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1.
Artigo em Inglês | MEDLINE | ID: mdl-31967210

RESUMO

A 37-year-old male patient, Fitzpatrick skin phototype IV, a student living in Belem, Amazon region, in 2015 had a confirmed diagnosis of acquired immunodeficiency virus (HIV) infection, but did not initiate antiretroviral treatment at his own option. Three years after the diagnosis, erythematous maculae appeared on the dorsum of the nose with rapid progression to the entire face, with posterior diffuse infiltration and appearance of nodules on the chin and shoulder. In December 2018, the patient presented with exacerbation of the condition with an increase in infiltrated violaceous plaques and disseminated violaceous nodules. A histopathological biopsy of the skin was performed, confirming the diagnosis of angiomatoid proliferation suggestive of Kaposi's sarcoma (KS), with an important dissemination of this disease to the noble organs. In addition, it is important to note that he only started antiretroviral therapy (ART) after the exacerbation of Kaposi (December 2018). In such cases, chemotherapy associated with ART is crucial for the treatment and follow-up of the patient, since Kaposi's sarcoma develops relatively low in patients who do not have immunodeficiency.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Infecções por HIV/complicações , Sarcoma de Kaposi/etiologia , Neoplasias Cutâneas/etiologia , Adulto , Infecções por HIV/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Humanos , Lamivudina/administração & dosagem , Masculino , Sarcoma de Kaposi/diagnóstico , Tenofovir/administração & dosagem
2.
Expert Opin Drug Saf ; 19(1): 23-41, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31809218

RESUMO

Introduction: Antiretroviral and anti-tuberculosis (TB) drugs are often co-administered in people living with HIV (PLWH). Early initiation of antiretroviral therapy (ART) during TB treatment improves survival in patients with advanced HIV disease. However, safety concerns related to clinically significant changes in drug exposure resulting from drug-drug interactions, development of overlapping toxicities and specific challenges related to co-administration during pregnancy represent barriers to successful combined treatment for HIV and TB.Areas covered: Pharmacokinetic interactions of different classes of ART when combined with anti-TB drugs used for sensitive-, drug-resistant (DR) and latent TB are discussed. Overlapping drug toxicities, implications of immune reconstitution inflammatory syndrome (IRIS), safety in pregnancy and research gaps are also explored.Expert opinion: New antiretroviral and anti-tuberculosis drugs have been recently introduced and international guidelines updated. A number of effective molecules and clinical data are now available to build treatment regimens for PLWH with latent or active TB. Adopting a systematic approach that also takes into account the need for individualized variations based on the available evidence is the key to successfully integrate ART and TB treatment and improve treatment outcomes.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Antituberculosos/administração & dosagem , Animais , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/farmacocinética , Antituberculosos/efeitos adversos , Interações de Medicamentos , Infecções por HIV/tratamento farmacológico , Humanos , Tuberculose Latente/tratamento farmacológico , Tuberculose/tratamento farmacológico
3.
Expert Rev Clin Pharmacol ; 12(12): 1129-1143, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31774001

RESUMO

Introduction: Modern antiretroviral therapy (ART) has revolutionized HIV treatment. ART regimens are now highly efficacious, well-tolerated, safe, often with one multi-drug pill, once-daily regimens available. However, clinical challenges persist in managing ART in persons with HIV (PWH), such as drug-drug interactions, side effects, pregnancy, co-morbidities, and adherence.Areas Covered: In this review, we discuss the ongoing challenges of ART for adults in the United States. We review the difficulties of initiating ART and maintaining therapy throughout adulthood and discuss new agents and strategies under investigation to address these issues. A PubMed search was utilized to identify relevant publications and guidelines through July 2019.Expert Opinion: Challenges persist in initiation and maintenance of ART. An individual's coexisting medical, social and personal factors must be considered in selecting and continuing ART to ensure safety, tolerability, and efficacy throughout adulthood. Continued development of new therapeutics and novel approaches to ART, such as long acting drugs or dual therapy, are needed to respond to many of these challenges. In addition, future research must address therapeutic disparities for populations historically underrepresented in clinical trials, including women, people aging with HIV, and those with complex comorbidities.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Desenvolvimento de Medicamentos , Infecções por HIV/tratamento farmacológico , Adulto , Fármacos Anti-HIV/efeitos adversos , Esquema de Medicação , Interações de Medicamentos , Humanos , Estados Unidos
4.
Pan Afr Med J ; 34: 39, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31762906

