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1.
Medicine (Baltimore) ; 100(14): e25236, 2021 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-33832083

RESUMEN

ABSTRACT: Metabolic syndrome (MetS) is a constellation of factors including hypertension, abdominal obesity, dyslipidemia, and insulin resistance that separately and together significantly increase risk for cardiovascular disease (CVD) and diabetes. In sub-Saharan Africa, with a substantial burden of human immunodeficiency virus (HIV) and increasing prevalence of CVD and diabetes, there is a paucity of epidemiological data on demographic, laboratory, and clinical characteristics associated with MetS among people with HIV (people with human [PWH]). Therefore, this study aimed to determine the burden and factors influencing MetS in antiretroviral therapy (ART)-experienced individuals in Zambia.We collected cross-sectional demographic, lifestyle, anthropometric, clinical, and laboratory data in a cohort of ART-experienced (on ART for ≥6 months) adults in 24 urban HIV treatment clinics of Zambia between August, 2016 and May, 2020. MetS was defined as having ≥3 of the following characteristics: low high density lipoprotein cholesterol (HDL-c) (<1.0 mmol/L for men, <1.3 for women), elevated waist circumference (≥94 cm for men, ≥80 cm for women), elevated triglycerides (≥1.7 mmol/L), elevated fasting blood glucose (≥5.6 mmol/L), and elevated blood pressure (BP) (systolic BP ≥130 or diastolic BP ≥85 mm Hg). Virological failure (VF) was defined as HIV viral load ≥1000 copies/mL. The following statistical methods were used: Chi-square test, Wilcoxon rank-sum test, and multivariable logistic regression.Among 1108 participants, the median age (interquartile range [IQR]) was 41 years (34, 49); 666 (60.1%) were females. The prevalence of MetS was 26.3% (95% confidence interval [CI] 23.9-29.1). Age (adjusted odds ratio [OR] 1.07; 95% CI 1.04-1.11), female sex (OR 3.02; 95% CI 1.55-5.91), VF (OR 1.98; 95% CI 1.01-3.87), dolutegravir (DTG)-based regimen (OR 2.10; 95% CI 1.05-4.20), hip-circumference (OR 1.03; 95% CI 1.01-1.05), T-lymphocyte count (OR 2.23; 95% CI 1.44-3.43), high-sensitivity C-reactive protein (hsCRP) (OR 1.14; 95% CI 1.01-1.29), and fasting insulin (OR 1.02; 95% CI 1.01-1.04) were significantly associated with MetS.Metabolic syndrome was highly prevalent among HIV+ adults receiving ART in Zambia and associated with demographic, clinical, anthropometric, and inflammatory characteristics. The association between MetS and dolutegravir requires further investigation, as does elucidation of the impact of MetS on ART outcomes in sub-Saharan African PWH.


Asunto(s)
Infecciones por VIH/epidemiología , Síndrome Metabólico/epidemiología , Adulto , Antirretrovirales/uso terapéutico , Estudios Transversales , Femenino , Infecciones por VIH/tratamiento farmacológico , Humanos , Masculino , Síndrome Metabólico/diagnóstico , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Zambia/epidemiología
2.
Medicine (Baltimore) ; 100(15): e25399, 2021 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-33847636

RESUMEN

ABSTRACT: Obesity is associated with detrimental changes in cardiovascular and metabolic parameters, including blood pressure, dyslipidemia, markers of systemic inflammation, and insulin resistance. In the elderly living with the human immunodeficiency virus (EPLHIV), and being treated with antiretroviral medications, the obesity complications escalate and expose the elderly to the risk of noncommunicable diseases. Given that over 3 million EPLHIV in sub-Sahara Africa, we assessed the prevalence of obesity and its associated factors among EPLHIV in a low-resource setting.This was a cross sectional study of EPLHIV aged 50 years and older, being treated with antiretroviral medications from 2004 to 2018. HIV treatment data collected from multiple treatment sites were analyzed. Baseline characteristics of the participants were described, and multivariable relative risk model was applied to assess the associations between obesity (body mass index [BMI] ≥30 kg/m2) and the prespecified potential risk factors.Of the 134,652 in HIV cohort, 19,566 (14.5%) were EPLHIV: 12,967 (66.3%) were normal weight (18.5 ≤ BMI < 25), 4548 (23.2%) were overweight (25 ≤ BMI < 30), while 2,051 (10.5%) were obese (BMI ≥30). The average age the normal weight (57.1; standard deviation 6.6) and the obese (56.5; standard deviation 5.5) was similar. We observed that being an employed (relative risk [RR] 1.71; 95% confidence interval [CI] 1.48-2.00; P < .001), educated (RR 1.93; 95% CI 1.54-2.41; P < .001), and presence of hypertension (RR 1.78; 95% CI 1.44-2.20; P < .001), increased the risk of obesity. Also, being male (RR 0.38; 95% CI 0.33-0.44; P < .001), stages III/IV of the World Health Organization clinical stages of HIV (RR 0.58; 95% CI 0.50-0.68; P < .001), tenofovir-based regimen (RR 0.84; 95% CI 0.73-0.96, P < .001), and low CD4 count (RR 0.56; 95% CI 0.44-0.71; P < .001) were inversely associated with obesity.This study demonstrates that multiple factors are driving obesity prevalence in EPLHIV. The study provides vital information for policy-makers and HIV program implementers in implementing targeted-interventions to address obesity in EPLHIV. Its findings would assist in the implementation of a one-stop-shop model for the management of HIV and other comorbid medical conditions in EPLHIV.


