Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 25.732
Filtrar
1.
BMC Pregnancy Childbirth ; 24(1): 278, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622544

RESUMO

BACKGROUND: In 2015, Togo introduced the "test-and-treat" strategy for the prevention of mother-to-child transmission (PMTCT) of HIV. Pediatric HIV infection remains a public health problem in Togo, with a mother-to-child transmission (MTCT) rate of 3.6% in 2020. This study aimed to estimate cases of HIV seroconversion during pregnancy and to identify pregnant women at high risk of transmitting HIV to their children in Lomé, Togo. METHODS: A descriptive cross-sectional study was carried out from 18 March to 22 May 2022 among women who had given birth in five maternity units providing PMTCT services in Lomé. Umbilical cord blood samples were taken from the maternal side by midwives after delivery. HIV serology was performed in the laboratory using the Alere™ HIV Combo SET and First Response HIV 1-2. Card Test version 2.0. A sample was considered positive if both tests were positive. The HIV-1 viral load in HIV-1-positive samples was measured using Cobas/Roche 4800 equipment. Information on the women was extracted from maternal antenatal records and antenatal consultation registers. RESULTS: A total of 3148 umbilical cord blood samples (median maternal age: 28 years (interquartile range [24-32]) were collected. Among them, 99.3% (3145/3148) had presented for at least one antenatal clinic visit before giving birth, and 78.7% (2456/3122) had presented for at least four visits. One hundred and twenty-one (121) cord samples were HIV-1 positive, representing a seroprevalence of 3.8% (95% CI = [3.2-4.6]). Among them, 67.8% (82/121) were known HIV-positive before the current pregnancy, 29.7 (36/121) were diagnosed as HIV-positive at the antenatal visits and 2.5% (3/121) were diagnosed as HIV-positive in the delivery room. Of the HIV-positive women, 85.9% (104/121) were on ARV treatment before delivery. The viral load was < 1000 copies/ml in 97.5% (118/121) cases. CONCLUSION: This study explored the virologic and epidemiological aspects of HIV among pregnant women in Togo. The results show significant viral suppression at delivery in women ART. Surveillance based on umbilical cord blood specimen screening is an interesting approach for monitoring the effectiveness of PMTCT programmes.


Assuntos
Infecções por HIV , Soropositividade para HIV , HIV-1 , Complicações Infecciosas na Gravidez , Gravidez , Feminino , Humanos , Adulto , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/prevenção & controle , Gestantes , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Togo/epidemiologia , Estudos Transversais , Estudos Soroepidemiológicos
2.
Proc Natl Acad Sci U S A ; 121(15): e2316662121, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38557187

RESUMO

Drug resistance in HIV type 1 (HIV-1) is a pervasive problem that affects the lives of millions of people worldwide. Although records of drug-resistant mutations (DRMs) have been extensively tabulated within public repositories, our understanding of the evolutionary kinetics of DRMs and how they evolve together remains limited. Epistasis, the interaction between a DRM and other residues in HIV-1 protein sequences, is key to the temporal evolution of drug resistance. We use a Potts sequence-covariation statistical-energy model of HIV-1 protein fitness under drug selection pressure, which captures epistatic interactions between all positions, combined with kinetic Monte-Carlo simulations of sequence evolutionary trajectories, to explore the acquisition of DRMs as they arise in an ensemble of drug-naive patient protein sequences. We follow the time course of 52 DRMs in the enzymes protease, RT, and integrase, the primary targets of antiretroviral therapy. The rates at which DRMs emerge are highly correlated with their observed acquisition rates reported in the literature when drug pressure is applied. This result highlights the central role of epistasis in determining the kinetics governing DRM emergence. Whereas rapidly acquired DRMs begin to accumulate as soon as drug pressure is applied, slowly acquired DRMs are contingent on accessory mutations that appear only after prolonged drug pressure. We provide a foundation for using computational methods to determine the temporal evolution of drug resistance using Potts statistical potentials, which can be used to gain mechanistic insights into drug resistance pathways in HIV-1 and other infectious agents.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Soropositividade para HIV , HIV-1 , Humanos , HIV-1/genética , Farmacorresistência Viral/genética , Genótipo , Infecções por HIV/tratamento farmacológico , Infecções por HIV/genética , Mutação , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico
3.
S Afr Fam Pract (2004) ; 66(1): e1-e8, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38572873

