free and open-source R package that models the decline of HIV during antiretroviral treatment (ART) using a popular mathematical framework. ushr can be applied to longitudinal data of viral load measurements, and provides processing tools to prepare it for computational analysis. By mathematically fitting the data, important biological parameters can then be estimated, including the lifespans of short and long-lived infected cells, and the time to reach viral suppression below a defined detection threshold. The package also provides visualization and summary tools for fast assessment of model results. CONCLUSIONS: ushr enables researchers without a strong mathematical or computational background to model the dynamics of HIV using longitudinal clinical data. Increasing accessibility to such methods may facilitate quantitative analysis across a broader range of independent studies, so that greater insights on HIV infection and treatment dynamics may be gained.


Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Programas Informáticos , VIH/aislamiento & purificación , Humanos , Modelos Biológicos , Carga Viral
13.
BMC Infect Dis ; 20(1): 147, 2020 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-32066392

RESUMEN

BACKGROUND: Low level viremia (LLV) often occurs during antiretroviral therapy (ART) against HIV-1. However, whether LLV increases the risk of virologic failure (VF) is controversial because of the non-uniform definitions of LLV and VF. METHODS: A long-term first line regimen ART cohort from 2002 to 2018 from Shenyang, northeast China, was retrospectively studied. All participants were followed up every 3 to 6 months to evaluate the treatment effect. The high-risk LLV subgroups leading to VF (with strict standards) were explored with Cox proportional hazards model and linear mixed-effect model. The association factors of high-risk LLV were further explored using multivariate logistic regression analyses. RESULTS: A total of 2155 HIV-1 infected participants were included; of these, 38.7% showed LLV. Both high level LLV (HLLV) and any other level LLV coupled with high level blip (HLB) showed higher risk of VF (hazards ratios, HRHLLV = 5.93, and HRHLB = 2.84, p <  0.05 respectively). Moreover, HR increased with prolonged duration of LLV. Independent factors associated with high-risk LLV included the zenith baseline viral load (VL) above 6 log copies/ml (aOR = 3.49, p = 0.002), nadir baseline CD4 + T cell counts below 200 cells/mm3 (aOR = 1.78, p = 0.011), Manchu (aOR = 2.03, p = 0.003), ART over 60 months (aOR = 1.81, p = 0.004), AZT + 3TC + NVP (aOR = 2.26, p <  0.001) or DDI-based regimen (aOR = 9.96, p = 0.002), and subtype B' infection (aOR = 8.22, p = 0.001). CONCLUSIONS: In case of VF with strict standards, high-risk LLV leading to VF includes VL above 400 copies/ml, occurring at least once. Serious laboratory indicators or advanced stage of infection, long term ART and subtype B' infection might also predict the occurrence of high-risk LLV.


Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , VIH-1/fisiología , Viremia/tratamiento farmacológico , Adulto , China/epidemiología , Femenino , Infecciones por VIH/epidemiología , Infecciones por VIH/virología , VIH-1/efectos de los fármacos , VIH-1/genética , Humanos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Riesgo , Factores de Tiempo , Insuficiencia del Tratamiento , Carga Viral , Viremia/epidemiología , Viremia/virología
14.
Arch Virol ; 165(4): 967-972, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32060792

RESUMEN

In Pakistan, the HIV situation has gone from an outbreak to a concentrated epidemic, and the virus has now crossed into the low-risk population. In addition, several new HIV outbreaks have occurred in different parts of the country. HIV-1 subtype A has been the major epidemic subtype in Pakistan; however, as the epidemic has grown, the emergence of several new subtypes and recombinant forms has been observed. Here, we present the first case and genetic analysis of an unassigned, complex recombinant form in a Pakistani HIV-infected individual with virological failure. Genetic analysis of the sequence indicated that this recombinant form is multi-drug resistant, harboring drug resistance mutations against more than one class of antiretroviral drugs.


