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1.
N Engl J Med ; 382(12): 1124-1135, 2020 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-32130806

RESUMO

BACKGROUND: Long-acting injectable regimens may simplify therapy for patients with human immunodeficiency virus type 1 (HIV-1) infection. METHODS: We conducted a phase 3, randomized, open-label trial in which adults with HIV-1 infection who had not previously received antiretroviral therapy were given 20 weeks of daily oral induction therapy with dolutegravir-abacavir-lamivudine. Participants who had an HIV-1 RNA level of less than 50 copies per milliliter after 16 weeks were randomly assigned (1:1) to continue the current oral therapy or switch to oral cabotegravir plus rilpivirine for 1 month followed by monthly injections of long-acting cabotegravir plus rilpivirine. The primary end point was the percentage of participants who had an HIV-1 RNA level of 50 copies per milliliter or higher at week 48 (Food and Drug Administration snapshot algorithm). RESULTS: At week 48, an HIV-1 RNA level of 50 copies per milliliter or higher was found in 6 of 283 participants (2.1%) who received long-acting therapy and in 7 of 283 (2.5%) who received oral therapy (adjusted difference, -0.4 percentage points; 95% confidence interval [CI], -2.8 to 2.1), a result that met the criterion for noninferiority for the primary end point (margin, 6 percentage points). An HIV-1 RNA level of less than 50 copies per milliliter at week 48 was found in 93.6% who received long-acting therapy and in 93.3% who received oral therapy (adjusted difference, 0.4 percentage points; 95% CI, -3.7 to 4.5), a result that met the criterion for noninferiority for this end point (margin, -10 percentage points). Of the participants who received long-acting therapy, 86% reported injection-site reactions (median duration, 3 days; mild or moderate severity, 99% of cases); 4 participants withdrew from the trial for injection-related reasons. Grade 3 or higher adverse events and events that met liver-related stopping criteria occurred in 11% and 2%, respectively, who received long-acting therapy and in 4% and 1% who received oral therapy. Treatment satisfaction increased after participants switched to long-acting therapy; 91% preferred long-acting therapy at week 48. CONCLUSIONS: Therapy with long-acting cabotegravir plus rilpivirine was noninferior to oral therapy with dolutegravir-abacavir-lamivudine with regard to maintaining HIV-1 suppression. Injection-site reactions were common. (Funded by ViiV Healthcare and Janssen; FLAIR ClinicalTrials.gov number, NCT02938520.).


Assuntos
Fármacos Anti-HIV/administração & dosagem , Infecções por HIV/tratamento farmacológico , HIV-1/isolamento & purificação , Piridonas/administração & dosagem , Rilpivirina/administração & dosagem , Administração Oral , Adulto , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/sangue , Antirretrovirais/uso terapêutico , Contagem de Linfócito CD4 , Farmacorresistência Viral/genética , Quimioterapia Combinada , Feminino , HIV-1/genética , Humanos , Quimioterapia de Indução , Injeções Intramusculares , Quimioterapia de Manutenção , Masculino , Pessoa de Meia-Idade , Mutação , Medidas de Resultados Relatados pelo Paciente , Piridonas/efeitos adversos , Piridonas/sangue , RNA Viral/sangue , Rilpivirina/efeitos adversos , Rilpivirina/sangue , Carga Viral
2.
N Engl J Med ; 382(12): 1112-1123, 2020 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-32130809

