Compliance with national guidelines for HIV treatment and its association with mortality and treatment outcome: a study in a Spanish cohort.

OBJECTIVES: The aim of the study was to assess the adequacy of initial antiretroviral therapy (ART), in terms of its timing and the choice of regimens, according to the Spanish national treatment guidelines [Spanish AIDS Study Group-National Plan for AIDS (GeSIDA-PNS) Guidelines] for treatment-naïve HIV-infected patients. METHODS: A prospective cohort study of HIV-positive ART-naïve subjects attending 27 centres in Spain from 2004 to 2010 was carried out. Regimens were classified as recommended, alternative or nonrecommended according to the guidelines. Delayed start of treatment was defined as starting treatment later than 12 months after the patient had fulfilled the treatment criteria. Multivariate logistic and Cox regression analyses were performed. RESULTS: A total of 6225 ART-naïve patients were included in the study. Of 4516 patients who started treatment, 91.5% started with a recommended or alternative treatment. The use of a nonrecommended treatment was associated with a CD4 count > 500 cells/µL [odds ratio (OR) 2.03; 95% confidence interval (CI) 1.14-3.59], hepatitis B (OR 2.23; 95% CI 1.50-3.33), treatment in a hospital with < 500 beds, and starting treatment in the years 2004-2006. Fourteen per cent of the patients had a delayed initiation of treatment. Delayed initiation of treatment was more likely in injecting drug users, patients with hepatitis C, patients with higher CD4 counts and during the years 2004-2006, and it was less likely in patients with viral loads > 5 log HIV-1 RNA copies/ml. The use of a nonrecommended regimen was significantly associated with mortality [hazard ratio (HR) 1.61; 95% CI 1.03-2.52; P = 0.035] and lack of virological response. CONCLUSIONS: Compliance with the recommendations of Spanish national guidelines was high with respect to the timing and choice of initial ART. The use of nonrecommended regimens was associated with a lack of virological response and higher mortality.

A randomized trial comparing the efficacy and tolerability of two HAART strategies at two years in antiretroviral naive patients / Un ensayo randomizado que compara la eficacia y tolerancia de dos estrategias de HAART a dos años en pacientes sin tratamiento antirretroviral

Background. The use of HAART combining 2 nucleoside analogues reverse transcriptase inhibitors (NRTIs) plus one protease inhibitor (PI) or 2 NRTIs + 1 non-nucleoside reverse transcriptase inhibitor (NNRTI) has shown comparable efficacy. The study was designed to compare long term (2 years) effectiveness of two antiretroviral (ARV) treatment strategies in patients not previously treated: starting with a nelfinavir based HAART switching to nevirapine in case of failure or side effects or the reverse sequence. Methods. This multicenter, randomized, open label clinical trial enrolled ARV-naïve HIV patients with CD4 counts below 500 cells/mm³. They were randomly assigned to start ddI + d4T + nelfinavir (switching to ZDV + 3TC + NEV in case of failure or toxicity) (PI-NEV arm) or ddI + d4T + nevirapine, switching to ZDV + 3TC + NFV in case of failure or toxicity (NEV-PI arm). The primary study endpoint was the Kaplan-Meier estimates of the time to failure after switching to second regimen if necessary (considering failure as two consecutive plasma HIV-1 RNA determinations above 200 copies/mL, death, a new category C event or toxicity leading to treatment discontinuation of the second regimen) after a minimum follow-up of two years. Results. A total of 137 patients were evaluable (67 and 70 in the PI-NEV and NEV-PI arms respectively). Baseline characteristics did not differ among groups. Kaplan-Meier estimates of time to failure did not show differences between the two arms neither in the on-treatment (OT) analysis (log rank test, p = 0.81) nor in the intent-to-treat (ITT) analysis (p = 0.58). At 24 months, the estimated proportion of patients free of failure were 72% and 66% respectively in the PI-NEV and NEV-PI arms OT analysis (p = 0.54) and 73% and 64% in the PI-NEV and NEV-PI arms in the ITT analysis (p = 0.49). The difference in the median in CD4+ lymphocyte count at 24 months was not significantly different in the two groups: 393 and 307 CD4 cells/mm3 in the PI-NEV and NEV-PI arms respectively (p = 0.167). The incidence of adverse events (AEs) in the two arms was very similar: 50 (75%) in the PI-NEV and 54 (70%) in the NEV-PI group, as it was for grade 3-4 AEs leading to drug switching. Conclusion. At two years both treatments strategies (PI-NEV vs NEV-PI) had a high and comparable efficacy and were generally well tolerated (AU)

Introducción. El uso del tratamiento antirretroviral de alta eficacia (TARGA) que combina 2 análogos de nucleósidos (NRTI) más un inhibidor de proteasas (IP) o 2 NRTI más 1 no-análogo de nucleósido (NNRTI) ha demostrado tener eficacia comparable. Este estudio fue diseñado para comparar la efectividad a largo plazo (2 años) de 2 estrategias de tratamiento antirretroviral (ARV) en pacientes no tratados previamente: empezando con un TARGA utilizando nelfinavir (NFV) y cambiando a nevirapina (NEV) en caso de fallo o de efectos adversos o viceversa. Métodos. Éste es un ensayo clínico, abierto, randomizado y multicéntrico que incluye pacientes infectados por el virus de la inmunodeficiencia humana (VIH) que nunca han recibido ARV y con menos de 500 CD4. Los pacientes fueron aleatorizados a recibir ddI mas d4T mas NFV (cambiando a ZDV más 3TC más NEV en caso de fallo o toxicidad; brazo PI-NEV) o ddI más d4T más NEV (cambiando a ZDV más 3TC más NFV en caso de fallo o toxicidad; brazo NEV-PI). El objetivo primario del estudio fue el tiempo estimado hasta el fracaso después de cambiar al segundo régimen terapéutico cuando fue necesario (considerando fracaso como 2 determinaciones de carga viral del VIH por encima de 200 copias/ml, muerte, un nuevo evento de la categoría C o toxicidad que lleve a la discontinuación del segundo régimen) después de un mínimo de seguimiento de 2 años. Resultados. Se evaluaron un total de 137 pacientes (67 y 70 en el brazo PI-NEV y NEV-PI, respectivamente). Las características basales de los pacientes fueron similares en ambos grupos. El tiempo estimado hasta el fracaso del tratamiento mediante las curvas de Kaplan-Meier no mostraron diferencias entre los 2 brazos de tratamiento ni en el análisis por tratamiento (OT) (p = 0,81) ni en el análisis por intención de tratar (p = 0,58). A los 24 meses, la proporción estimada de pacientes libres de fracaso fue del 72 y el 66%, respectivamente, en el brazo de PI-NEV y NEV-PI en el análisis OT (p = 0,54) y del 73 y el 64% en el PI-NEV y NEV-PI en el análisis ITT (p = 0,49). La diferencia en la mediana de linfocitos CD4 a los 24 meses no fue significativamente diferente entre ambos grupos: 393 y 307 CD4 células/mm3 en el grupo PI-NEV y NEV-PI, respectivamente (p = 0,167). La aparición de efectos adversos del tratamiento fue muy similar: 50 (75%) en el grupo PI-NEV y 54 (70%) en el grupo NEV-PI, así como los efectos adversos de grado 3-4 que llevaron a la discontinuación del tratamiento. Conclusión. Las estrategias de tratamiento PI-NEV frente a NEV-PI tienen una eficacia alta y comparable a los 2 años de seguimiento y en general fueron bien toleradas (AU)