Asunto(s)
Infecciones por VIH/virología , VIH-1/genética , Recombinación Genética , Adulto , Fármacos Anti-VIH/uso terapéutico , Farmacorresistencia Viral , Genotipo , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , VIH-1/clasificación , VIH-1/efectos de los fármacos , VIH-1/aislamiento & purificación , Humanos , Masculino , Pakistán/epidemiología , Filogenia
15.
PLoS One ; 15(2): e0228370, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32040523

RESUMEN

BACKGROUND: The rapid scale-up of HIV therapy across Africa has failed to adequately engage adolescents living with HIV (ALWHIV). Retention and viral suppression for this group (ALWHIV) is 50% lower than for adults. Indeed, on the African continent, HIV remains the single leading cause of mortality among adolescents. Strategies tailored to the unqiue developmental and social vulnerabilities of this group are urgently needed to enhance successful treatment. METHODS: We carried out a five-year longitudinal cluster randomized trial (ClinicalTrials.gov ID: NCT01790373) with adolescents living with HIV (ALWHIV) ages 10 to 16 years clustered at health care clinics to test the effect of a family economic empowerment (EE) intervention on viral suppression in five districuts in Uganda. In total, 39 accredited health care clinics from study districts with existing procedures tailored to adolescent adherence were eligible to participate in the trial. We used data from 288 youth with detectable HIV viral loads (VL) at baseline (158 -intervention group from 20 clinics, 130 -non-intervention group from 19 clinics). The primary end point was undetectable plasma HIV RNA levels, defined as < 40 copies/ml. We used Kaplan-Meier (KM) analysis and Cox proportional hazard models to estimate intervention effects. FINDINGS: The Kaplan-Meier (KM) analysis indicated that an incidence of undetectable VL (0.254) was significantly higher in the intervention condition compared to 0.173 (in non-intervention arm) translated into incidence rate ratio of 1.468 (CI: 1.064-2.038), p = 0.008. Cox regression results showed that along with the family-based EE intervention (adj. HR = 1.446, CI: 1.073-1.949, p = 0.015), higher number of medications per day had significant positive effects on the viral suppression (adj.HR = 1.852, CI: 1.275-2.690, p = 0.001). INTERPRETATION: A family economic empowerment intervention improved treatment success for ALWHIV in Uganda. Analyses of cost effectiveness and scalability are needed to advance incorporation of this intervention into routine practice in low and middle-income countries.


Asunto(s)
Salud del Adolescente/economía , Empoderamiento , Infecciones por VIH/economía , Infecciones por VIH/prevención & control , VIH/aislamiento & purificación , Cumplimiento de la Medicación/psicología , Carga Viral/efectos de los fármacos , Adolescente , Conducta del Adolescente , Antirretrovirales , Estudios de Casos y Controles , Niño , Femenino , Infecciones por VIH/virología , Humanos , Estudios Longitudinales , Masculino , Pobreza , Factores Socioeconómicos , Resultado del Tratamiento
16.
AIDS Patient Care STDS ; 34(2): 51-58, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-32049556

RESUMEN

Issues have been raised concerning clinical relevance of HIV-1 proviral DNA genotypic resistance test (DNA GRT). To assess impact of DNA GRT on choice of antiretroviral therapy (ART) and subsequent virological outcome, we retrospectively reviewed decision-making and viral load (VL) evolution following DNA GRT performed in our center between January 2012 and December 2017, except those prescribed within the framework of a clinical trial. A total of 304 DNA GRTs were included, 185 (62%) performed in a context of virological success. Only 34% of tests were followed by ART change, more frequently in situation of virological success (39% vs. 26%, p = 0.02). In this situation, ART change guided by DNA GRT led to VL >20 copies/mL after 6 months in 5% of cases. In multivariate analysis, higher HIV DNA quantification (p = 0.01) was associated with occurrence of viremia. A higher nadir of CD4 count (p = 0.04) and a longer time with VL <20 copies/mL (p = 0.04) were independently associated with a lower risk of viremia. In situation of low-level viremia, ART change guided by DNA GRT led to VL <20 copies/mL after 6 months in 52% of cases, while decision to maintain the same treatment led to VL <20 copies/mL in 74% of cases. In multivariate analysis, longer time with VL >20 copies/mL (p = 0.02) was associated with persistence of virological replication. In conclusion, in situation of virological success, use of DNA GRT in addition to analysis of historical RNA GRT to guide ART optimization appears safe. Its prescription framework in situation of low-level viremia deserves to be better defined.


Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Antirretrovirales/uso terapéutico , Farmacorresistencia Viral/genética , Infecciones por VIH/tratamiento farmacológico , VIH-1/efectos de los fármacos , Carga Viral/efectos de los fármacos , Adulto , Terapia Antirretroviral Altamente Activa , Recuento de Linfocito CD4 , Estudios de Cohortes , Femenino , Genotipo , Infecciones por VIH/genética , Infecciones por VIH/virología , VIH-1/genética , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Viremia/tratamiento farmacológico , Viremia/virología
17.
BMC Infect Dis ; 20(1): 159, 2020 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-32075599

RESUMEN

BACKGROUND: Varicella-zoster virus (VZV) infection can be diagnosed clinically once classical rash occurs but the diagnosis is challenging when typical rash is absent. We reported a case of fulminant central nervous system (CNS) VZV infection in a human immunodeficiency virus (HIV)-infected patient without typical VZV-related rash. CNS VZV infection was unexpected identified by metagenomic next-generation sequencing (mNGS). CASE PRESENTATION: A 28-year-old HIV-infected patient presented with neurological symptoms for 3 days. The patient, who was not suspected of VZV infection at admission, quickly progressed to deep coma during the first 24 h of hospitalization. An unbiased mNGS was performed on DNA extract from 300 µL cerebrospinal fluid (CSF) with the BGISEQ-50 platform. The sequencing detection identified 97,248 (out of 38,561,967) sequence reads uniquely aligned to the VZV genome, and these reads covered a high percentage (99.91%) of the VZV. Presence of VZV DNA in CSF was further verified by VZV-specific polymerase chain reaction and Sanger sequencing. Altogether, those results confirmed CNS VZV infection. CONCLUSIONS: This study suggests that mNGS may be a useful diagnostic tool for CNS VZV infection. As mNGS could identify all pathogens directly from CSF sample in a single run, it has the promise of strengthening our ability to diagnose CNS infections in HIV-infected patients.


Asunto(s)
Enfermedades Virales del Sistema Nervioso Central/diagnóstico , Infecciones por VIH/virología , Herpesvirus Humano 3/genética , Infección por el Virus de la Varicela-Zóster/diagnóstico , Adulto , Enfermedades Virales del Sistema Nervioso Central/tratamiento farmacológico , Enfermedades Virales del Sistema Nervioso Central/etiología , Enfermedades Virales del Sistema Nervioso Central/virología , Líquido Cefalorraquídeo/virología , ADN Viral/líquido cefalorraquídeo , Herpesvirus Humano 3/patogenicidad , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Metagenoma , Infección por el Virus de la Varicela-Zóster/tratamiento farmacológico , Infección por el Virus de la Varicela-Zóster/etiología , Infección por el Virus de la Varicela-Zóster/virología
18.
Nat Commun ; 11(1): 632, 2020 01 31.
Artículo en Inglés | MEDLINE | ID: mdl-32005813

RESUMEN

APOBEC3G, a member of the double-domain cytidine deaminase (CD) APOBEC, binds RNA to package into virions and restrict HIV-1 through deamination-dependent or deamination-independent inhibition. Mainly due to lack of a full-length double-domain APOBEC structure, it is unknown how CD1/CD2 domains connect and how dimerization/multimerization is linked to RNA binding and virion packaging for HIV-1 restriction. We report rhesus macaque A3G structures that show different inter-domain packing through a short linker and refolding of CD2. The A3G dimer structure has a hydrophobic dimer-interface matching with that of the previously reported CD1 structure. A3G dimerization generates a surface with intensified positive electrostatic potentials (PEP) for RNA binding and dimer stabilization. Unexpectedly, mutating the PEP surface and the hydrophobic interface of A3G does not abolish virion packaging and HIV-1 restriction. The data support a model in which only one RNA-binding mode is critical for virion packaging and restriction of HIV-1 by A3G.


Asunto(s)
Desaminasa APOBEC-3G/química , Infecciones por VIH/enzimología , VIH-1/fisiología , Desaminasa APOBEC-3G/genética , Desaminasa APOBEC-3G/metabolismo , Animales , Dimerización , Infecciones por VIH/virología , VIH-1/genética , Interacciones Huésped-Patógeno , Humanos , Macaca mulatta , Dominios Proteicos , ARN Viral/genética , ARN Viral/metabolismo , Ensamble de Virus , Replicación Viral
19.
Medicine (Baltimore) ; 99(7): e18777, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32049783

