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1.
Medicine (Baltimore) ; 100(6): e23626, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33578511

RESUMO

BACKGROUND: The number of adult patients affected by the human immunodeficiency virus (HIV) still remains high, mainly in the developing countries. However, only a few affected patients fail to experience oral lesions in the course of their experience with the virus. In particular, oral mucosa ulcers detected among HIV patients may be severe, which depictions may inhibit oral functioning and change patients' quality of life. Thus, it can result in considerable morbidity among this group of patients. To this end, the present study aims to examine the topical agent's clinical therapeutic efficacy among adult patients suffering from HIV-related oral mucosa ulcers. METHODS: For the investigation, only randomized controlled trials on any topical agent used to treat adult patients with HIV oral mucosa ulcers are to be explored from different databases: PubMed, the Cochrane Library, PsycINFO, EMBASE, SCOPUS, Web of Science, China Biomedical Literature Database, China National Knowledge Infrastructure, VIP, and WanFang databases. All databases will be searched from their inceptions to October 2020. Additionally, 2 independent authors will evaluate the possibly eligible studies to be included in the study. They will also perform data's trial extraction and risk of bias assessment. Accordingly, all data will be analysed by means of the RevMan 5.3 software. RESULTS: The present study seeks to evaluate the topical agents' clinical therapeutic efficacy to treat adult patients with HIV-related oral mucosa ulcers. CONCLUSION: The study can be applicable in providing evidence of any topical agents for treating adult patients with HIV-related oral mucosa ulcers for clinical practice. PROTOCOL REGISTRATION NUMBER: DOI 10.17605/OSF.IO/5CYR2 (https://osf.io/5cyr2/).


Assuntos
Anti-Infecciosos Locais/uso terapêutico , Infecções por HIV/complicações , Mucosa Bucal/patologia , Úlceras Orais/tratamento farmacológico , Adulto , Anti-Infecciosos Locais/administração & dosagem , Estudos de Casos e Controles , HIV/efeitos dos fármacos , Infecções por HIV/epidemiologia , Humanos , Mucosa Bucal/virologia , Úlceras Orais/psicologia , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
2.
Lancet HIV ; 8(2): e106-e113, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33539757

RESUMO

Ending the AIDS epidemic by 2030 will require addressing stigma more systematically and at a larger scale than current efforts. Existing global evidence shows that stigma is a barrier to achieving each of the 90-90-90 targets; it undermines HIV testing, linkage to care, treatment adherence, and viral load suppression. However, findings from both research studies and programmatic experience have helped to inform the growing body of knowledge regarding how to reduce stigma, leading to key principles for HIV stigma reduction. These principles include immediately addressing actionable drivers of stigma, centring groups affected by stigma at the core of the response, and engaging opinion leaders and building partnerships between affected groups and opinion leaders. Although there is still room to strengthen research on stigma measurement and reduction, in particular for intersectional stigma, the proliferation of evidence over the past several decades on how to measure and address stigma provides a solid foundation for immediate and comprehensive action.


Assuntos
Síndrome de Imunodeficiência Adquirida/prevenção & controle , Síndrome de Imunodeficiência Adquirida/psicologia , Epidemias/prevenção & controle , Medo/psicologia , Estigma Social , Síndrome de Imunodeficiência Adquirida/diagnóstico , Síndrome de Imunodeficiência Adquirida/virologia , Fármacos Anti-HIV/uso terapêutico , Feminino , HIV/efeitos dos fármacos , HIV/crescimento & desenvolvimento , HIV/patogenicidade , Humanos , Masculino , Cooperação do Paciente/psicologia , Cooperação do Paciente/estatística & dados numéricos , Isolamento Social/psicologia , Cooperação e Adesão ao Tratamento/psicologia , Cooperação e Adesão ao Tratamento/estatística & dados numéricos , Carga Viral/efeitos dos fármacos
3.
PLoS One ; 15(12): e0242710, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33362248

RESUMO

INTRODUCTION: The use of patient-reported outcomes (PROs) to systematically quantify adverse events (AE) will assist in the improvement of medical care and the QoL of patients living with HIV (PLWH). The aim of this study was to investigate the associations between self-reported side effects and other PROs, demographics and laboratory data, and further evaluate the Health Questionnaire (HQ) as a tool for following trends in patient-reported side effects over time in relation to trends in prescribed third agent in ART. MATERIALS AND METHODS: The Swedish National Registry InfCareHiv includes an annual self-reported nine-item HQwhich is used in patient-centered HIV care in all Swedish HIV units. In this study, the experience of side effects was addressed. We analyzed 9,476 HQs completed by 4,186 PLWH together with details about their prescribed ART and relevant biomarkers collected during 2011-2017. Data were analyzed using descriptive statistics, Pearson's correlation coefficient and mixed logistic regression. RESULTS: The cross-sectional analysis of the HQs showed that the frequency of reported side effects decreased from 32% (2011) to 15% (2017). During the same period, there was a shift in ART prescription from efavirenz (EFV) to dolutegravir (DTG) (positive correlation coefficient r = 0.94, p = 0.0016). Further, PLWH who reported being satisfied with their physical health (OR: 0.47, p = <0.001) or psychological health (OR: 0.70, p = 0.001) were less likely to report side effects than those less satisfied. CONCLUSIONS: Self-reported side effects were found to have a close relationship with the patient's ratings of their overall health situation and demonstrated a strong correlation with the sharp decline in use of EFV and rise in use of DTG, with reported side effects being halved. This study supports the feasibility of using the HQ as a tool for longitudinal follow up of trends in PROs.


