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1.
Pan Afr Med J ; 42: 136, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36060855

RESUMO

Introduction: the introduction of the point-of-care in HIV-1 viral load quantification appears to be a complementary strategy to the existing conventional system of the acceleration plan for the achievement of the three 90s in Senegal. The objective of this study was to evaluate the performance of the Xpert® HIV-1 viral load in the context of circulation of non-B, non-C subtypes. Methods: two hundred samples, were tested on Xpert® HIV-1 Viral Load using 1 ml of plasma in comparison to 600 µl on Abbott Real-time HIV-1 assay. The difference between viral load values was considered significant for Dlog <0.5 log copies/ml. Results: a good correlation (r=0.985) was noted and confirmed using passing-bablok regression (slope 1.048; 95% CI: 1.036 to 1.069) for 188 samples with samples. A mean difference of 0.0075 log10 copies/ml for a 95% confidence interval (CI) of 0.002 log10 copies/ml to 0.013 log10 copies/ml was obtained. Sensitivity and specificity were respectively 93.6% and 93.5% at the threshold of 1.6 log10 copies/ml and 100% and 99% at the threshold of 3.0 log10 copies/ml. Conclusion: these results show that Xpert® HIV-1 Viral Load has excellent performance. In Senegal, and can be used for HIV viral load monitoring.


Assuntos
Infecções por HIV , HIV-1 , Infecções por HIV/diagnóstico , HIV-1/genética , Humanos , RNA Viral , Senegal , Carga Viral
2.
Antivir Ther ; 27(4): 13596535221119932, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36062614

RESUMO

We report a case of an infant with HIV receiving raltegravir granules for oral suspension and rifampicin-based TB prophylaxis. Raltegravir trough levels remained subtherapeutic and viral load increased during concurrent rifampicin therapy despite using double-dosed raltegravir. Even after rifampicin therapy, a higher dose was needed. This highlights the importance of therapeutic drug monitoring and dose adjustments of raltegravir in infants with rifampicin as comedication.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Lactente , Raltegravir Potássico/uso terapêutico , Rifampina/uso terapêutico , Carga Viral
3.
PLoS One ; 17(9): e0273639, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36048781

RESUMO

BACKGROUND: Malawi spearheaded the development and implementation of Option B+ for prevention of mother-to-child transmission of HIV (PMTCT), providing life-long ART for all HIV-positive pregnant and breastfeeding women. We used data from the 2015-2016 Malawi Population-based HIV Impact Assessment (MPHIA) to estimate progress toward 90-90-90 targets (90% of those with HIV know their HIV-positive status; of these, 90% are receiving ART; and of these, 90% have viral load suppression [VLS]) for HIV-positive women reporting a live birth in the previous 3 years. METHODS: MPHIA was a nationally representative household survey; consenting eligible women aged 15-64 years were interviewed on pregnancies and outcomes, including HIV status during their most recent pregnancy, PMTCT uptake, and early infant diagnosis (EID) testing. Descriptive analyses were weighted to account for the complex survey design. Viral load (VL) results were categorized by VLS (<1,000 copies/mL) and undetectable VL (target not detected/below the limit of detection). RESULTS: Of the 3,153 women included in our analysis, 371 (10.1%, 95% confidence interval [CI]: 8.8%-11.3%) tested HIV positive in the survey. Most HIV-positive women (84.2%, 95% CI: 79.9%-88.6%) reported knowing their HIV-positive status; of these, 94.9% (95% CI: 91.7%-98.2%) were receiving ART; and of these, 91.2% (95% CI: 87.4%-95.0%) had VLS. Among the 371 HIV-positive women, 76.0% (95% CI: 70.4%-81.7%) had VLS and 66.5% (95% CI: 59.8%-73.2%) had undetectable VL. Among 262 HIV-exposed children, 50.8% (95% CI: 42.8%-58.8%) received EID testing within 2 months of birth, whereas 17.9% (95% CI: 11.9%-23.8%) did not receive EID testing. Of 190 HIV-exposed children with a reported HIV test result, 2.1% (95% CI: 0.0%-4.6%) had positive results. CONCLUSIONS: MPHIA data demonstrate high PMTCT uptake at a population level. However, our results identify some gaps in VLS in postpartum women and EID testing.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Complicações Infecciosas na Gravidez , Fármacos Anti-HIV/uso terapêutico , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Lactente , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Malaui/epidemiologia , Período Pós-Parto , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Carga Viral
4.
J Int AIDS Soc ; 25(9): e25990, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36052462

