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1.
Artigo em Inglês | MEDLINE | ID: mdl-34205036

RESUMO

The study sought to determine the impact of COVID-19 on HIV/AIDS programming in the Kibera informal settlement and COVID-19 hotspot counties during the first wave of the pandemic. The study was conducted in two phases. The first phase entailed the analysis of HIV care and treatment secondary data (2018-2020) from the Kenya Health Information System. In the second phase, a prospective cohort study was conducted among people living with HIV in the Kibera informal settlement. A total of 176 participants aged 18 years and above accessing HIV services at selected healthcare facilities in Kibera were randomly sampled from facility electronic medical records and followed up for three months. Socio-demographics and contact details were abstracted from the records and telephone interviews were conducted with consenting participants. Results from the retrospective review of HIV program data indicated a 56% (p < 0.000, 95% CI: 31.3%-62.8%) reduction in uptake of HIV services. Clients starting antiretroviral therapy (ART) reduced significantly by 48% (p < 0.001, 95% CI: 35.4%-77%) in hotspot counties. However, pre-exposure prophylaxis uptake increased significantly by 24% (p < 0.019, 95% CI: 4%-49%). In Kibera, 14% reported missing medications at the onset of the COVID-19 pandemic because of lack of food (38%) and government measures (11%), which affected ART access; 11% did not access health facilities due to fear of contracting COVID-19, government regulations and lack of personal protective equipment. Socioeconomic factors, food insecurity and government measures affected uptake of HIV/AIDS services; hence, the need for scaling up measures to increase access to HIV/AIDS services during the onset of pandemics.


Assuntos
COVID-19 , Infecções por HIV , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Quênia/epidemiologia , Pandemias , Estudos Prospectivos , Estudos Retrospectivos , SARS-CoV-2
2.
Rev Soc Bras Med Trop ; 54: e01032021, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34320130

RESUMO

INTRODUCTION: The concomitant use of antituberculosis and antiretroviral drugs, as well as drugs to treat other diseases, can cause drug-drug interactions. This study aimed to describe potential drug-drug interactions (pDDI) in patients with TB and HIV/AIDS co-infection, as well as to analyze possible associated factors. METHODS: This study was performed in a reference hospital for infectious and contagious diseases in the southeastern region of Brazil and evaluated adult patients co-infected with tuberculosis and HIV/AIDS. A cross-sectional study was conducted in which sociodemographic, clinical, and pharmacotherapeutic characteristics were assessed. The pDDI were identified using the Drug-Reax software. Association analysis was performed using either a chi-squared test or a Fisher's exact test. Correlation analysis was performed using the Spearman's coefficient. RESULTS: The study included 81 patients, of whom 77 (95.1%) were exposed to pDDI. The most frequent interactions were between antituberculosis and antiretroviral drugs, which can cause therapeutic ineffectiveness and major adverse reactions. A positive correlation was established between the number of associated diseases, the number of drugs used, and the number of pDDI. An association was identified between contraindicated and moderate pDDI with excessive polypharmacy and hospitalization. CONCLUSIONS: We found a high frequency of pDDI, especially among those hospitalized and those with excessive polypharmacy. These findings highlight the importance of pharmacists in the pharmacotherapeutic monitoring in these patients.


Assuntos
Síndrome de Imunodeficiência Adquirida , Infecções por HIV , Preparações Farmacêuticas , Tuberculose , Adulto , Brasil , Estudos Transversais , Interações Medicamentosas , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Tuberculose/complicações , Tuberculose/tratamento farmacológico
3.
J Acquir Immune Defic Syndr ; 87(5): 1167-1172, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34229329