Assuntos
Alquinos/efeitos adversos , Fármacos Anti-HIV/efeitos adversos , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Benzoxazinas/efeitos adversos , Ciclopropanos/efeitos adversos , Infecções por HIV/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Oxazinas/efeitos adversos , Piperazinas/efeitos adversos , Piridonas/efeitos adversos , Qualidade de Vida/psicologia , Sistema de Registros , Adulto , Alquinos/administração & dosagem , Fármacos Anti-HIV/administração & dosagem , Artralgia/induzido quimicamente , Artralgia/diagnóstico , Artralgia/fisiopatologia , Benzoxazinas/administração & dosagem , Estudos Transversais , Ciclopropanos/administração & dosagem , Disfunção Erétil/induzido quimicamente , Disfunção Erétil/diagnóstico , Disfunção Erétil/fisiopatologia , Feminino , HIV/efeitos dos fármacos , Infecções por HIV/fisiopatologia , Infecções por HIV/psicologia , Infecções por HIV/virologia , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Náusea/diagnóstico , Náusea/fisiopatologia , Oxazinas/administração & dosagem , Medidas de Resultados Relatados pelo Paciente , Piperazinas/administração & dosagem , Piridonas/administração & dosagem , Suécia
4.
Afr J AIDS Res ; 19(4): 304-311, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33337979

RESUMO

Background: The human immunodeficiency virus (HIV) pandemic increased the demand for health care resources in South Africa. To decrease the burden on specialised facilities, the Department of Health decentralised antiretroviral (ARV) management. In the uMgungundlovu district, adult HIV primary care services reported lower rates of HIV viral load (VL) suppression after initiation of ARVs compared to other levels of care. The aim of the study was to evaluate paediatric HIV services in the same district. Methods: Four ARV clinics, at different levels of care, initiating and monitoring paediatric HIV infection treatment in uMgungundlovu district, KwaZulu Natal, were selected: primary healthcare services, general practitioner services, general paediatric services and subspecialist infectious diseases services were included. Paediatric patients newly diagnosed between January 2014 and June 2015 were included in the study. The rate of HIV VL suppression at one year after treatment initiation was the primary outcome measure. A total of 377 patients were included, 35 at the nurse-led primary care clinic, 25 at the general practitioner-led primary care clinic, 156 at the paediatrician-led secondary care clinic, and 161 at the HIV paediatric subspecialist-led tertiary care clinic. Of the 377 patients, 154 (59.9%) achieved VL suppression at one year, with 75% (18/24), 61.9% (13/21), 51.7% (60/116) and 66.7% (63/96) achieving HIV VL suppression at the four clinic types, respectively. Conclusion: HIV VL suppression rates were variable, but did not differ statistically across levels of health care. Outcomes were not improved by initiation in specialist or subspecialist-led clinics, which supports the strategy of increasing access by decentralising HIV care for paediatric patients.


Assuntos
Antirretrovirais/uso terapêutico , Assistência à Saúde/organização & administração , Infecções por HIV/tratamento farmacológico , Criança , Pré-Escolar , Assistência à Saúde/estatística & dados numéricos , Feminino , HIV/efeitos dos fármacos , Infecções por HIV/epidemiologia , Humanos , Lactente , Recém-Nascido , Masculino , Avaliação de Programas e Projetos de Saúde , África do Sul/epidemiologia , Resposta Viral Sustentada
5.
PLoS One ; 15(12): e0243625, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33382756