RESUMO

INTRODUCTION: Optimal antiretroviral therapy (ART) adherence is crucial for improved patient outcomes; however, ART adherence among adolescents living with HIV (ALHIV) is low. Also, the performance of various adherence measures among ALHIV is under contention. We monitored ART adherence and compared Self-report (SR) and Wisepill electronic monitoring (EM) performance in measuring ART adherence and predicting HIV viral suppression among ALHIV. METHODS: Between January 2014 and December 2015, we recruited 702 ALHIV aged 10-16 years into our cluster-randomized controlled trial (2012-2018) in 39 clinics in Uganda. The intervention included a long-term savings child development account, four micro-enterprise workshops and 12 mentorship sessions. Using the entire sample, we performed multilevel logistic regression to predict monthly ART adherence trends for the first year of follow-up. Since it is possible that the intervention had different effects on SR and EM adherence, we used participants in the control arm only to compare adherence using SR and EM and to calculate their sensitivity and specificity in predicting viral suppression. RESULTS: There was a significant decline in adherence for each month throughout the entire follow-up period regardless of the group assigned. Good ART adherence was measured at 79.2% (75.2-82.6%) and 97.0% (95.4-98.1%) using EM and SR, respectively. Overall, 64.3% (60.6-67.9%) had suppressed viral loads. The specificities for EM and SR in predicting viral non-suppression were 80.4% (73.6-85.7%) and 96.7% (93.3-98.4%), while the sensitivities were 22.9% (15.0-33.3%) and 1.8% (0.4-6.9%), respectively. The area under the curve was low for both EM and SR, at 53.6% (45.7-61.5%) and 56.2% (53.2-59.3%), respectively. There was high agreement (78%) between SR and EM in monitoring adherence. CONCLUSIONS: Our findings highlighted the need for strategies for sustained optimal adherence. SR and EM measure adherence with a considerable agreement; however, neither is an accurate predictor of virological outcome. There is still a need for an acceptable, feasible and affordable method that predicts viral suppression among ALHIV.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Adolescente , Fármacos Anti-HIV/uso terapêutico , Antirretrovirais/uso terapêutico , Criança , Infecções por HIV/tratamento farmacológico , Humanos , Adesão à Medicação , Autorrelato , Uganda , Carga Viral
5.
Lancet HIV ; 9(9): e638-e648, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36055295