RESUMO

BACKGROUND: Data on clinical characteristics and outcomes of people living with HIV (PLWH) hospitalized with coronavirus disease 2019 (COVID-19) who develop acute kidney injury (AKI) are limited. SETTING: Large tertiary health care system in the Bronx, NY. METHODS: We performed a retrospective cohort study of 83 PLWH and 4151 patients without HIV hospitalized with COVID-19 from March 10, 2020, to May 11, 2020. We compared the clinical characteristics and outcomes associated with AKI by HIV serostatus and evaluated HIV-related factors for AKI among PLWH. AKI was defined and staged using Kidney Disease Improving Global Outcomes criteria. RESULTS: The incidence of AKI in hospitalized patients with COVID-19 did not differ significantly by HIV serostatus (54.2% in PLWH vs 49.5% in patients without HIV, P = 0.6). Despite a higher incidence of stage 3 AKI (28.9% vs 17.1% P = 0.05) in PLWH compared with those without HIV, there was no significant difference in the need for renal replacement therapy (22.2% vs 13.4% P = 0.12), renal recovery (76.9% vs 82.5% P = 0.61), or dependence on renal replacement therapy (7.7% vs 3.8% P = 0.27). CD4 T-cell count, HIV-1 RNA viral suppression, and antiretroviral therapy use were not associated with AKI. AKI was associated with increased need for invasive ventilation and in-hospital death, but HIV was not an independent risk factor of in-hospital death after AKI [adjusted hazard ratio 1.01 (95% CI: 0.59 to 1.72), P = 0.98]. CONCLUSIONS: HIV-related factors were not associated with increased risk of AKI in PLWH hospitalized with COVID-19. PLWH hospitalized with COVID-19 had more stage 3 AKI, but outcomes after AKI were similar to those without HIV.


Assuntos
Injúria Renal Aguda/tratamento farmacológico , COVID-19/complicações , Infecções por HIV/tratamento farmacológico , Injúria Renal Aguda/complicações , Injúria Renal Aguda/epidemiologia , Idoso , Antirreumáticos/uso terapêutico , COVID-19/epidemiologia , Feminino , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Mortalidade Hospitalar , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2
4.
J Med Case Rep ; 15(1): 341, 2021 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-34243803

RESUMO

INTRODUCTION: Since its debut recognition in 1981, human immunodeficiency virus/acquired immunodeficiency syndrome has affected over 77 million people and has resulted in premature cessation of 35.4 million lives worldwide. Commonly, human immunodeficiency virus is transmitted by sexual contact across mucosal surfaces, by sharing of injecting equipment, through contaminated blood transfusions, and by maternal-infant exposure. Nevertheless, accidental transmission incidences involving family members are rare but possible. CASE PRESENTATION: A 78-year-old woman of African descent from Mtwara Region south of Tanzania was referred to us for further evaluation and treatment. She is 30 years postmenopausal and has a 35-year history of hypertension. Her last attendance to our institute was 11 months prior the index visit and she tested negative for human immunodeficiency virus. She came with complaints of weight loss, recurrent fevers, and cough. Her hematological tests revealed leukopenia with lymphocytosis, together with a normocytic normochromic anemia. Enzyme-linked immunosorbent assay for human immunodeficiency virus was positive, and she had a CD4 count of 177 cells/µL. We went back to history taking to identify the potential source of infection. We were informed that for the past 6 months, the 78-year-old lady has been living with her unwell 24-year-old granddaughter who has been divorced. The granddaughter had a history of recurrent fevers, significant weight loss, and a suppurative skin condition. As a way to show love and care, the old lady was puncturing the suppurative lesions with bare hands; then she would suck them to clear away the discharge. We requested to see the young lady, and she tested positive for human immunodeficiency virus. Both were started on tenofovir/lamivudine/dolutegravir combination plus cotrimoxazole 960 mg. The family was in total disarray following these findings. The patient was discharged through infectious diseases department and died of Pneumocystis jirovecii pneumonia 12 weeks later. CONCLUSIONS: Certain sociocultural norms that are believed to express love, care, and togetherness in developing rural communities, particularly Sub-Saharan Africa, have a potential of spreading human immunodeficiency virus, thus warranting prompt transformation.


Assuntos
Avós , Infecções por HIV , Adulto , Idoso , Contagem de Linfócito CD4 , Feminino , HIV , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Tanzânia , Adulto Jovem
5.
Medicina (Kaunas) ; 57(6)2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34200527

RESUMO

The pathophysiology of accelerated atherosclerosis in people living with Human Immunofediciency virus (HIV) is complex. Coronary artery disease (CAD) has become an important cause of mortality in these patients. They often have atypical symptoms, leading to frequently missed diagnoses. We report a case of a 51-year-old male undergoing antiretroviral therapy who was admitted for acute coronary syndrome. He had severe coronary artery disease that involved difficult management.