RESUMO

OBJECTIVES: To compare virologic and immunologic outcomes of integrase inhibitor (INSTI)-containing, contemporary boosted protease inhibitor (PI/b)-containing and non-nucleotide reverse transcriptase inhibitor (NNRTI)-containing regimens in a real-life setting. METHODS: Using logistic regression, virologic and immunologic outcomes of INSTI use were compared to outcomes of PI/b or NNRTI treatment 12 months after treatment start or switch, for participants in the RESPOND cohort consortium. A composite treatment outcome (cTO) was used, defining success as viral load (VL) <200 copies/mL and failure as at least one of: VL ≥200 copies/mL, unknown VL in the time window, any changes of antiretroviral therapy (ART) regimen, AIDS, or death. In addition, on-treatment analysis including only individuals with known VL and no regimen changes was performed. Favorable immunologic response was defined as a 25% increase in CD4 count or as reaching ≥750 CD4 cells/µL. RESULTS: Between January 2012 and January 2019, 13,703 (33.0% ART-naïve) individuals were included, of whom 7,147 started/switched to a regimen with an INSTI, 3,102 to a PI/b and 3,454 to an NNRTI-containing regimen. The main reason for cTO failure in all treatment groups were changes in ART regimen. Compared to INSTIs, the adjusted odds ratio (aOR) of cTO success was significantly lower for PI/b (0.74 [95% confidence interval, CI 0.67-0.82], p <0.001), but similar for NNRTIs (1.07 [CI 0.97-1.17], p = 0.11). On-treatment analysis and sensitivity analyses using a VL cut-off of 50 copies/mL were consistent. Compared to INSTIs, the aORs of a 25% increase in CD4 count were lower for NNRTIs (0.80 [CI 0.71-0.91], p<0.001) and PI/b (0.87 [CI 0.76-0.99], p = 0.04). CONCLUSION: In this large analysis of a real-world population, cTO and on-treatment success were similar between INSTIs and NNRTIs, but lower for PI/b, though residual confounding cannot be fully excluded. Obtaining favorable immunologic outcomes were more likely for INSTIs than the other drug classes.


Assuntos
Infecções por HIV/tratamento farmacológico , Inibidores de Integrase de HIV/uso terapêutico , Inibidores da Protease de HIV/uso terapêutico , Inibidores da Transcriptase Reversa/uso terapêutico , Adulto , Contagem de Linfócito CD4 , Estudos de Coortes , Feminino , HIV/efeitos dos fármacos , HIV/imunologia , Infecções por HIV/imunologia , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Carga Viral/efeitos dos fármacos , Carga Viral/imunologia
6.
Int J Mol Sci ; 22(1)2020 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-33375194

RESUMO

Infectious diseases represent a relevant issue in lung cancer patients. Bacterial and viral infections might influence the patients' prognosis, both directly affecting the immune system and indirectly impairing the outcome of anticancer treatments, mainly immunotherapy. In this analysis, we aimed to review the current evidence in order to clarify the complex correlation between infections and lung cancer. In detail, we mainly explored the potential impact on immunotherapy outcome/safety of (1) bacterial infections, with a detailed focus on antibiotics; and (2) viral infections, discriminating among (a) human immune-deficiency virus (HIV), (b) hepatitis B/C virus (HBV-HCV), and (c) Sars-Cov-2. A series of studies suggested the prognostic impact of antibiotic therapy administration, timing, and exposure ratio in patients treated with immune checkpoint inhibitors, probably through an antibiotic-related microbiota dysbiosis. Although cancer patients with HIV, HBV, and HCV were usually excluded from clinical trials evaluating immunotherapy, some retrospective and prospective trials performed in these patient subgroups reported similar results compared to those described in not-infected patients, with a favorable safety profile. Moreover, patients with thoracic cancers are particularly at risk of COVID-19 severe outcomes and mortality. Few reports speculated about the prognostic implications of anticancer therapy, including immunotherapy, in lung cancer patients with concomitant Sars-Cov-2 infection, showing, to date, inconsistent results. The correlation between infectious diseases and immunotherapy remains to be further explored and clarified in the context of dedicated trials. In clinical practice, the accurate and prompt multidisciplinary management of lung cancer patients with infections should be encouraged in order to select the best treatment options for these patients, avoiding unexpected toxicities, while maintaining the anticancer effect.


Assuntos
Infecções Bacterianas/complicações , Carcinoma Pulmonar de Células não Pequenas/complicações , Carcinoma Pulmonar de Células não Pequenas/terapia , Imunoterapia , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/terapia , Viroses/complicações , Síndrome de Imunodeficiência Adquirida/complicações , Síndrome de Imunodeficiência Adquirida/imunologia , Síndrome de Imunodeficiência Adquirida/patologia , Síndrome de Imunodeficiência Adquirida/terapia , Antibacterianos/administração & dosagem , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/patologia , /patologia , Carcinoma Pulmonar de Células não Pequenas/microbiologia , Carcinoma Pulmonar de Células não Pequenas/virologia , HIV/efeitos dos fármacos , Hepatite B/complicações , Hepatite B/imunologia , Hepatite B/patologia , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Hepatite C/patologia , Humanos , Neoplasias Pulmonares/microbiologia , Neoplasias Pulmonares/virologia , Microbiota/efeitos dos fármacos , Microbiota/imunologia
7.
Molecules ; 25(21)2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33105694

