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1.
J Clin Invest ; 134(6)2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38194272

RESUMO

BACKGROUNDSanaria PfSPZ Vaccine, composed of attenuated Plasmodium falciparum (Pf) sporozoites (SPZ), protects against malaria. We conducted this clinical trial to assess the safety and efficacy of PfSPZ Vaccine in HIV-positive (HIV+) individuals, since the HIV-infection status of participants in mass vaccination programs may be unknown.METHODSThis randomized, double-blind, placebo-controlled trial enrolled 18- to 45-year-old HIV-negative (HIV-) and well-controlled HIV+ Tanzanians (HIV viral load <40 copies/mL, CD4 counts >500 cells/µL). Participants received 5 doses of PfSPZ Vaccine or normal saline (NS) over 28 days, followed by controlled human malaria infection (CHMI) 3 weeks later.RESULTSThere were no solicited adverse events in the 9 HIV- and 12 HIV+ participants. After CHMI, 6 of 6 NS controls, 1 of 5 HIV- vaccinees, and 4 of 4 HIV+ vaccinees were Pf positive by quantitative PCR (qPCR). After immunization, anti-Pf circumsporozoite protein (anti-PfCSP) (isotype and IgG subclass) and anti-PfSPZ antibodies, anti-PfSPZ CD4+ T cell responses, and Vδ2+ γδ CD3+ T cells were nonsignificantly higher in HIV- than in HIV+ vaccinees. Sera from HIV- vaccinees had significantly higher inhibition of PfSPZ invasion of hepatocytes in vitro and antibody-dependent complement deposition (ADCD) and Fcγ3B binding by anti-PfCSP and ADCD by anti-cell-traversal protein for ookinetes and SPZ (anti-PfCelTOS) antibodies.CONCLUSIONSPfSPZ Vaccine was safe and well tolerated in HIV+ vaccinees, but not protective. Vaccine efficacy was 80% in HIV- vaccinees (P = 0.012), whose sera had significantly higher inhibition of PfSPZ invasion of hepatocytes and enrichment of multifunctional PfCSP antibodies. A more potent PfSPZ vaccine or regimen is needed to protect those living with HIV against Pf infection in Africa.TRIAL REGISTRATIONClinicalTrials.gov NCT03420053.FUNDINGEquatorial Guinea Malaria Vaccine Initiative (EGMVI), made up of the Government of Equatorial Guinea Ministries of Mines and Hydrocarbons, and Health and Social Welfare, Marathon Equatorial Guinea Production Limited, Noble Energy, Atlantic Methanol Production Company, and EG LNG; Swiss government, through ESKAS scholarship grant no. 2016.0056; Intramural Research Program of the National Institute of Allergy and Infectious Diseases, NIH; NIH grant 1U01AI155354-01.


Assuntos
Infecções por HIV , Vacinas Antimaláricas , Malária Falciparum , Adolescente , Adulto , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Anticorpos Antiprotozoários , População da África Oriental , Infecções por HIV/complicações , Vacinas Antimaláricas/imunologia , Malária Falciparum/prevenção & controle , Plasmodium falciparum , Tanzânia , Soronegatividade para HIV , Soropositividade para HIV , Eficácia de Vacinas
2.
Front Cell Infect Microbiol ; 13: 1163846, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37469600

RESUMO

Background: Sepsis is a life-threatening condition caused by a dysfunctional response to infection from the host. Septic shock, a subset of sepsis, caused by Talaromyces marneffei infection (talaromycosis) has rarely been reported. Owing to its slow culture and low yield, talaromycosis is typically misdiagnosed in HIV-negative patients as other infections, such as tuberculosis, bacterial pneumonia, and lung cancer, especially in non-endemic regions. Early and accurate diagnosis as well as efficient treatment options are required to improve prognosis. Method: A 30-year-old HIV-negative Chinese woman from a non-endemic area of T. marneffei was initially misdiagnosed with tuberculosis. She had a poor response to anti-tuberculosis treatment. On July 16, 2022, she was admitted to our hospital; the patient developed septic shock on the third day after hospitalization and was ultimately diagnosed with talaromycosis via metagenomic next-generation sequencing (mNGS). Result: The condition of the patient improved after appropriate treatment with amphotericin B. Furthermore, enzyme-linked immunosorbent assay results confirmed that the patient had a high-titer of anti-interferon gamma (IFN-γ) autoantibodies. Conclusion: HIV-negative individuals with anti-IFN-γ autoantibodies typically have relapsing, refractory, and fatal infections, such as talaromycosis, which is typically misdiagnosed in the initial course of the disease. This can lead to septic shock. Clinicians should be aware that they may encounter HIV-negative patients with T. marneffei infection in non-endemic areas. Thus, mNGS is an effective technology for detecting T. marneffei infection. Additionally, the detection of anti-IFN-γ autoantibodies in these patients would aid in knowing their susceptibility to fatal infections.


