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1.
AIDS ; 38(6): 803-812, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38578958

RESUMO

OBJECTIVES: There is conflicting data regarding the response of older people with HIV (PWH) to antiretroviral therapy (ART). The objective of this study was to evaluate the long-term immunological and virological responses, changes in regimen, and adverse drug reactions (ADRs) in older participants (50+ years) compared with younger (18-34 years) and middle-aged (35-49 years) PWH. METHODS: A retrospective review of medical records was conducted on 1622 participants who received ART in Yunnan Province, China, from 2010 to 2019. The study compared CD4+ T-cell counts, CD4+/CD8+ ratio, and relative numbers between different groups using the Kruskal-Wallis test. Cox proportional hazards regression models were used to identify variables associated with the occurrence of immune reconstitution insufficiency. The rates of immune reconstitution, incidence of ADRs, and rates of treatment change were analyzed using the chi-squared test or Fisher's exact test. RESULTS: Over 95% achieved viral load 200 copies/ml or less, with no age-related difference. However, older participants exhibited significantly lower CD4+ T-cell counts and CD4+/CD8+ recovery post-ART (P < 0.001), with only 32.21% achieving immune reconstitution (compared with young: 52.16%, middle-aged: 39.29%, P < 0.001) at the end of follow-up. Middle-aged and elderly participants changed ART regimens more because of ADRs, especially bone marrow suppression and renal dysfunction. CONCLUSION: Although the virological response was consistent across age groups, older individuals showed poorer immune responses and higher susceptibility to side effects. This underscores the need for tailored interventions and comprehensive management for older patients with HIV.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Pessoa de Meia-Idade , Idoso , Humanos , Infecções por HIV/tratamento farmacológico , Fármacos Anti-HIV/efeitos adversos , China , Resultado do Tratamento , Contagem de Linfócito CD4 , Carga Viral
2.
PLoS One ; 19(4): e0300335, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38564514

RESUMO

During the COVID-19 pandemic, HIV programs scaled up differentiated service delivery (DSD) models for people living with HIV (PLHIV). We evaluated the effects of COVID-19 on HIV service delivery and viral suppression in facilities in Northern Nigeria, and determined factors associated with viral suppression among adolescents and adults. We analysed a cross-sectional survey data from facility heads, and retrospective, routinely collected patient data from 63 facilities for PLHIV ≥10 years old in care between April 2019-March 2021, defining study periods as "pre-COVID-19" (before April 2020) and "during COVID-19" (after April 2020). For the pre-COVID and the COVID-19 periods we compared uptake of antiretroviral therapy (ART) refills of ≥3 months (MMD3), and ≥6 months (MM6), missed appointments, viral load (VL) testing, VL testing turnaround time (TAT) and viral suppression among those on ART for ≥6 months using two proportions Z-test and t-tests. We fit a multivariable logistic regression model to determine factors associated with maintaining or achieving viral suppression. Of 84,776 patients, 58% were <40 years, 67% were female, 55% on ART for >5 years, 93% from facilities with community-based ART refill, a higher proportion were on MMD3 (95% versus 74%, p<0.001) and MMD6 (56% versus 22%, p<0.001) during COVID-19 than pre-COVID-19, and a higher proportion had VL testing during COVID-19 (55,271/69,630, [84%]) than pre-COVID-19 (47,747/68,934, [73%], p<0.001). Viral suppression was higher during COVID-19 pandemic compared to the pre-COVID era (93% [51,196/55,216] versus 91% [43,336/47,728], p<0.001), and there was a higher proportion of missed visits (40% [28,923/72,359] versus 39% [26,304/67,365], p<0.001) and increased VL TAT (mean number of days: 38 versus 36, p<0.001) during COVID-19 pandemic and pre-COVID period respectively. Factors associated with maintaining or achieving suppression during COVID-19 were receiving MMD3 and MMD6 refills (OR: 2.8 [95% CI: 2.30-3.47] and OR: 6.3 [95% CI: 5.11-7.69], respectively) and attending clinics with community-based ART refill (OR: 1.6 [95% CI: 1.39-1.87]). The program in Northern Nigeria demonstrated resilience during the COVID-19 pandemic and adoption of MMD had a positive impact on HIV care. Though VL TAT and missed clinic visits slightly increased during the pandemic, VL testing improved and viral suppression moved closer to 95%. Adoption of MMD and community-based models of care at scale are recommended for future pandemic preparedness.