RESUMO

BACKGROUND: Young children living with HIV have few treatment options. We aimed to assess the efficacy and safety of dolutegravir-based antiretroviral therapy (ART) in children weighing between 3 kg and less than 14 kg. METHODS: ODYSSEY is an open-label, randomised, non-inferiority trial (10% margin) comparing dolutegravir-based ART with standard of care and comprises two cohorts (children weighing ≥14 kg and <14 kg). Children weighing less than 14 kg starting first-line or second-line ART were enrolled in seven HIV treatment centres in South Africa, Uganda, and Zimbabwe. Randomisation, which was computer generated by the trial statistician, was stratified by first-line or second-line ART and three weight bands. Dispersible 5 mg dolutegravir was dosed according to WHO weight bands. The primary outcome was the Kaplan-Meier estimated proportion of children with virological or clinical failure by 96 weeks, defined as: confirmed viral load of at least 400 copies per mL after week 36; absence of virological suppression by 24 weeks followed by a switch to second-line or third-line ART; all-cause death; or a new or recurrent WHO stage 4 or severe WHO stage 3 event. The primary outcome was assessed by intention to treat in all randomly assigned participants. A primary Bayesian analysis of the difference in the proportion of children meeting the primary outcome between treatment groups incorporated evidence from the higher weight cohort (≥14 kg) in a prior distribution. A frequentist analysis was also done of the lower weight cohort (<14 kg) alone. Safety analyses are presented for all randomly assigned children in this study (<14 kg cohort). ODYSSEY is registered with ClinicalTrials.gov, NCT02259127. FINDINGS: Between July 5, 2018, and Aug 26, 2019, 85 children weighing less than 14 kg were randomly assigned to receive dolutegravir (n=42) or standard of care (n=43; 32 [74%] receiving protease inhibitor-based ART). Median age was 1·4 years (IQR 0·6-2·0) and median weight 8·1 kg (5·4-10·0). 72 (85%) children started first-line ART and 13 (15%) started second-line ART. Median follow-up was 124 weeks (112-137). By 96 weeks, treatment failure occurred in 12 children in the dolutegravir group (Kaplan-Meier estimated proportion 31%) versus 21 (48%) in the standard-of-care group. The Bayesian estimated difference in treatment failure (dolutegravir minus standard of care) was -10% (95% CI -19% to -2%; p=0·020), demonstrating superiority of dolutegravir. The frequentist estimated difference was -18% (-36% to 2%; p=0·057). 15 serious adverse events were reported in 11 (26%) children in the dolutegravir group, including two deaths, and 19 were reported in 11 (26%) children in the standard-of-care group, including four deaths (hazard ratio [HR] 1·08 [95% CI 0·47-2·49]; p=0·86). 36 adverse events of grade 3 or higher were reported in 19 (45%) children in the dolutegravir group, versus 34 events in 21 (49%) children in the standard-of-care group (HR 0·93 [0·50-1·74]; p=0·83). No events were considered related to dolutegravir. INTERPRETATION: Dolutegravir-based ART was superior to standard of care (mainly protease inhibitor-based) with a lower risk of treatment failure in infants and young children, providing support for global dispersible dolutegravir roll-out for younger children and allowing alignment of adult and paediatric treatment. FUNDING: Paediatric European Network for Treatment of AIDS Foundation, ViiV Healthcare, UK Medical Research Council.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Adulto , Fármacos Anti-HIV/efeitos adversos , Teorema de Bayes , Criança , Pré-Escolar , Infecções por HIV/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Humanos , Lactente , Recém-Nascido , Oxazinas , Piperazinas , Inibidores de Proteases/uso terapêutico , Piridonas , Resultado do Tratamento , Carga Viral
6.
PLoS One ; 17(9): e0274923, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36112606

RESUMO

Housing and employment are key factors in the health and wellbeing of persons living with HIV (PLWH) in the United States. Approximately 14% of low-income PLWH report housing instability or temporary housing, and up to 70% report being unemployed. The purpose of this study was to examine the outcomes of an intervention to improve housing and employment for PLWH in the Midwest. Participants (N = 87) were recruited from the Kansas City metropolitan area to participate in a one-year intervention to improve housing and employment. All individuals were living with HIV and were not stably housed, fully employed, nor fully engaged in HIV medical care. A series of generalized estimating equations were conducted using client-level longitudinal data to examine how housing, employment, viral load, and retention in care changed over time. Housing improved from baseline to follow-up, with more individuals reporting having stable housing (OR = 23.5; p < 0.001). Employment also improved from baseline to follow-up, with more individuals reporting full-time employment (OR = 1.9; p < 0.001). Viral suppression improved from baseline to follow-up, with more individuals being virally suppressed (OR = 1.6; p < 0.05). Retention in care did not change significantly from baseline to follow-up (OR = 0.820; p = 0.370). Client navigation seems to be a promising intervention to improve housing and employment for PLWH in the Midwest. Additional research is needed on the impact of service coordination on client-level outcomes. Future studies should be conducted on the scalability of client navigation interventions to improve the lives of low-income, underserved PLWH.