RESUMO

Viral infections and associated diseases are responsible for a substantial number of mortality and public health problems around the world. Each year, infectious diseases kill 3.5 million people worldwide. The current pandemic caused by COVID-19 has become the greatest health hazard to people in their lifetime. There are many antiviral drugs and vaccines available against viruses, but they have many disadvantages, too. There are numerous side effects for conventional drugs, and active mutation also creates drug resistance against various viruses. This has led scientists to search herbs as a source for the discovery of more efficient new antivirals. According to the World Health Organization (WHO), 65% of the world population is in the practice of using plants and herbs as part of treatment modality. Additionally, plants have an advantage in drug discovery based on their long-term use by humans, and a reduced toxicity and abundance of bioactive compounds can be expected as a result. In this review, we have highlighted the important viruses, their drug targets, and their replication cycle. We provide in-depth and insightful information about the most favorable plant extracts and their derived phytochemicals against viral targets. Our major conclusion is that plant extracts and their isolated pure compounds are essential sources for the current viral infections and useful for future challenges.


Assuntos
Antivirais/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Herpes Simples/tratamento farmacológico , Influenza Humana/tratamento farmacológico , Compostos Fitoquímicos/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Antivirais/química , Antivirais/classificação , Antivirais/isolamento & purificação , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/patogenicidade , Betacoronavirus/fisiologia , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Descoberta de Drogas , HIV/efeitos dos fármacos , HIV/patogenicidade , HIV/fisiologia , Infecções por HIV/patologia , Infecções por HIV/virologia , Hepacivirus/efeitos dos fármacos , Hepacivirus/patogenicidade , Hepacivirus/fisiologia , Hepatite C Crônica/patologia , Hepatite C Crônica/virologia , Herpes Simples/patologia , Herpes Simples/virologia , Humanos , Influenza Humana/patologia , Influenza Humana/virologia , Orthomyxoviridae/efeitos dos fármacos , Orthomyxoviridae/patogenicidade , Orthomyxoviridae/fisiologia , Pandemias , Compostos Fitoquímicos/química , Compostos Fitoquímicos/classificação , Compostos Fitoquímicos/isolamento & purificação , Plantas Medicinais , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Simplexvirus/efeitos dos fármacos , Simplexvirus/patogenicidade , Simplexvirus/fisiologia , Internalização do Vírus/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos
8.
BMC Infect Dis ; 20(1): 773, 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33076866

RESUMO

BACKGROUND: Globally, the majority of people living with HIV have no or only limited access to HIV drug resistance testing to guide the selection of antiretroviral drugs. This is of particular concern for children and adolescents, who experience high rates of treatment failure. The GIVE MOVE trial assesses the clinical impact and cost-effectiveness of routinely providing genotypic resistance testing (GRT) to children and adolescents living with HIV who have an unsuppressed viral load (VL) while taking antiretroviral therapy (ART). METHODS: GIVE MOVE is an open-label randomised clinical trial enrolling children and adolescents (≥6 months to <19 years) living with HIV with a VL ≥400 copies/mL (c/mL) while taking first-line ART. Recruitment takes place at sites in Lesotho and Tanzania. Participants are randomised in a 1:1 allocation to a control arm receiving the standard of care (3 sessions of enhanced adherence counselling, a follow-up VL test, continuation of the same regimen upon viral resuppression or empiric selection of a new regimen upon sustained elevated viremia) and an intervention arm (GRT to inform onward treatment). The composite primary endpoint is the occurrence of any one or more of the following events during the 36 weeks of follow-up period: i) death due to any cause; ii) HIV- or ART-related hospital admission of ≥24 h duration; iii) new clinical World Health Organisation stage 4 event (excluding lymph node tuberculosis, stunting, oral or genital herpes simplex infection and oesophageal candidiasis); and iv) no documented VL <50 c/mL at 36 weeks follow-up. Secondary and exploratory endpoints assess additional health-related outcomes, and a nested study will assess the cost-effectiveness of the intervention. Enrolment of a total of 276 participants is planned, with an interim analysis scheduled after the first 138 participants have completed follow-up. DISCUSSION: This randomised clinical trial will assess if the availability of resistance testing improves clinical outcomes in children and adolescents with elevated viremia while taking ART. TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov ( NCT04233242 ; registered 18.01.2020). More information: www.givemove.org .