Asunto(s)
Infecciones por VIH/epidemiología , Sobrepeso/epidemiología , Pobreza , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida/epidemiología , África del Sur del Sahara/epidemiología , Anciano , Antirretrovirales/uso terapéutico , Índice de Masa Corporal , Recuento de Linfocito CD4 , Estudios Transversales , Femenino , Infecciones por VIH/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Obesidad/epidemiología , Prevalencia , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factores Sexuales , Factores Socioeconómicos
3.
Medicine (Baltimore) ; 100(15): e25403, 2021 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-33847637

RESUMEN

ABSTRACT: Brain atrophy has been observed in perinatally HIV-infected patients (PHIV) despite initiation on combined antiretroviral treatment (cART), but neuroimaging studies are limited. We aimed to evaluate cortical thickness (CT) and subcortical gray matter (GM) volumes of PHIV youths with stable immunovirological situation and with a normal daily performance.A prospective cross-sectional study was conducted. A total of 25 PHIV patients on cART and 25 HIV-negative (HIV-) controls matched by age, sex, level of education, and socioeconomic status underwent a magnetic resonance imaging scan. CAT12 toolbox was used to extract CT values from T1w images using parcellations from Desikan-Killiany atlas (DK40). To measure regional brain volumes, native segmented images were parceled in regions of interest according to the Neuromorphometrics Atlas. Neuropsychological assessment and psychopathological symptoms were documented.Fifty participants were included (60% females, median age 20 years [interquartile range, IQR 19-23], 64% Whites). No differences regarding neuropsychological tests or psychopathological symptoms were found between groups (all P > .05). All participants presented an average performance in the Fluid Intelligence (FI) test (PHIV mean: -0.12, HIV- mean: 0.24), When comparing CT, PHIV-infected patients showed thinner cortices compared with their peers in fusiform gyrus (P = .000, P = .009), lateral-orbitofrontal gyrus (P = .006, P = .0024), and right parsobitalis gyrus (P = .047). Regarding subcortical GM volumes, PHIV patients showed lower right amygdala (P = .014) and left putamen (P = .016) volumes when compared with HIV- controls. Within the PHIV group, higher CD4 count was associated with higher volumes in right putamen (B = 0.00000038, P = .045). Moreover, increased age at cART initiation and lower nadir CD4 count was associated with larger volumes in left accumbens (B = 0.0000046, P = .033; B = -0.00000008, P = .045, respectively).PHIV patients showed thinner cortices of areas in temporal, orbito-frontal and occipital lobes and lower volumes of subcortical GM volumes when compared with the HIV- control group, suggesting cortical and subcortical brain alterations in otherwise neuroasymptomatic patients. Nevertheless, larger and longitudinal studies are required to determine the impact of HIV on brain structure in PHIV patients and to further identify risk and protective factors that could be implicated.


Asunto(s)
Sustancia Gris/patología , Infecciones por VIH/fisiopatología , Infecciones por VIH/transmisión , Transmisión Vertical de Enfermedad Infecciosa/estadística & datos numéricos , Factores de Edad , Antirretrovirales/uso terapéutico , Atrofia , Ganglios Basales/diagnóstico por imagen , Ganglios Basales/patología , Recuento de Linfocito CD4 , Estudios Transversales , Femenino , Sustancia Gris/diagnóstico por imagen , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Humanos , Imagen por Resonancia Magnética , Masculino , Estudios Prospectivos , Factores Socioeconómicos , Adulto Joven
4.
Nat Commun ; 12(1): 1474, 2021 03 05.
Artículo en Inglés | MEDLINE | ID: mdl-33674572

RESUMEN

The establishment of a long-lived viral reservoir is the key obstacle for achieving an HIV-1 cure. However, the anatomic, virologic, and immunologic features of the viral reservoir in tissues during antiretroviral therapy (ART) remain poorly understood. Here we present a comprehensive necroscopic analysis of the SIV/SHIV viral reservoir in multiple lymphoid and non-lymphoid tissues from SIV/SHIV-infected rhesus macaques suppressed with ART for one year. Viral DNA is observed broadly in multiple tissues and is comparable in animals that had initiated ART at week 1 or week 52 of infection. In contrast, viral RNA is restricted primarily to lymph nodes. Ongoing viral RNA transcription is not the result of unsuppressed viral replication, as single-genome amplification and subsequent phylogenetic analysis do not show evidence of viral evolution. Gag-specific CD8+ T cell responses are predominantly observed in secondary lymphoid organs in animals chronically infected prior to ART and these responses are dominated by CD69+ populations. Overall, we observe that the viral reservoir in rhesus macaques is widely distributed across multiple tissue sites and that lymphoid tissues act as a site of persistent viral RNA transcription under conditions of long-term ART suppression.