Assuntos
Fármacos Anti-HIV , COVID-19 , Infecções por HIV , Adulto , Adolescente , Humanos , Feminino , Criança , Masculino , Pandemias , Estudos Retrospectivos , Nigéria/epidemiologia , Estudos Transversais , COVID-19/epidemiologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Carga Viral , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/farmacologia
3.
Rev Med Virol ; 34(3): e2536, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38578230

RESUMO

Cerebrospinal fluid (CSF) viral escape rarely occurs when HIV is detected in the CSF, while it is undetectable in the blood plasma or detectable in CSF at levels that exceed those in the blood plasma. We conducted this review to comprehensively synthesise its clinical presentation, diagnosis, management strategies and treatment outcomes. A review registered with PROSPERO (CRD42023475311) searched evidence across PubMed/MEDLINE, Embase, Web of Science, Scopus, and Google Scholar to gather articles (case reports/series) that report on CSF viral escape in people living with HIV (PLHIV) on antiretroviral therapy (ART). The quality of studies was assessed based on the domains of selection, ascertainment, causality, and reporting. A systematic search identified 493 articles and 27 studies that include 21 case reports, and six case series were involved in the review. The studies reported 62 cases of CSF viral escape in PLHIV. The majority were men (66.67%), with a median age of 43 (range: 28-73) years. Approximately, 31 distinct symptoms were documented, mostly being cognitive dysfunction, gait abnormalities, and tremors (12.51%). Diagnosis involved blood and CSF analysis, magnetic resonance imaging, and neuropsychological assessments. Over 36 ART regimens were employed, with a focus on ART intensification; almost one-third of the regimens contained Raltegravir (integrase strand transfer inhibitor). The outcomes showed 64.49% full recovery, 30.16% partial recovery, and 4.76% died. When neuropsychological symptoms manifest in PLHIV, monitoring for CSF viral escape is essential, regardless of plasma viral suppression. Personalised treatment strategies, particularly ART intensification, are strongly advised for optimising treatment outcomes in PLHIV diagnosed with CSF HIV escape.


Assuntos
Infecções por HIV , Humanos , Infecções por HIV/líquido cefalorraquidiano , Infecções por HIV/tratamento farmacológico , HIV-1 , Plasma , RNA Viral , Resultado do Tratamento , Carga Viral
4.
Pediatr Transplant ; 28(3): e14743, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38566336

RESUMO

BACKGROUND: There are scant data on the effect of rituximab on EBV DNA levels and prevention of post-transplant lymphoproliferative disorder (PTLD) in pediatric kidney transplant recipients with EBV DNAemia. METHODS: Kidney transplant recipients with EBV DNAemia treated with rituximab to prevent PTLD between 7/1999 and 7/2019 at five pediatric centers were included. Those with confirmed PTLD at the onset of rituximab were excluded. Primary outcomes included percentage change in EBV DNAemia and occurrence of PTLD post rituximab. RESULTS: Twenty-six pediatric kidney transplant recipients were included. Median age at transplant was 4 years (IQR 2.1-10.3). EBV DNA load monitoring by qPCR was performed at 1-3 month intervals. EBV DNAemia onset occurred at a median of 73 days post-transplant (IQR 52-307), followed by DNAemia peak at a median of 268 days (IQR 112-536). Rituximab was administered at a median of 9 days post peak (IQR 0-118). Rituximab regimens varied; median dose 375 mg/m2 (IQR 375-439) weekly for 1-4 doses per course. Following rituximab, EBV DNA load decreased to <10% of baseline at 120 days in 20/26 patients; however, only 30% achieved complete resolution at last follow-up (median 2094 days post-transplant [IQR 1538-3463]). Two (7%) developed PTLD at 915 and 1713 days post rituximab. All recipients had functioning grafts. One death occurred in a child with PTLD following remission due to unrelated reasons. CONCLUSIONS: In the largest pediatric kidney transplant recipient case series with EBV DNAemia given rituximab to prevent PTLD, rituximab achieved a short-term reduction in DNA load; however, recurrent DNAemia is common.


Assuntos
Infecções por Vírus Epstein-Barr , Transplante de Rim , Transtornos Linfoproliferativos , Nefrologia , Humanos , Criança , Pré-Escolar , Rituximab/uso terapêutico , Herpesvirus Humano 4/genética , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/prevenção & controle , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Transplante de Rim/efeitos adversos , DNA Viral , Transtornos Linfoproliferativos/etiologia , Transtornos Linfoproliferativos/prevenção & controle , Transtornos Linfoproliferativos/tratamento farmacológico , Transplantados , Carga Viral
5.
PLoS Pathog ; 20(4): e1012135, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38593120

