RESUMEN

In Argentina, transgender women (TGW) have a high HIV prevalence (34%). However, this population shows lower levels of adherence, retention in HIV care and viral suppression than cisgender patients. The World Health Organization (WHO) recommends the transition to dolutegravir (DTG)-based regimens to reduce adverse events and improve adherence and retention. The purpose of this study was to determine retention, adherence and viral suppression in naïve TGW starting a DTG-based first-line antiretroviral treatment (ART) and to identify clinical and psychosocial factors associated with retention. We designed a prospective, open-label, single-arm trial among ART-naïve HIV positive TGW (Clinical Trial Number: NCT03033836). Participants were followed at weeks 4, 8, 12, 24, 36 and 48, in a trans-affirmative HIV care service that included peer navigators, between December, 2015 and May, 2019. Retention was defined as the proportion of TGW retained at week 48 and adherence was self-reported. Viral suppression at <50 copies/mL was evaluated using snapshot algorithm and as per protocol analysis. Of 75 TGW screened, 61 were enrolled. At baseline, median age was 28 y/o., HIV-1-RNA (pVL) 46,908 copies/mL and CD4+ T-cell count 383 cells/mm3. At week 48, 77% were retained and 72% had viral suppression (97% per protocol). The regimen was well tolerated and participants reported high adherence (about 95%). Eleven of the fourteen TGW who discontinued or were lost to follow-up had undetectable pVL at their last visit. Older age was associated with better retention. DTG-based treatment delivered by a trans-competent team in a trans-affirmative service was safe and well tolerated by TGW and associated with high retention, high adherence and high viral suppression at 48 weeks among those being retained.

Asunto(s)

Infecciones por VIH , Personas Transgénero , Adulto , Femenino , Humanos , Antirretrovirales/uso terapéutico , Argentina/epidemiología , Emtricitabina/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/efectos adversos , Infecciones por VIH/tratamiento farmacológico , Lamivudine/efectos adversos , Estudios Prospectivos , Piridonas/uso terapéutico , Tenofovir/efectos adversos

RESUMEN

OBJECTIVES: To assess the risk of adverse diagnoses and laboratory abnormalities associated with a 300 or 150 mg daily dose of lamivudine (3TC) initiated by people with HIV (PWH) with an estimated glomerular filtration rate (eGFR) between at least 30 and 49 ml/min per 1.73 m2 or less. DESIGN: Longitudinal study based on electronic health records of 539 PWH with eGFR between at least 30 and 49 ml/min per 1.73 m2 or less from the Observational Pharmaco-Epidemiology Research and Analysis (OPERA) cohort. METHODS: Common unintended effects of 3TC were evaluated as composite outcomes. We estimated the incidence (univariate Poisson regression) and association between dose and incident composite outcomes (multivariate Poisson regression) among PWH without the relevant diagnoses or laboratory abnormalities at 3TC initiation. RESULTS: PWH initiating 150 mg 3TC had higher HIV RNA, lower eGFR, and more comorbidities than those initiating 300 mg 3TC. The prevalence of relevant diagnoses and laboratory abnormalities was similar in both groups. The most common lab abnormality was low hemoglobin. There was no statistically significant difference in incident adverse diagnoses/severe lab abnormalities with 300 mg versus 150 mg [incidence rate ratio (IRR): 1.51; 95% confidence interval (CI) 0.59--3.92). However, a statistically significant association was observed when gastrointestinal symptoms/moderate lab abnormalities were included in the outcome (IRR: 3.07, 95% CI 1.12--8.40). CONCLUSION: As 3TC is a well tolerated drug with a wide therapeutic window, dose adjustment may be unnecessary among PWH with eGFR between at least 30 and 49 ml/min per 1.73 m2 or less. Clinical judgement is key when weighing the risks and benefits of 3TC dose adjustment for PWH experiencing gastrointestinal symptoms or moderate lab abnormalities.

Asunto(s)

Fármacos Anti-VIH , Infecciones por VIH , Fármacos Anti-VIH/efectos adversos , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Humanos , Riñón , Lamivudine/efectos adversos , Estudios Longitudinales

RESUMEN

ABSTRACT Antiretroviral therapy (ART) has modified the outcome of patients with HIV infection, providing virological control and reducing mortality. However, there are several reasons as to why patients may discontinue their antiretroviral therapy, with adverse events being one of the main reasons reported in the literature. This is a case-control nested in a cohort of people living with HIV/AIDS, conducted to identify the incidence of ART modification due to adverse events and the associated factors, in two referral services in Recife, Brazil, between 2011 and 2014. Of the modifications occurred in the first year of ART, 25.7% were driven by adverse events. The median time elapsed between initiating ART and the first modification due to adverse events was 70.5 days (95% CI: 26-161 days). The main adverse events were dermatological, neuropsychiatric and gastrointestinal. Dermatological events were the earliest to appear after initiating ART. Efavirenz was the most prescribed and most modified drug during the study period. The group of participants who used zidovudine, lamivudine, and efavirenz had a 2-fold greater chance (adjusted OR: 2.16 95% CI: 1.28-3.65) of switching ART due to adverse events when compared to the group that used tenofovir with lamivudine and efavirenz.

Asunto(s)

Humanos , Masculino , Femenino , Adolescente , Adulto , Persona de Mediana Edad , Adulto Joven , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Fármacos Anti-VIH/efectos adversos , Factores de Tiempo , Brasil , Zidovudina/efectos adversos , Modelos Logísticos , Factores de Riesgo , Síndrome de Inmunodeficiencia Adquirida/mortalidad , Ritonavir/efectos adversos , Lamivudine/efectos adversos , Terapia Antirretroviral Altamente Activa/efectos adversos , Benzoxazinas/efectos adversos , Combinación de Medicamentos , Estimación de Kaplan-Meier , Lopinavir/efectos adversos , Tenofovir/efectos adversos

RESUMEN

Antiretroviral therapy (ART) has modified the outcome of patients with HIV infection, providing virological control and reducing mortality. However, there are several reasons as to why patients may discontinue their antiretroviral therapy, with adverse events being one of the main reasons reported in the literature. This is a case-control nested in a cohort of people living with HIV/AIDS, conducted to identify the incidence of ART modification due to adverse events and the associated factors, in two referral services in Recife, Brazil, between 2011 and 2014. Of the modifications occurred in the first year of ART, 25.7% were driven by adverse events. The median time elapsed between initiating ART and the first modification due to adverse events was 70.5 days (95% CI: 26-161 days). The main adverse events were dermatological, neuropsychiatric and gastrointestinal. Dermatological events were the earliest to appear after initiating ART. Efavirenz was the most prescribed and most modified drug during the study period. The group of participants who used zidovudine, lamivudine, and efavirenz had a 2-fold greater chance (adjusted OR: 2.16 95% CI: 1.28-3.65) of switching ART due to adverse events when compared to the group that used tenofovir with lamivudine and efavirenz.