RESUMO

BACKGROUND:  The study explored and described the meaning attached to the lived experiences of women living with human immunodeficiency virus (HIV) in the rural context of Zimbabwe. Stigma and discrimination negatively impact one's ability to perform the expected social roles, the quality of life, and the efforts to prevent the spread of HIV and acquired immunodeficiency syndrome (AIDS) and reduce HIV-related mortality. Thus, the study aims to understand the meaning attached to the lived experiences of HIV-positive women living in rural areas or villages of Matabeleland South province in Zimbabwe. METHODS:  The study used a qualitative, descriptive, and exploratory design. Four focus group discussions were conducted with 24 HIV-positive rural women living in Matabeleland South province, Zimbabwe. An Interpretative Phenomenological Analysis (IPA) was adopted to explore and describe the meaning attached to the lived experiences of women living with HIV. RESULTS:  Two interconnected themes were identified in the analysis with their sub-themes. These were: (1) struggle for social belonging, with subthemes - loss of social belonging and reduced access to community-based empowerment opportunities and (2) struggle for maintaining the quality of life with subthemes - lack of need-based community healthcare and food insecurity. CONCLUSION:  Being a woman living with HIV in rural Zimbabwe means a perpetual struggle to maintain one's humanness and quality of life.Contribution: This study's results will support the efforts of the Zimbabwean government to improve the quality of life of HIV-positive women living in rural areas.


Assuntos
Síndrome de Imunodeficiência Adquirida , Infecções por HIV , Soropositividade para HIV , Humanos , Feminino , Grupos Focais , Zimbábue , Qualidade de Vida
4.
Sci Rep ; 14(1): 8700, 2024 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622191

RESUMO

HIV infection has been a global public health threat and overall reported ~ 40 million deaths. Acquired immunodeficiency syndrome (AIDS) is attributed to the retroviruses (HIV-1/2), disseminated through various body fluids. The temporal progression of AIDS is in context to the rate of HIV-1 infection, which is twice as protracted in HIV-2 transmission. Q-PCR is the only available method that requires a well-developed lab infrastructure and trained personnel. Micro-PCR, a portable Q-PCR device, was developed by Bigtec Labs, Bangalore, India. It is simple, accurate, fast, and operationalised in remote places where diagnostic services are inaccessible in developing countries. This novel micro-PCR determines HIV-1 and HIV-2 viral load using a TruePrep™ extractor device for RNA isolation. Five ml blood samples were collected at the blood collection centre at AIIMS, New Delhi, India. Samples were screened for serology, and a comparison of HIV-1/2 RNA was done between qPCR and micro-PCR in the samples. The micro-PCR assay of HIV-RNA has compared well with those from real-time PCR (r = 0.99, i < 0.002). Micro-PCR has good inter and intra-assay reproducibility over a wide dynamic range (1.0 × 102-1.0 × 108 IU/ml). The linear dynamic range was 102-108 IU/ml. The clinical and analytical specificity of the assay was comparable, i.e., 100%. Intra-assay and inter-assay coefficients of variation ranged from 1.17% to 3.15% and from 0.02% to 0.46%, respectively. Moreover, due to the robust, simple, and empirical method, the Probit analysis has also been done for qPCR LODs to avoid uncertainties in target recoveries. The micro-PCR is reliable, accurate, and reproducible for early detection of HIV-1 and HIV-2 viral loads simultaneously. Thus, it can easily be used in the field and in remote places where quantification of both HIV-1/2 is not reachable.


Assuntos
Síndrome de Imunodeficiência Adquirida , Infecções por HIV , Soropositividade para HIV , HIV-1 , Humanos , HIV-1/genética , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , RNA Viral/análise , Índia , Reação em Cadeia da Polimerase em Tempo Real/métodos , HIV-2/genética , Carga Viral/métodos
5.
JCI Insight ; 9(7)2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38587079

RESUMO

BACKGROUNDBroadly neutralizing monoclonal antibodies (bNAbs) represent a promising strategy for HIV-1 immunoprophylaxis and treatment. 10E8VLS and VRC07-523LS are bNAbs that target the highly conserved membrane-proximal external region (MPER) and the CD4-binding site of the HIV-1 viral envelope glycoprotein, respectively.METHODSIn this phase 1, open-label trial, we evaluated the safety and pharmacokinetics of 5 mg/kg 10E8VLS administered alone, or concurrently with 5 mg/kg VRC07-523LS, via s.c. injection to healthy non-HIV-infected individuals.RESULTSEight participants received either 10E8VLS alone (n = 6) or 10E8VLS and VRC07-523LS in combination (n = 2). Five (n = 5 of 8, 62.5%) participants who received 10E8VLS experienced moderate local reactogenicity, and 1 participant (n = 1/8, 12.5%) experienced severe local reactogenicity. Further trial enrollment was stopped, and no participant received repeat dosing. All local reactogenicity resolved without sequelae. 10E8VLS retained its neutralizing capacity, and no functional anti-drug antibodies were detected; however, a serum t1/2 of 8.1 days was shorter than expected. Therefore, the trial was voluntarily stopped per sponsor decision (Vaccine Research Center, National Institute of Allergy and Infectious Diseases [NIAID], NIH). Mechanistic studies performed to investigate the underlying reason for the reactogenicity suggest that multiple mechanisms may have contributed, including antibody aggregation and upregulation of local inflammatory markers.CONCLUSION10E8VLS resulted in unexpected reactogenicity and a shorter t1/2 in comparison with previously tested bNAbs. These studies may facilitate identification of nonreactogenic second-generation MPER-targeting bNAbs, which could be an effective strategy for HIV-1 immunoprophylaxis and treatment.TRIAL REGISTRATIONClinicaltrials.gov, accession no. NCT03565315.FUNDINGDivision of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH.