Assuntos
Infecções por HIV , Habitação , Emprego , Infecções por HIV/tratamento farmacológico , Humanos , Inquéritos e Questionários , Estados Unidos , Carga Viral
8.
Can Respir J ; 2022: 5460400, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36072643

RESUMO

Objectives: Viral load is important when evaluating viral transmission potential, involving the use of a polymerase chain reaction (PCR) cycle threshold (Ct) value. We aimed to analyze the PCR Ct values of respiratory tract samples taken from patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant strains to evaluate these strains' viral dynamics. Methods: This study comprised 361 patients. The Ct values of SARS-CoV-2-related respiratory samples were compared between symptomatic and asymptomatic patients. Results: The median (25th percentile and 75th percentile) nasopharynx and oropharynx SARS-CoV-2 Ct values were 30.5 (24.5-35.0) and 34.5 (30.0-37.0) in the symptomatic group, respectively, and 27.8 (23.4-34.5) and 33.5 (26.0-35.0) in the asymptomatic group, respectively, without significance. In the symptomatic group, subgroup analyses according to age showed the mean nasal Ct value for patients aged >18 years was 29.0 (23.5-34.5), which was significantly lower than that of patients aged 0-4 years and 5-13 years (36.0 (30.5-38.0) and 34.5 (31.0-39.0), respectively). The nasal Ct value for asymptomatic patients aged >18 years was 25.5 (20.9-28.4), which was significantly lower than of patients aged 5-13 years (34.5 (25.6-36.4)). Conclusion: Our findings suggest that the viral loads of asymptomatic and symptomatic patients did not differ significantly. However, adults infected with SARS-CoV-2 had higher nasal viral loads that those of young children.


Assuntos
COVID-19 , RNA Viral , Adulto , Criança , Pré-Escolar , Humanos , RNA Viral/análise , SARS-CoV-2 , Carga Viral
9.
J Acquir Immune Defic Syndr ; 91(S1): S16-S19, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36094510

RESUMO

BACKGROUND: Some inpatients with HIV-RNA ≥500,000 copies/mL in China need to use 2-drug regimen for some reasons, although limited data are available for dolutegravir plus lamivudine (3TC) in those patients with ultra-high viral loads. METHODS: We conducted a single-center retrospective-prospective study in China and enrolled 42 ART-naive HIV-infected inpatients who use a once-daily 2-drug regimen because of various reasons (drug interaction, renal impairment, age, and other related comorbidities).They were divided into 2 groups, low viral load group (baseline viral load <500,000 copies/mL, n = 20) and high viral load group (baseline viral load ≥500,000 copies/mL, n = 22). All patients were followed up for 48 weeks. RESULTS: The median of baseline viral load was 5.74 log10 copies/mL and CD4+ T-cell count was 59 cells/µL. At week 48, there was no significant difference (P = 0.598) in proportions of participants with HIV-1 RNA <50 copies/mL [90%, 95% confidence interval (CI) (75.6% to 104.4%) in low viral load groups vs 95.5%, 95% CI (86.0% to 104.9%) in high viral load groups]. No differences were found in mean increase of CD4+ T-cell count from baseline between 2 groups (218 ± 122 vs 265 ± 127 cells/µL, P = 0.245). There is no grade 3 or higher treatment-related adverse events and none discontinued treatment because of adverse events. CONCLUSIONS: The results of our study in real world support dolutegravir + 3TC dual regimen as a promising therapy option for treatment-naive HIV-infected patient with baseline viral load ≥500,000 copies/mL.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Soropositividade para HIV , HIV-1 , Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Soropositividade para HIV/tratamento farmacológico , HIV-1/genética , Compostos Heterocíclicos com 3 Anéis , Humanos , Lamivudina/uso terapêutico , Oxazinas , Piperazinas , Dados Preliminares , Estudos Prospectivos , Piridonas , RNA Viral , Estudos Retrospectivos , Carga Viral
10.
J Acquir Immune Defic Syndr ; 91(S1): S20-S26, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36094511