Asunto(s)

Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Fármacos Anti-VIH/efectos adversos , Síndrome de Inmunodeficiencia Adquirida/mortalidad , Adolescente , Adulto , Alquinos , Terapia Antirretroviral Altamente Activa/efectos adversos , Benzoxazinas/efectos adversos , Brasil , Ciclopropanos , Combinación de Medicamentos , Femenino , Humanos , Estimación de Kaplan-Meier , Lamivudine/efectos adversos , Modelos Logísticos , Lopinavir/efectos adversos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Ritonavir/efectos adversos , Tenofovir/efectos adversos , Factores de Tiempo , Adulto Joven , Zidovudina/efectos adversos

RESUMEN

BACKGROUND: Perinatal HIV transmission has substantially decreased with combination antiretroviral regimens, but complications in children who are HIV-exposed but uninfected, such as microcephaly, warrant ongoing surveillance. We aimed to evaluate whether individual in utero antiretroviral exposures were associated with increased risk of microcephaly based on long-term follow-up of infants and children who are HIV-exposed but uninfected. METHODS: We evaluated children aged younger than 18 years who were HIV-exposed but uninfected with at least one head circumference measurement while enrolled in the Surveillance Monitoring for ART Toxicities (SMARTT) study at 22 clinical sites in the USA, including Puerto Rico. This prospective cohort study was done by the Pediatric HIV/AIDS Cohort Study network. Microcephaly was defined as having a head circumference Z score <-2 according to the 2000 US Centers for Disease Control and Prevention growth charts for children 6-36 months old and according to Nellhaus standards (head circumference <2nd percentile) after 36 months (SMARTT criteria); an alternate definition for microcephaly was based on applying Nellhaus standards across all ages (Nellhaus criteria). Modified Poisson regression models were fit to obtain relative risks (RRs) for associations between in utero antiretroviral exposure and microcephaly status, adjusted for potential confounders. Neurodevelopmental functioning was compared in children who are HIV-exposed but uninfected with or without microcephaly. FINDINGS: Between March 21, 2007, and Aug 1, 2017, 3055 participants enrolled in SMARTT had at least one head circumference measurement. The cumulative incidence of microcephaly over a median of 5·1 years of follow-up (IQR 3·0-7·2) was 159 (5·2%, 95% CI 4·4-6·1) by Nellhaus criteria and 70 (2·3%, 1·8-2·9) by SMARTT criteria. In adjusted models, in utero exposure to efavirenz (4·7% exposed) was associated with increased risk of microcephaly by both Nellhaus standards (adjusted RR 2·02, 95% CI 1·16-3·51) and SMARTT criteria (2·56, 1·22-5·37). These associations were more pronounced in children exposed to combination regimens of efavirenz that included zidovudine plus lamivudine than those including tenofovir plus emtricitabine. Protective associations were observed for darunavir exposure (adjusted RR 0·50, 95% CI 0·24-1·00). Children who are HIV-exposed but uninfected with microcephaly had lower mean scores on neurodevelopmental assessments at age 1 and 5 years and a higher prevalence of neurodevelopmental impairment than those without microcephaly. INTERPRETATION: These findings support consideration of alternatives to efavirenz as part of first-line antiretroviral therapy for pregnant women. FUNDING: Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Asunto(s)

Fármacos Anti-VIH/efectos adversos , Infecciones por VIH/tratamiento farmacológico , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Microcefalia/etiología , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Adolescente , Adulto , Alquinos , Fármacos Anti-VIH/uso terapéutico , Benzoxazinas/efectos adversos , Benzoxazinas/uso terapéutico , Niño , Preescolar , Ciclopropanos , Combinación de Medicamentos , Femenino , Estudios de Seguimiento , Infecciones por VIH/transmisión , Infecciones por VIH/virología , VIH-1/efectos de los fármacos , VIH-1/fisiología , Humanos , Lactante , Lamivudine/efectos adversos , Lamivudine/uso terapéutico , Masculino , Microcefalia/epidemiología , Embarazo , Complicaciones Infecciosas del Embarazo/virología , Estudios Prospectivos , Puerto Rico , Tenofovir/efectos adversos , Tenofovir/uso terapéutico , Adulto Joven , Zidovudina/efectos adversos , Zidovudina/uso terapéutico

RESUMEN

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.

Asunto(s)

Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Lamivudine/uso terapéutico , Adulto , Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/efectos adversos , Fármacos Anti-VIH/economía , Recuento de Linfocito CD4 , Análisis Costo-Beneficio , Quimioterapia Combinada , Economía Farmacéutica , Honorarios Farmacéuticos/estadística & datos numéricos , Femenino , VIH-1 , Compuestos Heterocíclicos con 3 Anillos/administración & dosificación , Compuestos Heterocíclicos con 3 Anillos/efectos adversos , Compuestos Heterocíclicos con 3 Anillos/economía , Humanos , Lamivudine/administración & dosificación , Lamivudine/efectos adversos , Lamivudine/economía , Masculino , Persona de Mediana Edad , Oxazinas , Piperazinas , Piridonas , Estudios Retrospectivos , Carga Viral

RESUMEN

ABSTRACT Aim: To determine the prevalence of chronic kidney disease (CKD) and the epidemiological, clinical, and laboratory factors associated with CKD in Mexican HIV-infected patients. Methods: Cross-sectional study. We included 274 patients with HIV/AIDS. CKD was defined by the estimated glomerular filtration rate (eGFR < 60 mL/min/1.73 m2 assessed by CKD-EPI) and albuminuria criteria from KDIGO guidelines. Clinical, epidemiological, and laboratory characteristics were compared between patients with and without CKD. The factors associated with CKD were assessed by logistic regression analysis. Results: The mean age was 41±11 years, and 72.3% of the patients were men. The global prevalence of CKD was 11.7% (n = 32); 7.2% (n = 20) were defined by eGFR criterion; 7.6% (n = 21), by the albuminuria criterion; and 3.2% (n = 9), by both CKD criteria. The most frequently observed stages of CKD were KDIGO G3A1 stage with 4.7% (n = 13), KDIGO G1A2 stage with 3.6% (n = 10) and KDIGO G3A2 stage with 1.7% (n = 5). The factors associated with CKD were use of abacavir/lamivudine (OR 3.2; 95% CI 1.1-8.9; p = 0.03), a CD4 lymphocyte count < 400 cells/µL (OR 2.6; 95% 1.03-6.4, p = 0.04), age (OR 1.1; 95% CI 1.04-1.2, p = 0.001) and albuminuria (OR 19.98; 95% CI: 5.5-72.2; p < 0.001). Conclusions: CKD was a frequent complication in HIV-infected patients. These findings confirm the importance of screening and the early detection of CKD, as well as the importance of identifying and treating traditional and non-traditional risk factors associated with CKD.