RESUMO

The rebound competent viral reservoir (RCVR)-virus that persists during antiretroviral treatment (ART) and can reignite systemic infection when treatment is stopped-is the primary barrier to eradicating HIV. We used time to initiation of ART during primary infection of rhesus macaques (RMs) after intravenous challenge with barcoded SIVmac239 as a means to elucidate the dynamics of RCVR establishment in groups of RMs by creating a multi-log range of pre-ART viral loads and then assessed viral time-to-rebound and reactivation rates resulting from the discontinuation of ART after one year. RMs started on ART on days 3, 4, 5, 6, 7, 9 or 12 post-infection showed a nearly 10-fold difference in pre-ART viral measurements for successive ART-initiation timepoints. Only 1 of 8 RMs initiating ART on days 3 and 4 rebounded after ART interruption despite measurable pre-ART plasma viremia. Rebounding plasma from the 1 rebounding RM contained only a single barcode lineage detected at day 50 post-ART. All RMs starting ART on days 5 and 6 rebounded between 14- and 50-days post-ART with 1-2 rebounding variants each. RMs starting ART on days 7, 9, and 12 had similar time-to-measurable plasma rebound kinetics despite multiple log differences in pre-ART plasma viral load (pVL), with all RMs rebounding between 7- and 16-days post-ART with 3-28 rebounding lineages. Calculated reactivation rates per pre-ART pVL were highest for RMs starting ART on days 5, 6, and 7 after which the rate of accumulation of the RCVR markedly decreased for RMs treated on days 9 and 12, consistent with multiphasic establishment and near saturation of the RCVR within 2 weeks post infection. Taken together, these data highlight the heterogeneity of the RCVR between RMs, the stochastic establishment of the very early RCVR, and the saturability of the RCVR prior to peak viral infection.


Assuntos
Infecções por HIV , Síndrome de Imunodeficiência Adquirida dos Símios , Vírus da Imunodeficiência Símia , Animais , Síndrome de Imunodeficiência Adquirida dos Símios/tratamento farmacológico , Vírus da Imunodeficiência Símia/fisiologia , Macaca mulatta , Replicação Viral , Antirretrovirais/uso terapêutico , Antirretrovirais/farmacologia , Infecções por HIV/tratamento farmacológico , Carga Viral
6.
Science ; 383(6690): 1434-1440, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38547259

RESUMO

The emergence of SARS-CoV-2 variants and drug-resistant mutants calls for additional oral antivirals. The SARS-CoV-2 papain-like protease (PLpro) is a promising but challenging drug target. We designed and synthesized 85 noncovalent PLpro inhibitors that bind to a recently discovered ubiquitin binding site and the known BL2 groove pocket near the S4 subsite. Leads inhibited PLpro with the inhibitory constant Ki values from 13.2 to 88.2 nanomolar. The co-crystal structures of PLpro with eight leads revealed their interaction modes. The in vivo lead Jun12682 inhibited SARS-CoV-2 and its variants, including nirmatrelvir-resistant strains with EC50 from 0.44 to 2.02 micromolar. Oral treatment with Jun12682 improved survival and reduced lung viral loads and lesions in a SARS-CoV-2 infection mouse model, suggesting that PLpro inhibitors are promising oral SARS-CoV-2 antiviral candidates.


Assuntos
Tratamento Farmacológico da COVID-19 , COVID-19 , Proteases Semelhantes à Papaína de Coronavírus , Inibidores de Protease de Coronavírus , Desenho de Fármacos , SARS-CoV-2 , Animais , Camundongos , Proteases Semelhantes à Papaína de Coronavírus/antagonistas & inibidores , Proteases Semelhantes à Papaína de Coronavírus/química , Modelos Animais de Doenças , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/enzimologia , Inibidores de Protease de Coronavírus/administração & dosagem , Inibidores de Protease de Coronavírus/química , Inibidores de Protease de Coronavírus/farmacologia , Administração Oral , Cristalografia por Raios X , Relação Estrutura-Atividade , Carga Viral/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos BALB C
7.
Microbiol Spectr ; 12(4): e0424923, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38451228

RESUMO

The aim of this study was to compare the performance of the newly developed SMG HHV-6 Q Real-Time PCR Kit (SMG assay) with the RealStar HHV-6 PCR Kit (RealStar assay). The analytical sensitivity and specificity, linearity, and precision of the SMG assay were evaluated. The clinical performance of the SMG assay was assessed and compared with that of the RealStar assay using 207 clinical specimens (HHV-6A positive, n = 51; HHV-6B positive, n = 64; HHV-6A/B negative, n = 92). The limit of detection of the SMG assay was 2.92 log10 copies/mL for HHV-6A DNA and 2.88 log10 copies/mL for HHV-6B DNA. The linear range was determined to be 3.40-9.00 log10 copies/mL for both viruses. Intra- and inter-assay variability were below 5% at concentrations ranging from 4 to 9 log10 copies/mL. No cross-reactivity was observed with the 25 microorganisms included in the specificity panel. The clinical sensitivity and specificity of the SMG and RealStar assays compared to in-house polymerase chain reaction and sequencing were as follows: SMG assay, 98.0% and 100% for HHV-6A DNA, respectively, and 96.9% and 100% for HHV-6B DNA, respectively; RealStar assay, 98.0% and 100% for HHV-6A DNA, respectively, and 90.6% and 100% for HHV-6B DNA, respectively. The correlation coefficients between viral loads measured by the two assays were 0.948 and 0.975, with mean differences of 0.62 and 0.32 log10 copies/mL for HHV-6A and HHV-6B DNA, respectively. These results demonstrate that the SMG assay is a sensitive and reliable tool for the quantitative detection and differentiation of HHV-6A and HHV-6B DNA.IMPORTANCEQuantitative real-time PCR (qPCR) that can distinguish between HHV-6A and HHV-6B DNA is recommended for diagnosis of active infection. The SMG HHV-6 Q Real-Time PCR Kit (SMG assay) is a newly developed qPCR assay that can differentiate between HHV-6A and HHV-6B DNA; however, little is known about its performance. In this study, we assessed the performance of the SMG assay and compared it with that of a commercially available qPCR assay, the RealStar HHV-6 PCR Kit (RealStar assay). The SMG assay demonstrated excellent analytical sensitivity and specificity, precision, and linearity. Furthermore, the viral loads measured by the SMG assay were highly correlated with those measured by the RealStar assay. Our results suggest that the SMG assay is a useful diagnostic tool for quantitative detection and differentiation of HHV-6A and HHV-6B DNA.