Assuntos
Síndrome Coronariana Aguda , Doença da Artéria Coronariana , Infecções por HIV , Ponte de Artéria Coronária , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico por imagem , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Resultado do Tratamento
6.
Am J Case Rep ; 22: e930828, 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34267172

RESUMO

BACKGROUND Antituberculosis drug-induced hepatotoxicity (ADIH) is a possible adverse event of antitubercular treatment. There are still no official guidelines for ADIH management in children. Recurrent ADIH is infrequently reported. CASE REPORT In this article, we report 6 unusual cases of recurrent ADIH in children. Five children developed ADIH during the intensive phase. Streptomycin and ethambutol were given to those with tuberculosis meningitis, urinary tract tuberculosis, and one patient with pulmonary tuberculosis with HIV infection and cardiac comorbidities. Five patients experienced a second ADIH episode after reintroduction. One patient developed ADIH symptoms again before reaching a full dose of isoniazid. The patient with pulmonary tuberculosis, HIV infection, and dilated cardiomyopathy experienced secondary episodes of ADIH and received levofloxacin and ethambutol as additional drugs. CONCLUSIONS Recurrent ADIH is relatively uncommon in children but may be encountered in daily practice. Reintroduction of previous treatment regimens should be tailored individually. There is an urgent need for standardized guidelines for ADIH in children.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Infecções por HIV , Antituberculosos/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Criança , Infecções por HIV/tratamento farmacológico , Humanos , Isoniazida , Recidiva Local de Neoplasia/tratamento farmacológico
7.
Afr J AIDS Res ; 20(2): 165-171, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34264163

RESUMO

Background: Many people living with HIV struggle to adhere to their antiretroviral therapy, leading to suboptimal health outcomes and increased costs to the healthcare system. Due to their unique training and position in the health care system, South African pharmacists and pharmacy support personnel have the potential to improve adherence through effective patient counselling. However, they are often underutilised and face multiple barriers to providing these services. The aim of this study was to examine how pharmacists and pharmacy personnel view their impact upon the medication adherence behaviours of people living with and receiving medication therapy for HIV.Methods: The study used an exploratory qualitative research design. Our research team conducted in-depth interviews with 24 pharmacy personnel working in public health clinics in the Eastern Cape of South Africa, then used thematic analysis of the qualitative research data to determine the results.Results: Pharmacy personnel identified three key sets of communication challenges that limited effective patient counselling on antiretroviral therapy. These included environmental barriers presented by clinic design, language barriers between patients and pharmacy personnel, and varying communication styles and education levels of pharmacy staff and patients. Additionally, pharmacy personnel described innovative strategies they use to improve patient-provider communication and address adherence issues.Conclusions: Pharmacy personnel working in public health clinics face daily communication challenges as they attempt to provide counselling to patients with HIV. Both the clinic environment and the complex nature of HIV treatment serve as barriers to patient comprehension. In the face of these challenges, pharmacy personnel do their best to implement strategies that enhance patient counselling and address concerns about adherence. Increased attention should be paid to reducing the barriers to pharmacy-based patient counselling and utilising pharmacy personnel to enhance patient understanding and adherence to antiretroviral therapy.


Assuntos
Infecções por HIV/tratamento farmacológico , Pessoal de Saúde/estatística & dados numéricos , Adesão à Medicação , Farmácias , Papel Profissional , Barreiras de Comunicação , Aconselhamento , Infecções por HIV/epidemiologia , Letramento em Saúde , Pessoal de Saúde/educação , Humanos , Assistência Centrada no Paciente , Pesquisa Qualitativa , África do Sul/epidemiologia
8.
BMC Infect Dis ; 21(1): 694, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34281502

RESUMO

BACKGROUND: Support groups for people living with HIV (PLWH) may improve HIV care adherence and outcomes. We assessed the impact of support group attendance on antiretroviral therapy (ART) adherence and viral suppression in four African countries. METHODS: The ongoing African Cohort Study (AFRICOS) enrolls participants at 12 clinics in Kenya, Uganda, Tanzania, and Nigeria. Self-reported attendance of any support group meetings, self-reported ART adherence, and HIV RNA are assessed every 6 months. Logistic regression models with generalized estimating equations were used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (95% CIs) for support group attendance and other factors potentially associated with ART adherence and viral suppression. RESULTS: From January 2013 to December 1, 2019, 1959 ART-experienced PLWH were enrolled and 320 (16.3%) reported any support group attendance prior to enrollment. Complete ART adherence, with no missed doses in the last 30 days, was reported by 87.8% while 92.4% had viral suppression <1000copies/mL across all available visits. There was no association between support group attendance and ART adherence in unadjusted (OR 1.01, 95% CI 0.99-1.03) or adjusted analyses (aOR 1.00, 95% CI 0.98-1.02). Compared to PLWH who did not report support group attendance, those who did had similar odds of viral suppression in unadjusted (OR 0.99, 95% CI 0.978-1.01) and adjusted analyses (aOR 0.99, 95% CI 0.97-1.01). CONCLUSION: Support group attendance was not associated with significantly improved ART adherence or viral suppression, although low support group uptake may have limited our ability to detect a statistically significant impact.


