RESUMO
INTRODUCTION: Disease and deaths from HIV/AIDS have decreased since antiretroviral treatment was introduced in 1996. Since 2005, as treatment availability has increased worldwide, deaths from HIV/AIDS have declined 48%. As of November 2019, 26,952 cases have been reported in Cuba, of which 5159 (19.1%) are deceased. The country has experienced a reduction in mortality rates since 2002, when antiretroviral treatment became available. Although there are clearly benefits to treatment, it is important to understand antiretroviral safety profiles as their toxicity may lower treatment adherence. OBJECTIVE: Describe adverse reactions attributable to antiretrovirals used in Cuban patients living with HIV/AIDS. METHODS: I studied notifications of adverse reactions to antiretrovirals used in Cuban patients with HIV/AIDS from January 2003 to December 2017. The sample consisted of 352 notifications in the National Pharmacovigilance Database regarding adverse reactions attributed to antiretrovirals. The variables considered were sex, notification year, antiretroviral drug, and number, type, frequency and severity of adverse reactions, whether or not they were preventable, and the reasons for categorizing them as they were. RESULTS: Antiretrovirals reported an average adverse reaction rate of 2.1 per million population per year, representing 24.2% of adverse reactions produced by the antiviral drug group in that period. Adult males represented 75% (264/352) of patients who had adverse reactions to antiretrovirals. Most adverse reactions were in response to nevirapine (29.0%; 102/352) and zidovudine (26.7%; 94/352). The most frequent reactions were hypersensitivity (24.4%; 86/352), digestive disorders (15.9%; 56/352) and anemia (15.6%; 55/352). Reactions were common (62.5%; 220/352) and moderate in severity (70.4%; 248/352). Preventable reactions made up 52.6% (185/352) of adverse reactions. Of preventable reactions, 68.1% (126/185) were associated with drug interactions and 16.2% (30/185) with improper dosage or prescription errors. CONCLUSIONS: Adverse reactions to antiretrovirals in Cuban patients are common and moderate in severity. The drug with the most notifications was nevirapine, and the most common adverse reaction was hypersensitivity. More than half of adverse reactions are considered preventable, and their main causes are prescription errors.
Assuntos
Fármacos Anti-HIV/efeitos adversos , Infecções por HIV/tratamento farmacológico , Adolescente , Adulto , Fármacos Anti-HIV/uso terapêutico , Criança , Pré-Escolar , Cuba/epidemiologia , Feminino , Infecções por HIV/epidemiologia , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Nevirapina/efeitos adversos , Nevirapina/uso terapêutico , Adulto Jovem , Zidovudina/efeitos adversos , Zidovudina/uso terapêuticoRESUMO
Studies of viral suppression on first-line antiretroviral therapy (ART) in persons living with human immunodeficiency virus (PLHIV) in Haiti are limited, particularly among PLHIV outside of the Ouest department, where the capital Port-au-Prince is located. This study described the prevalence and risk factors for delayed viral suppression among PLHIV in all geographic departments of Haiti between 2013 and 2017. Individuals who received viral load testing 3 to 12 months after ART initiation were included. Data on demographics and clinical care were obtained from the Haitian Active Longitudinal Tracking of HIV database. Multivariable logistic regression was performed to predict delayed viral suppression, defined as a viral load ≥1000 HIV-1 RNA copies/mL after at least 3 months on ART. Viral load test results were available for 3,368 PLHIV newly-initiated on ART. Prevalence of delayed viral suppression was 40%, which is slightly higher than previous estimates in Haiti. In the multivariable analysis, delayed viral suppression was significantly associated with younger age, receiving of care in the Ouest department, treatment with lamivudine (3TC), zidovudine (AZT), and nevirapine (NVP) combined ART regimen, and CD4 counts below 200 cells/mm3. In conclusion, this study was the first to describe and compare differences in delayed viral suppression among PLHIV by geographic department in Haiti. We identified populations to whom public health interventions, such as more frequent viral load testing, drug resistance testing, and ART adherence counseling should be targeted.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade/métodos , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Adolescente , Adulto , Fármacos Anti-HIV/efeitos adversos , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Criança , Pré-Escolar , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , HIV-1/patogenicidade , Haiti/epidemiologia , Humanos , Lamivudina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Nevirapina/efeitos adversos , Nevirapina/uso terapêutico , Fatores de Risco , Carga Viral/efeitos dos fármacos , Adulto Jovem , ZidovudinaRESUMO