Assuntos
Fármacos Anti-HIV/farmacologia , Farmacorresistência Viral , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV/efeitos dos fármacos , Adolescente , Fármacos Anti-HIV/uso terapêutico , Criança , Pré-Escolar , Análise Custo-Benefício , Aconselhamento , Feminino , Genótipo , Herpes Genital , Humanos , Lactente , Lesoto , Estudos Longitudinais , Masculino , Tanzânia , Falha de Tratamento , Carga Viral , Viremia/tratamento farmacológico , Viremia/virologia
9.
Molecules ; 25(17)2020 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-32899354

RESUMO

Peptidyl fluoromethyl ketones occupy a pivotal role in the current scenario of synthetic chemistry, thanks to their numerous applications as inhibitors of hydrolytic enzymes. The insertion of one or more fluorine atoms adjacent to a C-terminal ketone moiety greatly modifies the physicochemical properties of the overall substrate, especially by increasing the reactivity of this functionalized carbonyl group toward nucleophiles. The main application of these peptidyl α-fluorinated ketones in medicinal chemistry relies in their ability to strongly and selectively inhibit serine and cysteine proteases. These compounds can be used as probes to study the proteolytic activity of the aforementioned proteases and to elucidate their role in the insurgence and progress on several diseases. Likewise, if the fluorinated methyl ketone moiety is suitably connected to a peptidic backbone, it may confer to the resulting structure an excellent substrate peculiarity and the possibility of being recognized by a specific subclass of human or pathogenic proteases. Therefore, peptidyl fluoromethyl ketones are also currently highly exploited for the target-based design of compounds for the treatment of topical diseases such as various types of cancer and viral infections.


Assuntos
Clorometilcetonas de Aminoácidos/síntese química , Fenilalanina/análogos & derivados , Vírus da SARS/efeitos dos fármacos , Inibidores de Serino Proteinase/síntese química , Proteínas não Estruturais Virais/antagonistas & inibidores , Clorometilcetonas de Aminoácidos/farmacologia , Química Farmacêutica/métodos , Cisteína Endopeptidases/química , Cisteína Endopeptidases/metabolismo , HIV/efeitos dos fármacos , HIV/enzimologia , Protease de HIV/química , Protease de HIV/metabolismo , Humanos , Cinética , Fenilalanina/síntese química , Fenilalanina/farmacologia , Vírus da SARS/enzimologia , Inibidores de Serino Proteinase/farmacologia , Relação Estrutura-Atividade , Proteínas não Estruturais Virais/química , Proteínas não Estruturais Virais/metabolismo
11.
PLoS One ; 15(9): e0238839, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32915862

RESUMO

In patients who are HIV infected, hepatitis B virus (HBV) infection is an important co-morbidity. However, antiretroviral options for HIV/HBV co-infected children are limited and, at the time of this study, only included lamivudine. These children may remain on this regimen for many years until late adolescence. They are at high risk of developing HBV drug resistance and uncontrolled HBV disease. The aim of this study was to characterize HBV infection in HIV/HBV co-infected children. Known HIV-infected/HBsAg-positive children, previously exposed to lamivudine monotherapy against HBV, and their mothers were recruited at the Katutura Hospital paediatric HIV clinic in Windhoek, Namibia. Dried blood spot and serum samples were collected for HBV characterization and serological testing, respectively. Fifteen children and six mothers participated in the study. Eight of the 15 children (53.3%) tested HBV DNA positive; all eight children were on lamivudine-based ART. Lamivudine-associated resistance variants, together with immune escape mutants in the surface gene, were identified in all eight children. Resistance mutations included rtL80I, rtV173L, rtL180M, rtM204I/V and the overlapping sE164D, sW182*, sI195M and sW196LS variants. HBV strains belonged to genotypes E (6/8, 75%) and D3 (2/8, 25%). Further analysis of the HBV core promoter region revealed mutations associated with reduced expression of HBeAg protein and hepatocarcinogenesis. All six mothers, on HBV-active ART containing tenofovir and lamivudine, tested HBV DNA negative. This study confirms the importance of screening HIV-infected children for HBV and ensuring equity of drug access to effective HBV treatment if co-infected.


Assuntos
Coinfecção/epidemiologia , Farmacorresistência Viral/genética , Infecções por HIV/epidemiologia , Hepatite B/epidemiologia , Mutação , Proteínas do Core Viral/genética , Carga Viral , Adolescente , Adulto , Antirretrovirais/uso terapêutico , Criança , Estudos de Coortes , Coinfecção/genética , Coinfecção/virologia , Estudos Transversais , DNA Viral/análise , Feminino , HIV/efeitos dos fármacos , HIV/isolamento & purificação , Infecções por HIV/complicações , Infecções por HIV/genética , Infecções por HIV/virologia , Hepatite B/complicações , Hepatite B/genética , Hepatite B/virologia , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/isolamento & purificação , Humanos , Masculino , Namíbia/epidemiologia , Adulto Jovem
12.
Medicine (Baltimore) ; 99(37): e21661, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32925712