RESUMO

BACKGROUND: Simplified regimens for the treatment of human immunodeficiency virus type 1 (HIV-1) infection may increase patient satisfaction and facilitate adherence. METHODS: In this phase 3, open-label, multicenter, noninferiority trial involving patients who had had plasma HIV-1 RNA levels of less than 50 copies per milliliter for at least 6 months while taking standard oral antiretroviral therapy, we randomly assigned participants (1:1) to either continue their oral therapy or switch to monthly intramuscular injections of long-acting cabotegravir, an HIV-1 integrase strand-transfer inhibitor, and long-acting rilpivirine, a nonnucleoside reverse-transcriptase inhibitor. The primary end point was the percentage of participants with an HIV-1 RNA level of 50 copies per milliliter or higher at week 48, determined with the use of the Food and Drug Administration snapshot algorithm. RESULTS: Treatment was initiated in 308 participants per group. At week 48, HIV-1 RNA levels of 50 copies per milliliter or higher were found in 5 participants (1.6%) receiving long-acting therapy and in 3 (1.0%) receiving oral therapy (adjusted difference, 0.6 percentage points; 95% confidence interval [CI], -1.2 to 2.5), a result that met the criterion for noninferiority for the primary end point (noninferiority margin, 6 percentage points). An HIV-1 RNA level of less than 50 copies per milliliter at week 48 was found in 92.5% of participants receiving long-acting therapy and in 95.5% of those receiving oral therapy (adjusted difference, -3.0 percentage points; 95% CI, -6.7 to 0.7), a result that met the criterion for noninferiority for this end point (noninferiority margin, -10 percentage points). Virologic failure was confirmed in 3 participants who received long-acting therapy and 4 participants who received oral therapy. Adverse events were more common in the long-acting-therapy group and included injection-site pain, which occurred in 231 recipients (75%) of long-acting therapy and was mild or moderate in most cases; 1% withdrew because of this event. Serious adverse events were reported in no more than 5% of participants in each group. CONCLUSIONS: Monthly injections of long-acting cabotegravir and rilpivirine were noninferior to standard oral therapy for maintaining HIV-1 suppression. Injection-related adverse events were common but only infrequently led to medication withdrawal. (Funded by ViiV Healthcare and Janssen; ATLAS ClinicalTrials.gov number, NCT02951052.).


Assuntos
Fármacos Anti-HIV/administração & dosagem , Infecções por HIV/tratamento farmacológico , HIV-1/isolamento & purificação , Piridonas/administração & dosagem , Rilpivirina/administração & dosagem , Administração Oral , Adulto , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/sangue , Antirretrovirais/uso terapêutico , Contagem de Linfócito CD4 , Farmacorresistência Viral/genética , Quimioterapia Combinada , Feminino , HIV-1/genética , Humanos , Injeções Intramusculares/efeitos adversos , Quimioterapia de Manutenção , Masculino , Pessoa de Meia-Idade , Mutação , Medidas de Resultados Relatados pelo Paciente , Piridonas/efeitos adversos , Piridonas/sangue , RNA Viral/sangue , Rilpivirina/efeitos adversos , Rilpivirina/sangue , Carga Viral
3.
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
4.
PLoS One ; 14(12): e0226375, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31856189

RESUMO

To assess and compare the prevalence of persistent hepatic abnormalities, including nonalcoholic fatty liver disease (NAFLD) and/or hepatic fibrosis, among perinatally HIV-monoinfected Asian adolescents with history of abnormal hepatic enzymes to those without, using noninvasive diagnostic tools. A multicenter cohort study was conducted in Thailand and Indonesia. Adolescents aged 10-25 years who were on antiretroviral treatment (ART), had virologic suppression (HIV RNA<400 copies/mL within the past 6 months), and had no history of chronic hepatitis B/C infection were enrolled. Participants were pre-classified into 2 subgroups (1:1 ratio) as participants with history of elevated versus normal aminotransferase enzymes. NAFLD was defined as hepatic steatosis (any severity) evaluated by liver ultrasonography. Significant hepatic fibrosis was defined as liver stiffness ≥7.4 kPa evaluated by transient elastography. Participants who met the criteria for protocol-defined NAFLD and/or hepatic fibrosis were re-assessed to evaluate disease progression (persistent versus transient hepatic abnormalities) at one year later. Of 120 participants, 62 (51.7%) were male, 7 (5.8%) had central obesity, and 19 (15.8%) had insulin resistance (homeostasis model assessment of insulin resistance [HOMA-IR] >3.16). At enrollment, the median age and duration of ART (IQR) were 17.0 (14.6-19.2) years and 10.5 (7.1-12.0) years, respectively. Persistent hepatic abnormalities were identified in 5/60 participants listed in the group having history of elevated aminotransferases, corresponding to the prevalence of 8.3% (95% CI: 2.8-18.4%), whereas none (0/60) were among the group having history of normal hepatic enzymes. All 5 participants had persistent aminotransferase elevation (≥2 episodes within the past 12 months). Baseline alanine aminotransferase (ALT) >30 U/L (adjusted odds ratio [aOR]: 29.1; 95% CI: 1.7-511.8), and HOMA-IR >3.16 (aOR: 17.9; 95% CI: 1.1-289.7) were independently associated with persistent hepatic abnormalities. Among perinatally HIV-monoinfected Asian adolescents with history of elevated aminotransferase enzymes, persistent hepatic abnormalities are not uncommon. Screening for liver complications by noninvasive diagnostic tools might be considered in at risk individuals, including those with persistent ALT elevation and insulin resistance.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Cirrose Hepática/complicações , Hepatopatia Gordurosa não Alcoólica/complicações , Adolescente , Adulto , Fármacos Anti-HIV/efeitos adversos , Ásia/epidemiologia , Criança , Estudos de Coortes , Feminino , Humanos , Cirrose Hepática/epidemiologia , Masculino , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Adulto Jovem
5.
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
6.
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
7.
Medicine (Baltimore) ; 98(43): e17585, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31651864

