Metabolic-Related Outcomes After Switching From Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide in Adults With Human Immunodeficiency Virus (HIV): A Multicenter Prospective Cohort Study.

BACKGROUND: Tenofovir alafenamide (TAF) has replaced tenofovir disoproxil fumarate (TDF) in many clinical settings. However, concerns remain about potential metabolic complications of TAF. We aimed to evaluate changes in weight, laboratory markers, and metabolic-related clinical events after replacing TDF with TAF. METHODS: Multicenter prospective cohort study in the Spanish CoRIS cohort. We included virologically suppressed adults with human immunodeficiency virus (HIV) receiving TDF for more than 12 months who either switched to TAF or maintained TDF, with no changes in the core agent. Participants were matched by propensity score. We fitted generalized equation models to assess changes in weight, blood lipids, and hepatic steatosis index, and to compare the incidence of diabetes, hypertension, and lipid-lowering drug use after 144 weeks. RESULTS: In total, 1446 participants were matched in each group. Median age was 38 years, 85% were male, mean weight at baseline was 73 kg. Participants who switched to TAF had a mean weight increase of +0.5 kg at 144 weeks over those who maintained TDF, with no difference in the occurrence of overweight or obesity. Individuals who switched to TAF had a significant increase in total cholesterol (+7.9 mg/dL) and triglycerides (+11.2 mg/dL), with no differences in the total cholesterol-high-density lipoprotein (HDL) ratio. However, no increased incidence of diabetes, hypertension, or lipid-lowering drug use was observed after the follow-up period. CONCLUSIONS: Switching from TDF to TAF is associated with modest weight gain and increases in total cholesterol and triglycerides, without an impact on the incidence of obesity or metabolic-related clinical events, in this Spanish cohort with a majority White male population.

Uptake and Discontinuation of Integrase Inhibitors (INSTIs) in a Large Cohort Setting.

BACKGROUND: Despite increased integrase strand transfer inhibitor (INSTI) use, limited large-scale, real-life data exists on INSTI uptake and discontinuation. SETTING: International multicohort collaboration. METHODS: RESPOND participants starting dolutegravir (DTG), elvitegravir (EVG), or raltegravir (RAL) after January 1, 2012 were included. Predictors of INSTI used were assessed using multinomial logistic regression. Kaplan-Meier and Cox proportional hazards models describe time to and factors associated with discontinuation. RESULTS: Overall, 9702 persons were included; 5051 (52.1%) starting DTG, 1933 (19.9%) EVG, and 2718 (28.0%) RAL. The likelihood of starting RAL or EVG vs DTG decreased over time and was higher in Eastern and Southern Europe compared with Western Europe. At 6 months after initiation, 8.9% (95% confidence interval: 8.3% to 9.5%) had discontinued the INSTI (6.4% DTG, 7.4% EVG, and 14.0% RAL). The main reason for discontinuation was toxicity (44.2% DTG, 42.5% EVG, 17.3% RAL). Nervous system toxicity accounted for a higher proportion of toxicity discontinuations on DTG (31.8% DTG, 23.4% EVG, 6.6% RAL). Overall, treatment simplification was highest on RAL (2.7% DTG, 1.6% EVG, and 19.8% RAL). Factors associated with a higher discontinuation risk included increasing year of INSTI initiation, female gender, hepatitis C coinfection, and previous non-AIDS-defining malignancies. Individuals in Southern and Eastern Europe were less likely to discontinue. Similar results were seen for discontinuations after 6 months. CONCLUSIONS: Uptake of DTG vs EVG or RAL increased over time. Discontinuation within 6 months was mainly due to toxicity; nervous system toxicity was highest on DTG. Discontinuation was highest on RAL, mainly because of treatment simplification.

Intestinal lymphangiectasia: an undescribed cause of malabsorption and incomplete immunological recovery in HIV-infected patients.

BACKGROUND: Although paradoxical virological and immunological response after HAART has been well studied, intestinal lymphangiectasia (IL) in HIV-1 infected patients has not previously described. METHODS: To describe HIV patients who developed IL. DESIGN: Clinical Case series. PATIENTS: 4 patients with HIV and IL diagnosis based on clinical, endoscopic and pathological findings. RESULTS: All four cases had prior mycobacterial infections with abdominal lymph node involvement and a very low CD4 cell count nadir. They developed intestinal lymphangiectasia despite appropriate virological suppression with HAART and repeatedly negative mycobacterial cultures. Two patients were clinically symptomatic with oedemas, ascites, diarrhoea, asthenia, weight loss; but the other two were diagnosed with malabsorption as a result of laboratory findings, with hypoproteinemia and hypoalbuminemia. Three of them were diagnosed by video capsule endoscopy. CONCLUSIONS: IL should be considered in HIV-1 infected patients who present with clinical or biochemical malabsorption parameters when there is no immunological recovery while on HAART.

Intestinal lymphangiectasia: an undescribed cause of malabsorption and incomplete immunological recovery in HIV-infected patients

Background Although paradoxical virological and immunological response after HAART has been well studied, intestinal lymphangiectasia (IL) in HIV-1 infected patients has not previously described. Methods To describe HIV patients who developed IL. Design Clinical Case series.Patients4 patients with HIV and IL diagnosis based on clinical, endoscopic and pathological findings. Results All four cases had prior mycobacterial infections with abdominal lymph node involvement and a very low CD4 cell count nadir. They developed intestinal lymphangiectasia despite appropriate virological suppression with HAART and repeatedly negative mycobacterial cultures. Two patients were clinically symptomatic with oedemas, ascites, diarrhoea, asthenia, weight loss; but the other two were diagnosed with malabsorption as a result of laboratory findings, with hypoproteinemia and hypoalbuminemia. Three of them were diagnosed by video capsule endoscopy. Conclusions IL should be considered in HIV-1 infected patients who present with clinical or biochemical malabsorption parameters when there is no immunological recovery while on HAART (AU)

Antecedentes Aunque las respuestas paradójicas al tratamiento antirretroviral, con ausencia de respuesta inmunológica a pesar de buen control virológico, han sido extensamente estudiadas, no se ha descrito hasta ahora la presencia de linfangiectasia intestinal (LI) como causa de las mismas. Método Serie de pacientes con infección VIH que desarrollaron LI. Diseño Series de casos clínicos. Pacientes Incluye 4 pacientes que desde el año 2002 han sido diagnosticados de LI en función de los datos clínicos y los hallazgos endoscópicos y patológicos. Resultados Los cuatro pacientes habían sido diagnósticados previamente de infecciones por micobacterias con afectación de ganglios abdominales y presentaron un recuento de linfocitos CD4 nadir muy bajo. Todos desarrollaron LI a pesar de mantener una supresión virológica mantenida con el tratamiento antirretroviral y cultivos frente a micobacterias repetidamente negativos. Dos pacientes desarrollaron clínica asociada con edemas, ascitis, diarrea, astenia y pérdida de peso, pero en los otros dos se llegó al diagnóstico por presentar parámetros bioquímicos de malabsorción pierde proteínas. En tres de ellos se llegó al diagnóstico mediante videocápsula-endoscópica. Conclusión La LI debe considerarse una causa más de falta de respuesta inmunológica al tratamiento antirretroviral, debiendo considerarse principalmente en pacientes con infección VIH y otras alteraciones clínicas o analíticas sugestivas de malabsorción. Enferm Infecc Microbiol Clin. 2011;29:117-20 (AU)