Assuntos
Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , Adesão à Medicação , Grupos de Autoajuda , Adulto , África Oriental , Estudos de Coortes , Feminino , Infecções por HIV/psicologia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Autorrelato , Carga Viral
9.
Blood Adv ; 5(14): 2852-2862, 2021 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-34283175

RESUMO

Data addressing prognostication in patients with HIV related Burkitt lymphoma (HIV-BL) currently treated remain scarce. We present an international analysis of 249 (United States: 140; United Kingdom: 109) patients with HIV-BL treated from 2008 to 2019 aiming to identify prognostic factors and outcomes. With a median follow up of 4.5 years, the 3-year progression-free survival (PFS) and overall survival (OS) were 61% (95% confidence interval [CI] 55% to 67%) and 66% (95%CI 59% to 71%), respectively, with similar results in both countries. Patients with baseline central nervous system (CNS) involvement had shorter 3-year PFS (36%) compared to patients without CNS involvement (69%; P < .001) independent of frontline treatment. The incidence of CNS recurrence at 3 years across all treatments was 11% with a higher incidence observed after dose-adjusted infusional etoposide, doxorubicin, vincristine, prednisone, cyclophosphamide (DA-EPOCH) (subdistribution hazard ratio: 2.52; P = .03 vs other regimens) without difference by CD4 count 100/mm3. In multivariate models, factors independently associated with inferior PFS were Eastern Cooperative Oncology Group (ECOG) performance status 2-4 (hazard ratio [HR] 1.87; P = .007), baseline CNS involvement (HR 1.70; P = .023), lactate dehydrogenase >5 upper limit of normal (HR 2.09; P < .001); and >1 extranodal sites (HR 1.58; P = .043). The same variables were significant in multivariate models for OS. Adjusting for these prognostic factors, treatment with cyclophosphamide, vincristine, doxorubicin, and high-dose methotrexate, ifosfamide, etoposide, and high-dose cytarabine (CODOX-M/IVAC) was associated with longer PFS (adjusted HR [aHR] 0.45; P = .005) and OS (aHR 0.44; P = .007). Remarkably, HIV features no longer influence prognosis in contemporaneously treated HIV-BL.


Assuntos
Linfoma de Burkitt , Infecções por HIV , Linfoma de Burkitt/diagnóstico , Linfoma de Burkitt/tratamento farmacológico , Linfoma de Burkitt/epidemiologia , Intervalo Livre de Doença , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Recidiva Local de Neoplasia , Rituximab , Reino Unido , Estados Unidos/epidemiologia
10.
BMC Health Serv Res ; 21(1): 711, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34284785

RESUMO

BACKGROUND: Scaling up continuous quality improvement (CQI) processes could be key in achieving the 95:95:95 cascade and global HIV targets. This paper describes the experiences and outcomes related to implementing CQI processes to help reach these targets, with particular focus on clinical and programmatic settings in 6 countries from the global south. METHODS: The HIV program at the University of Maryland, Baltimore (UMB) implemented an adapted CQI model in Kenya, Tanzania, Botswana, Zambia, Nigeria and Rwanda that included the following steps: (1) analysing the problem to identify goals and objectives for improvement; (2) developing individual changes or 'change packages', (3) developing a monitoring system to measure improvements; and (4) implementing and measuring changes through continuous 'plan-do-study-act' (PDSA) cycles. We describe country-level experiences related to implementing this adaptive design, a collaborative learning and scale-up/sustainability model that addresses the 95:95:95 global HIV targets via a CQI learning network, and mechanisms for fostering communication and the sharing of ideas and results; we describe trends both before and after model implementation. RESULTS: Our selected country-level experiences based on implementing our CQI approach resulted in an increased partner testing acceptance rate from 21.7 to 48.2 % in Rwanda, which resulted in an increase in the HIV testing yield from 2.1 to 6.3 %. In Botswana, the overall linkage to treatment improved from 63 to 94 %, while in Kenya, the viral load testing uptake among paediatric and adolescent patients improved from 65 to 96 %, and the viral load suppression improved from 53 to 88 %. CONCLUSIONS: Adopting CQI processes is a useful approach for accelerating progress towards the attainment of the global 95:95:95 HIV targets. This paper also highlights the value of institutionalizing CQI processes and building the capacity of Ministry of Health (MoH) personnel in sub-Saharan Africa for the effective quality improvement of HIV programs and subsequent sustainability efforts.