RESUMO

This study sought to examine the human immunodeficiency virus type 1 (HIV-1) genetic diversity on drug resistance among men who have sex with men (MSM) with virologic failure in antiretroviral therapy (ART), and investigate linking-associated factors for genetic transmission networks.Seven hundred and thirty-four HIV-positive MSM with virologic failure in ART were recruited into our study from 2011 to 2017. HIV-1 pol gene sequences were used for phylogenetic and genotypic drug resistance analyses. The drug resistance mutations were determined using the Stanford University HIV Drug Resistance Database. The genetic transmission networks were analyzed for CRF01_AE and CRF07_BC sequences by the genetic distance-based method.Of 734 subjects, 372 (50.68%) showed drug resistance, in which CRF01_AE and CRF07_BC were the predominating subtypes. Drug resistance more frequently occurred in non-nucleoside reverse transcriptase inhibitors (NNRTIs) treatment (48.64%), and followed by nucleoside reverse transcriptase inhibitors (NRTIs) (36.51%) and PIs (4.03%). The most common drug resistance-associated mutations in protease inhibitors (PIs), NRTIs and NNRTIs were K20I/R, M184V/I and K103N/KN, respectively. For 283CRF01_AE sequences, 64 (22.61%) fell into clusters at a genetic distance of 0.011, resulting in 17 clusters ranging in size from 2 to 16 individuals. For 230 CRF07_BC sequences, 66 (28.69%) were connected to at least one other sequence with 0.005 genetic distances, resulting in 8 clusters ranging in size from 2 to 52 individuals. Individuals who showed drug resistance to ART were less likely to fall into clusters than those who did not. The genetic linkage was robust by the exclusion of sites associated with drug resistance.CRF01_AE and CRF07_BC were the main strains among MSM with virologic failure in ART, and the drug resistance more frequently occurred in NNRTIs, followed by NRTIs and PIs. Genetic transmission networks revealed a complexity of transmission pattern, suggesting early-diagnosis and in-time intervention among MSM.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Farmacorresistência Viral/genética , Infecções por HIV/tratamento farmacológico , HIV-1/genética , Inibidores da Transcriptase Reversa/efeitos adversos , Adolescente , Adulto , China , Homossexualidade Masculina , Humanos , Masculino , Minorias Sexuais e de Gênero/estatística & dados numéricos , Falha de Tratamento , Adulto Jovem
9.
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
10.
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
11.
Pregnancy Hypertens ; 17: 178-190, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31487638