RESUMO

To support optimal third-line antiretroviral therapy (ART) selection in Namibia, we investigated the prevalence of HIV drug resistance (HIVDR) at time of failure of second-line ART. A cross-sectional study was conducted between August 2016 and February 2017. HIV-infected people ≥15 years of age with confirmed virological failure while receiving ritonavir-boosted protease inhibitor (PI/r)-based second-line ART were identified at 15 high-volume ART clinics representing over >70% of the total population receiving second-line ART. HIVDR genotyping of dried blood spots obtained from these individuals was performed using standard population sequencing methods. The Stanford HIVDR algorithm was used to identify sequences with predicted resistance; genotypic susceptibility scores for potential third-line regimens were calculated. Two hundred thirty-eight individuals were enrolled; 57.6% were female. The median age and duration on PI/r-based ART at time of enrolment were 37 years and 3.46 years, respectively. 97.5% received lopinavir/ritonavir-based regimens. The prevalence of nucleoside reverse transcriptase inhibitor (NRTI), non-nucleoside reverse transcriptase inhibitor (NNRTI), and PI/r resistance was 50.6%, 63.1%, and 13.1%, respectively. No significant association was observed between HIVDR prevalence and age or sex. This study demonstrates high levels of NRTI and NNRTI resistance and moderate levels of PI resistance in people receiving PI/r-based second-line ART in Namibia. Findings underscore the need for objective and inexpensive measures of adherence to identify those in need of intensive adherence counselling, routine viral load monitoring to promptly detect virological failure, and HIVDR genotyping to optimize selection of third-line drugs in Namibia.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Farmacorresistência Viral , Infecções por HIV/tratamento farmacológico , Adolescente , Adulto , Estudos Transversais , Feminino , HIV/efeitos dos fármacos , Humanos , Lopinavir/uso terapêutico , Masculino , Pessoa de Meia-Idade , Namíbia/epidemiologia , Prevalência , Inibidores da Transcriptase Reversa/uso terapêutico , Ritonavir/uso terapêutico , Falha de Tratamento , Adulto Jovem
13.
Proc Natl Acad Sci U S A ; 117(36): 22436-22442, 2020 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-32820072

RESUMO

Cholesterol-PIE12-trimer (CPT31) is a potent d-peptide HIV entry inhibitor that targets the highly conserved gp41 N-peptide pocket region. CPT31 exhibited strong inhibitory breadth against diverse panels of primary virus isolates. In a simian-HIV chimeric virus AD8 (SHIVAD8) macaque model, CPT31 prevented infection from a single high-dose rectal challenge. In chronically infected animals, CPT31 monotherapy rapidly reduced viral load by ∼2 logs before rebound occurred due to the emergence of drug resistance. In chronically infected animals with viremia initially controlled by combination antiretroviral therapy (cART), CPT31 monotherapy prevented viral rebound after discontinuation of cART. These data establish CPT31 as a promising candidate for HIV prevention and treatment.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , HIV , Vírus da Imunodeficiência Símia , Internalização do Vírus/efeitos dos fármacos , Animais , Fármacos Anti-HIV/química , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico , Avaliação Pré-Clínica de Medicamentos , Feminino , HIV/efeitos dos fármacos , HIV/genética , Proteína gp41 do Envelope de HIV/antagonistas & inibidores , Infecções por HIV/tratamento farmacológico , Infecções por HIV/prevenção & controle , Infecções por HIV/virologia , Macaca mulatta , Masculino , Vírus da Imunodeficiência Símia/efeitos dos fármacos , Vírus da Imunodeficiência Símia/genética
14.
BMC Infect Dis ; 20(1): 460, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32611405

RESUMO

BACKGROUND: Although the United Nations program on HIV/AIDS 90-90-90-targets recommends achieving 90% of viral suppression for patients on first-line antiretroviral therapy by 2020, virological failure is still high and it remains a global public health problem. Therefore, assessing the incidence and predictors of virological failure among adult HIV patients on first-line ART in Amhara regional referral hospitals, Ethiopia is vital to design appropriate prevention strategies for treatment failure and preventing the unnecessary switching to second-line regimens. METHOD: An institution-based retrospective follow-up study was conducted on 490 adult HIV patients. The simple random sampling technique was used, and data were entered into Epi data Version 4.2.0.0 and was exported to Stata version 14 for analysis. The proportional hazard assumption was checked, and the Weibull regression was fitted. Cox-Snell residual was used to test the goodness of fit, and the appropriate model was selected by AIC/BIC. Finally, an adjusted hazard ratio with a 95% CI was computed, and variables with P-value < 0.05 in the multivariable analysis were taken as significant predictors of virological failure. RESULTS: The overall incidence rate of virological failure was 4.9 events per 1000 person-month observations (95%CI: 3.86-6.38). Users of CPT (AHR = 0.55, 95%CI: 0.31-0.97), poor adherence (AHR = 5.46, 95%CI: 3.07-9.74), CD4 Count <=200 cells/mm3 (AHR = 3.9, 95%CI: 1.07-13.9) and 201-350 cells/mm3 (AHR 4.1, 95%CI: 1.12-15) respectively, and NVP based first line drug regimen (AHR = 3.53, 95%CI: 1.73-7.21) were significantly associated with virological failure. CONCLUSION: The incidence rate of virological failure was high. CPT, poor adherence, low baseline CD4 count and NVP based first-line drug regimen were independent risk factors associated with virological failure. Therefore, strengthening HIV care intervention and addressing these significant predictors is highly recommended in the study setting.