RESUMO

BACKGROUND: Few large investigations have evaluated the association of cerebrospinal fluid/plasma (CSF/plasma) discordance with opportunistic neurological infections. We aimed to determine risk factors for CSF/plasma discordance to further assess whether CSF/plasma discordance is associated with antiretroviral therapy (ART) and opportunistic neurological infections. METHODS: A retrospective study was conducted based on HIV RNA viral load and associated risk factors in plasma and CSF samples from 491 HIV-infected patients. HIV RNA levels higher in CSF compared with plasma was defined as CSF/plasma discordance. RESULTS: In this study, the rate of CSF/plasma discordance was 18.3%. We observed that headache, cryptococcal antigen, CSF cell count, Treponema pallidum particle assay positivity, and ART use were significantly associated with CSF/plasma discordance in the multivariate logistic regression model. The CSF RNA/plasma RNA ratio was significantly higher in HIV-infected patients with neurological infections than in HIV-infected cases without neurological infections (P < 0.001). CSF/plasma discordance was significantly different between HIV-infected patients without central nervous system (CNS) infection and those with CNS infection, tuberculous meningitis, cryptococcal meningitis, and neurosyphilis (P < 0.05). CONCLUSIONS: ART and CNS inflammation may influence CSF/plasma discordance.


Assuntos
Infecções por HIV , HIV-1 , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , HIV-1/genética , Humanos , RNA Viral , Estudos Retrospectivos , Fatores de Risco , Carga Viral
11.
Klin Lab Diagn ; 67(9): 530-537, 2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-36099463

RESUMO

A method has been developed for HBV DNA finding in biological material at low viral load based on nested PCR with real-time detection of three viral targets. When developing the method, blood plasma samples were used from 128 CHB patients living in the regions of the Russian Federation and countries of Central Asia and 173 hemodialysis center patients living in the North-West Federal District. Analytical sensitivity was tested using the stepwise dilution method. HBV was detected by nested PCR. According to the method developed by us, at the first stage, the HBV DNA is amplified using at the first stage oligonucleotides complementary to the greatest similarity regions of the various HBV isolates genomes flanking the entire virus genome. At the second stage, when using the amplification product of the first stage as a template, PCR was performed using three pairs of oligonucleotides and the corresponding oligonucleotide fluorescently labeled probes to three virus genome regions (Core gene, S gene and X gene), as well as one pair of primers and the corresponding probe complementary to a human HPRT gene region. The method sensitivity for DNA extraction from plasma with a 100 µl volume was 10 IU/ml. Obtaining a threshold Ct cycle for only one fluorophore may indicate the presence of HBV DNA in the sample at a load of less than 10 IU/ml, HBV detection in this case is possible with a repeated PCR study of the corresponding sample with HBV DNA extraction from an increased plasma volume (200-1000 µl). The developed method makes it possible to identify the disease in various HBV subgenotypes and can be used to diagnose CHB in the population and risk groups, including those with the HBsAg-negative form of the disease.


Assuntos
DNA Viral , Vírus da Hepatite B , Primers do DNA/genética , DNA Viral/genética , Vírus da Hepatite B/genética , Humanos , Reação em Cadeia da Polimerase/métodos , Carga Viral/genética , Carga Viral/métodos
12.
AIDS Patient Care STDS ; 36(9): 336-342, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36099481

RESUMO

The prevalence of HIV-associated neurocognitive impairment persists despite highly effective antiretroviral therapy (ART). In this study we explore the role of internalized stigma, acceptance of negative societal characterizations, and perceptions about people living with HIV (PLWH) on neurocognitive functioning (executive function, learning, memory, attention/working memory, psychomotor speed, fluency, motor skills) in a national cohort of women living with HIV (WLWH) in the United States. We utilized observational data from a multicenter study of WLWH who are mostly African American living in low-resource settings. Neurocognitive function was measured using an eight-test battery. A multiple linear regression model was constructed to investigate the relationship between internalized stigma and overall neurocognitive functioning (mean of all neurocognitive domain standardized T-scores), adjusting for age, education, race, previous neuropsychological battery scores, illicit drug use, viral load, and years on ART. Our analysis revealed that internalized HIV-related stigma is significantly associated with worse performance on individual domain tests and overall neurocognitive performance (B = 0.27, t = 2.50, p = 0.01). This suggests HIV-related internalized stigma may be negatively associated with neurocognitive functioning for WLWH. This finding highlights a specific psychosocial factor associated with poor neurocognitive function that may be targeted to better promote the health of PLWH. Future research on the longitudinal relationship between these variables and the effects of other stigma dimensions on poor neurocognitive function would provide further insights into the pathways explaining the relationship between internalized stigma and neurocognition.