Assuntos
Micoses , Sepse , Choque Séptico , Adulto , Feminino , Humanos , Antifúngicos/uso terapêutico , Autoanticorpos , Sequenciamento de Nucleotídeos em Larga Escala , Interferon gama , Recidiva Local de Neoplasia/tratamento farmacológico , Sepse/tratamento farmacológico , Choque Séptico/diagnóstico , Talaromyces , Soronegatividade para HIV , Micoses/diagnóstico
3.
PLoS One ; 18(7): e0288129, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37410770

RESUMO

BACKGROUND: Sexual minority men (SMM) who engage in condomless anal sex and injection drug use are at increased risk for viral Hepatitis C (HCV) infection. Additionally, studies have found racial disparities in HCV cases across the United States. However, very few epidemiological studies have examined factors associated with HCV infection in HIV-negative Black and Latino SMM. This paper describes the rationale, design, and methodology of a prospective epidemiological study to quantify the HCV prevalence and incidence and investigate the individual and environmental-level predictors of HCV infection among HIV-negative, Black and Latino SMM in the Southern U.S. METHODS: Beginning in September 2021, 400 Black and Latino SMM, aged 18 years and above, will be identified, recruited and retained over 12-months of follow-up from two study sites: greater Washington, DC and Dallas, TX areas. After written informed consent, participants will undergo integrated HIV/STI testing, including HCV, HIV, syphilis, gonorrhea, and chlamydia. Subsequently, participants will complete a quantitative survey-including a social and sexual network inventory-and an exit interview to review test results and confirm participants' contact information. Individual, interpersonal, and environmental factors will be assessed at baseline and follow-up visits (6 and 12 months). The primary outcomes are HCV prevalence and incidence. Secondary outcomes are sexual behavior, substance use, and psychosocial health. RESULTS: To date (March 2023) a total of 162 participants have completed baseline visits at the DC study site and 161 participants have completed baseline visits at the Texas study site. CONCLUSION: This study has several implications that will directly affect the health and wellness of Black and Latino SMM. Specifically, our results will inform more-focused HCV clinical guidelines (i.e., effective strategies for HCV screening among Black/Latino SMM), intervention development and other prevention and treatment activities and development of patient assistance programs for the treatment of HCV among uninsured persons, especially in Deep South, that have yet to expand Medicaid.


Assuntos
Hepatite C , Minorias Sexuais e de Gênero , Infecções Sexualmente Transmissíveis , Humanos , Masculino , Hepatite C/epidemiologia , Hispânico ou Latino , Homossexualidade Masculina , Estudos Prospectivos , Comportamento Sexual , Estados Unidos/epidemiologia , Negro ou Afro-Americano , Projetos de Pesquisa , Soronegatividade para HIV
4.
PLoS One ; 17(12): e0277120, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36480500

RESUMO

Human immunodeficiency virus (HIV) infection still represents a major public health problem worldwide, and its vaccine remains elusive. The study of HIV-exposed seronegative individuals (HESN) brings important information about the natural resistance to HIV, allows a better understanding of the infection, and opens doors for new preventive and therapeutic strategies. Among HESN groups, there are some men who have sex with men (MSM) with high-risk sexual behaviors, who represent an adequate cohort for HESN study because of their major HIV exposure without infection. This study aimed to compare the immunological profile of Colombian seronegative MSM with different risk sexual behaviors. This study included 60 MSM at high-risk (n = 16) and low-risk (n = 44) of HIV-1 acquisition. No sex worker nor homozygous delta 32 mutation subjects were included. All participants were negative for anti-HIV-1/2 antibodies and HIV-1 proviral DNA. A higher frequency of sexual partners in the last 3 months before the study participation (median, 30 vs. 2), lifetime sexual partners (median, 1,708 vs. 26), and unprotected anal intercourse (median 12.5 vs. 2) was determined in high-risk MSM than low-risk MSM. High-risk MSM also showed a quiescent profile of T cells and natural killer (NK) cells, with a significantly lower percentage of CD4+CD38+, CD4+HLADR-CD38+, CD4+Ki67+ T cells, and NKG2D+ NK cells (CD3-CD16+CD56+), a significantly higher percentage of CD4+HLADR-CD38-, and a tendency to show a higher percentage of CD8+HLADR+CD38- T cells than the low-risk group. Likewise, they showed higher mRNA levels of Serpin A1 from PBMCs. The results suggest that this MSM cohort could be HESN individuals and their resistance would be explained by a quiescent profile of T cells and NK cells and an increased Serpin A1 expression. Further study on MSM at high risk of exposure to HIV-1 is necessary to better understand the natural resistance to HIV.


Assuntos
Resistência à Doença , Infecções por HIV , Soronegatividade para HIV , Minorias Sexuais e de Gênero , Humanos , Masculino , alfa 1-Antitripsina , Homossexualidade Masculina , Imunidade , Infecções por HIV/imunologia , Colômbia , Resistência à Doença/imunologia
5.
N Engl J Med ; 386(11): 1013-1025, 2022 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-35294811