RESUMO

Introduction: The number of HIV exposed uninfected (HEU) infants is increasing as vertical transmission is reducing. This subpopulation requires more investigations. This study aimed at comparing the expression level of soluble Fas receptors (FasR) and ligands (FasL) between HIV infected, HEU and unexposed children. Methods: Eighty eight HIV-1infected, 86 HEU and 38 HIV unexposed children were recruited. Soluble FasR and FasL were measured in their plasma. Mann-Whitney U-Test was used to compare groups with 95% confidence. Spearman coefficient was used to test the correlation with CD4 and viral load (VL). Results: Overall plasma levels of FasR were higher than that of FasL. The concentration of FasR and FasL were significantly higher in HIV-1 infected children in comparison to HEU and unexposed children. There was no difference in the plasma level of FasL in HIV infected compared to HEU children. A significant difference was observed between HIV infected children and HEU children (P=0.001) for the FasL. FasR were higher in both HIV infected and unexposed children compared to HEU children. There was a positive correlation (rs=+0.4; p=0.01) in ARV treated children between CD4 count and FasL concentration. Significant negative correlation (rs=-0.3; p=0.040) in ARV naïve children was observed between CD4 percentage and FasL. Significant and positive correlation (rs=+0.4; p=0.008) was observed between the VL and FasL in HIV infected, treated or not. Conclusion: HEU children differ from HIV infected and unexposed children as the level of FasL/R expression is concerned. HEU should be considered different from HIV unexposed although exempt from virus as some immune dysfunctions have been reported among them.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Proteína Ligante Fas/sangue , Infecções por HIV/epidemiologia , Receptor fas/sangue , Adolescente , Contagem de Linfócito CD4 , Camarões , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Infecções por HIV/sangue , Infecções por HIV/tratamento farmacológico , Humanos , Lactente , Transmissão Vertical de Doença Infecciosa/estatística & dados numéricos , Masculino , Carga Viral
5.
BMC Infect Dis ; 19(1): 982, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31752729

RESUMO

BACKGROUND: Hepatitis B (HBV) and Human Immunodeficiency Virus (HIV) share common risk factors for exposure. Co-infected patients have an increased liver-related mortality risk and may have accelerated HIV progression. The epidemiology and demographic characteristics of HIV-HBV co-infection in Canada remain poorly defined. We compared the demographic and clinical characteristics and factors associated with advanced hepatic fibrosis between HIV and HIV-HBV co-infected patients. METHODS: A retrospective cohort analysis was conducted using data from the Canadian Observational Cohort (CANOC) Collaboration, including eight sites from British Columbia, Quebec, and Ontario. Eligible participants were HIV-infected patients who initiated combination ARV between January 1, 2000 and December 14, 2014. Demographic and clinical characteristics were compared between HIV-HBV co-infected and HIV-infected groups using chi-square or Fisher exact tests for categorical variables, and Wilcoxon's Rank Sum test for continuous variables. Liver fibrosis was estimated by the AST to Platelet Ratio Index (APRI). RESULTS: HBV status and APRI values were available for 2419 cohort participants. 199 (8%) were HBV co-infected. Compared to HIV-infected participants, HIV-HBV co-infected participants were more likely to use injection drugs (28% vs. 21%, p = 0.03) and be HCV-positive (31%, vs. 23%, p = 0.02). HIV-HBV co-infected participants had lower baseline CD4 T cell counts (188 cells/mm3, IQR: 120-360) compared to 235 cells/mm3 in HIV-infected participants (IQR: 85-294) (p = 0.0002) and higher baseline median APRI scores (0.50 vs. 0.37, p < 0.0001). This difference in APRI was no longer clinically significant at follow-up (0.32 vs. 0.30, p = 0.03). HIV-HBV co-infected participants had a higher mortality rate compared to HIV-infected participants (11% vs. 7%, p = 0.02). CONCLUSION: The prevalence, demographic and clinical characteristics of the HIV-HBV co-infected population in Canada is described. HIV-HBV co-infected patients have higher mortality, more advanced CD4 T cell depletion, and liver fibrosis that improves in conjunction with ARV therapy. The high prevalence of unknown HBV status demonstrates a need for increased screening among HIV-infected patients in Canada.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Antivirais/administração & dosagem , Coinfecção/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , Hepatite B/tratamento farmacológico , Adulto , Colúmbia Britânica/epidemiologia , Coinfecção/epidemiologia , Coinfecção/virologia , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Hepatite B/epidemiologia , Hepatite B/virologia , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/genética , Vírus da Hepatite B/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Ontário/epidemiologia , Prevalência , Quebeque/epidemiologia , Estudos Retrospectivos , Fatores de Risco
6.
Expert Opin Drug Metab Toxicol ; 15(11): 927-935, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31668105