Assuntos
Infecções por HIV , Afro-Americanos , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/psicologia , Humanos , Estigma Social , Estados Unidos/epidemiologia , Carga Viral
13.
Annu Int Conf IEEE Eng Med Biol Soc ; 2022: 2244-2247, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36086157

RESUMO

This study explores the natural control system in the body for responding to exposure to the Influenza A virus. More specifically, it delves into the development of a model to simulate the responses of target uninfected cell counts, infected cell counts, and viral titers. There are two particular models of interest: a delayed model that incorporates the brief inactive period for newly infected cells, and a non-delayed model reflecting only infected cells without delay after initial infection. Both models are commonly used in the literature and the benefits of each model are studied and explained. We generate Simulink models for both the delayed and non-delayed sets of ordinary differential equations (ODEs) to simulate responses to different viral titer impulses. Additionally, this study aims to extrapolate these models to the case for a vaccinated individual. To do this, we modify the viral clearance rate and infected cell death rate of our initial model to account for the improved immune response generated by vaccines.


Assuntos
Vírus da Influenza A , Influenza Humana , Humanos , Cinética , Carga Viral
14.
Medicine (Baltimore) ; 101(36): e30182, 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36086717

RESUMO

Double-negative T (DNT) cells are a T-cell subset with a CD4-CD8- phenotype. They represent 1% to 5% of circulating lymphocytes, but an increase in this proportion can be found during lymphoproliferative and autoimmune diseases. This increase has also been reported in persons with HIV (PWH). The aim of this work was to better describe the proportion of DNT cell subset in PWH. We retrospectively collected 984 samples from PWH referred for lymphocyte immunophenotyping over a 7.5-year period. Quantification of DNT cells was performed by flow cytometry. DNT cell proportion was calculated by subtracting the CD4+ and CD8+ subsets proportions from the total of T cells. A total of 984 blood samples from PWH were collected. Mean CD4 T-cell count was decreased in such patients while DNT cell frequency was increased with a mean of 6.7%. More than half of the patients had a DNT cell proportion >5%. Patients with DNT cell proportion over 5% exhibited significantly reduced CD3+ and CD4+ T-cell counts, while CD8+ T-cell count was unchanged compared to patients with normal DNT cell rates. Interestingly, DNT cell percentage was negatively correlated with CD4 and CD3 T-cell counts in all included patients. Moreover, the DNT cell proportion was significantly increased in subjects with CD4+ T cells <200/mm3 compared to those with CD4+ T cells >200/mm3. Interestingly, DNT cell proportions were significantly higher in patients with high viral load compared with those presenting undetectable viral load. HIV infection is associated with an increase in DNT cell proportion. This increase is more frequent as the CD4 count is decreased and the viral load is increased. DNT cell subset should not be omitted when interpreting immunophenotyping in PWH as it appears to be associated with disease progression in patients under antiretroviral therapy.


Assuntos
Infecções por HIV , Contagem de Linfócito CD4 , Infecções por HIV/complicações , Humanos , Contagem de Linfócitos , Estudos Retrospectivos , Carga Viral
16.
J Acquir Immune Defic Syndr ; 91(2): 189-196, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36094486