Assuntos
Herpesvirus Humano 6 , Infecções por Roseolovirus , Humanos , Reação em Cadeia da Polimerase em Tempo Real/métodos , Herpesvirus Humano 6/genética , DNA Viral/genética , Sensibilidade e Especificidade , Carga Viral/métodos , Infecções por Roseolovirus/diagnóstico
8.
J Virol Methods ; 326: 114912, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38447645

RESUMO

Optimal sampling, preservation, and culturing of SARS-CoV-2 from COVID-19 patients are critical for successful recovery of virus isolates and to accurately estimate contagiousness of the patient. In this study, we investigated the influence of the type of sampling media, storage time, freezing conditions, sterile filtration, and combinations of these to determine the optimal pre-analytic conditions for virus recovery and estimation of infectious viral load in COVID-19 patients. Further, we investigated the viral shedding kinetics and mucosal antibody response in 38 COVID-19 hospitalized patients. We found Universal Transport Medium (Copan) to be the most optimal medium for preservation of SARS-CoV-2 infectivity. Our data showed that the probability of a positive viral culture was strongly correlated to Ct values, however some samples did not follow the general trend. We found a significant correlation between plaque forming units and levels of mucosal antibodies and found that high levels of mucosal antibodies correlated with reduced chance of isolating the virus. Our data reveals essential parameters to consider from specimen collection over storage to culturing technique for optimal chance of isolating SARS-CoV-2 and accurately estimating patient contagiousness.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , COVID-19/diagnóstico , Carga Viral , Teste para COVID-19 , Manejo de Espécimes/métodos , RNA Viral
9.
J Virol Methods ; 326: 114913, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38452821

RESUMO

Hepatitis B virus (HBV) infection is a global public health burden and affects approximatively 300 million people around the world. Since, HBV population is represented with genetic diversity, having different viral effects. Development of a new prognosis method play a key role on the efficiency of the different treatment. The HBx protein of HBV has a potential role in Hepatocellular Carcinoma (HCC), which makes it a valuable target for HCC prognosis. In this context, the first quantitative real-time PCR (qRT-PCR) assay in the Mediterranean area was developed and validated. Specific primers and probes of a conserved X region across all HBV genotypes were designed and the qRT-PCR was performed with the TaqPath 1-Step Multiplex Master Mix on 441 Moroccan plasma samples in Pasteur Institute of Morocco. The assay demonstrated a linear quantification range of 1010-101 IU/reaction (R2 = 0.99) and a quantification limit of 15 IU/mL. Comparative evaluations with the COBAS Ampliprep/COBAS TaqMan (CAP/CTM) HBV, v2.0 and the artus HBV QS-RGQ assays showed strong correlations (R2 = 0.92 and R2 = 0.89, respectively). Our test is fast, highly sensitive, specific, reproducible, and labor-saving. This system will be of great advantage to Mediterranean countries in their efforts to eliminate viral hepatitis B and C by 2030, enabling precise monitoring and effective treatment of HBV infections.


Assuntos
Carcinoma Hepatocelular , Hepatite B , Neoplasias Hepáticas , Humanos , Vírus da Hepatite B/genética , Reação em Cadeia da Polimerase em Tempo Real , DNA Viral/genética , Hepatite B/diagnóstico , Carga Viral/métodos , Sensibilidade e Especificidade
10.
J Int Assoc Provid AIDS Care ; 23: 23259582241236061, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38444361

RESUMO

Adolescents living with HIV (ALHIV) face unique challenges resulting in persistent treatment gaps, particularly viral non-suppression. Country programs adopt policies, guidelines, and innovations, based on WHO recommendations and best practices from elsewhere. However, it is unclear to what extent these tools address the management of adolescents with viral non-suppression. We report on a review of guidelines for the provision of HIV services to ALHIV in Namibia. We conducted a systematic document review using Content Analysis and Thematic Analysis methodology, and the READ approach. We identified seven relevant policy documents, four of which somewhat addressed viral non-suppression (treatment gap) in ALHIV and outlined interventions to improve treatment outcomes in adolescents considering their lived experience and unique challenges. The persistent treatment gap may reflect policy implementation gaps in specifically addressing viral non-suppression. It may be worthwhile to leverage existing documents to develop specific operational guidance for ALHIV with unsuppressed viral loads.