Asunto(s)
Antirretrovirales/uso terapéutico , Infecciones por VIH/virología , Ganglios Linfáticos/virología , ARN Viral/genética , Síndrome de Inmunodeficiencia Adquirida del Simio/virología , Virus de la Inmunodeficiencia de los Simios/inmunología , Animales , Linfocitos T CD8-positivos , ADN Viral , Modelos Animales de Enfermedad , Femenino , Infecciones por VIH/tratamiento farmacológico , VIH-1/genética , Ganglios Linfáticos/inmunología , Tejido Linfoide/virología , Macaca mulatta , Filogenia , Síndrome de Inmunodeficiencia Adquirida del Simio/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida del Simio/inmunología , Virus de la Inmunodeficiencia de los Simios/efectos de los fármacos , Virus de la Inmunodeficiencia de los Simios/genética , Carga Viral , Replicación Viral
5.
MMWR Morb Mortal Wkly Rep ; 70(12): 421-426, 2021 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-33764965

RESUMEN

In 2018, an estimated 1.8 million persons living in Nigeria had HIV infection (1.3% of the total population), including 1.1 million (64%) who were receiving antiretroviral therapy (ART) (1). Effective ART reduces morbidity and mortality rates among persons with HIV infection and prevents HIV transmission once viral load is suppressed to undetectable levels (2,3). In April 2019, through the U.S. President's Emergency Plan for AIDS Relief (PEPFAR),* CDC launched an 18-month ART Surge program in nine Nigerian states to rapidly increase the number of persons with HIV infection receiving ART. CDC analyzed programmatic data gathered during March 31, 2019-September 30, 2020, to describe the ART Surge program's progress on case finding, ART initiation, patient retention, and ART Surge program growth. Overall, the weekly number of newly identified persons with HIV infection who initiated ART increased approximately eightfold, from 587 (week ending May 4, 2019) to 5,329 (week ending September 26, 2020). The ART Surge program resulted in 208,202 more HIV-infected persons receiving PEPFAR-supported ART despite the COVID-19 pandemic (97,387 more persons during March 31, 2019-March 31, 2020 and an additional 110,815 persons during April 2020-September 2020). Comprehensive, data-guided, locally adapted interventions and the use of incident command structures can help increase the number of persons with HIV infection who receive ART, reducing HIV-related morbidity and mortality as well as decreasing HIV transmission.


Asunto(s)
Antirretrovirales/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Cooperación Internacional , Desarrollo de Programa , Centers for Disease Control and Prevention, U.S. , Infecciones por VIH/epidemiología , Humanos , Nigeria/epidemiología , Evaluación de Programas y Proyectos de Salud , Estados Unidos/epidemiología
8.
Am Fam Physician ; 103(7): 407-416, 2021 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-33788514

RESUMEN

The HIV epidemic is an important public health priority. Transmissions continue to occur despite effective therapies that make HIV preventable and treatable. Approximately one-half of people with HIV are not receiving suppressive antiretroviral therapy (ART). Starting ART early, followed by continuous lifetime treatment, most effectively achieves durable virologic suppression and restoration of immune function that can improve clinical outcomes and prevent transmission to partners who are seronegative. National treatment guidelines include ART options that can be offered immediately after diagnosis, even before the results of baseline HIV drug-resistance testing are available. Initial ART selection should be guided by co-occurring conditions, including viral hepatitis, medications, and other factors such as pregnancy. Identifying and addressing psychosocial barriers to care is a key element of ensuring long-term adherence to treatment. The initial physical examination typically reveals no clinical manifestations of HIV in the absence of advanced disease. A comprehensive laboratory evaluation, including HIV viral load and CD4 lymphocyte monitoring, is necessary to guide decision-making for treatment, opportunistic infection prophylaxis, and vaccinations. The initial management of people with HIV presents a unique opportunity for family physicians to improve patients' long-term health care and reduce HIV transmissions.


Asunto(s)
Antirretrovirales/uso terapéutico , Terapia Antirretroviral Altamente Activa/métodos , Infecciones por VIH/terapia , Guías de Práctica Clínica como Asunto , Infecciones Oportunistas Relacionadas con el SIDA/prevención & control , Neoplasias del Ano/diagnóstico , Recuento de Linfocito CD4 , Manejo de la Enfermedad , Detección Precoz del Cáncer , Femenino , Infecciones por VIH/diagnóstico , Infecciones por VIH/transmisión , Vacunas contra la Hepatitis A/uso terapéutico , Vacunas contra Hepatitis B/uso terapéutico , Hepatitis Viral Humana/diagnóstico , Hepatitis Viral Humana/prevención & control , Herpes Zóster/prevención & control , Vacuna contra el Herpes Zóster/uso terapéutico , Humanos , Vacunas contra la Influenza/uso terapéutico , Gripe Humana/prevención & control , Masculino , Tamizaje Masivo , Cumplimiento de la Medicación , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/prevención & control , Vacunas contra Papillomavirus/uso terapéutico , Infecciones por Pneumocystis/prevención & control , Enfermedades de Transmisión Sexual/diagnóstico , Tuberculosis/diagnóstico , Neoplasias del Cuello Uterino/diagnóstico , Carga Viral
10.
BMC Infect Dis ; 21(1): 214, 2021 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-33632139