RESUMO

BACKGROUND: We aimed to evaluate the analytic performance of 3 rapid HIV viral load assays: the novel Xpert HIV-1 VL XC (Xpert XC), Xpert HIV-1 VL (Xpert VL), and m-PIMA HIV-1/2 VL (m-PIMA). SETTING: Two South African clinics. METHODS: We conducted a prospective diagnostic accuracy study. Site-laboratory technicians and nurses used the Xpert XC, Xpert VL, and m-PIMA to test plasma samples from people with HIV receiving antiretroviral therapy. We compared results with the Roche cobas HIV-1 reference assay. We determined accuracy to detect viraemia at the World Health Organization (WHO) failure threshold of 1000 copies/mL on all 3 assays, and 50 and 200 copies/mL on the Xpert assays. We assessed the agreement using Bland-Altman plots. RESULTS: We enrolled 140 participants (98 [70%] women, median age 37 years), who provided 189 paired samples at one or more timepoints. We tested 174 samples with the Xpert XC, 188 with the Xpert VL, and 128 with the m-PIMA. At 1000 copies/mL, sensitivity and specificity (95% confidence intervals) were 97% (82 to 100) and 98% (93 to 99) (Xpert XC), 100% (87 to 100) and 96% (91 to 98) (Xpert VL), and 92% (72 to 99) and 99% (93 to 100) (m-PIMA) respectively. At 50 copies/mL, sensitivity and specificity were 93% (81 to 98) and 96% (91 to 99) (Xpert XC), and 95% (84 to 99) and 95% (90 to 98) (Xpert VL) respectively. Mean bias was -0.10 (-0.54 to 0.34) log10 copies/mL (Xpert XC), 0.07 (-0.37 to 0.52) log10 copies/mL (Xpert VL), and -0.26 (-0.83 to 0.31) log10 copies/mL (m-PIMA). CONCLUSIONS: In these South African clinics, the accuracy of all 3 assays was clinically acceptable to detect viraemia at the WHO failure threshold, whereas both Xpert assays were also accurate at detecting low-level viraemia.


Assuntos
Infecções por HIV , HIV-1 , Adulto , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , HIV-1/genética , Humanos , Masculino , Iodeto de Potássio , Estudos Prospectivos , RNA Viral , África do Sul , Carga Viral/métodos , Viremia
17.
Antivir Ther ; 27(3): 13596535221092182, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36029009

RESUMO

BACKGROUND: Etravirine (ETR) is approved as a component of second or third-line antiretroviral treatment (ART) for children living with HIV. We assessed the outcomes of ETR-based ART in children in routine care in Europe and Thailand. METHODS: Data on children aged <18 years at ETR start were pooled from 17 observational cohorts. Characteristics at ETR start, immunological and virological outcomes at 12 months, discontinuations, adverse events (AEs) and serious adverse events (SAEs) were described. Follow-up was censored at ETR discontinuation, death or last visit. RESULTS: 177 children ever received ETR. At ETR start, median [IQR] age was 15 [12,16] years, CD4 count 480 [287, 713] cells/mm3, 70% had exposure to ≥3 ART classes and 20% had viral load (VL) <50 copies/mL. 95% received ETR in combination with ≥1 potent drug class, mostly protease inhibitor-based regimens. Median time on ETR was 24 [7, 48] months. Amongst those on ETR at 12 months (n=141), 69% had VL<50 copies/mL. Median CD4 increase since ETR start (n=83) was 147 [16, 267] cells/mm3. Overall, 81 (46%) discontinued ETR by last follow-up. Median time to discontinuation was 23 [8, 47] months. Common reasons for discontinuation were treatment simplification (19%), treatment failure (16%) and toxicity (12%). Eight children (5%) had AEs causally associated with ETR, all dermatological/hypersensitivity reactions. Two were SAEs, both Stevens-Johnson Syndrome in children on regimens containing ETR and darunavir and were causally related to either drugs; both resolved following ART discontinuation. CONCLUSION: Children receiving ETR were predominantly highly treatment-experienced, over two-thirds were virally suppressed at 12 months.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Piridazinas , Adolescente , Antirretrovirais , Contagem de Linfócito CD4 , Criança , Humanos , Nitrilas , Pirimidinas , Tailândia , Resultado do Tratamento , Carga Viral
18.
Nat Commun ; 13(1): 5055, 2022 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-36030289