RESUMO

Introduction: Ritonavir and cobicistat are pharmacoenhancers used to improve the disposition of other HIV antiretrovirals. These drugs are, however, characterized by important pharmacokinetic differences.Areas covered: Here, the authors firstly update the available information on the pharmacokinetics of ritonavir and cobicistat. Subsequently, the review focuses on the description of drug-drug interactions (DDIs) involving cobicistat and comedications that might beneficiate from a shift-back to ritonavir. A MEDLINE Pubmed search for articles published from January 1995 to April 2019 was completed matching the term ritonavir or cobicistat with pharmacokinetics, DDIs, and pharmacology. Moreover, additional studies were identified from the reference list of retrieved articles.Expert opinion: Despite more than 20 years after its introduction on the market, ritonavir still represents a valid option for the treatment of selected HIV-infected patients. The large-scale switch to cobicistat may result in some unexpected DDIs not previously reported for ritonavir. Besides the issue of DDIs, additional advantage of ritonavir over cobicistat is its use in pregnancy, and its availability as single component of pharmaceutical formulations allowing the fine-tuning of antiretroviral regimens in patients with heavy polypharmacy when other unboosted-based therapeutic options cannot be used.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Cobicistat/administração & dosagem , Ritonavir/administração & dosagem , Fármacos Anti-HIV/farmacocinética , Cobicistat/farmacocinética , Interações de Medicamentos , Quimioterapia Combinada , Infecções por HIV/tratamento farmacológico , Humanos , Ritonavir/farmacocinética
7.
Pan Afr Med J ; 33: 290, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31692824

RESUMO

We present a 34-year-old HIV positive woman who presented with a 2-month history of abdominal pain, abdominal distension, night sweats and fever. She had a firm, immobile and irregular abdominopelvic mass of about 30 weeks uterine size. Investigations showed a haemoglobin of 6.5g/dl, (NR 12-14) cancer antigen 125 of 44U/ml (NR 0-35), serum beta human chorionic gonadotropin (HCG) of 0.258mIU/ml (NR 0-5) and alpha fetoprotein of 7ng/ml (NR <10). Her CD4 count was 63cells/mm3. At laparotomy there was a left ovarian mass and the rest of the abdomen and omentum looked grossly normal, leading to the conclusion that the primary was in the ovaries. A total abdominal hysterectomy, bilateral adnexectomy and infracolic omentectomy were done. Sigmoidectomy and Hartmann's procedure were also performed. Histology of the specimens showed a large B cell lymphoma. She has since been commenced on chemotherapy and antiretroviral therapy and has been doing well.


Assuntos
Doenças dos Anexos/diagnóstico , Infecções por HIV/tratamento farmacológico , Linfoma Difuso de Grandes Células B/diagnóstico , Neoplasias Ovarianas/diagnóstico , Doenças dos Anexos/patologia , Adulto , Fármacos Anti-HIV/administração & dosagem , Contagem de Linfócito CD4 , Feminino , Humanos , Histerectomia/métodos , Linfoma Difuso de Grandes Células B/terapia , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia
8.
Pan Afr Med J ; 33: 277, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31692880