This is a substudy of the Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS) Comparison of Nevirapine and Efavirenz for the Treatment of HIV-TB Co-infected Patients (ANRS 12146-CARINEMO) trial, which assessed the pharmacokinetics of rifampin or isoniazid with or without the coadministration of nonnucleoside reverse transcriptase inhibitor-based HIV antiretroviral therapy in HIV-tuberculosis-coinfected patients in Mozambique. Thirty-eight patients on antituberculosis therapy based on rifampin and isoniazid participated in the substudy (57.9% males; median age, 33 years; median weight, 51.9 kg; median CD4(+) T cell count, 104 cells/µl; median HIV-1 RNA load, 5.5 log copies/ml). The daily doses of rifampin and isoniazid were 10 and 5 mg/kg of body weight, respectively. Twenty-one patients received 200 mg of nevirapine twice a day (b.i.d.), and 17 patients received 600 mg of efavirenz once a day (q.d.) in combination with lamivudine and stavudine from day 1 until the end of the study. Blood samples were collected at regular time-dosing intervals after morning administration of a fixed-dose combination of rifampin and isoniazid. When rifampin was administered alone, the median maximum concentration of drug in serum (Cmax) and the area under the concentration-time curve (AUC) at steady state were 6.59 mg/liter (range, 2.70 to 14.07 mg/liter) and 27.69 mg · h/liter (range, 11.41 to 109.75 mg · h/liter), respectively. Concentrations remained unchanged when rifampin was coadministered with nevirapine or efavirenz. When isoniazid was administered alone, the median isoniazid Cmax and AUC at steady state were 5.08 mg/liter (range, 1.26 to 11.51 mg/liter) and 20.92 mg · h/liter (range, 7.73 to 56.95 mg · h/liter), respectively. Concentrations remained unchanged when isoniazid was coadministered with nevirapine; however, a 29% decrease in the isoniazid AUC was observed when isoniazid was combined with efavirenz. The pharmacokinetic parameters of rifampin and isoniazid when coadministered with nevirapine or efavirenz were not altered to a clinically significant extent in these severely immunosuppressed HIV-infected patients. Patients experienced favorable clinical outcomes. (This study has been registered at ClinicalTrials.gov under registration no. NCT00495326.).
Assuntos
Antituberculosos/farmacocinética , Antituberculosos/uso terapêutico , Benzoxazinas/uso terapêutico , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Isoniazida/farmacocinética , Isoniazida/uso terapêutico , Nevirapina/uso terapêutico , Inibidores da Transcriptase Reversa/uso terapêutico , Rifampina/farmacocinética , Rifampina/uso terapêutico , Tuberculose/complicações , Tuberculose/tratamento farmacológico , Adulto , Alcinos , Antituberculosos/efeitos adversos , Benzoxazinas/efeitos adversos , Coinfecção , Ciclopropanos , Feminino , Meia-Vida , Humanos , Isoniazida/efeitos adversos , Masculino , Pessoa de Meia-Idade , Nevirapina/efeitos adversos , Rifampina/efeitos adversos , Resultado do Tratamento , Adulto JovemRESUMO
The global prevalence of HIV infection in the female population presents a significant healthcare burden in terms of mother-to-child transmission (MTCT) of the disease. This review aims to discuss current trends and treatment guidelines for the use of antiretroviral therapy during pregnancy and associated complications in this population. Historically, antiretroviral monotherapy with zidovudine was commonly used for preventing MTCT, and monotherapy with single-dose nevirapine is still used for prevention in resource-limited settings. Evidence suggests that combination therapy with HAART is a more effective treatment option than monotherapy when managing HIV in