RESUMEN

BACKGROUND: HIV-1C has been shown to have a greater risk of virological failure and reduced susceptibility towards boosted protease inhibitors (bPIs), a component of second-line combination antiretroviral therapy (cART) in South Africa. This study entailed an evaluation of HIV-1 drug resistance-associated mutations (RAMs) among minor viral populations through high-throughput sequencing genotypic resistance testing (HTS-GRT) in patients on the South African national second-line cART regimen receiving bPIs. METHODS: During 2017 and 2018, 67 patient samples were sequenced using high-throughput sequencing (HTS), of which 56 samples were included in the final analysis because the patient's treatment regimen was available at the time of sampling. All patients were receiving bPIs as part of their cART. Viral RNA was extracted, and complete pol genes were amplified and sequenced using Illumina HiSeq2500, followed by bioinformatics analysis to quantify the RAMs according to the Stanford HIV Drug Resistance Database. RESULTS: Statistically significantly higher PI RAMs were observed in minor viral quasispecies (25%; 14/56) compared to non-nucleoside reverse transcriptase inhibitors (9%; 5/56; p = 0.042) and integrase inhibitor RAM (4%; 2/56; p = 0.002). The majority of the drug resistance mutations in the minor viral quasispecies were observed in the V82A mutation (n = 13) in protease and K65R (n = 5), K103N (n = 7) and M184V (n = 5) in reverse transcriptase. CONCLUSIONS: HTS-GRT improved the identification of PI and reverse transcriptase inhibitor (RTI) RAMs in second-line cART patients from South Africa compared to the conventional GRT with ≥20% used in Sanger-based sequencing. Several RTI RAMs, such as K65R, M184V or K103N and PI RAM V82A, were identified in < 20% of the population. Deep sequencing could be of greater value in detecting acquired resistance mutations early.


Asunto(s)
Farmacorresistencia Viral/genética , Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH/uso terapéutico , VIH-1/efectos de los fármacos , Cuasiespecies/efectos de los fármacos , Antirretrovirales/uso terapéutico , Farmacorresistencia Viral/efectos de los fármacos , Genes pol/genética , Genotipo , Infecciones por VIH/virología , VIH-1/genética , VIH-1/aislamiento & purificación , Humanos , Mutación , Cuasiespecies/genética , ARN Viral/genética , Sudáfrica/epidemiología
11.
BMC Infect Dis ; 21(1): 216, 2021 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-33632144

RESUMEN

BACKGROUND: HIV-associated chronic lung disease (CLD) is common among children living with HIV (CLWH) in sub-Saharan Africa, including those on antiretroviral therapy (ART). However, the pathogenesis of CLD and its possible association with microbial determinants remain poorly understood. We investigated the prevalence, and antibiotic susceptibility of Streptococcus pneumoniae (SP), Staphylococcus aureus (SA), Haemophilus influenzae (HI), and Moraxella catarrhalis (MC) among CLWH (established on ART) who had CLD (CLD+), or not (CLD-) in Zimbabwe and Malawi. METHODS: Nasopharyngeal swabs (NP) and sputa were collected from CLD+ CLWH (defined as forced-expiratory volume per second z-score < - 1 without reversibility post-bronchodilation with salbutamol), at enrolment as part of a randomised, placebo-controlled trial of azithromycin (BREATHE trial - NCT02426112 ), and from age- and sex-matched CLD- CLWH. Samples were cultured, and antibiotic susceptibility testing was conducted using disk diffusion. Risk factors for bacterial carriage were identified using questionnaires and analysed using multivariate logistic regression. RESULTS: A total of 410 participants (336 CLD+, 74 CLD-) were enrolled (median age, 15 years [IQR = 13-18]). SP and MC carriage in NP were higher in CLD+ than in CLD- children: 46% (154/336) vs. 26% (19/74), p = 0.008; and 14% (49/336) vs. 3% (2/74), p = 0.012, respectively. SP isolates from the NP of CLD+ children were more likely to be non-susceptible to penicillin than those from CLD- children (36% [53/144] vs 11% [2/18], p = 0.036). Methicillin-resistant SA was uncommon [4% (7/195)]. In multivariate analysis, key factors associated with NP bacterial carriage included having CLD (SP: adjusted odds ratio (aOR) 2 [95% CI 1.1-3.9]), younger age (SP: aOR 3.2 [1.8-5.8]), viral load suppression (SP: aOR 0.6 [0.4-1.0], SA: 0.5 [0.3-0.9]), stunting (SP: aOR 1.6 [1.1-2.6]) and male sex (SA: aOR 1.7 [1.0-2.9]). Sputum bacterial carriage was similar in both groups (50%) and was associated with Zimbabwean site (SP: aOR 3.1 [1.4-7.3], SA: 2.1 [1.1-4.2]), being on ART for a longer period (SP: aOR 0.3 [0.1-0.8]), and hot compared to rainy season (SP: aOR 2.3 [1.2-4.4]). CONCLUSIONS: CLD+ CLWH were more likely to be colonised by MC and SP, including penicillin-non-susceptible SP strains, than CLD- CLWH. The role of these bacteria in CLD pathogenesis, including the risk of acute exacerbations, should be further studied.