RESUMO

Introduction: Adherence is vital to effective antiretroviral therapy (ART) for reducing viral load and HIV/AIDS-related morbidity and mortality. This study was aimed at evaluating the adherence of HIV seropositive patients to ART in a tertiary institution in Nigeria. Methods: A cross sectional observational study was conducted among 400 HIV seropositive patients. The study was carried out between December 2016 and February 2017 at the HIV clinic of the Ekiti State University Teaching Hospital, Ado-Ekiti, Nigeria. Results: The mean age of the HIV patients was 42.2±9.5 years with a predominant female gender (Male:Female = 1:2.8). The median CD4 counts increased from 302.1±15.0cells/mm3 at diagnosis to 430.8±13.3cells/mm3 at the time of the study. Majority of participants were unaware of their spouses' HIV status (59.3%) while 32.5% of participants had a serodiscordant spouse. Poverty was a major challenge as 73.3% earned less than 140 dollars per month. Depressive symptoms, anxiety disorder and insomnia were also reported in 40.7%, 33.2% and 47.2% respectively. Poor adherence to ART was observed in almost 20% of the patients. Logistic regression indicated that predictors of poor adherence were depression, anxiety and low CD4 counts. Conclusion: Adherence to anti-retroviral therapy was good amongst the majority of HIV seropositive patients. Depression, anxiety disorder and low CD4 count were however associated with poor adherence. This emphasizes the role of the psychology units as integral part of the HIV clinic to assist patients' adherence to anti-retroviral regimens.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Contagem de Linfócito CD4 , Infecções por HIV/tratamento farmacológico , Adesão à Medicação/estatística & dados numéricos , Adulto , Ansiedade/epidemiologia , Estudos Transversais , Depressão/epidemiologia , Feminino , Infecções por HIV/psicologia , Humanos , Masculino , Adesão à Medicação/psicologia , Pessoa de Meia-Idade , Nigéria , Inquéritos e Questionários
9.
Expert Opin Drug Metab Toxicol ; 15(12): 1043-1052, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31715109

RESUMO

Introduction: With the introduction of highly active anti-retroviral therapy (HAART), treatment of HIV infection has improved radically, shifting the concept of HIV disease from a highly mortal epidemic to a chronic illness which needs systematic management. However, HAART does not target the integrated proviral DNA. Hence, prolonged use of antiviral drugs is needed for sustaining life. As a consequence, severe side effects emerge. Several parameters involve in causing these adverse effects. Mitochondrial dysfunctions were pointed as common factor among them. It is, therefore, necessary to critically examine mitochondrial dysfunction in order to understand the side effects.Areas covered: There are many events involved in causing drug-induced side-effects; in this review, we only highlight mitochondrial dysfunctions as one of the events. We present up-to-date findings on mitochondrial dysfunction caused by HIV infection and antiviral drug treatment. Both in vivo and in vitro studies on mitochondrial dysfunction like change in morphology, membrane depolarization, mitophagy, mitochondrial DNA depletion, and intrinsic apoptosis have been discussed.Expert opinion: Mitochondrial dysfunction is associated with severe complications that often lead to discontinuation or change in treatment regimen. Prior knowledge of side effects of antiviral drugs would help in better management and future research should focus to avoid mitochondrial targeting of antiviral drugs while maintaining their antiviral properties.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Infecções por HIV/tratamento farmacológico , Mitocôndrias/patologia , Animais , Fármacos Anti-HIV/efeitos adversos , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Terapia Antirretroviral de Alta Atividade/métodos , DNA Mitocondrial/efeitos dos fármacos , Infecções por HIV/virologia , Humanos
10.
Expert Opin Drug Metab Toxicol ; 15(11): 975-984, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31619082

RESUMO

Objectives: Riociguat is a soluble guanylate cyclase stimulator licensed for the treatment of pulmonary arterial hypertension (PAH), a potentially fatal complication of human immunodeficiency virus infection. This study investigated the inhibitory potency of selected antiretroviral regimens on the metabolic clearance of riociguat.Methods: The inhibitory potential of the components of six antiretroviral combinations (ATRIPLA® (efavirenz/emtricitabine/tenofovir disoproxil), COMPLERA® (rilpivirine/emtricitabine/tenofovir disoproxil), STRIBILD® (elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil), TRIUMEQ® (abacavir/dolutegravir/lamivudine), and two ritonavir-boosted regimens) on riociguat metabolism were evaluated in recombinant human CYP1A1 and CYP3A4 as well as in human hepatocytes exhibiting both CYP1A1 and CYP3A4 activity. In vitro-in vivo correlation was performed between calculated and observed increases in riociguat exposure in vivo.Results: Using both in vitro systems, the predicted increase in exposure of riociguat was highest with components of TRIUMEQ® followed by COMPLERA®, ATRIPLA®, STRIBILD®, and the ritonavir-boosted regimens. Further experiments in human hepatocytes confirmed CYP1A1 to be the predominant enzyme in the metabolic clearance of riociguat.Conclusion: Antiretroviral treatment containing the potent CYP1A1 inhibitor abacavir had the greatest impact on riociguat metabolic clearance. The impact of comedications containing only strong CYP3A4 inhibitors e.g. ritonavir was less pronounced, suggesting a benefit of riociguat over PAH-targeting medications with contraindications for use with strong CYP3A4 inhibitors.