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RESUMO Objetivo: Determinar a prevalência de doença renal crônica (DRC) e os fatores epidemiológicos, clínicos e laboratoriais associados à DRC em pacientes mexicanos infectados pelo HIV. Métodos: Estudo transversal. Incluímos 274 pacientes com HIV/AIDS. A DRC foi definida pela taxa de filtração glomerular estimada (TFGe < 60 mL/min/1,73 m2, avaliada pelo CKD-EPI) e pelos critérios de albuminúria das diretrizes do KDIGO. As características clínicas, epidemiológicas e laboratoriais foram comparadas entre pacientes com e sem DRC. Os fatores associados à DRC foram avaliados por análise de regressão logística. Resultados: A média da idade foi de 41 ± 11 anos e 72,3% dos pacientes eram homens. A prevalência global de DRC foi de 11,7% (n = 32); 7,2% (n = 20) foram definidos pelo critério TFGe; 7,6% (n = 21), pelo critério da albuminúria; e 3,2% (n = 9), pelos dois critérios para DRC. Os estágios mais frequentemente observados da DRC foram o estágio KDIGO G3A1 com 4,7% (n = 13); estágio KDIGO G1A2 com 3,6% (n = 10) e estágio KDIGO G3A2 com 1,7% (n = 5). Os fatores associados à DRC foram o uso de abacavir/lamivudina (OR 3,2; IC95% 1,1-8,9; p = 0,03), contagem de linfócitos CD4 < 400 células/µL (OR 2,6; 95% 1,03-6,4, p = 0,04), idade (OR 1,1; IC95% 1,04-1,2, p = 0,001) e albuminúria (OR 19,98; IC95%: 5,5-72,2; p < 0,001). Conclusões: A DRC foi uma complicação frequente em pacientes infectados pelo HIV. Esses achados confirmam a importância do rastreamento e da detecção precoce da DRC, bem como a importância de identificar e tratar os fatores de risco tradicionais e não tradicionais associados à DRC.

Asunto(s)

Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Infecciones por VIH/complicaciones , Insuficiencia Renal Crónica/etiología , Insuficiencia Renal Crónica/epidemiología , Didesoxinucleósidos/efectos adversos , Modelos Logísticos , Prevalencia , Estudios Transversales , Estudios Retrospectivos , Factores de Riesgo , Factores de Edad , Recuento de Linfocito CD4 , Lamivudine/efectos adversos , Fármacos Anti-VIH/efectos adversos , Complicaciones de la Diabetes , Albuminuria , Tasa de Filtración Glomerular , Hipertensión/complicaciones , México/epidemiología

RESUMEN

AIM: To determine the prevalence of chronic kidney disease (CKD) and the epidemiological, clinical, and laboratory factors associated with CKD in Mexican HIV-infected patients. METHODS: Cross-sectional study. We included 274 patients with HIV/AIDS. CKD was defined by the estimated glomerular filtration rate (eGFR < 60 mL/min/1.73 m2 assessed by CKD-EPI) and albuminuria criteria from KDIGO guidelines. Clinical, epidemiological, and laboratory characteristics were compared between patients with and without CKD. The factors associated with CKD were assessed by logistic regression analysis. RESULTS: The mean age was 41±11 years, and 72.3% of the patients were men. The global prevalence of CKD was 11.7% (n = 32); 7.2% (n = 20) were defined by eGFR criterion; 7.6% (n = 21), by the albuminuria criterion; and 3.2% (n = 9), by both CKD criteria. The most frequently observed stages of CKD were KDIGO G3A1 stage with 4.7% (n = 13), KDIGO G1A2 stage with 3.6% (n = 10) and KDIGO G3A2 stage with 1.7% (n = 5). The factors associated with CKD were use of abacavir/lamivudine (OR 3.2; 95% CI 1.1-8.9; p = 0.03), a CD4 lymphocyte count < 400 cells/µL (OR 2.6; 95% 1.03-6.4, p = 0.04), age (OR 1.1; 95% CI 1.04-1.2, p = 0.001) and albuminuria (OR 19.98; 95% CI: 5.5-72.2; p < 0.001). CONCLUSIONS: CKD was a frequent complication in HIV-infected patients. These findings confirm the importance of screening and the early detection of CKD, as well as the importance of identifying and treating traditional and non-traditional risk factors associated with CKD.

Asunto(s)

Infecciones por VIH/complicaciones , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/etiología , Adulto , Factores de Edad , Albuminuria , Fármacos Anti-VIH/efectos adversos , Recuento de Linfocito CD4 , Estudios Transversales , Complicaciones de la Diabetes , Didesoxinucleósidos/efectos adversos , Femenino , Tasa de Filtración Glomerular , Humanos , Hipertensión/complicaciones , Lamivudine/efectos adversos , Modelos Logísticos , Masculino , México/epidemiología , Persona de Mediana Edad , Prevalencia , Estudios Retrospectivos , Factores de Riesgo