Study analysing the potential gaps in the contents of policies and programme documents meant to address management of adolescents living with HIV with high viral load Viral load suppression is a huge challenge in adolescents living with HIV (ALHIV). Globally, adolescents lag when compared to children and adults in achieving viral suppression levels set for achieving HIV epidemic control. The WHO and global HIV program initiatives recommend evidence-based interventions to be included in policies and guidelines to address unique barriers adolescents face that prevent them from staying in HIV care and adhering to their medication. The extent to which country policies guide service providers in managing high viral load cases among adolescents is important in identifying and addressing the persistent gaps. We reviewed the contents of policies, guidelines and other programmatic documents that address HIV management in adolescents in Namibia to assess the extent to which the documents guide management of ALHIV who have high viral load. Seven documents addressing management of ALHIV in Namibia were identified. Four documents address viral suppression among adolescents and recommend some interventions to improve treatment outcomes in adolescents in general. The documents acknowledge the uniqueness of the adolescence, with unique experiences and challenges. However, the documents fall short in providing comprehensive and specific guidance in managing adolescents with high viral loads, for program implementers and direct service providers for ALHIV. The fragmented guidance on managing adolescents with unsuppressed viral loads may be leading to implementation gaps or uncertainties among service providers on how to manage unique cases. It would be essential to focus future efforts on consolidation or development of comprehensive guidance on management of adolescents with high viral load, and capacitating the healthcare providers and stakeholders engaged in addressing social determinants of health affecting these adolescents. A multisectoral approach may provide a pathway to improved viral suppression among ALHIV.


Assuntos
Infecções por HIV , Adolescente , Humanos , Namíbia , Infecções por HIV/tratamento farmacológico , Políticas , Carga Viral
11.
J Biol Dyn ; 18(1): 2325523, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38445631

RESUMO

The adaptive immune system has two types of plasma cells (PC), long-lived plasma cells (LLPC) and short-lived plasma cells (SLPC), that differ in their lifespan. In this paper, we propose that LLPC is crucial to the clearance of viral particles in addition to reducing the viral basic reproduction number in secondary infections. We use a sequence of within-host mathematical models to show that, CD8 T cells, SLPC and memory B cells cannot achieve full viral clearance, and the viral load will reach a low positive equilibrium level because of a continuous replenishment of target cells. However, the presence of LLPC is crucial for viral clearance.


Assuntos
Coinfecção , Plasmócitos , Humanos , Modelos Biológicos , Número Básico de Reprodução , Carga Viral
12.
Curr Opin HIV AIDS ; 19(3): 110-115, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38457193

RESUMO

PURPOSE OF REVIEW: Elite controllers (ECs) and Posttreatment controllers (PTCs) represent a small subset of individuals who are capable of maintaining drug-free control of HIV plasma viral loads despite the persistence of a replication-competent viral reservoir. This review aims to curate recent experimental studies evaluating viral reservoirs that distinguish EC/PTC and may contribute to their ability to maintain undetectable viral loads in the absence of antiretroviral therapy. RECENT FINDINGS: Recent studies on ECs have demonstrated that integration sites of intact proviruses in EC/PTC are markedly biased towards heterochromatin regions; in contrast, intact proviruses in accessible and permissive chromatin were profoundly underrepresented. Of note, no such biases were noted when CD4 + T cells from EC were infected directly ex vivo, suggesting that the viral reservoir profile in EC is not related to altered integration site preferences during acute infection, but instead represents the result of immune-mediated selection mechanisms that can eliminate proviruses in transcriptionally-active euchromatin regions while promoting preferential persistence of intact proviruses in nonpermissive genome regions. Proviral transcription in such "blocked and locked" regions may be restricted through epigenetic mechanisms, protecting them from immune-recognition but presumably limiting their ability to drive viral rebound. While the exact immune mechanisms driving this selection process remain undefined, recent single-cell analytic approaches support the hypothesis that HIV reservoir cells are subject to immune selection pressure by host factors. SUMMARY: A "blocked and locked" viral reservoir profile may constitute a structural virological correlate of a functional cure of HIV-1 infection. Further research into the immunological mechanism promoting HIV-1 reservoir selection and evolution in EC/PTC is warranted and could inform foreseeable cure strategies.