Assuntos
Fármacos Anti-HIV/farmacologia , Citocromo P-450 CYP1A1/metabolismo , Ativadores de Enzimas/metabolismo , Pirazóis/metabolismo , Pirimidinas/metabolismo , Fármacos Anti-HIV/administração & dosagem , Citocromo P-450 CYP1A1/antagonistas & inibidores , Citocromo P-450 CYP3A/efeitos dos fármacos , Citocromo P-450 CYP3A/metabolismo , Inibidores do Citocromo P-450 CYP3A/administração & dosagem , Inibidores do Citocromo P-450 CYP3A/farmacologia , Interações de Medicamentos , Ativadores de Enzimas/administração & dosagem , Hepatócitos/enzimologia , Hepatócitos/metabolismo , Humanos , Técnicas In Vitro , Pirazóis/administração & dosagem , Pirimidinas/administração & dosagem
12.
Pan Afr Med J ; 33: 158, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31565120

RESUMO

Introduction: While HIV care among tuberculosis (TB) patients is successfully implemented and monitored, it is not routinely reported among "presumptive TB patients without TB". The present study describes the ascertainment of HIV status and receipt of antiretroviral therapy (ART) and the associated factors among presumptive TB patients (with and without TB) in 35 public health facilities of Masvingo district of Zimbabwe from January to June 2017. Methods: This was an analysis of secondary programme data. We performed log binomial regression to calculate adjusted relative risks (aRR) and 95% confidence intervals (CI). Results: Of 1369 presumptive TB patients, 1181 (86%) were ascertained for HIV status (98% among those subsequently diagnosed with TB, 83% among non-TB). Of them, 748 (63%) were HIV positive, more among TB patients (69%) than those without TB (61%). Among HIV-positive patients, 475 (64%) received ART, significantly higher among TB patients (78%) compared to those without TB (57%). Patients without TB were significantly more likely to have non-ascertained for HIV status (aRR=2.4, 95% CI=1.4-5.0) and not receiving ART (aRR=1.8, 95% CI=1.6-2.0), compared to those with TB. Conclusion: We found high rates of HIV status ascertainment among presumptive TB patients. But, ART uptake was poor among "presumptive TB patients without TB", despite implementation of "test and treat" strategy in Zimbabwe. The programme should step up the monitoring of HIV status and ART receipt among presumptive TB patients, by introducing an indicator in the quarterly reports of the national TB programme.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Infecções por HIV/diagnóstico , Programas de Rastreamento/métodos , Tuberculose/epidemiologia , Adolescente , Adulto , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde , Análise de Regressão , Tuberculose/diagnóstico , Adulto Jovem , Zimbábue
13.
Expert Opin Drug Metab Toxicol ; 15(10): 813-829, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31556749

RESUMO

Introduction: Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are essential components of highly active antiretroviral therapy against HIV-1 infections. Here, we provide a comprehensive overview of approved and emerging NNRTIs. Areas covered: This review covers the latest trend of NNRTIs regarding their pharmacodynamics, pharmacokinetics, mechanisms of drug action, drug resistance as well as new applications such as two-drug regimens and long-acting formulations. Expert opinion: Since the first NNRTI, nevirapine, was approved in 1996, antiviral drug discovery led to the approval of seven NNRTIs, including nevirapine, delavirdine (discontinued), etravirine, elsulfavirine, efavirenz, rilpivirine, and doravirine. The latter three compounds with favorable pharmacodynamic profiles and minimal adverse effects are often combined with one integrase inhibitor or two NRTIs in once-daily fixed-dose tablets. NNRTI-anchored regimens have been approved as initial therapies in treatment-naïve patients (efficacy: 72% to 86%) or maintaining therapies in virologically-suppressed patients (efficacy: 91% to 95%). Future development of NNRTIs includes: (i) better resistance and cross-resistance profiles; (ii) reduction of drug burden by optimizing two-drug or three-drug combinations; and (iii) improvement of patient adherence by novel long-acting formulations with weekly or monthly administration. Overall, NNRTIs play an important role in the management of HIV-1 infections, especially in resource-limited countries.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Infecções por HIV/tratamento farmacológico , Inibidores da Transcriptase Reversa/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/farmacocinética , Terapia Antirretroviral de Alta Atividade/métodos , Preparações de Ação Retardada , Farmacorresistência Viral , HIV-1/efeitos dos fármacos , Humanos , Adesão à Medicação , Inibidores da Transcriptase Reversa/efeitos adversos , Inibidores da Transcriptase Reversa/farmacocinética
14.
Toxicol Lett ; 317: 13-23, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31562912