RESUMO

OBJECTIVE: To assess if there is a relationship between use of combined antiretroviral therapy among pregnant women living with HIV and hypertensive disorders of pregnancy (HDP). DESIGN: Due to the heterogeneity of study designs in the literature and the utilization of different outcome measures in regards to assessing the presence of HDP, a systematic review was performed. METHODS: ClinicalTrials.gov and MEDLINE, via PubMed, EMBASE, Scopus, CINAHL, ProQuest Dissertations & Theses Global, EBSCOHost, DARE, and the Cochrane Library, were queried from January 1997 to October 2017. Studies were included if they reported HDP and focused on pregnant women living with HIV who used combined antiretroviral therapy. The Cochrane Collaboration's tool for assessment of risk of bias and the U.S. Preventive Services Task Force grading scale were used to assess the studies. RESULTS: Of 1055 abstracts, 28 articles met inclusion criteria. The data are marked by multiple biases and poor study design. All studies demonstrate an increased risk of HDP among pregnant women living with HIV who used combined antiretroviral therapy when compared to seropositive pregnant women not using antiretroviral therapy. Three studies suggest protease inhibitors may be associated with a higher risk of HDP. CONCLUSION: Despite all studies indicating a higher frequency of HDP among pregnant women living with HIV using combined antiretroviral therapy when compared with seropositive pregnant women not using antiretroviral therapy, the quality of the studies is mixed, necessitating further research.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Infecções por HIV/tratamento farmacológico , Pré-Eclâmpsia/induzido quimicamente , Complicações Infecciosas na Gravidez/tratamento farmacológico , Fármacos Anti-HIV/administração & dosagem , Quimioterapia Combinada , Feminino , Humanos , Gravidez , Risco
12.
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
13.
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
14.
BMC Infect Dis ; 19(1): 708, 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31399063

RESUMO

BACKGROUND: Thymidine analogues (TA) and didanosine (ddI) are associated with long-lasting adipose tissue redistribution. Adiponectin is a widely used marker of adipocyte activity, and adipose tissue density assessed by CT-scan is associated with adipocyte size and function. We hypothesized that prior exposure to TA and ddI was associated with long-lasting adipose tissue dysfunction in people living with HIV (PLWH). Thus, we tested possible associations between markers of adipose tissue dysfunction (adipose tissue density and adiponectin) and prior exposure to TA and/or ddI, years after treatment discontinuation. METHODS: Eight hundred forty-eight PLWH from the COCOMO study were included and stratified according to prior exposure to TA and/or ddI (with, n = 451; without n = 397). Visceral (VAT) and subcutaneous (SAT) adipose tissue area and density were determined by single slice abdominal CT-scan at lumbar 4th level. Venous blood was collected and analyzed for adiponectin. Multivariable linear and logistic regression analyses were used to test our hypotheses. Multivariable models were adjusted for age, sex, smoking, origin, physical activity, BMI, and adipose tissue area (VAT or SAT area, accordingly to the outcome). RESULTS: prior exposure to TA and/or ddI was associated with excess risk of low VAT (adjusted OR (aOR) 1.74 [1.14; 2.67]) and SAT density (aOR 1.74 [1.18; 2.58]), for a given VAT and SAT area, respectively. No association between VAT and SAT density with time since TA and/or ddI discontinuation was found. 10 HU increase in VAT density was associated with higher adiponectin plasma level and this association was not modified by prior exposure to TA and/or ddI. Prior exposure to TA and/or ddI was associated with 9% lower [- 17;-2] plasma adiponectin levels and with excess risk of low adiponectin (aOR 1.74 [1.10; 2.76]). CONCLUSIONS: We described low adipose tissue density and impaired adiponectin production to be associated with prior exposure to TA and/or ddI even years after treatment discontinuation and independently of adipose tissue area. These findings suggest that prior TA and ddI exposure may have long-lasting detrimental effects on adipose tissue function and, consequently, on cardiometabolic health in PLWH.


Assuntos
Adiponectina/sangue , Tecido Adiposo/efeitos dos fármacos , Fármacos Anti-HIV/efeitos adversos , Infecções por HIV/tratamento farmacológico , Tecido Adiposo/patologia , Adulto , Biomarcadores/sangue , Estudos Transversais , Didanosina/efeitos adversos , Feminino , Infecções por HIV/fisiopatologia , Humanos , Gordura Intra-Abdominal/efeitos dos fármacos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Gordura Subcutânea/efeitos dos fármacos , Timidina/análogos & derivados
15.
Braz J Infect Dis ; 23(4): 268-270, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31374183

