Biterapia con atazanavir/ritonavir más raltegravir versus terapia triple en segunda línea: Ensayo ARTE / ATV/r+RAL (DT) after failure with NNRTI

Antecedentes: La terapia dual ha surgido como un nuevo concepto para el tratamiento del VIH. Este estudio tenía como objetivo comparar un régimen dual basado en ATV/r + RAL (TD) frente a estándar de tres drogas con ATV/r + TDF/FTC (TT) luego del fracaso de un primer esquema ba-sado en INNTR.ClinicalTrials.gov, Número: NCT01829802.Método: Estudio piloto abierto, multicéntrico y aleatoriza-do. Resultado primario: proporción de sujetos con ARN del VIH-1 menor a 50 copias/mL en semana 48 (S48). Resulta-dos secundarios: discontinuaciones asociadas a eventos adversos (EA), tiempo transcurrido hasta la supresión viral, desarrollo de mutaciones de resistencia a la integrasa y proteasa, cambio en recuento de CD4. Resultados: De los 57 participantes seleccionados, 34 fue-ron asignados aleatoriamente para recibir: TD (n: 18) o TT (n: 16). En semana 48, 67% (n: 12/18) en TD tuvo respues-ta virológica y 88% (n: 14/16) en rama según el análisis FDA, intención de tratamiento/expuestos (p = NS) y 73% (TD) y 93% (TT) según análisis por protocolo (p = NS). El cambio de CD4 entre basal - S48: +119 y +52 células/µL en DT y TT, respectivamente. Cuatro participantes en TD y uno en TT presentaron fracaso virológico en la semana 48. Un participante desarrolló una mutación de resistencia a integrasa (155H).Conclusión: ATV/r+RAL como terapia dual de segunda línea mostró una tendencia al fracaso virológico más frecuente, en comparación con TT, aunque el estudio piloto no tenía potencia para demostrar esta diferencia. Este estudio está registrado en ClinicalTrials.gov, Número: NCT01829802

Background: Dual therapy has emerged as a novel concept for HIV treatment. This study was aimed at comparing a nucleoside-sparing dual regimen consisting of ATV/r + RAL (DT) vs standard therapy of ATV/r + TDF/FTC (TT) among individuals failing first NNRTI-containing treatment.Methods: Randomized multicenter open-label pilot study. Primary outcome: proportion of subjects with plasma HIV-1 RNA below the limit of detection (<50 copies/mL) at 48 weeks (W48). Secondary outcomes: proportion of discontinuation due to adverse events (AEs), time until viral suppression, time until loss of virological response, development of integrase resistance mutations, and absolute change in CD4 counts. The primary outcome was analyzed using the FDA snapshot analysis.Results: Out of 57 participants screened, 34 were randomized to receive: DT (n: 18) or TT (n: 16). At W48, virological response was achieved in 67% (n: 12/18) of participants receiving DT and 88% (n: 14/16) receiving TT by FDA snapshot analysis (p = NS) and 73% and 93% by per-protocol analysis (p = NS). CD4 cell count median change from baseline to W48 was +119 and + 52 cell/µL in DT and TT, respectively. Four participants receiving DT and one TT presented virological failure at W48, with low pVL. One participant developed an integrase resistance mutation (155H) and suppressed later on TT.Conclusion: ATV/r+RAL as second-line therapy showed a trend to more frequent virological failure, compared to TT, although the study was unpowered to prove this difference. No major differences were seen in tolerance or toxicity.This study is registered with ClinicalTrials.gov, Number: NCT01829802

Craniofacial Growth Analysis of Individuals With and Without Cleft Lip and Palate in Colombia.

INTRODUCTION: Craniofacial growth is a dynamic and unpredictable process influenced by genetic and environmental factors, presenting phenotypic and gender differences. OBJECTIVE: Evaluate the differences in craniofacial growth and development in a group of Colombian individuals with complete unilateral and bilateral cleft lip and palate (CLP) and without CLP, classified by gender and age. SETTING AND SAMPLE POPULATION: Five hundred forty-one profile radiographs of 126 patients with unilateral CLP, 126 with bilateral CLP, and 289 without CLP. All patients of affected groups had a history of CLP correction surgery without nasoalveolar molding with orthopedic and orthodontic treatments. MATERIALS AND METHODS: This cross-sectional study was performed comparing 8 cephalometric measurements on radiographs, 5 linear/3 angular. Analysis was performed by median and interquartile range for all cephalometric measurements. Comparison between the groups was performed using Kruskal-Wallis and Mann-Whitney U, with a 95% confidence. RESULTS: Significant differences between the groups of patients with and without CLP, between types of clefts and genders. The skeletal structures of patients with CLP were smaller than those of control but improved with growth. Patients with unilateral CLP presented flat profiles and predominant class III malocclusions, while patients with bilateral CLP, at early ages, were class II and in the prepubertal stage, the values were progressively negative until the end of the growth period, suggesting class III. Patients with CLP presented posteroinferior rotation of the mandible, vertical measurements increased, and deflection of the cranial base. CONCLUSION: Given their growth alterations, patients with CLP benefit from orthopedic and orthodontic treatment.

Decreased bone mineral density in HIV-infected patients is independent of antiretroviral therapy.

OBJECTIVE: To describe the alterations in the bone metabolism of HIV-seropositive patients and evaluate the effects of antiretroviral therapies. DESIGN: Cross-sectional analytical study. METHOD AND MATERIALS: A total of 142 subjects (113 male, 29 female), aged 20-45 years were divided into four groups: group A, 33 HIV-seropositive antiretroviral-naive patients; group B1, 36 HIV-seropositive patients on antiviral therapy for over 1 year, without protease inhibitors (PI); group B2, 42 HIV-seropositive patients on combined therapy containing PI for over 1 year; and group C, 15 healthy, HIV-seronegative subjects. Bone mineral density (BMD) were determined by dual energy X-ray absorptiometry in total body, lumbar spine and proximal femur; and evaluation of serum osteocalcin, d-pyridinoline, parathyroid hormone (THP), calcium and phosphate, and urine calcium. RESULTS: BMD was significantly lower in HIV-seropositive patients in comparison with healthy controls, in all sites studied. However, no statistical differences were observed among all groups of HIV-infected patients, independently of the antiretroviral therapy. There was a significantly higher occurrence of osteopenia and osteoporosis in HIV-infected patients in comparison with controls (P < 0.0001), with no differences among treatment-naive patients and either of the treatment groups. Bone formation and resorption markers were similar among all studied groups. There was a significant correlation in all bone sites between time of infection and BMD (P < 0.02). CONCLUSIONS: BMD was significantly lower in HIV-seropositive patients in comparison with controls in lumbar spine, proximal femur and total body, without significant differences among treatment-naive patients and either of the treatment groups. Only time with HIV infection and not specific therapy was associated with BMD decreases.