RESUMO

BACKGROUND: Valoctocogene roxaparvovec (AAV5-hFVIII-SQ) is an adeno-associated virus 5 (AAV5)-based gene-therapy vector containing a coagulation factor VIII complementary DNA driven by a liver-selective promoter. The efficacy and safety of the therapy were previously evaluated in men with severe hemophilia A in a phase 1-2 dose-escalation study. METHODS: We conducted an open-label, single-group, multicenter, phase 3 study to evaluate the efficacy and safety of valoctocogene roxaparvovec in men with severe hemophilia A, defined as a factor VIII level of 1 IU per deciliter or lower. Participants who were at least 18 years of age and did not have preexisting anti-AAV5 antibodies or a history of development of factor VIII inhibitors and who had been receiving prophylaxis with factor VIII concentrate received a single infusion of 6×1013 vector genomes of valoctocogene roxaparvovec per kilogram of body weight. The primary end point was the change from baseline in factor VIII activity (measured with a chromogenic substrate assay) during weeks 49 through 52 after infusion. Secondary end points included the change in annualized factor VIII concentrate use and bleeding rates. Safety was assessed as adverse events and laboratory test results. RESULTS: Overall, 134 participants received an infusion and completed more than 51 weeks of follow-up. Among the 132 human immunodeficiency virus-negative participants, the mean factor VIII activity level at weeks 49 through 52 had increased by 41.9 IU per deciliter (95% confidence interval [CI], 34.1 to 49.7; P<0.001; median change, 22.9 IU per deciliter; interquartile range, 10.9 to 61.3). Among the 112 participants enrolled from a prospective noninterventional study, the mean annualized rates of factor VIII concentrate use and treated bleeding after week 4 had decreased after infusion by 98.6% and 83.8%, respectively (P<0.001 for both comparisons). All the participants had at least one adverse event; 22 of 134 (16.4%) reported serious adverse events. Elevations in alanine aminotransferase levels occurred in 115 of 134 participants (85.8%) and were managed with immune suppressants. The other most common adverse events were headache (38.1%), nausea (37.3%), and elevations in aspartate aminotransferase levels (35.1%). No development of factor VIII inhibitors or thrombosis occurred in any of the participants. CONCLUSIONS: In patients with severe hemophilia A, valoctocogene roxaparvovec treatment provided endogenous factor VIII production and significantly reduced bleeding and factor VIII concentrate use relative to factor VIII prophylaxis. (Funded by BioMarin Pharmaceutical; GENEr8-1 ClinicalTrials.gov number, NCT03370913.).


Assuntos
Terapia Genética , Vetores Genéticos , Hemofilia A , Hemorragia , Adulto , Humanos , Masculino , Alanina Transaminase/sangue , Dependovirus , Fator VIII/uso terapêutico , Terapia Genética/métodos , Hemofilia A/complicações , Hemofilia A/terapia , Hemorragia/epidemiologia , Hemorragia/etiologia , Hemorragia/prevenção & controle , Soronegatividade para HIV , Infusões Intravenosas , Análise de Intenção de Tratamento
6.
J Orthop Surg Res ; 17(1): 155, 2022 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-35264228

RESUMO

BACKGROUND: Patients with HIV have a higher prevalence of thrombocytopenia than those without HIV infection, increasing their risk of substantial perioperative blood loss (PBL) during total hip arthroplasty (THA). This study aimed to evaluate PBL risk factors in HIV-infected patients undergoing THA. METHODS: Eighteen HIV+ patients (21 hip joints) and 33 HIV- patients (36 joints) undergoing THA were enrolled in this study. PBL was calculated using the Gross equation, which comprises total blood loss (TBL), dominant blood loss (DBL), and hidden blood loss (HBL). Risk factors for post-THA PBL in both patient populations was evaluated using multivariable linear regression. RESULTS: At baseline, the HIV+ patients were younger, more likely to be male and to have elevated hemoglobin and albumin levels, and lower erythrocyte sedimentation rates than HIV- patients. There were no differences in the T-lymphocyte subsets or coagulation function between the two groups. Age and albumin level were identified as potential HBL risk factors after THA, and albumin level was associated with higher TBL. The unadjusted linear regression analysis showed that the HBL and TBL were significantly higher in HIV+ patients than in HIV- patients. However, after adjusting for other factors, no differences in DBL, HBL, or TBL were observed between HIV- and HIV+ patients. CONCLUSION: PBL was similar in both groups undergoing THA, regardless of their HIV-infection status. THA surgery is a safe and effective procedure in HIV+ patients.


Assuntos
Artroplastia de Quadril , Perda Sanguínea Cirúrgica , Soronegatividade para HIV , Soropositividade para HIV , Adolescente , Adulto , Idoso , Albuminas , Terapia Antirretroviral de Alta Atividade , Artroplastia de Quadril/efeitos adversos , Artroplastia de Quadril/métodos , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Osteonecrose , Período Perioperatório , Estudos Retrospectivos
7.
Viruses ; 14(2)2022 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-35215954

RESUMO

We have previously reported that the female genital tract (FGT) of Beninese HIV highly-exposed seronegative (HESN) commercial sex workers (CSWs), presented elevated frequencies of a myeloid HLA-DR+CD14+CD11c+ population presenting "tolerogenic" monocyte derived dendritic cells (MoDC) features. In order to assess whether a differential profile of monocytes may be involved in the generation of these genital MoDCs, we have herein characterized the blood monocyte compartment of Beninese HESNs (HIV-uninfected ≥ 10 years CSWs) and relevant controls (HIV-uninfected 2.5-5 years CSWs herein termed "early HESNs"), HIV-infected CSWs, and low-risk HIV-uninfected women from the general population. Transcriptomic analyses by RNA-Seq of total sorted blood monocytes demonstrate that in comparison to the control groups, HESNs present increased expression levels of FCGR2C, FCAR, ITGAX, ITGAM, CR2, CD68, and CD163 genes, associated with effector functions. Moreover, we found increased expression levels of genes associated with protection/control against SHIV/HIV such as CCL3, CCL4, CCL5, BHLHE40, and TNFSF13, as well as with immune regulation such as IL-10, Ahr, CD83, and the orphan nuclear receptor (NR)4A1, NR4A2, and NR4A3. Through multicolor flow cytometry analyses, we noticed that the frequencies of intermediate and non-classical monocyte populations tended to be elevated in the blood of HESNs, and exhibited increased expression levels of effector CD16, CD11c, CD11b, as well as regulatory HLA-G, IL-10, and IFN-α markers when compared to HIV-uninfected women and/or HIV-infected CSWs. This profile is compatible with that previously reported in the FGT of HESNs, and likely confers an enormous advantage in their resistance to HIV infection.