Assuntos
Infecções por HIV , Melhoria de Qualidade , Adolescente , Baltimore , Botsuana , Criança , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Institucionalização , Quênia/epidemiologia , Nigéria , Ruanda , Tanzânia , Zâmbia
11.
Molecules ; 26(13)2021 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-34206893

RESUMO

PF74 is a capsid-targeting inhibitor of HIV replication that effectively perturbs the highly sensitive viral uncoating process. A lack of information regarding the optical purity (enantiomeric excess) of the single stereogenic centre of PF74 has resulted in ambiguity as to the potency of different samples of this compound. Herein is described the synthesis of enantiomerically enriched (S)- and (R)-PF74 and further enrichment of the samples (≥98%) using chiral HPLC resolution. The biological activities of each enantiomer were then evaluated, which determined (S)-PF74 (IC50 1.5 µM) to be significantly more active than (R)-PF74 (IC50 19 µM). Computational docking studies were then conducted to rationalise this large discrepancy in activity, which indicated different binding conformations for each enantiomer. The binding energy of the conformation adopted by the more active (S)-PF74 (ΔG = -73.8 kcal/mol) was calculated to be more favourable than the conformation adopted by the less active (R)-enantiomer (ΔG = -55.8 kcal/mol) in agreement with experimental observations.


Assuntos
Fármacos Anti-HIV/farmacologia , Proteínas do Capsídeo/metabolismo , Capsídeo/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Indóis/farmacologia , Fenilalanina/análogos & derivados , Fármacos Anti-HIV/síntese química , Fármacos Anti-HIV/química , Capsídeo/química , Cromatografia Líquida de Alta Pressão , Células HEK293 , Humanos , Indóis/síntese química , Indóis/química , Concentração Inibidora 50 , Simulação de Acoplamento Molecular , Fenilalanina/síntese química , Fenilalanina/química , Fenilalanina/farmacologia , Estereoisomerismo
14.
Int J Mol Sci ; 22(13)2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34206330

RESUMO

The 'shock-and-kill' strategy to purge the latent HIV reservoir relies on latency-reversing agents (LRAs) to reactivate the provirus and subsequent immune-mediated killing of HIV-expressing cells. Yet, clinical trials employing histone deacetylase inhibitors (HDACis; Vorinostat, Romidepsin, Panobinostat) as LRAs failed to reduce the HIV reservoir size, stressing the need for more effective latency reversal strategies, such as 2-LRA combinations, and enhancement of the immune responses. Interestingly, several LRAs are employed to treat cancer because they up-modulate ligands for the NKG2D NK-cell activating receptor on tumor cells. Therefore, using in vitro T cell models of HIV latency and NK cells, we investigated the capacity of HDACis, either alone or combined with a distinct LRA, to potentiate the NKG2D/NKG2D ligands axis. While Bortezomib proteasome inhibitor was toxic for both T and NK cells, the GS-9620 TLR-7 agonist antagonized HIV reactivation and NKG2D ligand expression by HDACis. Conversely, co-administration of the Prostratin PKC agonist attenuated HDACi toxicity and, when combined with Romidepsin, stimulated HIV reactivation and further up-modulated NKG2D ligands on HIV+ T cells and NKG2D on NK cells, ultimately boosting NKG2D-mediated viral suppression by NK cells. These findings disclose limitations of LRA candidates and provide evidence that NK cell suppression of reactivated HIV may be modulated by specific 2-LRA combinations.


Assuntos
Infecções por HIV/tratamento farmacológico , HIV-1/fisiologia , Inibidores de Histona Desacetilases/uso terapêutico , Células Matadoras Naturais/imunologia , Linfócitos T/virologia , Latência Viral , Infecções por HIV/imunologia , Infecções por HIV/fisiopatologia , Infecções por HIV/terapia , Humanos , Células Matadoras Naturais/fisiologia
15.
Int J Mol Sci ; 22(12)2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34207212