RESUMEN

BACKGROUND: Effective two-drug regimens could decrease long-term drug exposure and toxicity with HIV-1 antiretroviral therapy (ART). We therefore aimed to evaluate the efficacy and safety of a two-drug regimen compared with a three-drug regimen for the treatment of HIV-1 infection in ART-naive adults. METHODS: We conducted two identically designed, multicentre, double-blind, randomised, non-inferiority, phase 3 trials: GEMINI-1 and GEMINI-2. Both studies were done at 192 centres in 21 countries. We included participants (≥18 years) with HIV-1 infection and a screening HIV-1 RNA of 500 000 copies per mL or less, and who were naive to ART. We randomly assigned participants (1:1) to receive a once-daily two-drug regimen of dolutegravir (50 mg) plus lamivudine (300 mg) or a once-daily three-drug regimen of dolutegravir (50 mg) plus tenofovir disoproxil fumarate (300 mg) and emtricitabine (200 mg). Both drug regimens were administered orally. We masked participants and investigators to treatment assignment: dolutegravir was administered as single-entity tablets (similar to its commercial formulation, except with a different film colour), and lamivudine tablets and tenofovir disoproxil fumarate and emtricitabine tablets were over-encapsulated to visually match each other. Primary endpoint was the proportion of participants with HIV-1 RNA of less than 50 copies per mL at week 48 in the intention-to-treat-exposed population, using the Snapshot algorithm and a non-inferiority margin of -10%. Safety analyses were done on the safety population. GEMINI-1 and GEMINI-2 are registered with ClinicalTrials.gov, numbers NCT02831673 and NCT02831764, respectively. FINDINGS: Between July 18, 2016, and March 31, 2017, 1441 participants across both studies were randomly assigned to receive either the two-drug regimen (n=719) or three-drug regimen (n=722). At week 48 in the GEMINI-1 intention-to-treat-exposed population, 320 (90%) of 356 participants receiving the two-drug regimen and 332 (93%) of 358 receiving the three-drug regimen achieved plasma HIV-1 RNA of less than 50 copies per mL (adjusted treatment difference -2·6%, 95% CI -6·7 to 1·5); in GEMINI-2, 335 (93%) of 360 in the two-drug regimen and 337 (94%) of 359 in the three-drug regimen achieved HIV-1 RNA of less than 50 copies per mL (adjusted treatment difference -0·7%, 95% CI -4·3 to 2·9), showing non-inferiority at a -10% margin in both studies (pooled analysis: 655 [91%] of 716 in the two-drug regimen vs 669 [93%] of 717 in the three-drug regimen; adjusted treatment difference -1·7%, 95% CI -4·4 to 1·1). Numerically, more drug-related adverse events occurred with the three-drug regimen than with the two-drug regimen (169 [24%] of 717 vs 126 [18%] of 716); few participants discontinued because of adverse events (16 [2%] in the three-drug regimen and 15 [2%] in the two-drug regimen). Two deaths were reported in the two-drug regimen group of GEMINI-2, but neither was considered to be related to the study medication. INTERPRETATION: The non-inferior efficacy and similar tolerability profile of dolutegravir plus lamivudine to a guideline-recommended three-drug regimen at 48 weeks in ART-naive adults supports its use as initial therapy for patients with HIV-1 infection. FUNDING: ViiV Healthcare.

Asunto(s)

Fármacos Anti-VIH/uso terapéutico , Antirretrovirales/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , VIH-1/aislamiento & purificación , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Adulto , Fármacos Anti-VIH/efectos adversos , Antirretrovirales/efectos adversos , Método Doble Ciego , Quimioterapia Combinada , Emtricitabina/efectos adversos , Emtricitabina/uso terapéutico , Femenino , Infecciones por VIH/virología , Compuestos Heterocíclicos con 3 Anillos/efectos adversos , Humanos , Lamivudine/efectos adversos , Lamivudine/uso terapéutico , Masculino , Persona de Mediana Edad , Oxazinas , Piperazinas , Piridonas , ARN Viral/sangre , Tenofovir/efectos adversos , Tenofovir/uso terapéutico , Carga Viral/efectos de los fármacos

RESUMEN

OBJECTIVE: To evaluate the prevalence of adverse drug reactions (ADR) and associated factors during the use of Highly Active Antiretroviral Therapy (HAART) in patients initiating treatment. METHODS: This is a cross-sectional analysis of a prospective study conducted in three public referral services specialized in HIV/AIDS care in Belo Horizonte, Brazil. Self-reported ADR and explanatory variables were obtained from face-to-face interview and from Information Systems. Associated factors with ADR were evaluated by logistic regression in SPSS software v.22. RESULTS: We included 399 patients, of which 85.5% reported at least one and 72.7% up to 5 ADRs after HAART initiation. Neurological reactions were the most frequent, with self-reported ADRs being distinct according to HAART regimen used. The global model showed higher chance of ADRs among females (OR = 3.52) and illicit drug users (OR = 2.28). Lower chance of ADRs was found for patients aged > 33 years (OR = 0.37), DTG/TDF/3TC users (OR = 0.41), and higher physical domain of quality of life (OR = 0.78). The model restricted to patients using the single-tablet regimen EFV/TDF/3TC showed lower ADRs among patients with CD4+ T lymphocyte count > 200 cells/mm3 (OR = 0.23) and higher independence domain of quality of life (OR = 0.74). The model restricted to DTG/TDF/3TC and to other regimens showed lower ADRs with higher physical domain of quality of life (OR = 0.74 and OR = 0.55, respectively). CONCLUSIONS: The prevalence of self-reported ADRs to first-line antiretroviral regimens was high and patients using DTG/TDF/3TC had a smaller number of ADRs. In addition to HAART regimen, sociodemographic, clinical, and quality of life characteristics were associated with ADRs.

Asunto(s)

Terapia Antirretroviral Altamente Activa/efectos adversos , Inhibidores de la Transcriptasa Inversa/efectos adversos , Adolescente , Adulto , Anciano , Alquinos , Benzoxazinas/efectos adversos , Brasil , Estudios Transversales , Ciclopropanos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Femenino , Infecciones por VIH/tratamiento farmacológico , Inhibidores de Integrasa VIH/administración & dosificación , Inhibidores de Integrasa VIH/efectos adversos , Compuestos Heterocíclicos con 3 Anillos/efectos adversos , Humanos , Lamivudine/efectos adversos , Masculino , Persona de Mediana Edad , Oxazinas , Piperazinas , Estudios Prospectivos , Piridonas , Calidad de Vida , Inhibidores de la Transcriptasa Inversa/administración & dosificación , Tenofovir/efectos adversos , Adulto Joven