pregnant women. Current treatment guidelines recommend the use of HAART with a protease inhibitor (PI) or a nonnucleoside reverse transcriptase inhibitor (NNRTI) plus two nucleoside reverse transcriptase inhibitors (NRTI) as first-line therapy for the management of HIV infection in pregnant women and for preventing MTCT. Complications associated with the use of antiretroviral therapy during pregnancy should be taken into consideration when selecting a new antiretroviral regimen, or when continuing certain antiretroviral regimens in HIV-infected women who become pregnant while on therapy. NNRTI have been associated with severe and sometimes fatal hepatoxicity in some pregnant women and potentially teratogenic side effects in the fetus, and their use raises concerns regarding the development of drug- and class-resistant mutations. PI-based HAART has been associated with an increased risk of adverse effects such as premature delivery, low birth weight, dyslipidemia, glucose intolerance, and lipodystrophy. Despite this, initiating antiretroviral therapy with a PI plus two NRTI may become the preferred treatment option in pregnant women. Many of the side effects associated with PI were more prevalent when older PI and PI-based regimens that included those in combination with thymidine analog NRTI were used. An individual's history and baseline clinical and laboratory parameters should also be taken into consideration when choosing the most appropriate antiretroviral regimen during pregnancy.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade/tendências , Infecções por HIV/tratamento farmacológico , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Complicações Infecciosas na Gravidez/tratamento farmacológico , Fármacos Anti-HIV/efeitos adversos , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Quimioterapia Combinada , Feminino , Infecções por HIV/prevenção & controle , Infecções por HIV/transmissão , Humanos , Recém-Nascido , Nevirapina/efeitos adversos , Nevirapina/uso terapêutico , Gravidez , Inibidores de Proteases/administração & dosagem , Inibidores de Proteases/uso terapêutico , Inibidores da Transcriptase Reversa/administração & dosagem , Inibidores da Transcriptase Reversa/efeitos adversos , Inibidores da Transcriptase Reversa/uso terapêutico , Zidovudina/administração & dosagem , Zidovudina/efeitos adversos , Zidovudina/uso terapêuticoRESUMO
INTRODUCTION: The objective of this study was to evaluate the frequency of thyroid function alterations and its associated factors in a group of patients from a university hospital in Colombia. METHODS: From June 2007 through June 2008, 636 HIV patients were followed in order to assess the relation of thyroid function with the use of HAART. RESULTS: The overall prevalence of hypothyroidism (TSH > 4.6 µUI/mL) was 15.5% (100/636). The association of hypothyroidism in the independent analysis showed significant relation only for the use of nevirapine (RR 1.6; CI 95% 1.1- 2.34) and stavudine (RR 1.5; CI 95%, 1 - 2.3). CONCLUSIONS: The prevalence of hypothyroidism was surprisingly high among the studied population.
Assuntos
Fármacos Anti-HIV/efeitos adversos , Infecções por HIV/tratamento farmacológico , Hipotireoidismo/induzido quimicamente , Nevirapina/efeitos adversos , Estavudina/efeitos adversos , Adolescente , Adulto , Idoso , Terapia Antirretroviral de Alta Atividade , Estudos de Coortes , Colômbia , Estudos Transversais , Feminino , Hospitais Universitários , Humanos , Hipotireoidismo/diagnóstico , Masculino , Pessoa de Meia-Idade , Tireotropina/sangue , Carga Viral , Adulto JovemRESUMO
Objetivos: Evaluar la frecuencia de alteración tiroidea y los factores asociados en los pacientes con VIH/SIDA de un hospital universitario en Colombia. Pacientes y Métodos: Estudio tipo corte transversal de pacientes con VIH/SIDA durante el periodo de 2007 a 2008. Se registró niveles hormonales, inmunológicos, carga viral y tratamiento anti-retroviral. Resultados: En 636 pacientes la prevalencia de hipotiroidismo (TSH > 4,6 μUI/mL) fue de 15,5 por ciento (100/636). El análisis independiente demostró relación significativa para el uso de nevirapina (RR 1,6; IC 95 por ciento 1,1 - 2,3) y estavudina (RR 1,5; IC 95 por cientoo 1 - 2,3). Conclusiones: La prevalencia de hipotiroidismo fue alta y se relacionó con el uso de nevirapina.