Assuntos
Soronegatividade para HIV/imunologia , HIV-1/imunologia , Monócitos/imunologia , Profissionais do Sexo/estatística & dados numéricos , Adulto , Fatores de Restrição Antivirais/genética , Fatores de Restrição Antivirais/metabolismo , Benin/epidemiologia , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Resistência à Doença/imunologia , Feminino , Citometria de Fluxo , Perfilação da Expressão Gênica , Infecções por HIV/imunologia , Humanos , Pessoa de Meia-Idade , Monócitos/metabolismo
8.
J Nutr ; 152(11): 2546-2554, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36774120

RESUMO

BACKGROUND: The prevalence of adverse birth outcomes is highest in resource-limited settings such as sub-Saharan Africa. Maternal consumption of diets with adequate nutrients during pregnancy may protect against these adverse outcomes. OBJECTIVES: The objective was to determine the association between maternal dietary consumption of animal source foods (ASFs) and the risk of adverse birth outcomes among HIV-negative pregnant women in Tanzania. METHODS: Using dietary intake data from 7564 HIV-negative pregnant women, we used Poisson regression with the empirical variance (generalized estimating equation) to estimate the RR of adverse birth outcomes-preterm birth, very preterm birth, small for gestational age (SGA), low birth weight (LBW), stillbirth, and neonatal death-for higher and lower frequency of ASF intake. RESULTS: Median daily dietary intake of animal protein was 17 g (IQR: 1-48 g). Higher frequency of ASF protein intake was associated with lower risk of neonatal death (quartile 4 compared with quartile 1; RR: 0.59; 95% CI: 0.38, 0.90; P-trend = 0.01). Higher fish intake was associated with lower risk of very preterm birth (high tertile compared with low; RR: 0.76; 95% CI: 0.58, 0.99; P-trend = 0.02). Any meat intake was protective of preterm birth (RR: 0.73; 95% CI: 0.65, 0.82; P < 0.001), very preterm birth (P < 0.001), LBW (P < 0.001), and neonatal death (P = 0.01) but was associated with increased risk of SGA (RR:1.19; 95% CI: 1.01, 1.36; P = 0.04). Any egg intake was protective of very preterm birth (RR: 0.50; 95% CI: 0.31, 0.83; P = 0.01) as compared with no egg intake. Finally, any dairy intake was associated with lower risk of preterm birth (RR: 0.82; 95% CI: 0.68, 0.98; P = 0.03) and very preterm birth (RR: 0.53; 95% CI: 0.34, 0.84; P = 0.01). CONCLUSIONS: Higher frequency of dietary intake of ASF is associated with lower risk of adverse birth outcomes in urban Tanzania. Promoting prenatal dietary intake of ASF may improve birth outcomes in this region and similar resource-limited settings.


Assuntos
Morte Perinatal , Complicações na Gravidez , Nascimento Prematuro , Animais , Feminino , Humanos , Recém-Nascido , Gravidez , Suplementos Nutricionais , Ingestão de Alimentos , Retardo do Crescimento Fetal , Resultado da Gravidez , Nascimento Prematuro/epidemiologia , Soronegatividade para HIV
9.
Am J Epidemiol ; 191(2): 287-297, 2022 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-34718381

RESUMO

We aimed to describe transitions between preexposure prophylaxis (PrEP) eligibility and human immunodeficiency virus (HIV) infection among HIV-negative men who have sex with men (MSM). We used data from 1,885 MSM, who had not used PrEP, enrolled in the Lisbon Cohort of MSM, with at least 2 consecutive measurements of PrEP eligibility from 2014-2020. A time-homogeneous Markov multistate model was applied to describe the transitions between states of PrEP eligibility-eligible and ineligible-and from these to HIV infection (HIV). The intensities of the transitions were closer for ineligible-to-eligible and eligible-to-ineligible transitions (intensity ratio, 1.107, 95% confidence interval (CI): 1.080, 1.176), while the intensity of the eligible-to-HIV transition was higher than that for ineligible-to-HIV transition (intensity ratio, 9.558, 95% CI: 0.738, 65.048). The probabilities of transitions increased with time; for 90 days, the probabilities were similar for the ineligible-to-eligible and eligible-to-ineligible transitions (0.285 (95% CI: 0.252, 0.319) vs. 0.258 (95% CI: 0.228, 0.287)), while the eligible-to-HIV transition was more likely than ineligible-to-HIV (0.004 (95% CI: 0.003, 0.007) vs. 0.001 (95% CI: 0.001, 0.008)) but tended to become closer with time. Being classified as ineligible was a short-term indicator of a lower probability of acquiring HIV. Once an individual moved to eligible, he was at a higher risk of seroconversion, demanding a timely delivery ofPrEP.


Assuntos
Definição da Elegibilidade/estatística & dados numéricos , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Profilaxia Pré-Exposição/estatística & dados numéricos , Minorias Sexuais e de Gênero/estatística & dados numéricos , Adulto , Soronegatividade para HIV , Humanos , Masculino , Cadeias de Markov , Portugal/epidemiologia
10.
Artigo em Inglês | LILACS | ID: biblio-1410043

RESUMO

ABSTRACT Knowledge about HIV transmission and prevention is a necessary step for adopting preventive behaviors. We assessed HIV knowledge and its correlation with the perceived accuracy of the "Undetectable = Untransmittable" (U=U) slogan in an online sample with 401 adult Brazilians. Overall, 28% of participants showed high HIV knowledge level. The perceived accuracy of the U=U slogan significantly correlated with HIV knowledge. Younger participants, those reporting lower income or lower education, or who had never tested for HIV showed poorer HIV knowledge. Filling gaps of knowledge among specific populations is urgent in order to increase preventive behaviors and decrease HIV stigma.