RESUMEN

INTRODUCTION: Initial treatment of the HIV is based on the use of three drugs, two of which are nucleoside analog reverse-transcriptase inhibitors. There are three combinations of these drugs which have been approved by different guidelines, each with divergent results in terms of efficacy and safety. OBJECTIVE: To compare the efficacy and safety of these three combinations. METHODS: Systematic review and network meta-analysis of randomized clinical trials comparing fixed doses of Tenofovir Disoproxil Fumarate / Emtricitabine (TDF/FTC), Abacavir / Lamivudine (ABC/3TC) and Zidovudine / Lamivudine (ZDV/3TC). RESULTS: Seven clinical trials met the eligibility criteria. The results suggested higher efficacy with TDF/FTC vs. ABC/3TC at 96 weeks and vs. ZDV/3TC at 48 weeks. However, there is clinical and statistical heterogeneity. Subgroup analysis were performed by third drug and by level of viral load prior to treatment, and found no differences in virological control. Network meta-analysis could only be carried out with TDF/FTC vs. ZDV/3TC, and the proportion of patients with virological response, with no differences at 48 weeks nor at 96 weeks. Direct comparisons showed an increased risk of bone marrow suppression of ZDV/3TC vs. TDF/FTC and of ABC/3TC hypersensitivity reactions vs. ZDV/3TC. CONCLUSIONS: The results did not show differences in effectiveness among the interventions. However, due to the heterogeneity of the third drug and the follow-up time between the included studies, this result is not definitive. The results raise the need for further studies to help improve treatment recommendations in patients infected with HIV.

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INTRODUCCIÓN: El tratamiento inicial de la infección por VIH se basa en el uso de tres medicamentos, dos de ellos inhibidores de transcriptasa reversa análogos de nucleósido. Existen tres combinaciones de estos medicamentos aprobadas por diferentes guías, con resultados divergentes en cuanto a eficacia y seguridad. OBJETIVO: Comparar la eficacia y seguridad de las 3 combinaciones. MÉTODOS: Revisión sistemática y metanálisis en red de ensayos clínicos con asignación aleatoria comparando dosis fijas de Tenofovir Disoproxil Fumarato/Emtricitabina (TDF/FTC), Abacavir/Lamivudina (ABC/3TC) y Zidovudina/Lamivudina (ZDV/3TC). RESULTADOS: Siete ensayos clínicos cumplieron los criterios de elegibilidad. Los resultados sugirieron mayor eficacia con TDF/FTC vs ABC/3TC a 96 semanas y vs. ZDV/3TC a 48 semanas. Sin embargo, existe heterogeneidad clínica y estadística. Se realizó análisis de subgrupos por tercer medicamento y por nivel de carga viral previa al tratamiento, sin encontrar diferencias en control virológico. Se pudo realizar metanálisis en red con TDF/FTC vs ZDV/3TC y proporción de pacientes con respuesta virológica, sin diferencias a las 48 semanas ni 96 semanas. Las comparaciones directas evidenciaron mayor riesgo de supresión de médula ósea de ZDV/3TC vs TDF/FTC y de reacciones de hipersensibilidad de ABC/3TC vs ZDV/3TC. CONCLUSIÓN: Los resultados no demostraron diferencias en efectividad entre las intervenciones; sin embargo, debido a heterogeneidad en cuanto al tercer medicamento y el tiempo de seguimiento entre los estudios incluidos, dicho resultado no es definitivo. Los resultados plantean la necesidad de realizar nuevos estudios que ayuden a mejorar las recomendaciones de tratamiento en los pacientes infectados por el VIH.

Asunto(s)

Fármacos Anti-VIH/administración & dosificación , Infecciones por VIH/tratamiento farmacológico , Fármacos Anti-VIH/efectos adversos , Didesoxinucleósidos/administración & dosificación , Didesoxinucleósidos/efectos adversos , Combinación de Medicamentos , Combinación Emtricitabina y Fumarato de Tenofovir Disoproxil/administración & dosificación , Combinación Emtricitabina y Fumarato de Tenofovir Disoproxil/efectos adversos , Humanos , Lamivudine/administración & dosificación , Lamivudine/efectos adversos , Metaanálisis en Red , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento , Zidovudina/administración & dosificación , Zidovudina/efectos adversos

RESUMEN

Abstract Introduction: Initial treatment of the HIV is based on the use of three drugs, two of which are nucleoside analog reverse-transcriptase inhibitors. There are three combinations of these drugs which have been approved by different guidelines, each with divergent results in terms of efficacy and safety. Objective: To compare the efficacy and safety of these three combinations. Methods: Systematic review and network meta-analysis of randomized clinical trials comparing fixed doses of Tenofovir Disoproxil Fumarate / Emtricitabine (TDF/FTC), Abacavir / Lamivudine (ABC/3TC) and Zidovudine / Lamivudine (ZDV/3TC). Results: Seven clinical trials met the eligibility criteria. The results suggested higher efficacy with TDF/FTC vs. ABC/3TC at 96 weeks and vs. ZDV/3TC at 48 weeks. However, there is clinical and statistical heterogeneity. Subgroup analysis were performed by third drug and by level of viral load prior to treatment, and found no differences in virological control. Network meta-analysis could only be carried out with TDF/FTC vs. ZDV/3TC, and the proportion of patients with virological response, with no differences at 48 weeks nor at 96 weeks. Direct comparisons showed an increased risk of bone marrow suppression of ZDV/3TC vs. TDF/FTC and of ABC/3TC hypersensitivity reactions vs. ZDV/3TC Conclusions: The results did not show differences in effectiveness among the interventions. However, due to the heterogeneity of the third drug and the follow-up time between the included studies, this result is not definitive. The results raise the need for further studies to help improve treatment recommendations in patients infected with HIV.

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Resumen Introducción: El tratamiento inicial de la infección por VIH se basa en el uso de tres medicamentos, dos de ellos inhibidores de transcriptasa reversa análogos de nucleósido. Existen tres combinaciones de estos medicamentos aprobadas por diferentes guías, con resultados divergentes en cuanto a eficacia y seguridad. Objetivo: Comparar la eficacia y seguridad de las 3 combinaciones Métodos: Revisión sistemática y metanálisis en red de ensayos clínicos con asignación aleatoria comparando dosis fijas de Tenofovir Disoproxil Fumarato/Emtricitabina (TDF/FTC), Abacavir/Lamivudina (ABC/3TC) y Zidovudina/Lamivudina (ZDV/3TC). Resultados: Siete ensayos clínicos cumplieron los criterios de elegibilidad. Los resultados sugirieron mayor eficacia con TDF/FTC vs ABC/3TC a 96 semanas y vs. ZDV/3TC a 48 semanas. Sin embargo, existe heterogeneidad clínica y estadística. Se realizó análisis de subgrupos por tercer medicamento y por nivel de carga viral previa al tratamiento, sin encontrar diferencias en control virológico. Se pudo realizar metanálisis en red con TDF/FTC vs ZDV/3TC y proporción de pacientes con respuesta virológica, sin diferencias a las 48 semanas ni 96 semanas. Las comparaciones directas evidenciaron mayor riesgo de supresión de médula ósea de ZDV/3TC vs TDF/FTC y de reacciones de hipersensibilidad de ABC/3TC vs ZDV/3TC. Conclusión: Los resultados no demostraron diferencias en efectividad entre las intervenciones; sin embargo, debido a heterogeneidad en cuanto al tercer medicamento y el tiempo de seguimiento entre los estudios incluidos, dicho resultado no es definitivo. Los resultados plantean la necesidad de realizar nuevos estudios que ayuden a mejorar las recomendaciones de tratamiento en los pacientes infectados por el VIH.