Assuntos
Infecções por HIV , Soropositividade para HIV , HIV-1 , Humanos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/prevenção & controle , Anticorpos Anti-HIV , Anticorpos Amplamente Neutralizantes/farmacologia , Anticorpos Monoclonais/farmacologia
6.
J Med Virol ; 96(4): e29594, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38576317

RESUMO

The HIV capsid (CA) protein is a promising target for anti-AIDS treatment due to its critical involvement in viral replication. Herein, we utilized the well-documented CA inhibitor PF74 as our lead compound and designed a series of low-molecular-weight phenylalanine derivatives. Among them, compound 7t exhibited remarkable antiviral activity with a high selection index (EC50 = 0.040 µM, SI = 2815), surpassing that of PF74 (EC50 = 0.50 µM, SI = 258). Furthermore, when evaluated against the HIV-2 strain, 7t (EC50 = 0.13 µM) demonstrated approximately 14-fold higher potency than that of PF74 (EC50 = 1.76 µM). Insights obtained from surface plasmon resonance (SPR) revealed that 7t exhibited stronger target affinity to the CA hexamer and monomer in comparison to PF74. The potential interactions between 7t and the HIV-1 CA were further elucidated using molecular docking and molecular dynamics simulations, providing a plausible explanation for the enhanced target affinity with 7t over PF74. Moreover, the metabolic stability assay demonstrated that 7t (T1/2 = 77.0 min) significantly outperforms PF74 (T1/2 = 0.7 min) in human liver microsome, exhibiting an improvement factor of 110-fold. In conclusion, 7t emerges as a promising drug candidate warranting further investigation.


Assuntos
Fármacos Anti-HIV , Soropositividade para HIV , Humanos , Capsídeo/metabolismo , Fenilalanina/farmacologia , Fenilalanina/metabolismo , Simulação de Acoplamento Molecular , Fármacos Anti-HIV/farmacologia , Proteínas do Capsídeo/metabolismo , Antirretrovirais
8.
AIDS Res Ther ; 21(1): 19, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561779

RESUMO

BACKGROUND: Syphilis is an infection caused by the bacteria Treponema pallidum. It is mainly transmitted through oral, vaginal and anal sex, in pregnancy and through blood transfusion. Syphilis develops in primary, secondary, latent and tertiary stages and presents with different clinical features at each stage. Infected patients can remain asymptomatic for several years and, without treatment, can, in extreme cases, manifest as damage in several organs and tissues, including the brain, nervous tissue, eyes, ear and soft tissues. In countries with a high human immunodeficiency virus (HIV) burden, syphilis increases the risk of HIV infections. We report the case of a young HIV-positive black woman who presented with alopecia and hypopigmentation as features of secondary syphilis. CASE PRESENTATION: A virologically suppressed 29-year-old woman on Anti-retroviral Therapy (ART) presented with a short history of generalized hair loss associated with a non-itchy maculopapular rash and skin depigmentation on the feet. Limited laboratory testing confirmed a diagnosis of secondary syphilis. She was treated with Benzathine Penicillin 2.4MU. After receiving three doses of the recommended treatment, the presenting features cleared, and the patient recovered fully. CONCLUSION: This case demonstrates the importance of a high index of clinical suspicion and testing for syphilis in patients presenting with atypical clinical features of secondary syphilis, such as hair loss and hypopigmentation. It also highlights the challenges in diagnosing and clinically managing syphilis in a resource-limited setting.