Assuntos
Infecções por HIV , HIV-1 , Humanos , HIV-1/genética , Provírus/genética , Replicação Viral , Linfócitos T CD4-Positivos , Integração Viral , Carga Viral , Latência Viral
13.
Curr Opin HIV AIDS ; 19(3): 124-132, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38502547

RESUMO

PURPOSE OF REVIEW: Despite suppressive antiretroviral therapy (ART), HIV-1 reservoirs persist and reignite viral replication if therapy is interrupted. Persistence of the viral reservoir in people with HIV-1 (PWH) is the main obstacle to an HIV-1 cure. The reservoirs are not transcriptionally silent, and viral transcripts can be detected in most ART-treated individuals. Here, we review the recent progress in the characterization of persistent HIV-1 transcription during ART. RECENT FINDINGS: Evidence from several studies indicates that, although cell-associated unspliced (US) HIV-1 RNA is abundantly expressed in ART-treated PWH, intact full-length US transcripts are rare and most US RNA is derived from defective proviruses. The transcription- and translation-competent defective proviruses, previously considered irrelevant, are increasingly being linked to residual HIV-1 pathogenesis under suppressive ART. Recent data suggest a continuous crosstalk between the residual HIV-1 activity under ART and the immune system. Persistent HIV-1 transcription on ART, despite being mostly derived from defective proviruses, predicts viral rebound upon therapy interruption, suggesting its role as an indicator of the strength of the host antiviral immune response that is shaping the viral rebound. SUMMARY: In light of the recent findings, the significance of persistent HIV-1 transcription during ART for the long-term health of PWH and the cure research should be reassessed.


Assuntos
Infecções por HIV , HIV-1 , Humanos , Infecções por HIV/tratamento farmacológico , HIV-1/genética , Antirretrovirais/uso terapêutico , Replicação Viral , Provírus/genética , RNA Viral/genética , Linfócitos T CD4-Positivos , Carga Viral
14.
BMC Infect Dis ; 24(1): 358, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38549051

RESUMO

BACKGROUND: HIV virological failure is one of the main problems in HIV-infected patients, and identifying the main predictors of such treatment failure may help in combating HIV/AIDS. METHODOLOGY: This cross-sectional study included 1800 HIV-infected patients with either virological failure or treatment response. HIV viral load, CD4 count, and other tests were performed. Statistical analysis was used to determine the predictors of virological failure. RESULTS: Clinical stage, treatment with reverse transcriptase inhibitors (RTIs), under therapy for three years or more, suboptimal adherence to antiretroviral treatment (ART), age > 40 years, CD4 count < 200 cells/mm3, unemployment, being infected through sex, and the presence of symptoms were the predominant risk factors for virological failure. In addition, 55% of patients who experienced virological failure failed to experience immunological and/or clinical failure. CONCLUSION: As the first study in southern Iran and the second in Iran, Iranian policymakers should focus on intensive counseling and adherence support and emphasize more effective treatment regimens such as protease and integrase inhibitors (PIs and INTIs), to increase the chance of a treatment response to ART. The accuracy of identifying clinical and immunological criteria in resource-limited settings is not promising. The present findings can be used to determine effective measures to control HIV treatment failure and design efficient strategies for the ambitious 95-95-95 plan.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Adulto , Humanos , Irã (Geográfico) , Estudos Transversais , Antirretrovirais/uso terapêutico , Antirretrovirais/farmacologia , Falha de Tratamento , Carga Viral , Contagem de Linfócito CD4 , Terapia Antirretroviral de Alta Atividade
15.
BMC Infect Dis ; 24(1): 312, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38486174

RESUMO

BACKGROUND: Availability and accessibility of Antiretroviral drugs (ARV's) improve the lives of People living with HIV (PLHIV) by improving client's immune system to overcome infections and prevent the development of AIDS and other HIV complications. Combination therapy, early initiation of ART, newer ART drugs, single dosage and drug affordability significantly contribute in the reduction of viral multiplication and suppression of HIV to undetectable plasma levels. METHODS: A retrospective longitudinal study design study was conducted from 1st October, 2018 to 30th June 2022 in all supported HIV care and treatment health facilities in Tanga region which were supported by Amref Health Africa, Tanzania. The participants were HIV adult patients aged 15 years and above on ART and attended the clinic at least once after ART initiation. Viral load suppression levels are defined with viral load <1,000 HIV RNA copies/ml (viral load suppression). Cox proportional hazard regression models were employed to identify risk factors for virological failure. P values were two-sided, and we considered a P<0.05 to be statistically significant. RESULTS: Fifty-nine thousand five hundred three adult clients >15 years whom were on ART were included in the analysis to determine the level of plasma Viral Load suppression after being on ART. Female 41,304 (69.4%) and male 18,199 (30.6%). Only four percent (2,290) were found to be unsuppressed i.e having plasma Viral Load >1,000cp/ml while 96% (57,213) were virally suppressed. Several factors were independently associated with virologic failure that included; age between 15 - <25 years (HR: 2.82, 95% CI 1.96 - 4.04), BMI <18.5 (HR: 1.69, 95% CI 1.23 - 2.30), advanced WHO stage IV (HR: 1.60, 95% CI 1.12 - 2.24), CD4 cell count <350 (HR: 2.61, 95% CI 2.12 - 3.23), poor adherence (HR: 1.98, 95% CI 1.80 - 2.18) and not using DTG based drug (HR: 11.8, 95% CI 9.74 - 14.3). CONCLUSION: Virologic failure was observed in this study among clients with young age, advanced WHO stage IV, not using DTG based regimen, poor drug adherence and second line regime. To improve Viral Load Suppression among these clients; the existing HIV intervention strategies should be taken care by targeting the identified risk factors.