Asunto(s)

Humanos , Infecciones por VIH/tratamiento farmacológico , Fármacos Anti-VIH/administración & dosificación , Didesoxinucleósidos/administración & dosificación , Didesoxinucleósidos/efectos adversos , Zidovudina/administración & dosificación , Zidovudina/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento , Lamivudine/administración & dosificación , Lamivudine/efectos adversos , Fármacos Anti-VIH/efectos adversos , Combinación de Medicamentos , Combinación Emtricitabina y Fumarato de Tenofovir Disoproxil/administración & dosificación , Combinación Emtricitabina y Fumarato de Tenofovir Disoproxil/efectos adversos , Metaanálisis en Red

RESUMEN

Importância do problema: Relatar um caso de hipersensibilidade à lamivudina, droga considerada segura e antirretroviral indicado como de primeira linha para início de tratamento para pacientes infectados pelo HIV. Comentários: É relatado o caso de paciente infectada pelo HIV que evoluiu com farmacodermia associada à terapia antirretroviral (TARV) utilizando tenofovir, lamivudina e efavirenz. Inicialmente, a hipersensibilidade foi atribuída ao efavirenz, pela maior incidência de eventos desta natureza com este medicamento e este foi substituído por fosamprenavir/ ritonavir. Apesar da substituição, paciente desenvolveu síndrome de Stevens-Johnson. Foi hospitalizada e iniciou novo esquema, com introdução de droga a droga, com atazanavir/ritonavir, seguido de zidovudina e lamivudina, desenvolvendo manifestação de eritema multiforme após a última droga, sendo esta considerada a responsá- vel pela hipersensibilidade. (AU)

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Relevance: To report a case of hypersensitivity to lamivudine, a medicine that is considered safe and is indicated as part of the initial therapy for HIV infected patients. Comments: It is reported the evolution of an HIV patient who developed a drug eruption due to the following antirretroviral therapy: tenofovir, lamivudine and efavirenz. It initially was attributed to efavirenz, due to its higher incidence in these adverse reactions and it was replaced by fosamprenavir/ritonavir. In spite of the replacement, the patient developed Stevens-Johnson's Syndrome. She was hospitalized and began a new therapy with atazanavir/ritonavir, followed by zidovudine and lamivudine and presented a drug reaction with the last one, which was considered to be the responsible for the hypersensitivity. (AU)

Asunto(s)

Humanos , Femenino , Persona de Mediana Edad , Síndrome de Inmunodeficiencia Adquirida , VIH , Lamivudine/efectos adversos , Terapia Antirretroviral Altamente Activa , Hipersensibilidad

RESUMEN

BACKGROUND: Patients with chronic hepatitis B virus (HBV) are often treated with nucleoside/nucleotide antiviral agents and metabolic bone toxicity is a possible concern. OBJECTIVE: To determine the relationships between fibroblast growth factor 23 (FGF23), a phosphaturic hormone, bone mineral density (BMD), and bone biochemical abnormalities in these patients. MATERIAL AND METHODS: This is a cross-sectional observational study comparing HBV-infected subjects treated for at least one year with tenofovir (TDF), lamuvidine (LVD), entacavir (ETV), or not treated (CON). Patients with abnormalities in either calcium (Ca), phosphate (PO4), intact parathyroid hormone (iPTH) or FGF23 were further evaluated with BMD by DXA. RESULTS: No difference in liver enzymes or renal function seen among groups, but hypophosphatemia was seen in all groups with the highest incidence with TDF-treatment (14%). FGF 23 levels were found to be elevated in 11.1% of TDF patients, 2.77% amongst controls. No elevations were found in the LVD or ETV groups. Among a subset of subjects (FGF23, PO4, and/or Ca abnormalities) who underwent further evaluation, 67% had insufficient 25-OH vitamin D, and 30% had elevated 24 h urinary Ca or PO4 excretion. No patients with FGF23 abnormalities had urine abnormalities. 40% had low DXA Z-score (&lt;-2) at spine or hip but there was no difference between control and antiviral treatment groups and the mean FRAX score was 2.33% for major osteoporotic fractures and 0.29% for hip fracture. CONCLUSION: Abnormalities in bone metabolism, particularly involving vitamin D insufficiency, in HBV-treated subjects were observed with a small increased likelihood in TDF treated patients.

Asunto(s)

Antivirales/uso terapéutico , Huesos/efectos de los fármacos , Calcio/sangre , Factores de Crecimiento de Fibroblastos/sangre , Guanina/análogos & derivados , Hepatitis B Crónica/tratamiento farmacológico , Lamivudine/uso terapéutico , Fosfatos/sangre , Tenofovir/uso terapéutico , Absorciometría de Fotón , Adulto , Anciano , Antivirales/efectos adversos , Biomarcadores/sangre , Densidad Ósea/efectos de los fármacos , Remodelación Ósea/efectos de los fármacos , Huesos/diagnóstico por imagen , Huesos/metabolismo , Estudios Transversales , Femenino , Factor-23 de Crecimiento de Fibroblastos , Fracturas Óseas/inducido químicamente , Guanina/efectos adversos , Guanina/uso terapéutico , Hepatitis B Crónica/sangre , Hepatitis B Crónica/diagnóstico , Humanos , Lamivudine/efectos adversos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Tenofovir/efectos adversos , Factores de Tiempo , Resultado del Tratamiento , Deficiencia de Vitamina D/inducido químicamente