RESUMO

Long-acting (LA) HIV pre-exposure prophylaxis (PrEP) can mitigate challenges of adhering to daily or on-demand regimens of antiretrovirals (ARVs). We are developing a subcutaneous implant comprising polycaprolactone (PCL) for sustained delivery of ARVs for PrEP. Here we use tenofovir alafenamide (TAF) as a model drug. Previously, we demonstrated that the release rates of drugs are controlled by the implant surface area and wall thickness, and the molecular weight (MW) of PCL. Here, we further advance the implant design and tailor the release rates of TAF and the mechanical integrity of the implant through unique polymer blend formulations. In vitro release of TAF from the implant exhibited zero-order release kinetics for ~120 days. TAF release rates were readily controlled via the MW of the polymer blend, with PCL formulations of higher MW releasing the drug faster than implants with lower MW PCL. Use of polymer MW to tune drug release rates is partly explained by PCL crystallinity, as higher PCL crystalline material is often associated with a slower release rate. Moreover, results showed the ability to tailor mechanical properties via PCL blends. Blending PCL offers an effective approach for tuning the ARV release rates, implant duration, and integrity, and ultimately the biodegradation profiles of the implant.


Assuntos
Implantes Absorvíveis , Fármacos Anti-HIV/administração & dosagem , Materiais Biocompatíveis , Preparações de Ação Retardada , Polímeros , Profilaxia Pré-Exposição/métodos , Materiais Biocompatíveis/química , Fenômenos Químicos , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/prevenção & controle , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , Humanos , Polímeros/química , Difração de Raios X
16.
BMC Infect Dis ; 21(1): 657, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34233630

RESUMO

BACKGROUND: HIV-positive patients are increasingly being affected by non-communicable diseases such as coronary artery disease (CAD). Data from high-income countries (HICs) indicate that HIV-positive patients have different risk-factor profiles for acute coronary syndrome (ACS) as well as different cardiac manifestations of this syndrome compared to HIV-negative patients. There is limited data from Sub-Saharan Africa (SSA), and particularly from South Africa with the biggest HIV epidemic in the world. The objective of this study was to determine the 12-month period prevalence of HIV in patients with ACS and to compare the risk-factor profile, ACS presentation and management between HIV-positive and HIV-negative adults. METHODS: We included all patients hospitalised with ACS from 01 January to 31 December 2018 in a tertiary hospital, Tygerberg Hospital, in Cape Town, South Africa. The HIV-status of all patients was determined using routine clinical records. We performed multiple conditional logistic regression on HIV-positive and HIV-negative patients (1:3 ratio) to compare the risk factor profile, ACS presentation and management between the groups. RESULTS: Among 889 patients, 30 (3.4%) were HIV-positive (95% confidence interval (CI): 2.3-4.8). HIV-positive patients were younger, more frequently men, and had a lower prevalence of medical comorbidities and a family history of CAD. They were more likely to present with ST-elevation myocardial infarction (STEMI) [odd's ratio (OR) (95% CI): 3.12 (1.2-8.4)], and have single-vessel disease [OR (95% CI): 3.03 (1.2-8.0)]. Angiographic and echocardiographic data, as well as management, did not differ between the groups. Among HIV-positive patients, 17 (65%) were virally suppressed (HIV viral load < 200 copies/mL) with a median CD4+ count of 271 cells/mm3. The majority (20, 67%) of HIV-positive patients were receiving antiretroviral therapy at the time of the ACS. CONCLUSIONS: We found an HIV-prevalence of 3.4% (95% CI 2.3-4.8) in adults with ACS in a high endemic HIV region. HIV-positive patients were younger and more likely to present with STEMIs and single-vessel disease, but had fewer CAD risk factors, suggesting additional mechanisms for the development of ACS.


Assuntos
Síndrome Coronariana Aguda/epidemiologia , Doença da Artéria Coronariana/epidemiologia , Infecções por HIV/epidemiologia , Síndrome Coronariana Aguda/terapia , Adulto , Idoso , Comorbidade , Estudos Transversais , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Risco , África do Sul/epidemiologia
17.
N Engl J Med ; 385(4): 330-341, 2021 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-34289276