Assuntos
Síndrome de Imunodeficiência Adquirida/tratamento farmacológico , Síndrome de Imunodeficiência Adquirida/epidemiologia , Antirretrovirais/efeitos adversos , Antirretrovirais/uso terapêutico , HIV/efeitos dos fármacos , Adolescente , Adulto , Contagem de Linfócito CD4 , Etiópia/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Encaminhamento e Consulta , Estudos Retrospectivos , Fatores de Risco , Falha de Tratamento , Adulto Jovem
16.
PLoS One ; 15(5): e0232358, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32469876

RESUMO

BACKGROUND: Kenya's guidelines for prevention of mother-to-child transmission of HIV (PMTCT) recommend routine viral load (VL) monitoring for pregnant and breastfeeding women. METHOD: We assessed PMTCT VL monitoring and clinical action occurring between last menstrual period (LMP) and 6 months postpartum at 4 Kenyan government hospitals. Pregnant women enrolled in the HIV Infant Tracking System from May 2016-March 2018 were included. We computed proportions who received VL testing within recommended timeframes and who received clinical action after unsuppressed VL result. RESULTS: Of 424 participants, any VL testing was documented for 305 (72%) women and repeat VL testing was documented for 79 (19%). Only 115 women (27%) received a guideline-adherent baseline VL test and 27 (6%) received a guideline-adherent baseline and repeat VL test sequence. Return of baseline and repeat VL test results to the facility was high (average 96%), but patient notification of VL results was low (36% baseline and 49% repeat). Clinical action for unsuppressed VL results was even lower: 11 of 38 (29%) unsuppressed baseline results and 2 of 14 (14%) unsuppressed repeat results triggered clinical action. DISCUSSION: Guideline-adherent VL testing and clinical intervention during PMTCT must be prioritized to improve maternal care and reduce the risk of HIV transmission to infants.


Assuntos
HIV/fisiologia , Hospitais/estatística & dados numéricos , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Mães , Carga Viral , Adulto , Fármacos Anti-HIV/farmacologia , Feminino , HIV/efeitos dos fármacos , Humanos , Lactente , Gravidez
17.
Infection ; 48(5): 681-686, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32394344

RESUMO

INTRODUCTION: Data on people living with human immunodeficiency virus (PLWH) in the current SARS-CoV-2 pandemic are still scarce. This case series of 33 PLWH patients with COVID-19 reveals symptoms and outcome in this special population. METHODS: Retrospective analysis of anonymized data including age, gender, HIV-associated parameters, symptoms, and outcome. RESULTS: Three out of 32 patients with documented outcomes died (9%). 91% of the patients recovered and 76% have been classified as mild cases. All patients were on antiretroviral treatment, of them 22 on tenofovir-containing regimen and 4 on the protease inhibitor darunavir. CONCLUSIONS: This preliminary case series does not support excess morbidity and mortality among symptomatic COVID-19 PLWH and with viral suppression on ART. SARS-CoV-2 infections may occur during boosted darunavir-based and/or on tenofovir-containing ART.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/virologia , Darunavir/uso terapêutico , Infecções por HIV/virologia , HIV/patogenicidade , Pneumonia Viral/virologia , Tenofovir/uso terapêutico , Adulto , Terapia Antirretroviral de Alta Atividade , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/imunologia , Coinfecção , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/patologia , Feminino , HIV/efeitos dos fármacos , HIV/imunologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/mortalidade , Infecções por HIV/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/mortalidade , Pneumonia Viral/patologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Análise de Sobrevida , Carga Viral/efeitos dos fármacos
18.
BMC Infect Dis ; 20(1): 248, 2020 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-32216752