Assuntos
Infecções por HIV , Soropositividade para HIV , Hipopigmentação , Sífilis , Adulto , Feminino , Humanos , Alopecia/complicações , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Soropositividade para HIV/complicações , Hipopigmentação/complicações , Sífilis/complicações , Sífilis/diagnóstico , Sífilis/tratamento farmacológico , População Negra
9.
Sci Rep ; 14(1): 8296, 2024 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594292

RESUMO

Late presentation to medical care of individuals infected with the human immunodeficiency virus (HIV) is linked to poor outcomes and increased morbidity and mortality. Missed opportunities for a prompt diagnosis are frequently reported among late presenters. We aimed to estimate the proportion of late presenters and missed opportunities in diagnosis among newly diagnosed HIV-positive subjects presenting to a specialty clinic in Lebanon. This is a retrospective chart review of all newly diagnosed adult HIV-positive subjects presenting to clinic from 2012 to 2022. Demographic, laboratory, and clinical data were collected at initial HIV diagnosis or presentation to medical care. We defined late presentation as having a CD4 count < 350 or AIDS-defining event regardless of CD4 count. Advanced disease is defined as having a CD4 count below 200 cells/µL or the presence of an AIDS-defining illness, regardless of the CD4 count. A missed opportunity was defined as the presence of an indicator condition (IC) that suggests infection with HIV/AIDS during 3 years preceding the actual HIV diagnosis and not followed by a recommendation for HIV testing. The proportions for demographic, epidemiological, and clinical characteristics are calculated by excluding cases with missing information from the denominator. Our cohort included 150 subjects (92.7% males; 63.6% men who have sex with men (MSM); 33.3% heterosexuals; median age 30.5 years at diagnosis). 77 (51.3%) were late presenters and 53 (35.3% of all subjects, 68.8% of late presenters) had advanced HIV on presentation. Up to 76.5% of late presenters had a presentation with an HIV-related condition at a healthcare provider without getting HIV test within the previous 3 years. The most frequent ICs were weight loss, generalized lymphadenopathy, constitutional symptoms, and chronic idiopathic diarrhea. Overall mortality rate was 4% (6/150 individuals). All-cause mortality among those who presented with AIDS was 15.4% (6/39 subjects). In our setting, late presentations and missed opportunities for HIV diagnosis are common. In the Middle East, AIDS mortality remains high with a large gap in HIV testing. To effectively influence policies, comprehensive analyses should focus on estimating the preventable health and financial burdens of late HIV presentations. Another concern pertains to healthcare providers' attitudes and competencies.


Assuntos
Síndrome de Imunodeficiência Adquirida , Infecções por HIV , Soropositividade para HIV , Minorias Sexuais e de Gênero , Masculino , Adulto , Humanos , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Homossexualidade Masculina , HIV , Estudos Retrospectivos , Fatores de Risco , Líbano/epidemiologia , Diagnóstico Tardio , Contagem de Linfócito CD4
10.
S Afr J Surg ; 62(1): 89-91, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38568134

RESUMO

SUMMARY: Gestational gigantomastia is a rare condition typified by disproportionate bilateral breast enlargement in pregnant women, resulting in skin thinning, ulceration, and bleeding. Less than sixty cases have been documented worldwide, and only one other in South Africa. Pseudo-angiomatous stromal hyperplasia (PASH) is a rare benign proliferation of stromal tissue in a tumorous or diffuse pattern. This, to the best of our knowledge, is the first published case, a 27-year-old human immunodeficiency virus (HIV) positive woman, to present with both conditions concurrently. Medical management with cabergoline was initiated and, seven months post-delivery, a novel Goldilocks mastectomy was performed with acceptable outcomes.


Assuntos
Neoplasias da Mama , Mama/anormalidades , Soropositividade para HIV , Hipertrofia , Gravidez , Feminino , Humanos , Adulto , Hiperplasia/complicações , Mastectomia
12.
AIDS Res Ther ; 21(1): 17, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38515183