Introduction: The objective of this study was to evaluate the frequency of thyroid function alterations and its associated factors in a group of patients from a university hospital in Colombia. Methods: From June 2007 through June 2008, 636 HIV patients were followed in order to assess the relation of thyroid function with the use of HAART. Results: The overall prevalence of hypothyroidism (TSH > 4.6 μUI/mL) was 15.5 percent (100/636). The association of hypothyroidism in the independent analysis showed significant relation only for the use of nevirapine (RR 1.6; CI 95 percent 1.1- 2.34) and stavudine (RR 1.5; CI 95 percent, 1 - 2.3). Conclusions: The prevalence of hypothyroidism was surprisingly high among the studied population.
Assuntos
Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Fármacos Anti-HIV/efeitos adversos , Infecções por HIV/tratamento farmacológico , Hipotireoidismo/induzido quimicamente , Nevirapina/efeitos adversos , Estavudina/efeitos adversos , Terapia Antirretroviral de Alta Atividade , Estudos de Coortes , Colômbia , Estudos Transversais , Hospitais Universitários , Hipotireoidismo/diagnóstico , Tireotropina/sangue , Carga ViralRESUMO
OBJECTIVES: The durability of combination antiretroviral therapy (cART) regimens can be measured as time to discontinuation because of toxicity or treatment failure, development of clinical disease or serious long-term adverse events. The aim of this analysis was to compare the durability of nevirapine, efavirenz and lopinavir regimens based on these measures. METHODS: Patients starting a nevirapine, efavirenz or lopinavir-based cART regimen for the first time after 1 January 2000 were included in the analysis. Follow-up started ≥ 3 months after initiation of treatment if viral load was <500 HIV-1 RNA copies/mL. Durability was measured as discontinuation rate or development/worsening of clinical markers. RESULTS: A total of 603 patients (21%) started nevirapine-based cART, 1465 (51%) efavirenz, and 818 (28%) lopinavir. After adjustment there was no significant difference in the risk of discontinuation for any reason between the groups on nevirapine and efavirenz (P=0.43) or lopinavir (P=0.13). Compared with the nevirapine group, those on efavirenz had a 48% (P=0.0002) and those on lopinavir a 63% (P<0.0001) lower risk of discontinuation because of treatment failure and a 31% (P=0.01) and 66% (P<.0001) higher risk, respectively, of discontinuation because of toxicities or patient/physician choice. There were no significant differences in the incidence of non-AIDS-related events, worsening anaemia, severe weight loss, increased aspartate aminotransferase (AST)/alanine aminotransferase (ALT) levels or increased total cholesterol. Compared with patients on nevirapine, those on lopinavir had an 80% higher incidence of high-density lipoprotein (HDL) cholesterol decreasing below 0.9 mmol/L (P=0.003), but there was no significant difference in this variable between those on nevirapine and those on efavirenz (P=0.39). CONCLUSIONS: The long-term durability of nevirapine-based cART, based on risk of all-cause discontinuation and development of long-term adverse events, was comparable to that of efavirenz or lopinavir, in patients in routine clinical practice across Europe who initially tolerated and virologically responded to their regimen.