RESUMO

Abacavir can cause a multi-systemic hypersensitivity reaction (HSR) in 5-8% of the patients, which is related to HLA-B*57-01 allele. In Brazil, the HLA-B*57-01 screening test became available only in March 2018, several years after abacavir was in use. In this retrospective study we reviewed medical charts of all patients receiving an abacavir-containing regimen to evaluate the frequency of HSR in patients followed at a referral center in Salvador, Brazil. A total of 192 patients who received abacavir were identified, most male (67.1%), black or racially mixed (77.8%), and having diagnosis of a previous AIDS defining conditions (83.7%). Only one patient developed HSR (incidence: 0.52%). The main reasons for abacavir-containing antiretroviral therapy discontinuation were virological failure (28%), adverse effects to other components of the regimen (25%), and simplification of therapy (16%). The low incidence of HSR to abacavir does not support the use of HLA-B*57-01 screening test, in Salvador, Brazil.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Didesoxinucleosídeos/efeitos adversos , Hipersensibilidade a Drogas/epidemiologia , Hipersensibilidade a Drogas/etiologia , Infecções por HIV/tratamento farmacológico , Adulto , Brasil/epidemiologia , Feminino , Humanos , Incidência , Masculino , Estudos Retrospectivos
16.
BMC Infect Dis ; 19(1): 715, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31409277

RESUMO

BACKGROUND: Gynecomastia is known to occur in some men taking an efavirenz-based antiretroviral therapy (ART) regimen. However, the incidence and outcomes of gynecomastia are not known in Zimbabwe. We described the characteristics and outcomes of gynecomastia among male patients on an efavirenz-based ART regimen. METHODS: We conducted a retrospective cohort review of data of all male patients aged ≥18 years taking an efavirenz-based regimen at Newlands Clinic, Harare, Zimbabwe before 31 March 2017. The primary outcome was gynecomastia as defined by breast/nipple enlargement reported by patient and confirmed by clinical palpation. Routinely collected data on demographics, baseline CD4, body mass index, duration on efavirenz, clinical presentation and outcomes were extracted from the clinic database and analysed using STATA 12.1. We investigated for any associations with concomitant medicines using cox regression. RESULTS: We analysed data for 1432 men with a median age of 40 years (IQR: 33-48). Half of the patients were in WHO stage 1 at ART commencement. Median body mass index and CD4 count at efavirenz commencement was 21 (IQR: 19-23) and 260 cells/mm3 (IQR: 126-412) respectively. The incidence of gynecomastia was 22/1000 person-years (IQR: 17.3-27.8). Over half of the cases (58%) were bilateral and 75% of all cases developed within two years of starting efavirenz. There were no significant associations with concomitant use of isoniazid (HR: 0.95, p = 0.87) or amlodipine (HR: 0.43, p = 0.24). Gynecomastia resolved in 83.5% of cases following withdrawal of efavirenz with a median time to resolution of 3 months (IQR: 2-9). CONCLUSION: The incidence of gynecomastia among patients taking efavirenz-based ART was low with most cases developing early on during treatment. Most cases resolved completely after withdrawing efavirenz.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Benzoxazinas/efeitos adversos , Ginecomastia/induzido quimicamente , Infecções por HIV/tratamento farmacológico , Adulto , Anlodipino/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , Benzoxazinas/uso terapêutico , Contagem de Linfócito CD4 , Estudos de Coortes , Feminino , Ginecomastia/epidemiologia , Humanos , Incidência , Isoniazida/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Inibidores da Transcriptase Reversa/efeitos adversos , Zimbábue/epidemiologia
17.
Trials ; 20(1): 522, 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31439004