Asunto(s)
Antibacterianos/farmacología , Farmacorresistencia Bacteriana , Infecciones por VIH/microbiología , Enfermedades Pulmonares/microbiología , Adolescente , Antirretrovirales/uso terapéutico , Bacterias/clasificación , Bacterias/efectos de los fármacos , Bacterias/aislamiento & purificación , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Humanos , Enfermedades Pulmonares/tratamiento farmacológico , Enfermedades Pulmonares/epidemiología , Malaui/epidemiología , Masculino , Microbiota , Nasofaringe/microbiología , Prevalencia , Factores de Riesgo , Zimbabwe/epidemiología
12.
BMC Infect Dis ; 21(1): 218, 2021 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-33632173

RESUMEN

BACKGROUND: People living with HIV (PLHIV) who reside in high tuberculosis burden settings remain at risk for tuberculosis disease despite treatment with anti-retroviral therapy and isoniazid preventive therapy (IPT). The performance of the World Health Organization (WHO) symptom screen for tuberculosis in PLHIV receiving anti-retroviral therapy is sub-optimal and alternative screening strategies are needed. METHODS: We enrolled HIV-positive adults into a prospective study in western Kenya. Individuals who were IPT-naïve or had completed IPT > 6 months prior to enrollment were eligible. We evaluated tuberculosis prevalence overall and by IPT status. We assessed the accuracy of the WHO symptom screen, GeneXpert MTB/RIF (Xpert), and candidate biomarkers including C-reactive protein (CRP), hemoglobin, erythrocyte sedimentation rate (ESR), and monocyte-to-lymphocyte ratio for identifying pulmonary tuberculosis. Some participants were evaluated at 6 months post-enrollment for tuberculosis. RESULTS: The study included 383 PLHIV, of whom > 99% were on antiretrovirals and 88% had received IPT, completed a median of 1.1 years (IQR 0.8-1.55) prior to enrollment. The prevalence of pulmonary tuberculosis at enrollment was 1.3% (n = 5, 95% CI 0.4-3.0%): 4.3% (0.5-14.5%) among IPT-naïve and 0.9% (0.2-2.6%) among IPT-treated participants. The sensitivity of the WHO symptom screen was 0% (0-52%) and specificity 87% (83-90%). Xpert and candidate biomarkers had poor to moderate sensitivity; the most accurate biomarker was CRP ≥ 3.3 mg/L (sensitivity 80% (28-100) and specificity 72% (67-77)). Six months after enrollment, the incidence rate of pulmonary tuberculosis following IPT completion was 0.84 per 100 person-years (95% CI, 0.31-2.23). CONCLUSIONS: In Kenyan PLHIV treated with IPT, tuberculosis prevalence was low at a median of 1.4 years after IPT completion. WHO symptoms screening, Xpert, and candidate biomarkers were insensitive for identifying pulmonary tuberculosis in antiretroviral-treated PLHIV.


Asunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/epidemiología , Antirretrovirales/uso terapéutico , Tamizaje Masivo/estadística & datos numéricos , Tuberculosis Pulmonar/epidemiología , Infecciones Oportunistas Relacionadas con el SIDA/diagnóstico , Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Infecciones Oportunistas Relacionadas con el SIDA/prevención & control , Adulto , Antituberculosos/uso terapéutico , Femenino , Humanos , Isoniazida/uso terapéutico , Kenia/epidemiología , Masculino , Tamizaje Masivo/métodos , Persona de Mediana Edad , Prevalencia , Estudios Prospectivos , Tuberculosis Pulmonar/diagnóstico , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis Pulmonar/prevención & control
13.
Int J Nanomedicine ; 16: 1189-1206, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33623382

RESUMEN

Introduction: Human immunodeficiency virus (HIV) remains a persistent global challenge, impacting 38 million people worldwide. Antiretrovirals (ARVs) including tenofovir (TFV), raltegravir (RAL), and dapivirine (DAP) have been developed to prevent and treat HIV-1 via different mechanisms of action. In parallel, a promising biological candidate, griffithsin (GRFT), has demonstrated outstanding preclinical safety and potency against HIV-1. While ARV co-administration has been shown to enhance virus inhibition, synergistic interactions between ARVs and the oxidation-resistant variant of GRFT (Q-GRFT) have not yet been explored. Here, we co-administered Q-GRFT with TFV, RAL, and DAP, in free and encapsulated forms, to identify unique protein-drug synergies. Methods: Nanoparticles (NPs) were synthesized using a single or double-emulsion technique and release from each formulation was assessed in simulated vaginal fluid. Next, each ARV, in free and encapsulated forms, was co-administered with Q-GRFT or Q-GRFT NPs to evaluate the impact of co-administration in HIV-1 pseudovirus assays, and the combination indices were calculated to identify synergistic interactions. Using the most synergistic formulations, we investigated the effect of agent incorporation in NP-fiber composites on release properties. Finally, NP safety was assessed in vitro using MTT assay. Results: All active agents were encapsulated in NPs with desirable encapsulation efficiency (15-100%), providing ~20% release over 2 weeks. The co-administration of free Q-GRFT with each free ARV resulted in strong synergistic interactions, relative to each agent alone. Similarly, Q-GRFT NP and ARV NP co-administration resulted in synergy across all formulations, with the most potent interactions between encapsulated Q-GRFT and DAP. Furthermore, the incorporation of Q-GRFT and DAP in NP-fiber composites resulted in burst release of DAP and Q-GRFT with a second phase of Q-GRFT release. Finally, all NP formulations exhibited safety in vitro. Conclusions: This work suggests that Q-GRFT and ARV co-administration in free or encapsulated forms may improve efficacy in achieving prophylaxis.