RESUMEN

Commonly used guidelines for the management of human immunodeficiency virus (HIV) infection (highly active antiretroviral therapy, HAART) include drug combinations such as tenofovir disoproxil fumarate (TDF) + lamivudine (3TC) and combivir [zidovudine (AZT) + 3TC] + efavirenz (EFV). These combinations may enhance the genotoxic effects induced by such drugs individually, since the therapy requires lifelong adherence and the drugs have unknown effects during treatment. Thus, the evaluation of the benefits and risks of HAART is of great importance. In order to assess the cytotoxic and genotoxic potential of three concentrations of each of the antiretroviral combinations TDF + 3TC (800 + 400, 1600 + 800, and 3200 + 1600 mg/kg body weight, BW) and combivir + EFV (200 + 100 + 400, 400 + 200 + 800, and 800 + 400 + 1600 mg/kg BW) after two exposure periods (24 h and 48 h), in the present study the in vivo comet assay (single-cell gel electrophoresis) and the mouse bone marrow micronucleus test were used. Neither TDF + 3TC nor combivir + EFV induced DNA damage at any concentrations tested after 24 h or 48 h using the comet assay. After 24 h, both combinations increased the micronucleus frequency at all concentrations tested. After 48 h, combivir + EFV increased the micronucleated polychromatic erythrocyte (MNPCE) frequency at the two highest concentrations tested. Polychromatic erythrocytes (PCE)/normochromatic erythrocytes (NCE) ratio was high for both combinations, suggesting that they can be mitogenic. Since genotoxicity may be related to carcinogenesis, it is necessary to conduct further studies to verify the long-term mutagenic effects of these drugs.

Asunto(s)

Quimioterapia Combinada/efectos adversos , Lamivudine/administración & dosificación , Tenofovir/administración & dosificación , Zidovudina/administración & dosificación , Animales , Terapia Antirretroviral Altamente Activa , Médula Ósea/efectos de los fármacos , Ensayo Cometa , Relación Dosis-Respuesta a Droga , Combinación de Medicamentos , Lamivudine/efectos adversos , Ratones , Micronúcleos con Defecto Cromosómico/inducido químicamente , Tenofovir/efectos adversos , Zidovudina/efectos adversos

RESUMEN

BACKGROUND: Generic drug policies are often associated with concerns about the quality and effectiveness of these products. Phase IV clinical trials may be a suitable design to assess the effectiveness and safety of generic drugs. The objective of this study was to describe the effectiveness and the safety of the generic abacavir/lamivudine and efavirenz in treatment-naïve HIV-infected patients. METHODS: A monocentric, nonrandomized, open-label, phase IV study in treatment naïve HIV-infected patients 18 years or older with indication to receive abacavir/lamivudine and efavirenz were recruited from a program that provides comprehensive outpatient consultation and continuing care. The primary end-point was to achieve viral load <40 copies/mL at 12 months after baseline to assess effectiveness. Secondary end-point of the study were 1) to asses increasing in T-CD4 lymphocytes levels as accompaniment to asses effectiveness, and 2) to assess both gastrointestinal, skin, and central nervous system symptoms, and lipid profile, cardiovascular risk, renal, and hepatic function as safety profile. Data were determined at baseline, 3, 6, and 12 months. Close clinical monitoring and pharmaceutical care were used for data collection. Wilcoxon matched-pairs signed-rank test was used to compare proportions or medians. RESULTS: Sixty patients were invited to participate in the study; 42 were enrolled and 33 completed the follow-up. Of the nine patients excluded from the study, only one was withdrawn due to adverse events. At 12 months, 31 of 42 patients (73.8 % in intention-to-treat analysis) achieved a viral load of HIV1 RNA <40 copies/mL. There was a significant increase (172 cells/mm3) in the median for CD4 T lymphocyte count. The adverse events were mild and met the safety profile for this antiretroviral regimen, mainly of central nervous system symptoms, skin rash, lipid abnormalities, and an increase of 2 % in the median of the percentage of cardiovascular risk. CONCLUSIONS: The clinical outcomes of generic version of abacavir/lamivudine and efavirenz in HIV treatment naïve patients showed the expected safety and effectiveness profile of proprietary ARV drugs. TRIAL REGISTRATION: Registro Público Cubano de Ensayos Clínicos (RPCEC) ID: RPCEC00000202 . Registered 19 November 2015.

Asunto(s)

Fármacos Anti-VIH/uso terapéutico , Benzoxazinas/uso terapéutico , Didesoxinucleósidos/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Lamivudine/uso terapéutico , Adulto , Alquinos , Fármacos Anti-VIH/efectos adversos , Benzoxazinas/efectos adversos , Enfermedades Cardiovasculares/inducido químicamente , Colombia , Ciclopropanos , Didesoxinucleósidos/efectos adversos , Combinación de Medicamentos , Medicamentos Genéricos , Femenino , VIH-1/efectos de los fármacos , VIH-1/patogenicidad , Humanos , Lamivudine/efectos adversos , Masculino , Resultado del Tratamiento , Carga Viral

RESUMEN

INTRODUCTION: Among the available nucleos(t)ide analogues adefovir dipivoxil (ADV) is relatively cheap and widely used in rural area in China. However, there are insufficient data on recommendation for patients with suboptimal response to ADV after 48 weeks of treatment in order to reduce the resistance rate in the long term. The aim of this study was to compare the efficacy and safety of LAM add-on combination therapy versus ETV monotherapy for patients with suboptimal response to ADV. MATERIAL AND METHODS: 136 patients with suboptimal response to ADV were randomly assigned to the add-on LAM with ADV combination therapy (68 patients) group and the ETV monotherapy (68 patients) group. Patients in the add-on group were prescribed 100 mg LAM and 10 mg ADV per day, while the monotherapy group received 0.5 mg ETV per day for 48 weeks. Tests for liver and kidney function, HBV serum markers, HBV DNA load, were performed every 3 months. RESULTS: The mean patient age in LAM add-on group and ETV monotherapy was 38.59 ± 7.65 and 37.56 ± 8.67 years respectively. The HBV DNA undetectable rate in the LAM add-on group and the ETV group were not significant difference at week 4, 12 and 24 (P > 0.05). However, the HBV undetectable rate in the ETV group was higher than that in the LAM add-on group at week 36 and 48 (P = 0.043 for week 36 and P = 0.038 for week 48). There was no significant difference both for HBeAg loss and HBeAg seroconversion between two groups (P > 0.05) at 48 weeks. Meanwhile, our study also demonstrated that the mean eGFR levels in LAM add-on group was decreased from 99.6 ± 8.71 at baseline to 86.4 ± 9.83 at the end of 48 weeks, which was significantly higher than that in the ETV monotherapy group (P < 0.05). 8.8% of patients in LAM add-on group experienced eGFR reduction by 20-30% from baseline at 48 weeks. No patients developed hyposphosphatemia in our study. CONCLUSION: Our study clearly showed that switch to ETV monotherapy was the more effective and more safe than that of LAM add-on combination therapy for patients with suboptimal response to ADV.