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Infecções por HIV/transmissão , Conhecimentos, Atitudes e Prática em Saúde , Soronegatividade para HIV , Sobreviventes de Longo Prazo ao HIV , Período de Transmissibilidade
11.
Rev. int. sci. méd. (Abidj.) ; 24(1): 26-33, 2022. figures, tables
Artigo em Francês | AIM (África) | ID: biblio-1396964

RESUMO

Introduction. Le spectre des atteintes cardiovasculaires au cours de l'infection à VIH a été modifi é par la trithérapie antirétrovirale. L'objectif de ce travail était de décrire le profi l des manifestations cardiovasculaires chez les patients vivants avec le VIH en le comparant à celui de patients séronégatifs. Méthodes. Il s'est agi d'une étude cas-témoins des dossiers de patients respectivement séropositifs et séronégatifs hospitalisés pour une pathologie cardiovasculaire au service de cardiologie du Centre Hospitalier Universitaire de Libreville de janvier 2015 à décembre 2018. L'analyse statistique a été réalisée à l'aide du logiciel Statview 5.0. Lestests de Chi-2 de Pearson ou Exact de Ficher ont été utilisés pour la comparaison des proportions. Résultats. L'étude a porté sur sur l'analyse de 82 et 150 dossiers de patients respectivement séropositifs et séronégatifs. Un âge inférieur à 50 ans était retrouvé chez 70,7% des séropositifs et 43,3% des séronégatifs (p<0,01). Le taux de CD4 moyen des séropositifs était de 189±170/mm3 et 45,1% d'entre eux étaient sous trithérapie antiretrovirale.La cardiomyopathie dilatée était l'atteinte cardiaque la plus fréquente chez les séropositifs (42,7%) et chez les séronégatifs (52,7%) (p=0,14). La maladie thromboembolique veineuse était relevée chez 7(8,5%) séropositifs et 14 (8,8%) séronégatifs (p=0,93). Une péricardite était diagnostiquée chez 25,6% des séropositifs avec une étiologie tuberculeuse dans 85,7% des cas. Les pathologies vasculaires athéromateuses étaient plus fréquentes chez les séronégatifs (23,1%) comparés aux séropositifs (6,1%) (p<0,01). La mortalité des séropositifs était principalement due aux péricardites (71,4%). Conclusion. les manifestations cardiovasculaires liées à l'immunodépression persistent chez les personnes vivant avec le VIH à Libreville. Un dépistage précoce de ces atteintes permettrait de réduire la mortalité.


Introduction. The spectrum of cardiovascular damage during HIV infection has been modified by triple antiretroviral therapy. The objective of this study was to describe the profile of cardiovascular manifestations in patients living with HIV by comparing it to the one of seronegative patients. Methods. This was a case-control study which focused on the files of patients hospitalized for a cardiovascular pathology in the cardiology department of the Center Hospitalier Universitaire de Libreville from january 2015 to december. 2018. Results. In total, there was on the analysis of the files of 82 seropositive patients and 150 seronegative patients. The age found was less than 50 years old in 70.7% of seropositives and 43.3% of seronegatives (p <0.01). The mean CD4 count in seropositives was 189 ± 170 /mm3 and 45.1% of them were on triple antiretroviral therapy. Dilated cardiomyopathy was the most common cardiac disease in HIVpositive (42.7%) and HIV-negative (52.7%) (p = 0.14). Venous thromboembolic disease was noted in 7 (8.5%) seropositives and 14 (8.8%) seronegatives (p=0.93).Pericarditis was diagnosed in 25.6% of seropositives patients with a tuberculous etiology in 85.7% of cases. Atheromatous vascular pathologies were more frequent in seronegative (23.1%) compared to seropositive (6.1%) (p <0.01). Mortality among seropositive was mainly due to pericarditis (71.4%)


Assuntos
Humanos , Masculino , Feminino , Infecções por HIV , Soropositividade para HIV , Soronegatividade para HIV , Tromboembolia Venosa , Fatores de Risco de Doenças Cardíacas , Pericardite , Mortalidade , Cardiomiopatias
12.
S. Afr. med. j ; 112(7): 494-501, 2022. figures, tables
Artigo em Inglês | AIM (África) | ID: biblio-1378231

RESUMO

Background. Maternal mental health during the perinatal period has been of interest to many researchers, with antenatal depression and postnatal depression (PND) being a leading cause of morbidity. The adverse effects of maternal depression on the offspring throughout infancy, childhood and adolescence are well documented. Studies on the mental health of persons living with HIV have also reported a high prevalence of depression. Objectives. To describe the prevalence of PND in a sample of HIV-positive and HIV-negative mothers delivering healthy singleton infants at one obstetric unit in KwaZulu-Natal (KZN) Province, South Africa, and the subsequent factors influencing neonatal behaviour and perceptions of caregiver competence. Correlations between the presence of PND and perceptions of caregiver competence (with the mother as caregiver), and between infant behaviour, the mother's confidence in her competence as caregiver, and demographic and medical variables, were also examined. Methods. Demographic and clinical data were collected from 132 mothers at initial contact and from 32 mothers at the 6-week follow-up appointment. Mothers independently completed the Edinburgh Postnatal Depression Scale at each time point, and the Mother and Baby Scales (MABS) at the 6-week follow-up appointment. Results. The prevalence of depression among all mothers at initial contact was 72.0%, remaining high (68.8%) among the mothers who returned for follow-up. There was a statistically significant correlation between depression and employment at follow-up (p=0.013), and between depression and delivery method (p=0.030). The majority of mothers reported being 'able to laugh and see the funny side of things' and 'looking forward with enjoyment to things' at initial contact and follow-up. Thoughts of self-harm were reported by 44.7% of mothers at baseline, and by 53.1% at follow-up. Although most infants scored in the average clinical band for neonatal behavioural factors in the MABS, mothers reported lack of confidence, globally and in caring for their infant. Conclusion. This study of maternal mental health of a sample of HIV-positive and HIV-negative mothers of infants in KZN revealed a higher prevalence of PND than reported in other studies. This population of mothers and infants is at risk of adverse outcomes of maternal depression, in addition to other possible risk factors.