Asunto(s)
Antirretrovirales/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Lectinas/uso terapéutico , Fármacos Anti-VIH/farmacología , Antirretrovirales/farmacología , Muerte Celular/efectos de los fármacos , Línea Celular , Composición de Medicamentos , Liberación de Fármacos , Sinergismo Farmacológico , Femenino , VIH-1/efectos de los fármacos , Humanos , Concentración 50 Inhibidora , Lectinas/farmacología , Nanopartículas/química , Nanopartículas/ultraestructura , Tamaño de la Partícula , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Pirimidinas/farmacología , Raltegravir Potásico/farmacología , Tenofovir/farmacología
14.
BMC Infect Dis ; 21(1): 160, 2021 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-33557775

RESUMEN

BACKGROUND: The widespread use of antiretroviral therapy (ART) has resulted in the development of transmitted drug resistance (TDR), which reduces ART efficacy. We explored TDR prevalence and its associated risk factors in newly diagnosed individuals in Guangxi. METHODS: We enrolled 1324 participants who were newly diagnosed with HIV-1 and had not received ART at voluntary counselling and testing centres (VCT) in Guangxi, China, who had not received ART. Phylogenetic relationship, transmission cluster, and genotypic drug resistance analyses were performed using HIV-1 pol sequences. We analysed the association of demographic and virological factors with TDR. RESULTS: In total, 1151 sequences were sequenced successfully, of which 83 (7.21%) showed evidence of TDR. Multivariate logistic regression analysis revealed that there was significant difference between the prevalence of TDR and unmarried status (adjusted odds ratio (aOR) = 2.41, 95% CI: 1.23-4.71), and CRF08_BC subtype (aOR = 2.03, 95% CI: 1.13-3.64). Most cases of TDR were related to resistance to non-nucleoside reverse transcriptase inhibitors (4.87%) and V179E was the most common mutation detected. We identified a total of 119 HIV transmission clusters (n = 585, 50.8%), of which 18 (15.1%) clusters showed evidence of TDR (36, 41.86%). Three clusters were identified that included drug-resistant individuals having a transmission relationship with each other. The following parameters were associated with TDR transmission risk: Unmarried status, educational level of junior high school or below, and CRF08_BC subtype may be a risk of the transmission of TDR. CONCLUSIONS: Our findings indicated that moderate TDR prevalence and highlighted the importance of continuous TDR monitoring and designing of strategies for TDR mitigation.


Asunto(s)
Farmacorresistencia Viral/genética , Infecciones por VIH/diagnóstico , VIH-1/genética , Adulto , Antirretrovirales/uso terapéutico , China , Femenino , Genotipo , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/transmisión , VIH-1/clasificación , VIH-1/aislamiento & purificación , Humanos , Modelos Logísticos , Masculino , Filogenia , Prevalencia , Factores de Riesgo , Productos del Gen pol del Virus de la Inmunodeficiencia Humana/genética
15.
Artículo en Inglés | MEDLINE | ID: mdl-33557412

RESUMEN

This study aimed to examine the effectiveness of Human Immunodeficiency Virus (HIV)-assisted smartphone applications in the treatment of HIV/AIDS patients in Vietnam. A cross-sectional study was performed in two urban outpatient clinics in Hanoi from May to December 2019. A simple random sampling method and a structured questionnaire were used to recruit 495 eligible participants and to collect data. Multivariable modified Poisson regression and multivariable linear regression models were employed to investigate the factors associated with the willingness to pay (WTP) and amount of money patients were willing to pay. Approximately 82.8% of respondents were willing to pay for the hypothetical applications, with the mean amount the participants were willing to pay of Vietnam Dong (VND) 72,100/month. Marital status (separate/divorced/widow: Odds ratio (OR) = 1.28, 95% confidence interval (CI) = (1.09; 1.50) and having spouse/partner: OR = 1.18, 95% CI = (1.03; 1.36)) and using health services (OR = 1.03, 95% CI = (1.01; 1.04)) were positively associated with nominating they would be WTP for the app, whereas the duration of antiretroviral treatment (ART) (OR = 0.98, 95% CI = (0.96; 0.99)) had a negative association. The frequency of using health services (ß = 0.04, 95% CI = (-0.07; -0.01)) was negatively associated with the amount of WTP. High levels of WTP revealed the feasibility of implementing smartphone-based apps for HIV treatment. This study implied the necessity to consider a co-payment system to reach populations who were in need but where such applications may be unaffordable in lieu of other treatment-associated expenses. Developers also need to pay attention to privacy features to attract single people living with HIV/AIDS and additional measures to initiate people with a long duration on ART into using the applications.