RESUMO

BACKGROUND: There is a need for evaluating community-based antiretroviral therapy (ART) delivery models to improve overall performance of HIV programs, specifically in populations that may have difficulties to access continuous care. This cluster-randomized clinical trial aims to evaluate the effectiveness of a multicomponent differentiated ART delivery model (VIBRA model) after home-based same-day ART initiation in remote villages in Lesotho, southern Africa. METHODS/DESIGN: The VIBRA trial (VIllage-Based Refill of ART) is a cluster-randomized parallel-group superiority clinical trial conducted in two districts in Lesotho, southern Africa. Clusters (i.e., villages) are randomly assigned to either the VIBRA model or standard care. The clusters are stratified by district, village size, and village access to the nearest health facility. Eligible individuals (HIV-positive, aged 10 years or older, and not taking ART) identified during community-based HIV testing campaigns are offered same-day home-based ART initiation. The intervention clusters offer a differentiated ART delivery package with two features: (1) drug refills and follow-ups by trained and supervised village health workers (VHWs) and (2) the option of receiving individually tailored adherence reminders and notifications of viral load results via SMS. The control clusters will continue to receive standard care, i.e., collecting ART refills from a clinic and no SMS notifications. The primary endpoint is viral suppression 12 months after enrolment. Secondary endpoints include linkage to and engagement in care. Furthermore, safety and cost-effectiveness analyses plus qualitative research are planned. The minimum target sample size is 262 participants. The statistical analyses will follow the CONSORT guidelines. The VIBRA trial is linked to another trial, the HOSENG (HOme-based SElf-testiNG) trial, both of which are within the GET ON (GETing tOwards Ninety) research project. DISCUSSION: The VIBRA trial is among the first to evaluate the delivery of ART by VHWs immediately after ART initiation. It assesses the entire HIV care cascade from testing to viral suppression. As most countries in sub-Saharan Africa have cadres like the VHW program in Lesotho, this model-if shown to be effective-has the potential to be scaled up. The system impact evaluation will provide valuable cost estimations, and the qualitative research will suggest how the model could be further modified to optimize its impact. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03630549 . Registered on 15 August 2018.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Assistência à Saúde/organização & administração , Infecções por HIV/tratamento farmacológico , HIV/efeitos dos fármacos , Adesão à Medicação , Serviços de Saúde Rural/organização & administração , Fármacos Anti-HIV/efeitos adversos , Prescrições de Medicamentos , Estudos de Equivalência como Asunto , HIV/crescimento & desenvolvimento , Infecções por HIV/diagnóstico , Infecções por HIV/virologia , Humanos , Lesoto , Estudos Multicêntricos como Assunto , Fatores de Tempo , Resultado do Tratamento , Carga Viral
18.
Ethiop J Health Sci ; 29(3): 299-308, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31447498

RESUMO

Background: Adherence is the most important factor in determining Antiretroviral Therapy (ART) treatment success and long-term viral suppression. Nonadherence to ART led to the human Immunodeficiency Virus (HIV) related morbidity and mortality. Moreover, it intensifies the risk of the emerging drug resistant HIV strains. This study aimed to assess the level of ART adherence and to identify its predictive associated factors among people living with HIV/AIDS in Hara Town and its surroundings, North-Eastern Ethiopia. Methods: An institutional facility based cross-sectional study was conducted from April-May 2017. A total of 454 individuals were on ART follow-up in the selected ART-clinic, and only 418 patients were recruited. Bivariate and multivariate logistic regression analyses were carried out to identify associated factors. Odds ratio and 95% Confidence Interval (CI) were calculated to determine the level of significance. Results: The level of ART adherence in the study setting was 300 (71.8%). Participants who had not disclosed their HIV status to their families were 88% less likely to adhere to their ART medication than those who had disclosed their HIV status ((Odds ratio (OR): 0.12, 95%CI:0.05-0.58; p<0.001). On the other hand, participants who had not encountered drug side effects were 2.69 times more likely to adhere to their ART medication than those who had ever encountered drug side effects (OR: 2.69, 95%CI:1.27-5.05; p<0.001). Conclusion: A very low level of ART adherence was shown in the study population. It was below the recommended good adherence standard. Therefore, patients should get adequate and comprehensive ART adherence counselling before initiation ART treatment and during the follow-up time.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Adesão à Medicação/estatística & dados numéricos , Adolescente , Adulto , Fármacos Anti-HIV/efeitos adversos , Contagem de Linfócito CD4/estatística & dados numéricos , Estudos Transversais , Escolaridade , Etiópia/epidemiologia , Feminino , Infecções por HIV/psicologia , Humanos , Masculino , Estado Civil , Adesão à Medicação/psicologia , Pessoa de Meia-Idade , Adulto Jovem
19.
J Microbiol Immunol Infect ; 52(5): 710-719, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31427111