Assuntos
Infecções por HIV , Adulto , Humanos , Masculino , Feminino , Adolescente , Estudos Retrospectivos , Tanzânia/epidemiologia , Carga Viral , Estudos Longitudinais , Adesão à Medicação , Instalações de Saúde
16.
Zhonghua Liu Xing Bing Xue Za Zhi ; 45(3): 353-357, 2024 Mar 10.
Artigo em Chinês | MEDLINE | ID: mdl-38514311

RESUMO

Objective: To understand the baseline viral load (VL) of newly reported HIV- infected patients before antiretroviral therapy and related factors in Tianjin. Methods: Data were obtained from the China Disease Control and Prevention Information System, and the study subjects were HIV-infected patients before the first antiretroviral therapy in Tianjin from 2019 to 2022, and the information about their socio-demographic characteristics, baseline CD4+T lymphocyte (CD4) counts before antiretroviral therapy and baseline VL test results were collected, the baseline high VL was defined as ≥100 000 copies/ml. The effect of different factors on viral load were analyzed. Software SPSS 24.0 was used for statistical analysis. Results: A total of 1 296 newly reported HIV-infected patients were included in the study, in whom 15.89% (206/1 296) had high baseline VL, and multifactorial logistic regression analysis showed that those with history of STD (aOR=1.45, 95%CI:1.00-2.08) were more likely to have high baseline VL. Compared with those with baseline CD4 counts <200 cells/µl, those with baseline CD4 counts 200-350 cells/µl (aOR=0.40, 95%CI: 0.27-0.57), 351-500 cells/µl (aOR=0.32, 95%CI: 0.20-0.49), and >500 cells/µl (aOR=0.30, 95%CI: 0.18-0.49) were less likely to have high baseline VL. Conclusions: The proportion of HIV-infected patients with high baseline VL before antiretroviral therapy was low in Tianjin during 2019-2022. History of STD and baseline CD4 counts <200 cells/µl were associated with high baseline VL in HIV-infected patients, to which close attention needs to be paid in AIDS prevention and control.


Assuntos
Síndrome de Imunodeficiência Adquirida , Infecções por HIV , Humanos , Carga Viral , Contagem de Linfócito CD4 , China/epidemiologia , Terapia Antirretroviral de Alta Atividade
17.
PLoS One ; 19(3): e0300508, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38507431

RESUMO

BACKGROUND: Smoking and alcohol use frequently co-occur and are the leading causes of preventable death in sub-Saharan Africa (SSA) and are common among people living with HIV (PLWH). While alcohol use has been shown to be associated with reduced adherence to antiretroviral treatment (ART), which may affect HIV viral suppression, the independent effect of smoking on HIV outcomes in SSA is unknown. We aimed to 1) describe the prevalence of current smoking and correlates of smoking; 2) assess the association of smoking with viral suppression, adjusting for level of alcohol use; 3) explore the relationship between smoking and CD4 cell count <350 cells/mm3, among participants who are virally suppressed. METHODS: We analyzed data from the Drinkers Intervention to Prevent Tuberculosis (DIPT) and the Alcohol Drinkers' Exposure to Preventive Therapy for TB (ADEPTT) studies conducted in Southwest Uganda. The studies enrolled PLWH who were on ART for at least 6 months and co-infected with latent tuberculosis and dominated with participants who had unhealthy alcohol use. Current smoking (prior 3 months) was assessed by self-report. Alcohol use was assessed using the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C, modified for prior 3 months) and phosphatidylethanol (PEth), an alcohol biomarker. We used logistic regression to estimate the cross-sectional association between smoking and lack of virological suppression (≥40 copies/ml), adjusting for level of alcohol use and other covariates, and to examine the association between smoking and CD4 cell counts among PLWH with viral suppression. RESULTS: Of the 955 participants enrolled from 2017 to 2021 who had viral load (VL) results, 63% were men, median age was 40 years (interquartile range [IQR] 32-47), 63% engaged in high/very high-risk alcohol use (AUDIT-C≥6 or PEth≥200 ng/mL), and 22% reported smoking in the prior 3 months. Among 865 participants (91%) with viral suppression and available CD4 count, 11% had a CD4 cell count <350 cells/mm3. In unadjusted and adjusted analyses, there was no evidence of an association between smoking and lack of virological suppression nor between smoking and CD4 count among those with viral suppression. CONCLUSIONS: The prevalence of smoking was high among a study sample of PLWH in HIV care with latent TB in Southwest Uganda in which the majority of persons engaged in alcohol use. Although there was no evidence of an association between smoking and lack of virological suppression, the co-occurrence of smoking among PLWH who use alcohol underscores the need for targeted and integrated approaches to reduce their co-existence and improve health.