Assuntos
Humanos , Masculino , Feminino , Competência Profissional , Saúde Mental , Soropositividade para HIV , Cuidadores , Soronegatividade para HIV , Saúde Materna , Prevalência
13.
Afr. health sci. (Online) ; 22(2): 27-36, 2022. figures, tables
Artigo em Inglês | AIM (África) | ID: biblio-1400454

RESUMO

Introduction: Literature is limited on HIV and colorectal cancer (CRC) in sub-Saharan Africa despite it being the epicentre of the HIV epidemic, Purpose: To compare clinicopathological features and outcome of CRC in HIV-negative and HIV-positive patients. Methods: Retrospective analysis of a prospective CRC database. Demographic details, HIV status, anatomical site, disease stage, treatment and follow-up were documented. Results: Of 715 patients with CRC, 145 and 570 tested positive and negative respectively for HIV. Median age was 45 (IQR 36-53 and 57 (IQR 45-66) years among HIV-positive and HIV-negative patients respectively (p<0.0001). Tumour differentiation differed between the two groups (p=0.003) but staging was not different (p=0.6). Surgical resection rate was 52% for HIV-positive patients versus 59% for HIV-negative patients (p=0.07). Median follow-up was 9 (IQR 2-20.5) months for HIV-positive patients and 12 (IQR 6-29) months for HIV-negative patients (p=0.154). Recurrence rate was 14.7% among HIV positive patients and 6.8% in HIV negative patients (p=0.089). Conclusion: When compared with HIV-negative patients, HIV-positive patients with CRC presented at a younger age and tended to have lower surgical resection rates. There was no difference between the two groups with CRC in terms of anatomical sub-site distribution, disease staging and recurrence rates


Assuntos
Humanos , Masculino , Feminino , Terapêutica , Neoplasias Colorretais , Infecções por HIV , Soropositividade para HIV , Soronegatividade para HIV , Neoplasias do Colo
14.
BMC Cardiovasc Disord ; 21(1): 593, 2021 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-34911457

RESUMO

BACKGROUND: The extent to which the risk of atherosclerotic cardiovascular disease (ACVD) is increased among people living with HIV (PLWH) in sub-Saharan Africa remains unknown. SETTING: Cross-sectional analysis nested within the Ugandan Noncommunicable Diseases and Aging Cohort, including PLWH in rural Uganda > 40 years taking antiretroviral therapy (ART) for at least 3 years, and a population-based control group of HIV-uninfected age- and sex-matched persons. METHODS: We conducted carotid ultrasonography and collected ACVD risk factor data. Our outcome of interest was carotid plaque, defined as > 1.5 mm thickness from the intima-lumen interface to the media-adventitia interface. We fit multivariable logistic regression models to estimate correlates of carotid plaque including HIV-specific and traditional cardiovascular risk factors. RESULTS: We enrolled 155 (50.2%) PLWH and 154 (49.8%) HIV-uninfected comparators, with a mean age of  51.4 years. Among PLWH, the median CD4 count was 433 cells/mm3 and 97.4% were virologically suppressed. Carotid plaque prevalence was higher among PLWH (8.4% vs 3.3%). HIV infection (aOR 3.90; 95% CI 1.12-13.60) and current smokers (aOR 6.60; 95% CI 1.22-35.80) had higher odds of carotid plaque, whereas moderate (aOR 0.13, 95% CI 0.01-1.55) and vigorous intensity of physical activity (aOR 0.34, 95% CI 0.07-1.52) were associated with decreased odds of carotid plaque. CONCLUSION: In rural Uganda, PLWH have higher prevalence of carotid plaque compared to age- and sex-matched HIV-uninfected comparators. Future work should explore how biomedical and lifestyle modifications might reduce atherosclerotic burden among PLWH in the region.


Assuntos
Doenças das Artérias Carótidas/epidemiologia , Infecções por HIV/epidemiologia , Soronegatividade para HIV , Soropositividade para HIV , Placa Aterosclerótica , Adulto , Doenças das Artérias Carótidas/diagnóstico por imagem , Espessura Intima-Media Carotídea , Estudos de Casos e Controles , Estudos Transversais , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prevalência , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Uganda/epidemiologia
15.
Nat Commun ; 12(1): 7323, 2021 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-34916520

RESUMO

T cell responses to Kaposi's sarcoma-associated herpesvirus (KSHV) are likely essential in the control of KSHV infection and protection from associated disease, but remain poorly characterised. KSHV prevalence in rural Uganda is high at >90%. Here we investigate IFN- γ T cell responses to the KSHV proteome in HIV-negative individuals from a rural Ugandan population. We use an ex-vivo IFN- γ ELISpot assay with overlapping peptide pools spanning 83 KSHV open reading frames (ORF) on peripheral blood mononuclear cells (PBMC) from 116 individuals. KSHV-specific T cell IFN- γ responses are of low intensity and heterogeneous, with no evidence of immune dominance; by contrast, IFN- γ responses to Epstein-Barr virus, Cytomegalovirus and influenza peptides are frequent and intense. Individuals with KSHV DNA in PBMC have higher IFN- γ responses to ORF73 (p = 0.02) and lower responses to K8.1 (p = 0.004) when compared with those without KSHV DNA. In summary, we demonstrate low intensity, heterogeneous T cell responses to KSHV in immune-competent individuals.