RESUMO

BACKGROUND: As the population of people with HIV ages, concerns over managing age-related comorbidities, polypharmacy, immune recovery, and drug-drug interactions while maintaining viral suppression have arisen. We present pooled TANGO and SALSA efficacy and safety results dichotomized by age (< 50 and ≥ 50 years). METHODS: Week 48 data from the open-label phase 3 TANGO and SALSA trials evaluating switch to once-daily dolutegravir/lamivudine (DTG/3TC) fixed-dose combination vs continuing current antiretroviral regimen (CAR) were pooled. Proportions of participants with HIV-1 RNA ≥ 50 and < 50 copies/mL (Snapshot, intention-to-treat exposed) and safety were analyzed by age category. Adjusted mean change from baseline in CD4 + cell count was assessed using mixed-models repeated-measures analysis. RESULTS: Of 1234 participants, 80% of whom were male, 29% were aged ≥ 50 years. Among those aged ≥ 50 years, 1/177 (< 1%) DTG/3TC participant and 3/187 (2%) CAR participants had HIV-1 RNA ≥ 50 copies/mL at 48 weeks; proportions with HIV-1 RNA < 50 copies/mL were high in both treatment groups (≥ 92%), consistent with overall efficacy and similar to observations in participants aged < 50 years (≥ 93%). Regardless of age category, CD4 + cell count increased or was maintained from baseline with DTG/3TC. Change from baseline in CD4 + /CD8 + ratio was similar across age groups and between treatment groups. One CAR participant aged < 50 years had confirmed virologic withdrawal, but no resistance was detected. In the DTG/3TC group, incidence of adverse events (AEs) was similar across age groups. Proportions of AEs leading to withdrawal were low and comparable between age groups. Although drug-related AEs were generally low, across age groups, drug-related AEs were more frequent in participants who switched to DTG/3TC compared with those who continued CAR. While few serious AEs were observed in both treatment groups, more were reported in participants aged ≥ 50 years vs < 50 years. CONCLUSIONS: Among individuals with HIV-1, switching to DTG/3TC maintained high rates of virologic suppression and demonstrated a favorable safety profile, including in those aged ≥ 50 years despite higher prevalence of concomitant medication use and comorbidities. TRIAL REGISTRATION NUMBER: TANGO, NCT03446573 (February 27, 2018); SALSA, NCT04021290 (July 16, 2019).


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Soropositividade para HIV , HIV-1 , Oxazinas , Piperazinas , Piridonas , Humanos , Masculino , Feminino , Lamivudina/efeitos adversos , Fármacos Anti-HIV/efeitos adversos , Infecções por HIV/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Antirretrovirais/uso terapêutico , Soropositividade para HIV/tratamento farmacológico , RNA
13.
Front Immunol ; 15: 1272493, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38433846

RESUMO

Introduction: A limited subset of HIV-1 infected adult individuals typically after at least 2-3 years of chronic infection, develop broadly neutralizing antibodies (bnAbs), suggesting that highly conserved neutralizing epitopes on the HIV-1 envelope glycoprotein are difficult for B cell receptors to effectively target, during natural infection. Recent studies have shown the evolution of bnAbs in HIV-1 infected infants. Methods: We used bulk BCR sequencing (BCR-seq) to profile the B cell receptors from longitudinal samples (3 time points) collected from a rare pair of antiretroviralnaïve, HIV-1 infected pediatric monozygotic twins (AIIMS_329 and AIIMS_330) who displayed elite plasma neutralizing activity against HIV-1. Results: BCR-seq of both twins revealed convergent antibody characteristics including V-gene use, CDRH3 lengths and somatic hypermutation (SHM). Further, antibody clonotypes with genetic features similar to highly potent bnAbs isolated from adults showed ongoing development in donor AIIMS_330 but not in AIIMS_329, corroborating our earlier findings based on plasma bnAbs responses. An increase in SHM was observed in sequences of the IgA isotype from AIIMS_330. Discussion: This study suggests that children living with chronic HIV-1 can develop clonotypes of HIV-1 bnAbs against multiple envelope epitopes similar to those isolated from adults, highlighting that such B cells could be steered to elicit bnAbs responses through vaccines aimed to induce bnAbs against HIV-1 in a broad range of people including children.


Assuntos
Soropositividade para HIV , HIV-1 , Adulto , Lactente , Humanos , Criança , Anticorpos Amplamente Neutralizantes , Receptores de Antígenos de Linfócitos B/genética , Anticorpos , Antígenos Virais , Epitopos , Gêmeos Monozigóticos
14.
Cell Rep ; 43(3): 113948, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38483908

RESUMO

Identifying individual functional B cell receptors (BCRs) is common, but two-dimensional analysis of B cell frequency versus BCR potency would delineate both quantity and quality of antigen-specific memory B cells. We efficiently determine quantitative BCR neutralizing activities using a single-cell-derived antibody supernatant analysis (SCAN) workflow and develop a frequency-potency algorithm to estimate B cell frequencies at various neutralizing activity or binding affinity cutoffs. In an HIV-1 fusion peptide (FP) immunization study, frequency-potency curves elucidate the quantity and quality of FP-specific immunoglobulin G (IgG)+ memory B cells for different animals, time points, and antibody lineages at single-cell resolution. The BCR neutralizing activities are mainly determined by their affinities to soluble envelope trimer. Frequency analysis definitively demonstrates dominant neutralizing antibody lineages. These findings establish SCAN and frequency-potency analyses as promising approaches for general B cell analysis and monoclonal antibody (mAb) discovery. They also provide specific rationales for HIV-1 FP-directed vaccine optimization.