RESUMO

Combination antiretroviral therapy (cART) has been hugely successful in reducing the mortality associated with human immunodeficiency virus (HIV) infection, resulting in a growing population of people living with HIV (PLWH). Since PLWH now have a longer life expectancy, chronic comorbidities have become the focus of the clinical management of HIV. For example, cardiovascular complications are now one of the most prevalent causes of death in PLWH. Numerous epidemiological studies show that antiretroviral treatment increases cardiovascular disease (CVD) risk and early onset of CVD in PLWH. Nucleoside reverse transcriptase inhibitors (NRTIs) are the backbone of cART, and two NRTIs are typically used in combination with one drug from another drug class, e.g., a fusion inhibitor. NRTIs are known to induce mitochondrial dysfunction, contributing to toxicity in numerous tissues, such as myopathy, lipoatrophy, neuropathy, and nephropathy. In in vitro studies, short-term NRTI treatment induces an endothelial dysfunction with an increased reactive oxygen species (ROS) production; long-term NRTI treatment decreases cell replication capacity, while increasing mtROS production and senescent cell accumulation. These findings suggest that a mitochondrial oxidative stress is involved in the pathogenesis of NRTI-induced endothelial dysfunction and premature senescence. Mitochondrial dysfunction, defined by a compromised mitochondrial quality control via biogenesis and mitophagy, has a causal role in premature endothelial senescence and can potentially initiate early cardiovascular disease (CVD) development in PLWH. In this review, we explore the hypothesis and present literature supporting that long-term NRTI treatment induces vascular dysfunction by interfering with endothelial mitochondrial homeostasis and provoking mitochondrial genomic instability, resulting in premature endothelial senescence.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Doenças Cardiovasculares/induzido quimicamente , Senescência Celular/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , Mitocôndrias/efeitos dos fármacos , Animais , Fármacos Anti-HIV/administração & dosagem , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologia , Esquema de Medicação , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Metabolismo Energético/efeitos dos fármacos , Infecções por HIV/metabolismo , Infecções por HIV/patologia , Humanos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Medição de Risco , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo
15.
Expert Opin Drug Metab Toxicol ; 15(10): 787-802, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31512529

RESUMO

Introduction: Drug-drug interactions (DDI) between antiretroviral drugs and drugs for the treatment of metabolic disturbances in people living with human immunodeficiency virus (HIV) (PLWH) have represented a problem of paramount importance in the recent times. The problem has been mainly driven by sharing common metabolizing pathways. This problem has classically been worsened by the frequent use of pharmacokinetic boosters to enhance protease inhibitors and some integrase inhibitors plasma levels. Areas covered: This article focuses on the interactions between antiretroviral drugs and those drugs used to treat metabolic disturbances which frequently appear in PLWH. These include dyslipidemia, diabetes mellitus, hyperuricemia, and finally, drugs for the treatment of overweight and clinical obesity. References from PubMed, Embase, or Web of Science, among others, were reviewed. Expert opinion: The advent of safer drugs, in terms of DDI, in the antiretroviral and the metabolic field,such as non-boosted antiretrovirals and drugs with divergent metabolizing paths. Besides, learning by the caregivers on how to decrease and manage DDI, together with the extensive use of online updated DDI databases, has undoubtedly minimized the problem. The foreseeable increase in the burden of HIV-associated comorbidities and their associated treatments anticipates further complexities in the management of DDI in PLWH.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Infecções por HIV/tratamento farmacológico , Doenças Metabólicas/tratamento farmacológico , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/farmacocinética , Interações de Medicamentos , Infecções por HIV/complicações , Inibidores da Protease de HIV/administração & dosagem , Inibidores da Protease de HIV/efeitos adversos , Inibidores da Protease de HIV/farmacocinética , Humanos , Doenças Metabólicas/etiologia , Doenças Metabólicas/fisiopatologia
17.
Pan Afr Med J ; 33: 87, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31489065