Asunto(s)

Adenina/análogos & derivados , Antivirales/uso terapéutico , Sustitución de Medicamentos , Guanina/análogos & derivados , Hepatitis B Crónica/tratamiento farmacológico , Lamivudine/uso terapéutico , Organofosfonatos/uso terapéutico , Adenina/efectos adversos , Adenina/uso terapéutico , Adulto , Antivirales/efectos adversos , Biomarcadores/sangre , China , Quimioterapia Combinada , Femenino , Guanina/efectos adversos , Guanina/uso terapéutico , Hepatitis B Crónica/sangre , Hepatitis B Crónica/diagnóstico , Humanos , Lamivudine/efectos adversos , Masculino , Persona de Mediana Edad , Organofosfonatos/efectos adversos , Estudios Prospectivos , Factores de Tiempo , Resultado del Tratamiento , Carga Viral

RESUMEN

This study assessed the clinical efficacy of lamivudine and adefovir dipivoxil combined with autologous bone marrow stem cell transplantation as treatment for patients with hepatitis B and decompensated liver cirrhosis. In total, 77 patients with hepatitis B and decompensated liver cirrhosis were randomly divided into two groups. Under general symptomatic and supportive treatment, the patients in group A (37 cases) were treated with lamivudine and adefovir dipivoxil, whereas those in group B (40 cases) were treated with autologous bone marrow stem cell transplantation in combination with lamivudine and adefovir dipivoxil. After 4 weeks of treatment, the liver function indicators and clinical signs and symptoms of the patients in group B improved more significantly than those of patients in group A. Lamivudine and adefovir dipivoxil in combination with autologous bone marrow stem cell transplantation effectively prevented hepatitis B virus infection and bone marrow stem cell damage. This combination treatment facilitates the differentiation of bone marrow stem cells into normal liver cells to restore liver structure and improve liver function, thereby improving the quality of life of patients.

Asunto(s)

Adenina/análogos & derivados , Virus de la Hepatitis B/efectos de los fármacos , Lamivudine/uso terapéutico , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/virología , Organofosfonatos/uso terapéutico , Trasplante de Células Madre , Adenina/efectos adversos , Adenina/farmacología , Adenina/uso terapéutico , Colinesterasas/metabolismo , Terapia Combinada , Femenino , Humanos , Lamivudine/efectos adversos , Lamivudine/farmacología , Cirrosis Hepática/fisiopatología , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Organofosfonatos/efectos adversos , Organofosfonatos/farmacología , Tiempo de Protrombina , Trasplante de Células Madre/efectos adversos , alfa-Fetoproteínas/metabolismo

RESUMEN

Nucleoside reverse-transcriptase inhibitor (NRTI) drugs are a major component of highly-active antiretroviral therapy (HAART). NRTI combinations have been demonstrated as producing a sustained reduction in plasma viremia with an increased CD4 count, thereby showing clear clinical benefits. Therefore, the secondary effects caused by the combination of two NRTIs, mainly those related to amplification of genotoxic effects, due to increased risk of DNA damage caused by these drugs, should be carefully examined. We employed the standard version of the wing SMART in Drosophila melanogaster to obtain more detailed knowledge about the genotoxic profile of NRTI combinations of AZT+ddI, AZT+3TC and AZT+d4T. Our results showed that all combinations increased the frequencies of induction of mutant spots. The combinations AZT+ddI and AZT+3TC were shown to induce recombination rates ranging from 86.38% to 98.36% while AZT+d4T showed a large discrepancy between recombination and mutation percentages. The combination index demonstrated that 3TC and d4T produced antagonism while ddI showed synergistic effects in combination with AZT.

Asunto(s)

Antivirales/efectos adversos , Daño del ADN/efectos de los fármacos , Drosophila melanogaster/efectos de los fármacos , Animales , Fármacos Anti-VIH/efectos adversos , Recuento de Linfocito CD4 , Didanosina/efectos adversos , Relación Dosis-Respuesta a Droga , Drosophila melanogaster/metabolismo , Combinación de Medicamentos , Femenino , Lamivudine/efectos adversos , Masculino , Mitosis , Mutación , Proteínas Recombinantes , Alas de Animales/efectos de los fármacos , Zidovudina/efectos adversos

RESUMEN

BACKGROUND: The MERIT study evaluated maraviroc versus efavirenz, both with zidovudine/lamivudine, in treatment-naïve patients with CCR5-tropic (R5) HIV-1. Post hoc analyses previously assessed week 48 outcomes in patients rescreened with R5 virus by a more sensitive tropism assay. METHODS: Week 96 efficacy (post hoc, n = 614) and safety (n = 721) were assessed. RESULTS: Proportions of subjects <50 copies/mL (58.8% maraviroc, 62.7% efavirenz) and time to loss of virologic response (TLOVR) responders (<50 copies/mL: 60.5% vs 60.7%) were similar. Maraviroc recipients had greater CD4 increases (+ 212 vs + 171 cells/mm(3)) and fewer adverse event discontinuations (6.1% vs 15.5%), malignancies, and category C events. CONCLUSION: Week 96 data confirm week 48 observations in MERIT.

Asunto(s)

Fármacos Anti-VIH/uso terapéutico , Benzoxazinas/uso terapéutico , Ciclohexanos/uso terapéutico , Inhibidores de Fusión de VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , VIH-1 , Lamivudine/uso terapéutico , Triazoles/uso terapéutico , Zidovudina/uso terapéutico , Adolescente , Adulto , Anciano , Alquinos , Fármacos Anti-VIH/efectos adversos , Benzoxazinas/efectos adversos , Antagonistas de los Receptores CCR5 , Ciclohexanos/efectos adversos , Ciclopropanos , Quimioterapia Combinada , Femenino , Inhibidores de Fusión de VIH/efectos adversos , Infecciones por VIH/inmunología , Infecciones por VIH/virología , Humanos , Lamivudine/efectos adversos , Masculino , Maraviroc , Persona de Mediana Edad , Resultado del Tratamiento , Triazoles/efectos adversos , Zidovudina/efectos adversos