RESUMO

Antiretroviral therapy (ART) is not curative due to the persistence of a reservoir of HIV-infected cells, particularly in tissues such as lymph nodes, with the potential to cause viral rebound after treatment cessation. In this study, fingolimod (FTY720), a lysophospholipid sphingosine-1-phosphate receptor modulator is administered to SIV-infected rhesus macaques at initiation of ART to block the egress from lymphoid tissues of natural killer and T-cells, thereby promoting proximity between cytolytic cells and infected CD4+ T-cells. When compared with the ART-only controls, FTY720 treatment during the initial weeks of ART induces a profound lymphopenia and increases frequencies of CD8+ T-cells expressing perforin in lymph nodes, but not their killing capacity; FTY720 also increases frequencies of cytolytic NK cells in lymph nodes. This increase of cytolytic cells, however, does not limit measures of viral persistence during ART, including intact proviral genomes. After ART interruption, a subset of animals that initially receives FTY720 displays a modest delay in viral rebound, with reduced plasma viremia and frequencies of infected T follicular helper cells. Further research is needed to optimize the potential utility of FTY720 when coupled with strategies that boost the antiviral function of T-cells in lymphoid tissues.


Assuntos
Infecções por HIV , Síndrome de Imunodeficiência Adquirida dos Símios , Vírus da Imunodeficiência Símia , Animais , Antirretrovirais , Linfócitos T CD4-Positivos , Cloridrato de Fingolimode , Macaca mulatta , Carga Viral
19.
Sci Rep ; 12(1): 14637, 2022 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-36030320

RESUMO

Determining accurate estimates for the characteristics of the severe acute respiratory syndrome coronavirus 2 in the upper and lower respiratory tracts, by fitting mathematical models to data, is made difficult by the lack of measurements early in the infection. To determine the sensitivity of the parameter estimates to the noise in the data, we developed a novel two-patch within-host mathematical model that considered the infection of both respiratory tracts and assumed that the viral load in the lower respiratory tract decays in a density dependent manner and investigated its ability to match population level data. We proposed several approaches that can improve practical identifiability of parameters, including an optimal experimental approach, and found that availability of viral data early in the infection is of essence for improving the accuracy of the estimates. Our findings can be useful for designing interventions.


Assuntos
COVID-19 , Humanos , Modelos Teóricos , SARS-CoV-2 , Testes Sorológicos , Carga Viral
20.
Pan Afr Med J ; 42: 114, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36034046

RESUMO

Introduction: children infected with HIV are at increased risk of impaired neurodevelopmental, due to several environmental factors. Methods: we conducted a cross-sectional analytical study on HIV-infected children aged 12 to 59 months, followed up in five hospitals in Yaounde, Cameroon. Sociodemographic, clinical, and biological variables as well as the antecedents were collected. Data analysis was performed using Statistical Package for the Social Sciences (SPSS) version 25 software. The Denver test was used to assess the psychomotor development of these children. Global psychomotor delay, defined as a global development quotient of less than 70 with an alteration in at least two of the four domains of the test, was retained as the primary endpoint. The significance threshold was set at 5%. Results: one hundred and eighty-one children were included in the study. The sex ratio was 0.6. The age range 48-59 months was the most represented. None of these children had a known chronic pathology other than HIV infection. The proportion of global psychomotor delay was 11.04%, with language (16%) and fine motor skills (16%) being the most affected domains of psychomotor development. The independent factors significantly associated with global psychomotor delay were birth weight below 2500 grams (OR= 17.61 [1.76-181.39], p= 0.022), growth retardation (OR= 17.64 [1.63-190.24], p= 0.018) and elevated viral load (OR= 22.75 [2.78-186.02], p= 0.004). Conclusion: psychomotor delay affects about one out of ten children living with HIV. Its occurrence is linked to various factors that must be taken into account in the development of public health policies in connection with the management of HIV infection in children.


Assuntos
Infecções por HIV , Camarões , Criança , Pré-Escolar , Estudos Transversais , Humanos , Transtornos Psicomotores , Carga Viral
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