Assuntos
Alcoolismo , Fármacos Anti-HIV , Infecções por HIV , Masculino , Humanos , Adulto , Feminino , Estudos Transversais , Alcoolismo/complicações , Fumar/epidemiologia , Uganda/epidemiologia , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Antirretrovirais/uso terapêutico , Contagem de Linfócito CD4 , Etanol/uso terapêutico , Carga Viral , Fármacos Anti-HIV/uso terapêutico
19.
Curr Opin HIV AIDS ; 19(3): 116-123, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38547340

RESUMO

PURPOSE OF REVIEW: To underline the complexity and the heterogeneity of the HIV reservoir. RECENT FINDINGS: While lymphoid tissues (spleen, lymph nodes, gut-associated lymphoid tissue) harbor specific subsets of specialized CD4 +  T cells enriched in HIV-infected cells, non-CD4 +  T cell reservoirs such as tissue-resident macrophages and dendritic cells have also been implicated to contribute to viral persistence. Moreover, studies have applied highly sensitive tools to detect transcriptional activity within HIV-infected cells during prolonged ART and revealed a broader spectrum of transcriptional activity for proviruses than previously thought. Finally, while a combination of factors might be involved in the regulation of HIV persistence within different tissues and remains to be fully elucidated, recent results from autopsy samples of HIV-infected ART suppressed individuals indicate extensive clonality of HIV reservoirs in multiple tissues and suggest that the recirculation of HIV-infected cells and their local expansions in tissues may also contribute to the complexity of the HIV reservoirs in humans. SUMMARY: HIV persistence in blood and multiple tissues despite long-standing and potent therapy is one of the major barriers to a cure. Given that the HIV reservoir is established early and is highly complex based on its composition, viral diversity, tissue distribution, transcriptional activity, replication competence, migration dynamics and proliferative potential across the human body and possible compartmentalization in specific tissues, combinatorial therapeutic approaches are needed that may synergize to target multiple viral reservoirs to achieve a cure for HIV infection.


Assuntos
Infecções por HIV , Humanos , Infecções por HIV/tratamento farmacológico , Linfócitos T CD4-Positivos , Provírus , Latência Viral , Carga Viral
20.
J Clin Microbiol ; 62(4): e0164923, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38470024

RESUMO

Scaling up of newer innovations that address the limitations of the dried blood spot and the logistics of plasma monitoring is needed. We employed a multi-site, cross-sectional assessment of the plasma separation card (PSC) on blood specimens collected from all consenting adults, assenting young and pediatric patients living with HIV from 10 primary healthcare clinics in South Africa. Venous blood for EDTA-plasma samples was collected and analyzed according to the standard of care assay, while collected capillary blood for the PSC samples was analyzed using the Roche COBAS AmpliPrep/Cobas TaqMan (CAP/CTM) HIV-1 Test at the National Reference laboratories. McNemar tests assessed the differences in concordance between the centrifuged plasma and dried plasma spots. The usability of PSC by blood spotting, PSC preparation, and pre-analytical work was assessed by collecting seven-point Likert-scale data from healthcare and laboratory workers. We enrolled 538 patients, mostly adults [n = 515, 95.7% (95% CI: 93.7%-97.1%)] and females [n = 322, 64.2% (95% CI: 60.0%-68.1%)]. Overall, 536 paired samples were collected using both PSC- and EDTA-plasma diagnostics, and 502 paired PSC- and EDTA-plasma samples assessed. Concordance between the paired samples was obtained for 446 samples. Analysis of these 446 paired samples at 1,000 copies per milliliter threshold yielded an overall sensitivity of 87.5% [95% CI: 73.2%-95.8%] and specificity of 99.3% [95% CI: 97.9%-99.8%]. Laboratory staff reported technical difficulties in most tasks. The usability of the PSC by healthcare workers was favorable. For policymakers to consider PSC scale-up for viral load monitoring, technical challenges around using PSC at the clinic and laboratory level need to be addressed. IMPORTANCE: Findings from this manuscript emphasize the reliability of the plasma separation card (PSC), a novel diagnostic method that can be implemented in healthcare facilities in resource-constrained settings. The agreement of the PSC with the standard of care EDTA plasma for viral load monitoring is high. Since the findings showed that these tests were highly specific, we recommend a scale-up of PSC in South Africa for diagnosis of treatment failure.


Assuntos
Infecções por HIV , HIV-1 , Adulto , Feminino , Humanos , Criança , Sensibilidade e Especificidade , HIV-1/genética , Carga Viral/métodos , África do Sul , Estudos Transversais , Ácido Edético , Reprodutibilidade dos Testes , RNA Viral
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