RESUMO

BACKGROUND: The World Health Organization recommends dolutegravir with two nucleoside reverse-transcriptase inhibitors (NRTIs) for second-line treatment of human immunodeficiency virus type 1 (HIV-1) infection. Evidence is limited for the efficacy of this regimen when NRTIs are predicted to lack activity because of drug resistance, as well as for the recommended switch of an NRTI from tenofovir to zidovudine. METHODS: In a two-by-two factorial, open-label, noninferiority trial, we randomly assigned patients for whom first-line therapy was failing (HIV-1 viral load, ≥1000 copies per milliliter) to receive dolutegravir or ritonavir-boosted darunavir and to receive tenofovir or zidovudine; all patients received lamivudine. The primary outcome was a week 48 viral load of less than 400 copies per milliliter, assessed with the Food and Drug Administration snapshot algorithm (noninferiority margin for the between-group difference in the percentage of patients with the primary outcome, 12 percentage points). RESULTS: We enrolled 464 patients at seven sub-Saharan African sites. A week 48 viral load of less than 400 copies per milliliter was observed in 90.2% of the patients in the dolutegravir group (212 of 235) and in 91.7% of those in the darunavir group (210 of 229) (difference, -1.5 percentage points; 95% confidence interval [CI], -6.7 to 3.7; P = 0.58; indicating noninferiority of dolutegravir, without superiority) and in 92.3% of the patients in the tenofovir group (215 of 233) and in 89.6% of those in the zidovudine group (207 of 231) (difference, 2.7 percentage points; 95% CI, -2.6 to 7.9; P = 0.32; indicating noninferiority of tenofovir, without superiority). In the subgroup of patients with no NRTIs that were predicted to have activity, a viral load of less than 400 copies per milliliter was observed in more than 90% of the patients in the dolutegravir group and the darunavir group. The incidence of adverse events did not differ substantially between the groups in either factorial comparison. CONCLUSIONS: Dolutegravir in combination with NRTIs was effective in treating patients with HIV-1 infection, including those with extensive NRTI resistance in whom no NRTIs were predicted to have activity. Tenofovir was noninferior to zidovudine as second-line therapy. (Funded by Janssen; NADIA ClinicalTrials.gov number, NCT03988452.).


Assuntos
Fármacos Anti-HIV/administração & dosagem , Darunavir/administração & dosagem , Infecções por HIV/tratamento farmacológico , HIV-1 , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Oxazinas/administração & dosagem , Piperazinas/administração & dosagem , Piridonas/administração & dosagem , Inibidores da Transcriptase Reversa/administração & dosagem , Tenofovir/administração & dosagem , Zidovudina/administração & dosagem , Adolescente , Adulto , Fármacos Anti-HIV/efeitos adversos , Criança , Darunavir/efeitos adversos , Resistência a Medicamentos , Quimioterapia Combinada , Feminino , Infecções por HIV/virologia , HIV-1/isolamento & purificação , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Oxazinas/efeitos adversos , Piperazinas/efeitos adversos , Piridonas/efeitos adversos , Inibidores da Transcriptase Reversa/efeitos adversos , Carga Viral , Adulto Jovem
18.
PLoS One ; 16(7): e0254994, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34288954

RESUMO

Since the onset of the COVID-19 pandemic, it has been unclear how vulnerable people with HIV (PwH) are to SARS-CoV-2 infection. We sought to determine if PwH are more likely to test positive for SARS-CoV-2 than people without HIV, and to identify risk factors associated with SARS-CoV-2 positivity among PwH. We conducted a cross-sectional study in which we collected electronic medical record data for all patients who underwent SARS-CoV-2 PCR testing at an academic medical center. Presence of HIV and other chronic diseases were based on the presence of ICD-10 diagnosis codes. We calculated the percent positivity for SARS-CoV-2 among PwH and among people without HIV. Among PwH, we compared demographic factors, comorbidities, HIV viral load, CD4 T-cell count, and antiretroviral therapy (ART) regimens between those who tested positive for SARS-CoV-2 and those who tested negative. Comparisons were made using chi squared tests or Wilcoxon rank sum tests. Multivariate models were created using logistic regression. Among 69,763 people tested for SARS-CoV-2, 0.6% (431) were PwH. PwH were not significantly more likely to test positive for SARS-CoV-2 than people without HIV (7.2% (31/431) vs 8.4% (5820/69763), p = 0.35), but were more likely to be younger, Black, and male (p-values < .0001). There were no significant differences in HIV clinical factors, chronic diseases, or ART regimens among PwH testing positive for SARS-CoV-2 versus those testing negative. In our sample, PwH were not more likely to contract SARS-CoV-2, despite being more likely to be members of demographic groups known to be at higher risk for infection. Differences between PwH who tested positive for SARS-CoV-2 and those who tested negative were only seen in Hispanic/Latino ethnicity (non-Hispanic or Latino vs unknown Hispanic or Latino ethnicity (OR 0.2 95% CI (0.6, 0.9)) and site of testing(inpatient vs outpatient OR 3.1 95% CI (1.3, 7.4)).