Assuntos
Benzoxazinas/uso terapêutico , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , Nevirapina/uso terapêutico , Pirimidinonas/uso terapêutico , Inibidores da Transcriptase Reversa/uso terapêutico , Alcinos , Argentina/epidemiologia , Benzoxazinas/efeitos adversos , Ciclopropanos , Esquema de Medicação , Resistência a Medicamentos , Quimioterapia Combinada , Europa (Continente)/epidemiologia , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , HIV-1 , Humanos , Israel/epidemiologia , Lopinavir , Masculino , Nevirapina/efeitos adversos , Estudos Prospectivos , Pirimidinonas/efeitos adversos , Resultado do Tratamento , Carga ViralRESUMO
OBJECTIVES: to determine the incidence and risk factors for nevirapine (NVP)-associated toxicity in a cohort of HIV-infected people in Buenos Aires, Argentina. DESIGN: retrospective study. METHODS: HIV-infected adults who received NVP-based highly active antiretroviral therapy (HAART) at least for 2 weeks between May 1997 and March 2008 were included in this study. We analyzed patients' age, gender, HIV transmission route, HIV disease stage, pregnancy, alcohol intake, adverse events, coinfection with hepatitis B or C virus, time until toxicity, and withdrawal rates. RESULTS: a total of 1110 patients (631 men) were included. Rash was the most frequently observed adverse event; it was more frequent in women. The incidence of severe rash and hepatotoxicity was similar in women and men. Female sex was the only variable significantly associated with mild-to-moderate rash. High CD4 count, pregnancy, and chronic hepatitis were not associated with NVP-related toxicity. An undetectable viral load at the time of starting NVP treatment resulted in a lower risk of NVP-related rash.
Assuntos
Fármacos Anti-HIV/efeitos adversos , Infecções por HIV/tratamento farmacológico , Nevirapina/efeitos adversos , Adulto , Argentina/epidemiologia , Contagem de Linfócito CD4 , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Análise Multivariada , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Complicações Infecciosas na Gravidez/virologia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Distribuição por SexoRESUMO
AIM: The aim of this article is to present the clinical characteristics and management of an oral adverse effect stemming from the use of the antiretroviral medication Nevirapine (NVP). BACKGROUND: NVP is a non-nucleoside reverse transcriptase inhibitor used in the treatment of Human Immunodeficiency Virus (HIV) infection. CASE REPORT: A 29-year-old black man, HIV-infected since 1996, began highly active antiretroviral therapy (HAART) with zidovudine, lamivudine, and indinavir. From 1996 to 2002 several medications were changed due to their adverse effects: indinavir (renal colic and fever), nelfinavir (cutaneous rash), and efavirenz (nausea and temporary memory loss). When the patient presented to our service he was taking NVP, zidovudine, and lamivudine. A whitish plaque in the lips and bilateral buccal mucosa, burning, taste disturbance, and xerostomia were observed. The discontinuation of HAART led to the complete resolution of signs and symptoms. The patient has received follow-up treatment for three years and five months without local or systemic effects observed. SUMMARY: Unfortunately, the clinical features of the oral adverse effect from NVP are not well known. This paper contributed to the identification of possible reactions in the oral cavity due to antiretroviral medication. Although HAART is very important in the treatment of HIV, its side effects are responsible for patients' non-adherence to medications. While more studies are needed to better understand the mechanism of action after suspending HAART, the complete resolution of the signs and symptoms was observed. Therefore, physicians and dentists alike must understand how to identify and prevent these adverse effects in order to further improve HIV patient treatments.