Assuntos
Infecções por Herpesviridae/imunologia , Herpesvirus Humano 8/imunologia , Linfócitos T/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Estudos de Coortes , Feminino , Anticorpos Anti-HIV/sangue , Infecções por HIV/sangue , Soronegatividade para HIV , Infecções por Herpesviridae/sangue , Infecções por Herpesviridae/virologia , Herpesvirus Humano 8/genética , Humanos , Interferon gama/imunologia , Leucócitos Mononucleares/imunologia , Masculino , Pessoa de Meia-Idade , Uganda , Adulto Jovem
16.
PLoS One ; 16(12): e0260729, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34855852

RESUMO

Intestinal microbiota facilitates food breakdown for energy metabolism and influences the immune response, maintaining mucosal homeostasis. Overall, HIV infection is associated with intestinal dysbiosis and immune activation, which has been related to seroconversion in HIV-exposed individuals. However, it is unclear whether microbiota dysbiosis is the cause or the effect of immune alterations and disease progression or if it could modulate the risk of acquiring the HIV infection. We characterize the intestinal microbiota and determine its association with immune regulation in HIV-exposed seronegative individuals (HESN), HIV-infected progressors (HIV+), and healthy control (HC) subjects. For this, feces and blood were collected. The microbiota composition of HESN showed a significantly higher alpha (p = 0.040) and beta diversity (p = 0.006) compared to HC, but no differences were found compared to HIV+. A lower Treg percentage was observed in HESN (1.77%) than HC (2.98%) and HIV+ (4.02%), with enrichment of the genus Butyrivibrio (p = 0.029) being characteristic of this profile. Moreover, we found that Megasphaera (p = 0.017) and Victivallis (p = 0.0029) also are enriched in the microbiota composition in HESN compared to HC and HIV+ subjects. Interestingly, an increase in Succinivibrio and Prevotella, and a reduction in Bacteroides genus, which is typical of HIV-infected individuals, were observed in both HESN and HIV+, compared to HC. Thus, HESNs have a microbiota profile, similar to that observed in HIV+, most likely because HESN are cohabiting with their HIV+ partners.


Assuntos
Microbioma Gastrointestinal , Infecções por HIV/patologia , Adolescente , Adulto , Butyrivibrio/isolamento & purificação , Estudos de Casos e Controles , Fezes/microbiologia , Feminino , Infecções por HIV/imunologia , Soronegatividade para HIV , Humanos , Masculino , Megasphaera/isolamento & purificação , Pessoa de Meia-Idade , Prevotella/isolamento & purificação , Linfócitos T Reguladores/citologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Células Th17/citologia , Células Th17/imunologia , Células Th17/metabolismo , Adulto Jovem
17.
Cells ; 10(11)2021 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-34831317

RESUMO

CD46 is the main receptor for complement protein C3 and plays an important role in adaptive immune responses. CD46 genetic variants are associated with susceptibility to several infectious and autoimmune diseases. Additionally, CD46 function can be subverted by HIV-1 to evade attack by complement, a strategy shared by viruses of other families. We sought to determine the association between CD46 gene variants and HIV-1 acquired through intravenous drug use (IDU) and sexual routes (n = 823). Study subjects were of European ancestry and were HIV-1 infected (n = 438) or exposed but seronegative (n = 387). Genotyping of the rs2796265 SNP located in the CD46 gene region was done by allele-specific real-time PCR. A meta-analysis merging IDU and sexual cohorts indicates that the minor genotype (CC) was associated with increased resistance to HIV-1 infection OR = 0.2, 95% CI (0.07-0.61), p = 0.004. The HIV-1-protective genotype is correlated with reduced CD46 expression and alterations in the ratio of CD46 mRNA splicing isoforms.


Assuntos
Predisposição Genética para Doença , Variação Genética , Infecções por HIV/genética , Proteína Cofatora de Membrana/genética , Feminino , Regulação da Expressão Gênica , Frequência do Gene/genética , Soronegatividade para HIV/genética , Humanos , Masculino , Polimorfismo de Nucleotídeo Único/genética , Abuso de Substâncias por Via Intravenosa/genética
18.
J Acquir Immune Defic Syndr ; 88(5): 426-438, 2021 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-34757972