Assuntos
Infecções por HIV , Soropositividade para HIV , HIV-1 , Animais , Anticorpos Neutralizantes , Anticorpos Anti-HIV , Imunoglobulina G , Células B de Memória
15.
Lancet Microbe ; 5(4): e345-e354, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38458206

RESUMO

BACKGROUND: In 2018, the tuberculosis molecular bacterial load assay (TB-MBLA), a ribosomal RNA-based test, was acknowledged by WHO as a molecular assay that could replace smear microscopy and culture for monitoring tuberculosis treatment response. In this study, we evaluated the accuracy of TB-MBLA for diagnosis and monitoring of treatment response in comparison with standard-of-care tests. METHODS: For this longitudinal prospective study, patients aged 18 years or older with presumptive tuberculosis (coughing for at least 2 weeks, night sweats, and weight loss) were enrolled at China-Uganda Friendship Hospital Naguru (Kampala, Uganda). Participants were evaluated for tuberculosis by TB-MBLA in comparison with Xpert MTB/RIF Ultra (Xpert-Ultra) and smear microscopy, with Mycobacteria Growth Indicator Tube (MGIT) culture as a reference test. Participants who were positive on Xpert-Ultra were enrolled on a standard 6-month anti-tuberculosis regimen, and monitored for treatment response at weeks 2, 8, 17, and 26 after initiation of treatment and then 3 months after treatment. FINDINGS: Between Nov 15, 2019, and June 15, 2022, 210 participants (median age 35 years [IQR 27-44]) were enrolled. 135 (64%) participants were male and 72 (34%) were HIV positive. The pretreatment diagnostic sensitivities of TB-MBLA and Xpert-Ultra were similar (both 99% [95% CI 95-100]) but the specificity was higher for TB-MBLA (90% [83-96]) than for Xpert-Ultra (78% [68-86]). Ten participants were Xpert-Ultra trace positive, eight (80%) of whom were negative by TB-MBLA and MGIT culture. Smear microscopy had lower diagnostic sensitivity (75% [65-83]) but higher specificity (98% [93-100]) than TB-MBLA and Xpert-Ultra. Among participants who were smear microscopy negative, the sensitivity of TB-MBLA was 96% (95 CI 80-100) and was 100% (95% CI 86-100) in those who were HIV positive. 129 (61%) participants were identified as tuberculosis positive by Xpert-Ultra and these individuals were enrolled in the treatment group and monitored for treatment response. According to TB-MBLA, 19 of these patients cleared bacillary load to zero by week 2 of treatment and remained negative throughout the 6-month treatment follow-up. Positivity for tuberculosis decreased with treatment as measured by all tests, but the rate was slower with Xpert-Ultra. Consequently, 31 (33%) of 95 participants were still Xpert-Ultra positive at the end of treatment but were clinically well and negative on TB-MBLA and culture at 6 months of treatment. Two patients were still Xpert-Ultra positive with a further 3 months of post-treatment follow-up. The rate of conversion to negative of the DNA-based Xpert-Ultra was 3·3-times slower than that of the rRNA-based TB-MBLA. Consequently for the same patient, it would take 13 weeks and 52 weeks to reach complete tuberculosis negativity by TB-MBLA and Xpert-Ultra, respectively. Participants who were positive on smear microscopy at 8 weeks, who received an extra month of intensive treatment, had a similar TB-MBLA-measured bacillary load at 8 weeks to those who were smear microscopy negative. INTERPRETATION: TB-MBLA has a similar performance to Xpert-Ultra for pretreatment diagnosis of tuberculosis, but is more accurate at detecting and characterising the response to treatment than Xpert-Ultra and standard-of-care smear microscopy. FUNDING: European and Developing Countries Clinical Trials Partnership, Makerere University Research and Innovation Fund, US National Institutes of Health.


Assuntos
Antibióticos Antituberculose , Soropositividade para HIV , Mycobacterium tuberculosis , Tuberculose Pulmonar , Tuberculose , Estados Unidos , Humanos , Masculino , Adulto , Feminino , Antibióticos Antituberculose/uso terapêutico , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/microbiologia , Rifampina/farmacologia , Rifampina/uso terapêutico , Uganda , Estudos Prospectivos , Carga Bacteriana , Microscopia , Sensibilidade e Especificidade , Mycobacterium tuberculosis/genética , Tuberculose/tratamento farmacológico , Soropositividade para HIV/tratamento farmacológico
16.
J Acquir Immune Defic Syndr ; 96(1): 1-10, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38427920