RESUMO

Introduction: The introduction of highly active antiretroviral therapy (HAART) in the treatment of HIV infection has provided different good results: like long-term viral suppression, the decrease of opportunistic infections, and repair of the immune system. Methods: We carried out a hospital-based cross-sectional analytic study involving 315 participants 228 were on HAART (group 1) and 87 were HAART-naïve (group 2) at the HIV treatment centre of the Bamenda regional hospital with our study population being all people living with HIV (PLWHIV) in the North West region of Cameroon. The sampling was performed from the 15th of March to the 30th of June 2017. The questionnaire was administered face to face with participants and their vital signs taken. Blood pressure was measured using an automated electronic blood pressure monitor and hypertension (HTN) was considered as systolic blood pressure (BP) ≥ 140 mmHg and/or diastolic BP ≥ 90mmHg. Results: The prevalence of hypertension in the HAART group was 36.44% (n=82, CI: 30.15%-43.10%) compared to that of the HAART-naïve group which was 13.33% (n=12, CI: 7.08%-22.13%, P=0.01). HAART was associated with HTN after controlling for gender, family history of hypertension, body mass index (BMI), smoking and alcohol consumption. The odds ratio of the HAART-treated versus the HAART-naïve was 3.86 (95% CI: 1.98-7.50). We also found an association between TDF/3TC/EFV (OR=2.83), AZT/3TC/NVP (OR=2.82), AZT/3TC+EFV (OR=3.48) and TDF/3TC+NVP (OR=2.36) and HTN whereas those on AZT+3TC+ATV/r (OR=0.84) and TDF+3TC+ATV/r (OR=0.45) were not associated to hypertension. Conclusion: Our result suggests that blood pressure should be periodically measured and treated when necessary in PLWHIV on HAART.


Assuntos
Síndrome de Imunodeficiência Adquirida/tratamento farmacológico , Fármacos Anti-HIV/administração & dosagem , Infecções por HIV/tratamento farmacológico , Hipertensão/epidemiologia , Adulto , Idoso , Fármacos Anti-HIV/efeitos adversos , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Terapia Antirretroviral de Alta Atividade/métodos , Pressão Sanguínea , Camarões , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Inquéritos e Questionários , Adulto Jovem
18.
Pan Afr Med J ; 33: 89, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31489067

RESUMO

Introduction: Mortality of adult patients who are on antiretroviral therapy (ART) is higher in low-income than in high-income countries. After the failure of standard first-line treatment, patients switch to second-line regimens. However, there are limited data about the outcome of patients after switching to a second-line regimen in the study area. This study aimed to measure the rate of mortality and its determinants among HIV patients on second-line ART regimens. Methods: Multicenter institution based retrospective follow up study was conducted among 1192 adult patients who started second-line ART between 2008 and 2016 in eight selected hospitals of Amhara region. Patients who started second-line treatment after the failure of first-line treatment were included. Patient medical records, registration books, and computer database were used to collect the data. Time to death after a switch to second-line ART was the primary outcome of interest. Cox proportional hazard model was fitted to identify determinant factors of mortality. Results: Among 1192 patients who were on second-line ART, 136 (11.4%) died with 3,157 person-years of follow up. Over the study period, the mortality rate was 4.33 per 100 person-years. Not taking isoniazid preventive therapy (IPT) (Adjusted Hazard Ratio (AHR): 6.6; 95% CI: 2.9, 15.0), did not make modification on second-line regimen (AHR: 4.4; 95% CI: 2.8, 6.8), poor clinical adherence (AHR: 2.5; 95% CI: 1.4, 4.5), functional status of bedridden (AHR: 2.7; 95% CI: 1.5, 4.8), and having attained a tertiary level of education (AHR: 0.4; 95% CI: 0.2, 0.8) were independent determinants of mortality. Conclusion: The incidence rate of mortality was high and most of the deaths occurred within 12 months after switching to second-line ART. Higher mortality among adult HIV-infected patients was associated with poor adherence, no formal education, not taking IPT, being bedridden at the time of the switch, and not modifying second-line treatment. Improving treatment adherence of patients by providing consistent adherence counseling, providing INH prophylaxis and monitoring patient's regimen more closely during the first twelve months after switch could decrease mortality of HIV patients on a second-line regimen.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Infecções por HIV/tratamento farmacológico , Isoniazida/administração & dosagem , Adesão à Medicação/estatística & dados numéricos , Adolescente , Adulto , Pessoas Acamadas/estatística & dados numéricos , Escolaridade , Etiópia/epidemiologia , Feminino , Seguimentos , Infecções por HIV/mortalidade , Hospitais , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Adulto Jovem
19.
Pan Afr Med J ; 33: 95, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31489073