RESUMEN

This study sought to determine the dominant circulating human immunodeficiency virus type 1 (HIV-1) subtype and associated drug resistance mutations in Ghana.This cross-sectional study was conducted with archived samples collected from patients who received care at 2 hospitals in Ghana from 2014 to 2016. Blood samples were earlier processed into plasma and peripheral blood mononuclear cells and stored at -80 °C. Ribonucleic acid (RNA) was extracted from the archived plasma. Two HIV-1 genes; protease and reverse transcriptase, were amplified, sequenced using gene-specific primers and analyzed for subtype and drug resistance mutations using the Stanford HIV Database.Of 16 patient samples successfully sequenced, we identified the predominance of HIV-1 subtype CRF02_AG (11/16, 68%). Subtypes G (2/16, 13%), dual CRF02_AG/G (2/16, 13%), and CRF01_AE (1/16, 6%) were also observed. Major nucleoside reverse transcriptase inhibitor (NRTI) resistance mutations, M184I/V, D67N, T215F, and K70R/E were found. Non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance mutations, K103N, Y181C, V90I, F227L, and V106A were also prevalent. Additionally, and at a lower level, protease inhibitor (PI)-resistance mutations, M46I, I54 V, V82A, L90 M, and I471 V, were also present in the sequences from antiretroviral therapy (ART)-experienced individuals. Two NRTI-associated drug resistance mutations (DRMs) (D67N and T69N) were present in sequences from 1 ART-naive individual.HIV-1 subtype CRF02_AG was most frequently detected in this study thus confirming earlier reports of dominance of this subtype in the West-African sub-region and Ghana in particular. The detection of these drug resistance mutations in individuals on first-line regimen composed of NRTI and NNRTI is an indication of prolonged drug exposure without viral load monitoring. Routine viral load monitoring is necessary for early detection of virologic failure and drug resistance testing will inform appropriate choice of regimens for such patients.


Asunto(s)
Farmacorresistencia Viral , Infecciones por VIH/virología , VIH-1/clasificación , Mutación , Adulto , Fármacos Anti-VIH/uso terapéutico , Estudios Transversales , Evolución Molecular , Femenino , Ghana , Infecciones por VIH/tratamiento farmacológico , Proteasa del VIH/genética , Transcriptasa Inversa del VIH/genética , VIH-1/genética , VIH-1/fisiología , Humanos , Masculino , Persona de Mediana Edad , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Carga Viral
20.
BMC Infect Dis ; 20(1): 178, 2020 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-32102660

RESUMEN

BACKGROUND: The impacts of genetic polymorphisms on drug resistance mutations (DRMs) among various HIV-1 subtypes have long been debated. In this study, we aimed to analyze the natural polymorphisms and acquired DRM profile in HIV-1 CRF01_AE-infected patients in a large first-line antiretroviral therapy (ART) cohort in northeastern China. METHODS: The natural polymorphisms of CRF01_AE were analyzed in 2034 patients from a long-term ART cohort in northeastern China. The polymorphisms in 105 treatment failure (TF) patients were compared with those in 1148 treatment success (TS) patients. The acquired DRM profile of 42 patients who experienced TF with tenofovir/lamivudine/efavirenz (TDF/3TC/EFV) treatment was analyzed by comparing the mutations at TF time point to those at baseline. The Stanford HIVdb algorithm was used to interpret the DRMs. Binomial distribution, McNemar test, Wilcoxon test and CorMut package were used to analyze the mutation rates and co-variation. Deep sequencing was used to analyze the evolutionary dynamics of co-variation. RESULTS: Before ART, there were significantly more natural polymorphisms of 31 sites on reverse transcriptase (RT) in CRF01_AE than subtype B HIV-1 (|Z value| ≥ 3), including five known drug resistance-associated sites (238, 118, 179, 103, and 40). However, only the polymorphism at site 75 was associated with TF (|Z value| ≥ 3). The mutation rate at 14 sites increased significantly at TF time point compared to baseline, with the most common DRMs comprising G190S/C, K65R, K101E/N/Q, M184 V/I, and V179D/I/A/T/E, ranging from 66.7 to 45.2%. Moreover, two unknown mutations (V75 L and L228R) increased by 19.0 and 11.9% respectively, and they were under positive selection (Ka/Ks > 1, log odds ratio [LOD] > 2) and were associated with several other DRMs (cKa/Ks > 1, LOD > 2). Deep sequencing of longitudinal plasma samples showed that L228R occurred simultaneously or followed the appearance of Y181C. CONCLUSION: The high levels of natural polymorphisms in CRF01_AE had little impact on treatment outcomes. The findings regarding potential new CRF01_AE-specific minor DRMs indicate the need for more studies on the drug resistance phenotype of CRF01_AE.


Asunto(s)
Farmacorresistencia Viral/genética , Infecciones por VIH/genética , VIH-1/genética , Antirretrovirales/uso terapéutico , China , Estudios de Cohortes , Genotipo , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , VIH-1/clasificación , VIH-1/aislamiento & purificación , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Oportunidad Relativa , Fenotipo , Filogenia , Polimorfismo Genético , Análisis de Secuencia de ARN , Insuficiencia del Tratamiento
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