RESUMO

BACKGROUND: Non-AIDS-defining cancers (NADCs) in patients infected with HIV have recently attracted attention because of the improved survival of this patient population. To obtain accurate data, a longitudinal study is warranted for the nationwide surveillance of the current status and national trend of NADCs in patients infected with HIV in Japan. SETTING: An annual nationwide surveillance of NADCs in patients infected with HIV-1 in Japan from 1999 to 2021. METHODS: An annual questionnaire was sent to 378 HIV/AIDS referral hospitals across Japan to collect data (clusters of differentiation 4-positive lymphocytes, time of onset, outcomes, and antiretroviral therapy status) of patients diagnosed with any of the NADCs between 1999 and 2021. RESULTS: The response and case-capture rates for the questionnaires in 2021 were 37.8% and 81.2%, respectively. The number of reported NADC cases subsequently increased since the beginning of this study. Evaluation of the case counts of NADCs demonstrated a high incidence of lung, colorectal, gastric, and liver cancers as the top 4 cancers. Pancreatic cancer (0.63), lung cancer (0.49), and leukemia (0.49) had the highest mortality rates among the NADCs. Trends of NADCs regarding transmission routes were maintained over the years in male individuals who have sex with male individuals compared with heterosexual male individuals and female individuals. CONCLUSIONS: We demonstrated an increasing trend in the incidence of NADCs over a period of 23 years in Japan. The current data highlighted the importance of raising awareness regarding cancer management for patients infected with HIV in Japan.


Assuntos
Síndrome de Imunodeficiência Adquirida , Infecções por HIV , Soropositividade para HIV , HIV-1 , Neoplasias Hepáticas , Neoplasias , Humanos , Masculino , Feminino , Síndrome de Imunodeficiência Adquirida/epidemiologia , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Estudos Longitudinais , Japão/epidemiologia , Fatores de Risco , Neoplasias/complicações , Neoplasias/epidemiologia , Neoplasias Hepáticas/epidemiologia , Hospitais , Encaminhamento e Consulta , Incidência
17.
Lancet HIV ; 11(4): e222-e232, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38538161

RESUMO

BACKGROUND: Long-acting injectable cabotegravir and rilpivirine have demonstrated safety, acceptability, and efficacy in adults living with HIV-1. The IMPAACT 2017 study (MOCHA study) was the first to use these injectable formulations in adolescents (aged 12-17 years) living with HIV-1. Herein, we report acceptability and tolerability outcomes in cohort 1 of the study. METHODS: In this a secondary analysis of a phase 1/2, multicentre, open-label, non-comparative dose-finding study, with continuation of pre-study oral combination antiretroviral treatment (ART), 55 adolescents living with HIV-1 were enrolled to receive sequential doses of either long-acting cabotegravir or rilpivirine and 52 received at least two injections. Participants had a body weight greater than 35 kg and BMI less than 31·5 kg/m2 and had been on stable ART for at least 90 consecutive days with an HIV-1 viral load of less than 50 copies per mL at a participating IMPAACT study site. Participants had to be willing to continue their pre-study ART during cohort 1. The primary objectives of the study were to confirm doses for oral and injectable cabotegravir and for injectable rilpivirine in adolescents living with HIV. This analysis of participant-reported outcomes included a face scale assessment of pain at each injection and a Pediatric Quality of Life Inventory (PedsQL) at baseline and week 16 for participants in the USA, South Africa, Botswana, and Thailand. A subset of 11 adolescents and 11 parents or caregivers in the USA underwent in-depth interviews after receipt of one or two injections. This trial is registered at ClinicalTrials.gov, NCT03497676. FINDINGS: Between March 19, 2019, and Nov 25, 2021, 55 participants were enrolled into cohort 1. Using the six-point face scale, 43 (83%) of participants at week 4 and 38 (73%) at week 8 reported that the injection caused "no hurt" or "hurts little bit", while only a single (2%) participant for each week rated the pain as one of the two highest pain levels. Quality of life was not diminished by the addition of one injectable antiretroviral. In-depth interviews revealed that parents and caregivers in the USA frequently had more hesitancy than adolescents about use of long-acting formulations, but parental acceptance was higher after their children received injections. INTERPRETATION: High acceptability and tolerability of long-acting cabotegravir or rilpivirine injections suggests that these are likely to be favoured treatment options for some adolescents living with HIV. FUNDING: National Institutes of Health and ViiV Healthcare.