Assuntos
Fármacos Anti-HIV/efeitos adversos , Exantema/induzido quimicamente , Infecções por HIV/tratamento farmacológico , Doenças da Boca/induzido quimicamente , Nevirapina/efeitos adversos , Adulto , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Síndrome da Ardência Bucal/induzido quimicamente , Contagem de Linfócito CD4 , Exantema/sangue , Infecções por HIV/sangue , Humanos , Masculino , Doenças da Boca/sangue , Distúrbios do Paladar/induzido quimicamente , Carga Viral , Xerostomia/induzido quimicamenteRESUMO
OBJETIVO: avaliar a freqüência de efeitos advesos com o uso da nevirapina e suas correlações em gestantes infectadas pelo vírus da imunodeficiência humana (HIV). MÉTODOS: estudo retrospectivo foi realizado entre janeiro de 2003 e dezembro de 2006, incluindo todas as mulheres que utilizaram nevirapina durante a gestação. Os critérios de exclusão foram: início da nevirapina antes da gestação; presença de enzimas hepáticas basais aumentadas e dados incompletos de bioquímica hepática no prontuário. Os parâmetros avaliados foram idade, duração de exposição à nevirapina, idade gestacional no início da medicação, semanas de seguimento, carga viral, contagem de CD4 e dosagens de transaminases. A incidência de efeitos adversos hepáticos e/ou cutâneos foi determinada e correlacionada com a contagem de CD4. As análises estatísticas foram realizadas utilizando o teste exato de Fisher e o teste t de Student quando apropriado. A significância estatística foi estabelecida quando p<"0,05. RESULTADOS: cento e cinqüenta e sete gestantes foram incluídas nos critérios estabelecidos. Trinta e uma mulheres (19,7 por cento) apresentaram toxicidade cutânea e/ou hepática. Rash cutâneo foi responsável por 77,4 por cento das toxicidades e anormalidade da função hepática por 22,6 por cento. Hepatotoxicidades graus 1, 2 e 3 foram observadas em 0,6, 2,5 e 1,3 por cento, respectivamente. Contagem de CD4, carga viral e dosagem de transaminases basais foram similares em gestantes com e sem reação induzida pela nevirapina. A contagem de CD4 média foi de 465,4 e 416,6 células/µL em mulheres com e sem efeitos colaterais, respectivamente (p=0,3). Todas as pacientes que apresentaram hepatotoxicidade apresentavam contagem de CD4 prévia ao tratamento superior a 250 células/µL. CONCLUSÕES: a incidência de eventos adversos com nevirapina em nosso estudo foi alta, mas a maioria deles foi cutâneo. Não houve correlação entre a alta contagem de CD4 e os eventos adversos quando se analisou conjuntamente as reações cutâneas e hepáticas; entretanto, a hepatotoxicidade ocorreu apenas em gestantes com contagem de CD4 > 250 células/µL.
PURPOSE: The aim of this article is to evaluate the use of nevirapine HIV-infected pregnant women in our service. METHODS: a retrospective study was performed between January 2003 and December 2006 analysing all women prescribed nevirapine in pregnancy. Exclusion criteria included: (1) women who started nevirapine before pregnancy, (2) patients with abnormal baseline liver enzymes, and (3) women with incomplete liver biochemistry data. Evaluated parameters included age, weeks of exposure to nevirapine, gestational age in the begginning of medication, weeks of follow-up, viral load, CD4 cells count and serum aminotransferase levels. The incidence of adverse hepatic and/or cutaneous effects was determined and correlated to the CD4 cells count. Statistical analysis were performed using Fishers exact test and t-Student test when appropriate, with a statistical significance level of p<0,05. RESULTS: one hundred fifty-seven women met the inclusion criteria. Thirty-one (19.7 percent) presented cutaneous and/or hepatic toxicity. Skin rash accounted for 77.4 percent of toxicities and liver function abnormalities were noted in 22.6 percent of women exhibiting toxicities. Grade 1, 2 and 3 hepatotoxicities were observed in 0.6, 2.5 and 1.3 percent, respectively. Baseline CD4 counts, viral loads and transaminases were similar in pregnant women with nevirapine adverse effects and those without reaction. Median absolute CD4 cell counts were 465.4 and 416.6 cells/µL in women with and without side effects, respectively (p=0.3). All patients who experienced hepatotoxicity had pretreatment CD4 counts superior to 250 cells/µL. CONCLUSIONS: The incidence of adverse events with nevirapine in our study was high, but most of them were cutaneous. There was no correlation between high CD4 counts and adverse events when analysing both cutaneous and hepatic reactions; nevertheless, hepatotoxicity occurred only in pregnant women with CD4 counts >250 cells/µL.