Asunto(s)
Infecciones por VIH , Teléfono Inteligente , Antirretrovirales/uso terapéutico , Estudios Transversales , Infecciones por VIH/tratamiento farmacológico , Humanos , Vietnam
16.
Am J Epidemiol ; 190(2): 251-264, 2021 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-33524120

RESUMEN

Mortality assessment in cohorts with high numbers of persons lost to follow-up (LTFU) is challenging in settings with limited civil registration systems. We aimed to assess mortality in a clinical cohort (the Kilombero and Ulanga Antiretroviral Cohort (KIULARCO)) of human immunodeficiency virus (HIV)-infected persons in rural Tanzania, accounting for unseen deaths among participants LTFU. We included adults enrolled in 2005-2015 and traced a nonrandom sample of those LTFU. We estimated mortality using Kaplan-Meier methods 1) with routinely captured data (method A), 2) crudely incorporating tracing data (method B), 3) weighting using tracing data to crudely correct for unobserved deaths among participants LTFU (method C), and 4) weighting using tracing data accounting for participant characteristics (method D). We investigated associated factors using proportional hazards models. Among 7,460 adults, 646 (9%) died, 883 (12%) transferred to other clinics, and 2,911 (39%) were LTFU. Of 2,010 (69%) traced participants, 325 (16%) were found: 131 (40%) had died and 130 (40%) had transferred. Five-year mortality estimates derived using the 4 methods were 13.1% (A), 16.2% (B), 36.8% (C), and 35.1% (D), respectively. Higher mortality was associated with male sex, referral as a hospital inpatient, living close to the index clinic, lower body mass index, more advanced World Health Organization HIV clinical stage, lower CD4 cell count, and less time since initiation of antiretroviral therapy. Adjusting for unseen deaths among participants LTFU approximately doubled the 5-year mortality estimates. Our approach is applicable to other cohort studies adopting targeted tracing.


Asunto(s)
Infecciones por VIH/mortalidad , Perdida de Seguimiento , Población Rural/estadística & datos numéricos , Adolescente , Adulto , Antirretrovirales/uso terapéutico , Índice de Masa Corporal , Recuento de Linfocito CD4 , Femenino , Infecciones por VIH/tratamiento farmacológico , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Derivación y Consulta , Índice de Severidad de la Enfermedad , Factores Sexuales , Factores Socioeconómicos , Tanzanía/epidemiología , Adulto Joven
17.
Clin Pharmacol Ther ; 109(4): 829-840, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33410134

RESUMEN

Modern viral kinetic modeling and its application to therapeutics is a field that attracted the attention of the medical, pharmaceutical, and modeling communities during the early days of the AIDS epidemic. Its successes led to applications of modeling methods not only to HIV but a plethora of other viruses, such as hepatitis C virus (HCV), hepatitis B virus and cytomegalovirus, which along with HIV cause chronic diseases, and viruses such as influenza, respiratory syncytial virus, West Nile virus, Zika virus, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which generally cause acute infections. Here we first review the historical development of mathematical models to understand HIV and HCV infections and the effects of treatment by fitting the models to clinical data. We then focus on recent efforts and contributions of applying these models towards understanding SARS-CoV-2 infection and highlight outstanding questions where modeling can provide crucial insights and help to optimize nonpharmaceutical and pharmaceutical interventions of the coronavirus disease 2019 (COVID-19) pandemic. The review is written from our personal perspective emphasizing the power of simple target cell limited models that provided important insights and then their evolution into more complex models that captured more of the virology and immunology. To quote Albert Einstein, "Everything should be made as simple as possible, but not simpler," and this idea underlies the modeling we describe below.


Asunto(s)
/epidemiología , Modelos Teóricos , Antirretrovirales/uso terapéutico , /prevención & control , Enfermedades Transmisibles/epidemiología , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Infecciones por VIH/inmunología , Hepatitis C/epidemiología , Hepatitis C/inmunología , Humanos , Pandemias , Carga Viral
18.
AIDS ; 35(4): 555-565, 2021 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-33394679

RESUMEN

OBJECTIVE: To assess plasma and vaginal inflammation in three antenatal groups (HIV-uninfected women, HIV-infected women entering care on preconceptional ART, and HIV-infected women not on preconceptional ART) and whether these measures are associated with spontaneous preterm birth (sPTB). DESIGN: Case--control study nested within a pregnancy cohort in Lusaka, Zambia. METHODS: We analyzed 11 pro-inflammatory and two anti-inflammatory markers in 207 women with paired plasma and vaginal specimens collected between 16 and 20 gestational weeks. Among 51 HIV-infected women, we repeated the assays in 24-34-week samples. We used confirmatory factor analysis to create inflammation scores and compared them among the three groups. RESULTS: At baseline, HIV-infected women not on ART had higher vaginal pro-inflammatory scores than HIV-uninfected women [mean 0.37 (95% CI -0.06 to 0.80) vs. -0.02 (-0.32 to 0.27), P = 0.02]. In repeat testing, women not on preconceptional ART had an increase in vaginal inflammation between the baseline and 24-34-week visits compared with those continuing preconceptional ART [mean 0.62 (95% CI -0.80 to 4.20) vs. -0.07 (-2.78 to 2.11), P = 0.04]. In multivariate analyses, baseline vaginal inflammation predicted sPTB (aOR 1.5; 95% CI 1.0-2.3; P = 0.02). Plasma inflammation did not differ by HIV or ART exposure and was not associated with sPTB. CONCLUSION: Women not receiving ART at entry into pregnancy care had more vaginal inflammation than women entering on treatment. They also experienced an increase in vaginal inflammation between the two sampling timepoints, possibly as a consequence of ART initiation. Vaginal (but not systemic) inflammation was associated with sPTB and offers a potential mechanistic insight into this important adverse birth outcome.