Assuntos
Fármacos Anti-HIV , Dicetopiperazinas , Infecções por HIV , Soropositividade para HIV , HIV-1 , Piridonas , Adulto , Criança , Humanos , Adolescente , Rilpivirina/uso terapêutico , Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Qualidade de Vida , Antirretrovirais/uso terapêutico , Soropositividade para HIV/tratamento farmacológico , Dor/tratamento farmacológico
18.
Int J Infect Dis ; 142: 106994, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38447753

RESUMO

OBJECTIVES: Despite successful human immunodeficiency virus (HIV) control with combination antiretroviral therapy (cART), individuals with HIV still face health risks, including cancers, cardiovascular and neurocognitive diseases. An HIV protein, Tat, is potentially involved in these HIV-related diseases. Previous studies demonstrated circulating Tat in the blood of untreated people with HIV. Here, we measured Tat levels in the serum of cART-treated people with HIV to examine the effect of cART on Tat production. METHODS: Serum samples from 63 HIV-positive and 20 HIV-seronegative individuals were analyzed using an ELISA assay that detected Tat concentrations above 2.5 ng/mL. RESULTS: Among HIV-positive individuals, the Tat level ranged from 0 to 14 ng/mL. 25.4% (16 out of 63) exceeded the 2.5 ng/mL cut-off, with a median HIV Tat level of 4.518 [3.329-8.120] ng/mL. No correlation was revealed between Tat levels and CD4+ T cell counts, serum HIV RNA, p24 antigen, or anti-Tat levels. CONCLUSIONS: Despite cART, circulating HIV Tat persists and may contribute to HIV-related diseases. This emphasizes the need for further research on the mechanisms of Tat action in non-infected cells where it can penetrate upon circulation in the blood.


Assuntos
Infecções por HIV , Soropositividade para HIV , HIV-1 , Humanos , HIV-1/genética , Linfócitos T CD4-Positivos , Contagem de Linfócito CD4
19.
Public Health ; 230: 38-44, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38492260

RESUMO

OBJECTIVES: Disease progression, loss to follow-up, and mortality of HIV-2 compared with HIV-1 in children is not well understood. This is the first nationwide study reporting outcomes in children with the two HIV types in Guinea-Bissau. STUDY DESIGN: Nationwide retrospective follow-up study. METHODS: This is a retrospective follow-up study among HIV-infected children <15 years at nine ART centers from 2006 to 2021. Baseline parameters and disease outcomes for children with HIV-2 and HIV-1 were compared. RESULTS: The annual number of children diagnosed with HIV peaked in 2017. HIV-2 (n = 64) and HIV-1 (n = 1945) infected children were different concerning baseline median age (6.5 vs 3.1 years, P < 0.01), but had similar levels of severe immunodeficiency (P = 0.58) and severe anemia (P = 0.26). Within the first year of follow-up, 36.3% were lost, 5.9% died, 2.7% had transferred clinic, and 55.2% remained for follow-up. Mortality (HR = 1.05 95% CI: 0.53-2.08 for HIV-2) and attrition (HR = 0.86 95% CI: 0.62-1.19 for HIV-2) rates were similar for HIV types. CONCLUSIONS: The decline in children diagnosed per year since 2017 is possibly due to lower HIV prevalence, lack of HIV tests, and the SARS-CoV-2 epidemic. Children with HIV-2 were twice as old as HIV-1 infected when diagnosed, which suggests a slower disease progression. However, once they develop immunosuppression mortality is similar.


Assuntos
Infecções por HIV , Soropositividade para HIV , HIV-1 , Criança , Humanos , Pré-Escolar , Seguimentos , Estudos Retrospectivos , Infecções por HIV/epidemiologia , HIV-2 , Guiné-Bissau/epidemiologia , Progressão da Doença
20.
AIDS Res Ther ; 21(1): 18, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38549087

RESUMO

We conducted secondary data analysis using a biobehavioral survey dataset of 1538 MSM from Zimbabwe. Survey participants were screened for the four symptoms suggestive of tuberculosis infection using the WHO TB screening algorithm. Results: All participants experienced at least one symptom suggestive of tuberculosis. 40% of HIV-positive MSM reported having had a cough in the last month and 13% of them experienced unexpected weight loss. The prevalence of experiencing any of the four TB symptoms amongst HIV-positive MSM was 23%. Contribution There is an urgent need for active TB case finding and treatment amongst HIV-positive MSM in Zimbabwe. Clinicians will need to ensure that MSM who need TB testing receive it timeously.


Assuntos
Infecções por HIV , Soropositividade para HIV , Minorias Sexuais e de Gênero , Tuberculose , Masculino , Humanos , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Homossexualidade Masculina , Zimbábue/epidemiologia , Soropositividade para HIV/complicações , Tuberculose/complicações , Tuberculose/diagnóstico , Tuberculose/epidemiologia , Prevalência
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...