RESUMO

BACKGROUND: Understanding factors driving virological failure, including the contribution of HIV drug resistance mutations (DRM), is critical to ensuring HIV treatment remains effective. We examine the contribution of drug resistance mutations for low viral suppression in HIV-positive participants in a population-based sero-prevalence survey in rural South Africa. METHODS: We conducted HIV drug resistance genotyping and ART analyte testing on dried blood spots (DBS) from HIV-positive adults participating in a 2014 survey in North West Province. Among those with virologic failure (> 5000 copies/mL), we describe frequency of DRM to protease inhibitors (PI), nucleoside reverse transcriptase inhibitors (NRTI), and non-nucleoside reverse transcriptase inhibitors (NNRTI), report association of resistance with antiretroviral therapy (ART) status, and assess resistance to first and second line therapy. Analyses are weighted to account for sampling design. RESULTS: Overall 170 DBS samples were assayed for viral load and ART analytes; 78.4% of men and 50.0% of women had evidence of virologic failure and were assessed for drug resistance, with successful sequencing of 76/107 samples. We found ≥1 DRM in 22% of participants; 47% were from samples with detectable analyte (efavirenz, nevirapine or lopinavir). Of those with DRM and detectable analyte, 60% showed high-level resistance and reduced predicted virologic response to ≥1 NRTI/NNRTI typically used in first and second-line regimens. CONCLUSIONS: DRM and predicted reduced susceptibility to first and second-line regimens were common among adults with ART exposure in a rural South African population-based sample. Results underscore the importance of ongoing virologic monitoring, regimen optimization and adherence counseling to optimize durable virologic suppression.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Farmacorresistência Viral/genética , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , HIV/efeitos dos fármacos , HIV/genética , Carga Viral/efeitos dos fármacos , Adolescente , Adulto , Estudos de Coortes , Teste em Amostras de Sangue Seco , Feminino , Genótipo , Infecções por HIV/virologia , Soroprevalência de HIV , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Prevalência , População Rural , África do Sul/epidemiologia , Adulto Jovem
19.
PLoS One ; 15(3): e0228601, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32119663

RESUMO

BACKGROUND: In 2015, Zimbabwe introduced third-line antiretroviral therapy (ART) through four designated treatment centers; three government clinics in Harare and Bulawayo, and Newlands Clinic (NC), operated by a private voluntary organization in Harare. We describe characteristics of patients receiving third line ART and analyzed treatment outcomes in this national programme as of 31 December 2018. METHODS: We described the population using proportions for categorical variables, and medians and interquartile ranges for continuous variables. Patients from NC, where data were more complete, were followed from the date of starting third-line ART until death, transfer, loss to follow up or 31 December 2018. RESULTS: A total of 209 patients had ever received third-line ART: 124 at NC and 85 from the three government clinics. HIV genotype results were available for 89 (72%) patients at NC and fourteen (16.5%) patients in the government clinics. Median duration of third line ART (years) in the government clinics was 2.3 (IQR:0.6-3.4), 1.3 (IQR: 0.7-1.7) and 1 (0.6-1.9). Of the 67 patients who received third line ART in the government clinics for at least six months, 53 (79%) had most recent viral load (VL) < 1000 copies/ml. Data on other treatment outcomes from government clinics were incomplete. From NC: a total of 109 (88%) patients were still in care, 13 (10.5%) had died and 2 (1.5%) were transferred. Median duration of third-line ART was 1.4 years (IQR: 0.6-2.8). Among the 111 NC patients who had received third-line ART for at least 6 months, 83 (75%) had a VL <50 copies/ml and 106 (95.5%) had a VL <1000 copies/ml. CONCLUSION: Our findings demonstrate that, with comprehensive care, patients failing second-line ART can achieve high rates of virological suppression on third-line regimens. There is need to decentralize the provision of third-line ART in Zimbabwe. More needs to be done to improve completeness of data in the government clinics.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , HIV/efeitos dos fármacos , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Resultado do Tratamento , Carga Viral/efeitos dos fármacos , Adulto Jovem , Zimbábue
20.
Science ; 367(6479): 810-814, 2020 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-32001521

RESUMO

The HIV intasome is a large nucleoprotein assembly that mediates the integration of a DNA copy of the viral genome into host chromatin. Intasomes are targeted by the latest generation of antiretroviral drugs, integrase strand-transfer inhibitors (INSTIs). Challenges associated with lentiviral intasome biochemistry have hindered high-resolution structural studies of how INSTIs bind to their native drug target. Here, we present high-resolution cryo-electron microscopy structures of HIV intasomes bound to the latest generation of INSTIs. These structures highlight how small changes in the integrase active site can have notable implications for drug binding and design and provide mechanistic insights into why a leading INSTI retains efficacy against a broad spectrum of drug-resistant variants. The data have implications for expanding effective treatments available for HIV-infected individuals.


Assuntos
Farmacorresistência Viral , Inibidores de Integrase de HIV/química , Integrase de HIV/química , HIV/efeitos dos fármacos , Compostos Heterocíclicos de 4 ou mais Anéis/química , Complexos Multiproteicos/química , Nucleoproteínas/química , Microscopia Crioeletrônica , Desenho de Fármacos , HIV/química , Humanos , Complexos Multiproteicos/genética , Naftiridinas/química , Nucleoproteínas/genética , Integração Viral/efeitos dos fármacos
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