Asunto(s)
Infecciones por VIH , Complicaciones Infecciosas del Embarazo , Nacimiento Prematuro , Antirretrovirales/uso terapéutico , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Humanos , Recién Nacido , Inflamación/tratamiento farmacológico , Embarazo , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Nacimiento Prematuro/epidemiología , Zambia/epidemiología
19.
PLoS Pathog ; 17(1): e1009214, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33465157

RESUMEN

The precise role of CD4 T cell turnover in maintaining HIV persistence during antiretroviral therapy (ART) has not yet been well characterized. In resting CD4 T cell subpopulations from 24 HIV-infected ART-suppressed and 6 HIV-uninfected individuals, we directly measured cellular turnover by heavy water labeling, HIV reservoir size by integrated HIV-DNA (intDNA) and cell-associated HIV-RNA (caRNA), and HIV reservoir clonality by proviral integration site sequencing. Compared to HIV-negatives, ART-suppressed individuals had similar fractional replacement rates in all subpopulations, but lower absolute proliferation rates of all subpopulations other than effector memory (TEM) cells, and lower plasma IL-7 levels (p = 0.0004). Median CD4 T cell half-lives decreased with cell differentiation from naïve to TEM cells (3 years to 3 months, p<0.001). TEM had the fastest replacement rates, were most highly enriched for intDNA and caRNA, and contained the most clonal proviral expansion. Clonal proviruses detected in less mature subpopulations were more expanded in TEM, suggesting that they were maintained through cell differentiation. Earlier ART initiation was associated with lower levels of intDNA, caRNA and fractional replacement rates. In conclusion, circulating integrated HIV proviruses appear to be maintained both by slow turnover of immature CD4 subpopulations, and by clonal expansion as well as cell differentiation into effector cells with faster replacement rates.


Asunto(s)
Antirretrovirales/uso terapéutico , Linfocitos T CD4-Positivos/patología , Diferenciación Celular , Infecciones por VIH/virología , VIH-1/inmunología , Carga Viral , Replicación Viral , Adulto , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/virología , Estudios de Casos y Controles , ADN Viral/análisis , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , Infecciones por VIH/patología , VIH-1/efectos de los fármacos , VIH-1/genética , Humanos , Masculino , Persona de Mediana Edad
20.
BMC Infect Dis ; 21(1): 129, 2021 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-33516173

RESUMEN

BACKGROUND: HIV infection has become a chronic disease and well-being of people living with HIV (PLHIV) is now of particular concern. The objectives of this paper were to describe self-rated health among PLHIV, on ART and on ART virally suppressed and to analyse its determinants. METHODS: Data were obtained from a second-generation surveillance system based on a cross-sectional one-day survey in public hospitals. Epidemiological and clinical data were collected among HIV-infected inpatients and outpatients receiving HIV-related care the day of the survey in 86 hospitals in 2019. Self-rated health was measured using a question included in the National Health Survey: "In the last 12 months, how would you rate your health status?" an ordinal variable with five categories (very good, good, moderate, bad and very bad). For the analysis, these responses were dichotomized into two categories: 1 = very good/good and 0 = moderate, bad or very bad health status. Factors associated with very good/good self-rated health were estimated using logistic regression. RESULTS: Of 800 PLHIV, 67.5% perceived their health as very good/good, 68.4% among PLHIV on ART and 71.7% of those virally suppressed. Having university education (adjusted odds ratio (aOR):2.1), being unemployed (aOR:0.3) or retired (aOR:0.2), ever being diagnosed of AIDS (aOR:0.6), comorbidities (aOR:0.3), less than 2 year since HIV diagnosis (aOR:0.3) and not receiving ART (aOR:0.3) were associated with good self-rated health. Moreover, among PLHIV on ART, viral load less than 200 copies (aOR:3.2) were related to better perceived health. Bad adherence was inversely associated with good self-rated health among PLHIV on ART (aOR:0.5) and of those virally suppressed (aOR:0.4). CONCLUSIONS: Nearly seven in 10 PLHIV in Spain considered their health status as very good/good, being higher among virally suppressed PLHIV. Both demographic and clinical determinants affect quality of life.


Asunto(s)
Autoevaluación Diagnóstica , Infecciones por VIH/epidemiología , Estado de Salud , Adulto , Antirretrovirales/uso terapéutico , Estudios Transversales , Femenino , Infecciones por VIH/diagnóstico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/psicología , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , España/epidemiología , Encuestas y Cuestionarios , Carga Viral , Adulto Joven
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