Assuntos
Centros Médicos Acadêmicos/estatística & dados numéricos , Infecções por HIV/virologia , SARS-CoV-2/isolamento & purificação , Adulto , Idoso , Fármacos Anti-HIV/uso terapêutico , COVID-19/complicações , COVID-19/epidemiologia , Cidades/estatística & dados numéricos , Comorbidade , Estudos Transversais , Demografia , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Fatores de Risco , SARS-CoV-2/fisiologia
19.
Medicine (Baltimore) ; 100(28): e26605, 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34260544

RESUMO

RATIONALE: The presentation of multiple intestinal perforations is a severe complication of enteric cytomegalovirus (CMV) infection, sometimes associated with immune reconstitution inflammatory syndrome (IRIS) after the initiation of antiretroviral therapy (ART) in patients with human immunodeficiency virus (HIV). Here we reported a rare case of a patient with HIV infection who developed multiple perforations in the small bowel shortly after ART initiation without any prodromal gastrointestinal symptoms. We also reviewed the literature of reported cases to clarify their clinical characteristics for early diagnosis and rapid intervention. PATIENT CONCERNS: A patient with HIV presented with fever after 16 days of ART initiation and was admitted to our hospital. He was treated with intravenous ganciclovir due to persistent CMV viremia. The fever resolved 10 days later. However, he reported persistent left lower abdominal pain. DIAGNOSES: The patient was diagnosed with multiple small bowel perforations, CMV-related IRIS, and acquired immune deficiency syndrome. An upright abdominal x-ray in a tertiary level hospital revealed bilateral moderate intraperitoneal free air. We performed a pathological examination and metagenomic next-generation sequencing. CMV enteritis was confirmed by immunohistochemical staining and other opportunistic infections were excluded by metagenomic next-generation sequencing. INTERVENTIONS: The patient was treated with intravenous ganciclovir and 24 hours later, the patient underwent exploratory laparotomy. Partial resection and surgical repair of the small intestine were performed. OUTCOMES: The patient ultimately died from intestinal obstruction and septic shock 55 days after surgery. LESSONS: Perforations due to CMV-related IRIS are very rare, and usually appear shortly after ART initiation. Most cases lack the prodromal symptoms of abdominal pain and diarrhea. Intestinal perforations are lethal, and early detection and surgical treatment are lifesaving.


Assuntos
Infecções por Citomegalovirus/complicações , Infecções por HIV/complicações , Síndrome Inflamatória da Reconstituição Imune/complicações , Perfuração Intestinal/complicações , Adulto , Antirretrovirais/uso terapêutico , Ganciclovir/uso terapêutico , Infecções por HIV/tratamento farmacológico , Humanos , Síndrome Inflamatória da Reconstituição Imune/tratamento farmacológico , Perfuração Intestinal/terapia , Perfuração Intestinal/virologia , Masculino
20.
Medicine (Baltimore) ; 100(28): e26653, 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34260568

RESUMO

RATIONALE: Acute retroviral syndrome is the symptomatic presentation of acute human immunodeficiency virus (HIV) infection, which often manifests as a self-limited infectious mononucleosis-like syndrome and occurs 2 to 6 weeks after exposure to HIV. Atypical manifestations including hepatitis, meningitis, or hemophagocytic lymphohistiocytosis have been reported. However, manifestations of acute acalculous cholecystitis during acute HIV infection are rarely reported. PATIENT CONCERNS: A 30-year-old man with nausea and loose stools, followed by fever and abdominal pain at the right upper quadrant for 10 days. DIAGNOSIS: Acute retroviral syndrome, complicated with acute acalculous cholecystitis. INTERVENTIONS: Percutaneous transhepatic gallbladder drainage was performed and treatment with co-formulated bictegravir/emtricitabine/tenofovir alafenamide was initiated upon HIV diagnosis. OUTCOMES: The patient's symptoms improved after the drainage. The levels of liver enzyme including aspartate transaminase alanine aminotransferase decreased to a level within normal limits 1 month after initiation of antiretroviral therapy. CONCLUSION: Acalculous cholecystitis in combination with acute hepatitis could be manifestations of acute HIV infection. For individuals at risk of acquiring HIV infection who present with manifestations of acute acalculous cholecystitis, HIV testing should be considered.


Assuntos
Colecistite Acalculosa/etiologia , Infecções por HIV/complicações , Colecistite Acalculosa/diagnóstico , Adulto , Antirretrovirais/uso terapêutico , Diagnóstico Diferencial , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Humanos , Masculino
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