RESUMO

Introduction: Successful and long-term positive impact of antiretroviral treatment requires high rates of adherence (> 90%). In Senegal, there is a lack of data regarding adherence to antiretroviral treatment and only a few studies have looked at the determinants. The aim of this study is to assess the prevalence and determinants contributing to antiretroviral (ARV) adherence among Human Immunodeficiency Virus (HIV) infected outpatients receiving care at four public hospitals in Dakar, Senegal. Methods: A cross-sectional based study was carried out among HIV-positive ART adults in Dakar, Senegal. Patients were systematically sampled during either their clinical visits or visit to collect ARV drugs from six public hospitals and data collected with a questionnaire. The study outcome was adherence to antiretroviral treatment assessed by a multiple approach method which combined three self-reported adherence tools: self-reporting, Visual Analog Scale (VAS), and the Simplified Medication Adherence Questionnaire (SMAQ). Data were entered with an Excel spreadsheet and transferred to STATA for descriptive, bivariate and multivariate analysis. All the statistical tests were done at the threshold level of 0.05. Results: A total of 150 HIV-positive patients on first line ART regimen at six public health facilities were enrolled into the study. The mean age of patients was 43.1 years with a sex ratio of 0.3. Most of the patients were prescribed Tenofovir-based regimen. Of these patients, 26.67% were found to be highly adherent. After adjusting for health-related variables, demographic and socio-economic variables, better adherence was associated with participating actively within an association of persons living with HIV (AoR=2.89; 95% CI: 1.04 - 7.99; p value 0.041) while being widowed patient was associated with lower adherence (AoR=0.17; 95% CI: 0.03 - 0.94; p value 0.043). Conclusion: Our study findings imply that adherence should be routinely assessed during medical visits. Ongoing strategies to improve adherence such as out-of-clinic group-based models or psychological support should be directed toward outpatients' clinics to assist in improving adherence and long term virologic suppression in Senegal.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Infecções por HIV/tratamento farmacológico , Adesão à Medicação/estatística & dados numéricos , Adulto , Estudos Transversais , Feminino , Hospitais Públicos , Humanos , Masculino , Pacientes Ambulatoriais , Prevalência , Senegal , Inquéritos e Questionários
20.
Pan Afr Med J ; 33: 32, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31384347

RESUMO

Introduction: Antiretroviral therapy (ART) is vital for people living with HIV (PLWHIV) and a substantial number of HIV/AIDS patients still face stigmatization from family and other members of the community. Stigma could lead to poor retention in HIV care and consequently result in decreased chances of survival and increased risk of HIV transmission. The aim of this study was to determine the retention of patients in HIV care and community participation in the retention of patients in HIV care at the Muyuka Health District, South-West Region, Cameroon. Methods: This was an analytic cross-sectional retrospective study where 385 hospital records of people living with HIV (PLWHIV) enrolled in HIV care were reviewed, and we administered 348 questionnaires to community members. Data were collected and analysed using bivariate analysis and chi-square test. The Susan Rifkin's scoring method was used to measure community participation. Statistical significance was set at P-value < 0.05. Results: A total number of 112(29.1%) of people living with HIV (PLWHIV) enrolled in HIV care were retained in HIV care against 273(70.9%), who were lost to follow-up over a two year and four months period. Patients on a Zidovudine containing ART regimen were about 7 times more likely to be lost to follow-up (OR 6.92; 95% CI 1.80-26.60, P-value = 0.005). The overall community participation in the retention of adults in HIV care in the Muyuka Health District was low; mean resource allocation score = 2.43, mean leadership score = 1.0; mean organization factor score = 1.30; but the mean needs assessment score was good (4.0). Conclusion: retention of patients enrolled in HIV care, and the community participation in the retention were low. Collaborations between health care structures and community initiatives should be resourced to foster continuum of care for people living with HIV (PLWHIV).


Assuntos
Fármacos Anti-HIV/administração & dosagem , Participação da Comunidade/estatística & dados numéricos , Infecções por HIV/tratamento farmacológico , Estereotipagem , Adulto , Camarões , Estudos Transversais , Feminino , Infecções por HIV/psicologia , Humanos , Perda de Seguimento , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estigma Social , Inquéritos e Questionários , Adulto Jovem
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