Predicted susceptibility of etravirine in HIV patients experiencing virological failure secondary to non-nucleoside reverse transcriptase inhibitor resistance in Argentina.

INTRODUCTION: Virological response to etravirine (ETR) is dependent on the type and number of non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance-associated mutations (RAMs). METHODS: Data on NNRTI used in HAART at the time of failure and the number of NNRTI-RAMs were collected and retrospectively analyzed. ETR-RAMs were defined as V90I, A98G, L100I, K101E/H/P, V106I, E138A, V179D/F/T, Y181C/I/V, G190A/S, and M230L, and were analyzed according to the weighted mutation score to predict susceptibility (Vingerhoets 2008). RESULTS: N=150. Efavirenz (EFV) containing regimen: 76.7%; nevirapine (NVP): 23.3%. Frequency of ETR-RAMs acquired after NNRTI failure: zero=38.7%, one=39.3%, two=17.3%, three=3.3%, four=1.3%. Most frequent ETR-RAMs after failure with EFV: G190A (28.1%), K101E (14.9%), L100I (10.5%); and with NVP: Y181C (41.7%), G190A (30.6%) and A98G (13.9%). Global predicted susceptibility of ETR: highest response: 69.3%, intermediate response: 24.7%, reduced response: 6%. Comparing maximal response with duration of virological failure: EFV-containing regimen: 94.4% (< 24-weeks) vs. 69.8% (>24-weeks) (p=0.02); NVP-containing regimen: 42.9% (< 24-weeks) vs. 56.5% (>24-weeks) (p=0.41). The presence of lamivudine regimen was associated with a better predicted susceptibility (highest response) to ETR (79% vs. 25%; P=.001). DISCUSSION: The majority of patients maintained susceptibility to ETR after the acquisition of NNRTI resistance. Failing with an EFV-containing regimen had a better predicted susceptibility to ETR than with NVP, especially after short-term virological failure.

Associations between baseline biomarkers and lung function in HIV-positive individuals.

OBJECTIVE: The aim of this study was to analyse the association of baseline biomarker data with cross-sectional lung function and subsequent decline in lung function in HIV-positive persons. DESIGN: Lung function was modelled in all START pulmonary substudy participants who had baseline biomarker data and good-quality spirometry. In longitudinal analyses, we restricted to those participants with at least one good-quality follow-up spirometry test. METHODS: We performed linear regression of baseline forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC and their longitudinal slopes on log2-transformed baseline biomarkers with adjustment for age, sex, race, region, smoking status, baseline CD4+ T-cell counts and baseline HIV-RNA. Biomarkers included D-dimer, high-sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, IL-27, serum amyloid A, soluble intercellular adhesion molecule (sICAM)-1, soluble vascular cell adhesion molecule (sVCAM)-1, albumin and total bilirubin. RESULTS: Among 903 included participants, baseline median age was 36 years, CD4+ cell count was 647 cells/µl, and 28.5% were current smokers. In adjusted analyses, elevated markers of systemic inflammation (hsCRP, IL-6 and serum amyloid A) were associated with lower baseline FEV1 and FVC. Elevated D-dimer and IL-6 were associated with worse airflow obstruction (lower FEV1/FVC). Despite these cross-sectional associations at baseline, no associations were found between baseline biomarkers and subsequent longitudinal lung function decline over a median follow-up time of 3.9 years (3293 spirometry-years of follow-up). CONCLUSION: Commonly available biomarkers, in particular markers of systemic inflammation, are associated with worse cross-sectional lung function, but do not associate with subsequent lung function decline among HIV-positive persons with early HIV infection and baseline CD4 T-cell counts more than 500 cells/µl.

[Prevalence of potential drug-drug interactions involving antiretroviral drugs in Buenos Aires, Argentina]. / Prevalencia de interacciones medicamentosas con fármacos anti-retrovirales en Buenos Aires, Argentina.