RESUMO

BACKGROUND: The regimen containing tenofovir disoproxil fumarate (TDF)+lamivudine or emtricitabine + efavirenz remains the recommended first-line antiretroviral therapy (ART) by the WHO. Limited studies, however, have been conducted on the incidence of renal impairment among Chinese patients with long-term exposure to TDF-containing ART regimens. METHODS: We retrospectively analyzed 269 eligible patients who had no comorbidities and received TDF-containing ART from July 2014 to April 2015. TDF-related renal impairment was defined as a decrease of eGFR by >25% from baseline or eGFR <90 ml/min/1.73 m2. Decreased renal function was defined as a decrease of eGFR by > 10 mL/min/1.73 m2 from baseline. RESULTS: 97.0% of study patients were male (median age 29, eGFR 124.0 ml/min/1.73 m2). After 168-week of ART, renal impairment occurred in 7 patients (2.7%). The incidence of decreased renal function was significantly higher at Week 168 compared with that observed at Week 12 (24.8% vs 3.7%, p < 0.001). In generalized estimating equation analysis, patients receiving ART for 144-week (aOR4.1, 95%CI 2.0-8.4) and 168-week (aOR8.4, 95%CI 4.2-16.4) were more likely to develop decreased renal function compared with those receiving ART for 12-week, so were the patients with a weight <58 kg (aOR2.3, 95%CI 1.2-4.3) and 58-66 kg (aOR2.0, 95%CI 1.0-3.8) compared to those with a weight ≥67 kg. At 168-week, 41.0% of 100 patients examined had elevated urine ß2-microglobulin levels, which were negatively correlated with eGFR (r = -0.22, p = 0.02). CONCLUSIONS: TDF-related renal impairment remained rare in HIV-positive Chinese patients with a median age of 29 years who had no comorbidities. A lower weight and duration of ART were associated with decreased renal function.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Infecções por HIV/tratamento farmacológico , Insuficiência Renal/induzido quimicamente , Tenofovir/efeitos adversos , Adulto , Grupo com Ancestrais do Continente Asiático , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Infecções por HIV/complicações , Hepatite B Crônica/etiologia , Humanos , Rim/efeitos dos fármacos , Túbulos Renais Proximais/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Proteinúria , Insuficiência Renal/etiologia , Estudos Retrospectivos , Adulto Jovem
20.
Medicine (Baltimore) ; 98(32): e16813, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31393412

RESUMO

Dolutegravir (DTG) has shown effectiveness in combination with rilpivirine in with experience of antiretroviral therapy (ART) and with 3TC in naïve patients (GEMINI trial). The main objectives of this real-life study were to analyze the effectiveness and safety of 3TC plus DTG in virologically suppressed HIV-1 patients and to conduct a pharmacoeconomic analysis.We conducted an observational, retrospective and multicenter study of HIV+ patients pretreated for at least 6 months with ART that was then simplified to 3TC + DTG for any reason. We gathered data on viral loads (VLs) during exposure to the DT, calculating the rate with VL < 50 copies/mL at week 48, and on associated adverse effects.The 177 HIV+ patients were collected, 77.4% male, with average age of 48.5 years and mean count of 252.2cell/µL CD4+ nadir lymphocytes; 96.6% had VL < 50 copies/mL and 674 cells/µL CD4+ lymphocytes. Median time since HIV diagnosis was 15 years, and median ART duration was 13 years, and 34.5% of patients were on mono- or dual-therapy before the switch. At week 48, 82.4% of patients had VL < 50 cop/µL using an intention-to-treat (ITT) analysis, 89.6% according to mITT, and 96.7% according to Per-Protocol analysis. 3.3% patients had virological failure (VF). These effectiveness data and costs were compared with those for 2 reference triple therapies (DTG/ABC/3TC and EVG/cobi/FTC/TAF) in a cost minimization analysis, showing cost savings with administration of DTG+3TC (2741 &OV0556;/year vs DTG/ABC/3TC and 4164 &OV0556;/year vs EVG/cobi/FTC/TAF) and in a cost-effectiveness analysis, finding the DT to be the most cost-effective approach (ICER = -548 vs DTG/ABC/3TC and ICER = -4,627&OV0556; vs EVG/cobi/FTC/TAF)The combination of 3TC with DTG appears to be a safe and effective option for the simplification of ART in pretreated and virologically stable HIV-positive patients, being cost-effective and offering the same effectiveness as the triple therapy it replaces.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Lamivudina/uso terapêutico , Adulto , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/economia , Contagem de Linfócito CD4 , Análise Custo-Benefício , Quimioterapia Combinada , Farmacoeconomia , Honorários Farmacêuticos/estatística & dados numéricos , Feminino , HIV-1 , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Compostos Heterocíclicos com 3 Anéis/economia , Humanos , Lamivudina/administração & dosagem , Lamivudina/efeitos adversos , Lamivudina/economia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Carga Viral
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