RESUMO

OBJECTIVES: This study describes prevention behavior and psychosocial health among people living with HIV (PLHIV) and HIV-negative people during the early wave of the coronavirus disease 2019 (COVID-19) pandemic in the United States. We assessed differences by HIV status and associations between social disruption and psychosocial health. DESIGN: A cross-sectional telephone/videoconference administered survey of 3411 PLHIV and HIV-negative participants in the Multicenter AIDS Cohort Study/WIHS Combined Cohort Study (MWCCS). METHODS: An instrument combining new and validated measures was developed to assess COVID-19 prevention efforts, social disruptions (loss of employment, childcare, health insurance, and financial supports), experiences of abuse, and psychosocial health. Interviews were performed between April and June 2020. Associations between social disruptions and psychosocial health were explored using multivariable logistic regression, adjusting for sociodemographics and HIV status. RESULTS: Almost all (97.4%) participants reported COVID-19 prevention behavior; 40.1% participants reported social disruptions, and 34.3% reported health care appointment disruption. Men living with HIV were more likely than HIV-negative men to experience social disruptions (40.6% vs. 32.9%; P < 0.01), whereas HIV-negative women were more likely than women with HIV to experience social disruptions (51.1% vs. 39.8%, P < 0.001). Participants who experienced ≥2 social disruptions had significantly higher odds of depression symptoms [aOR = 1.32; 95% confidence interval (CI): 1.12 to 1.56], anxiety (aOR = 1.63; 95% CI: 1.17 to 2.27), and social support dissatisfaction (aOR = 1.81; 95% CI: 1.26 to 2.60). CONCLUSIONS: This study builds on emerging literature demonstrating the psychosocial health impact related to the COVID-19 pandemic by providing context specific to PLHIV. The ongoing pandemic requires structural and social interventions to decrease social disruption and address psychosocial health needs among the most vulnerable populations.


Assuntos
COVID-19/epidemiologia , Soronegatividade para HIV , Soropositividade para HIV/epidemiologia , Soropositividade para HIV/psicologia , Saúde Mental/estatística & dados numéricos , COVID-19/psicologia , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Prevalência , Estados Unidos/epidemiologia
19.
Front Immunol ; 12: 744530, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34712231

RESUMO

HIV-2 is less pathogenic compared to HIV-1. Still, disease progression may develop in aviremic HIV-2 infection, but the driving forces and mechanisms behind such development are unclear. Here, we aimed to reveal the immunophenotypic pattern associated with CD8 T-cell pathology in HIV-2 infection, in relation to viremia and markers of disease progression. The relationships between pathological differences of the CD8 T-cell memory population and viremia were analyzed in blood samples obtained from an occupational cohort in Guinea-Bissau, including HIV-2 viremic and aviremic individuals. For comparison, samples from HIV-1- or dually HIV-1/2-infected and seronegative individuals were obtained from the same cohort. CD8 T-cell exhaustion was evaluated by the combined expression patterns of activation, stimulatory and inhibitory immune checkpoint markers analyzed using multicolor flow cytometry and advanced bioinformatics. Unsupervised multidimensional clustering analysis identified a cluster of late differentiated CD8 T-cells expressing activation (CD38+, HLA-DRint/high), co-stimulatory (CD226+/-), and immune inhibitory (2B4+, PD-1high, TIGIThigh) markers that distinguished aviremic from viremic HIV-2, and treated from untreated HIV-1-infected individuals. This CD8 T-cell population displayed close correlations to CD4%, viremia, and plasma levels of IP-10, sCD14 and beta-2 microglobulin in HIV-2 infection. Detailed analysis revealed that aviremic HIV-2-infected individuals had higher frequencies of exhausted TIGIT+ CD8 T-cell populations lacking CD226, while reduced percentage of stimulation-receptive TIGIT-CD226+ CD8 T-cells, compared to seronegative individuals. Our results suggest that HIV-2 infection, independent of viremia, skews CD8 T-cells towards exhaustion and reduced co-stimulation readiness. Further knowledge on CD8 T-cell phenotypes might provide help in therapy monitoring and identification of immunotherapy targets.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-2/imunologia , Imunossenescência/imunologia , Adulto , Feminino , Soronegatividade para HIV/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Viremia/imunologia
20.
J Acquir Immune Defic Syndr ; 88(3): 314-321, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34651606

RESUMO

BACKGROUND: Islatravir (MK-8591) is a novel nucleoside analog in development for the treatment and prevention of HIV-1 infection. Islatravir has potent antiviral activity and a long intracellular half-life. SETTING: A 3-panel, randomized, double-blind, placebo-controlled, multiple-dose study in 36 adults without HIV evaluated the safety, tolerability, and pharmacokinetics of islatravir after daily administration. METHODS: Islatravir or placebo was administered orally once daily for 42 days (5 mg) or 28 days (0.25 mg; 0.75 mg). Blood samples were taken at prespecified time points for pharmacokinetic analysis of islatravir (plasma) and islatravir-triphosphate (ISL-TP; peripheral blood mononuclear cells [PBMCs]). Rectal and vaginal tissue samples were also collected in a subset of participants. Safety and tolerability were evaluated throughout. RESULTS: The pharmacokinetics of islatravir were approximately dose proportional, with concentrations approaching a steady state between days 14 and 21 in plasma and by day 28 for ISL-TP in PBMCs. Plasma exposure accumulation was 1.5-fold to 1.8-fold, and ISL-TP exposure accumulation was ∼10-fold. The apparent terminal half-life of ISL-TP was 177-209 hours. The ISL-TP pharmacokinetic trough threshold-the minimal concentration required for efficacy-of 0.05 pmol/106 cells was achieved after a single administration at all dose levels. Rectal and vaginal tissue also exhibited potentially therapeutic concentrations. Islatravir was generally well tolerated at all doses. CONCLUSIONS: ISL-TP levels in PBMCs were above the threshold projected for antiviral efficacy against wild-type HIV after a single 0.25-mg dose. Multiple once-daily dosing of islatravir in adults without HIV was generally well tolerated up to doses of 5 mg administered for up to 6 weeks.


Assuntos
Desoxiadenosinas/farmacocinética , Soronegatividade para HIV , Administração Oral , Antivirais/uso terapêutico , Desoxiadenosinas/uso terapêutico , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Feminino , Meia-Vida , Humanos , Leucócitos Mononucleares
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