INTRODUCTION: Antiretroviral agents (ARVs) have a high potential for drug interactions. However, the prevalence and risk factors for clinically significant drug-drug interactions (CSDDIs) with ARVs from Latin American countries is unknown. AIM: To evaluate the prevalence and risk factors for CSDDIs in HIV outpatients attending at two centers in Buenos Aires, Argentina. METHODS: Descriptive cross-sectional study (september to november 2012). HIV-1 infected patients under ARV treatment at the time of the study were randomly assessed for concomitant medication. CSDDIs were screened using the University of Liverpool Drug Interactions Program (www.hiv-druginteractions.org). RESULTS: A total of 217 patients were included. Male sex: 64% (CI 95: 57-70). Median age (IQR): 41 (36-48). Presence of comorbidities: 19%. ARV regimen: NNRTI-based: 48%, PI-based: 50% and NNRTI plus PI: 2%. Median of CD4 T-cell count (IQR): 402 cells/mL (235-588). Viral load < 50 copies/mL: 78%. Overall, 64% (CI 95: 57-70) of patients had > 1 co-medication of whom a 49% had at least one CSDDI. Two patients had a CSDDI between ARVs. The most frequent co-medications observed were antimicrobial (40%), cardiovascular (25%) and gastrointestinal agents (22%). In the multivariate analysis the number of co-medications and use of CNS agents were associated with the presence of CSDDIs. CONCLUSIONS: Co-medications and CSDDIs were common in our setting. In this context, training of HIV physicians in drug interactions is of major importance for adequate management of these patients.

Prevalencia de interacciones medicamentosas con fármacos anti-retrovirales en Buenos Aires, Argentina / Prevalence of potential drug-drug interactions involving antiretroviral drugs in Buenos Aires, Argentina

Introduction: Antiretroviral agents (ARVs) have a high potential for drug interactions. However, the prevalence and risk factors for clinically significant drug-drug interactions (CSDDIs) with ARVs from Latin American countries is unknown. Aim: To evaluate the prevalence and risk factors for CSDDIs in HIV outpatients attending at two centers in Buenos Aires, Argentina. Methods: Descriptive cross-sectional study (september to november 2012). HIV-1 infected patients under ARV treatment at the time of the study were randomly assessed for concomitant medication. CSDDIs were screened using the University of Liverpool Drug Interactions Program (www.hiv-druginteractions.org). Results: A total of 217 patients were included. Male sex: 64% (CI 95: 57-70). Median age (IQR): 41 (36-48). Presence of comorbidities: 19%. ARV regimen: NNRTI-based: 48%, PI-based: 50% and NNRTI plus PI: 2%. Median of CD4 T-cell count (IQR): 402 cells/mL (235-588). Viral load < 50 copies/mL: 78%. Overall, 64% (CI 95: 57-70) of patients had > 1 co-medication of whom a 49% had at least one CSDDI. Two patients had a CSDDI between ARVs. The most frequent co-medications observed were antimicrobial (40%), cardiovascular (25%) and gastrointestinal agents (22%). In the multivariate analysis the number of co-medications and use of CNS agents were associated with the presence of CSDDIs. Conclusions: Co-medications and CSDDIs were common in our setting. In this context, training of HIV physicians in drug interactions is of major importance for adequate management of these patients.

Introducción: Los fármacos anti-retrovirales (ARVs) tienen un alto potencial de interaccionar farmacológicamente con otros medicamentos. Sin embargo, los datos sobre la prevalencia y los factores de riesgo para la presencia de interacciones medicamentosas clínicamente significativas (IMCS) con ARVs en países latinoamericanos son limitados. Objetivo: Evaluar la prevalencia y los factores de riesgo para estas IMCS en dos centros de atención ambulatoria en Buenos Aires, Argentina. Métodos: Estudio transversal y descriptivo (septiembre-noviembre de 2012). Se evaluó la presencia de medicación concomitante en pacientes infectados por VIH bajo tratamiento ARV. Para evaluar la presencia de IMCS se utilizó la base de datos de interacciones de la Universidad de Liverpool (www.hiv-druginteractions.org). Resultados: Se incluyeron 217 pacientes. Sexo masculino: 64% (IC 95: 57-70). Mediana de edad (IQR): 41 (36-48). Presencia de co-morbilidades: 19%. Tratamiento ARV basado en INNTI: 48%, basado en IP: 50% y basado en INNTI más IP: 2%. Mediana de linfocitos T-CD4 (IQR): 402 céls/ml (235-588). Carga viral < 50 copias/ml: 78%. El 64% (IC 95: 57-70) de los pacientes tenían > 1 medicación concomitante: antimicrobianos (40%), fármacos cardiovasculares (25%) y gastrointestinales (22%). De los pacientes que presentaban medicación concomitante 68 (49%) tenían > 1 IMCS y sólo tres (2%) presentaban una asociación contraindicada. Además, dos pacientes tenían una IMCS entre ARVs. En el análisis multivariado, el número de medicamentos concomitantes y el uso psicofármacos se asociaron con una mayor chance de presentar IMCS. Conclusiones: La presencia de medicación concomitante e IMCS fue común en nuestra población. En este contexto, la formación de profesionales de la salud en la detección de interacciones medicamentosas es de suma importancia para un manejo adecuado de pacientes con infección por VIH que reciban tratamiento ARV.