Faster lung function decline in people living with HIV despite adequate treatment: a longitudinal matched cohort study.

INTRODUCTION: Chronic lung disease is common among people living with HIV (PLWH). We hypothesised that PLWH receiving antiretroviral therapy (ART) have faster lung function decline than matched controls. METHODS: We performed a prospective matched cohort study by including ART-treated PLWH from the Copenhagen Co-morbidity in HIV Infection Study (n=705) and the INSIGHT Strategic Timing of Antiretroviral Treatment Pulmonary Substudy (n=425) and frequency matched population controls from the Copenhagen General Population Study (n=2895) in a 1:3 ratio. Eligible participants were ≥25 years old and had two spirometry tests separated by at least 2 years of follow-up. Forced expiratory volume in 1 s (FEV1) decline (mL/year) was compared between PLWH and controls using a linear mixed model adjusted for age, sex, ethnicity and smoking status. Effect modification by smoking was investigated in subgroup analyses. RESULTS: The majority of PLWH were virally suppressed (96.1%). The adjusted mean annual decline in FEV1 was faster in PLWH than in controls with 36.4 (95% CI 33.7 to 39.1) vs 27.9 (95% CI 26.9 to 28.8) mL/year, yielding a difference of 8.5 (95% CI 5.6 to 11.4) mL/year. The association between HIV and FEV1 decline was modified by smoking, with the largest difference in current smokers (difference: 16.8 (95% CI 10.5 to 23.0) mL/year) and the smallest difference in never-smokers (difference: 5.0 (95% CI 0.7 to 9.3) mL/year). FEV1 decline >40 mL/year was more prevalent in PLWH (adjusted OR: 1.98 (95% CI 1.67 to 2.34)). CONCLUSION: Well-treated PLWH have faster lung function decline than controls and smoking seems to modify this association, suggesting that smoking may lead to more rapid lung function decline in PLWH than in controls.

[Antimicrobial Stewardship programs in Peru: A fundamental agreement]. / Programas de optimización del uso de antimicrobianos en Perú: Un acuerdo sobre lo fundamental.

BACKGROUND: Antimicrobial resistance (AMR) is a global threat to public health. Antibiotic stewardship programs (AMSP) promote the proper use of antimicrobials, improve clinical and economic outcomes, and helps containing the AMR. AIM: To evaluate the diagnostic phase of the AMS programs and early implementation of AMS at three high complexity hospitals that belong to the social security system in Peru. METHODS: A quasi-experimental multicenter study was implemented. The construction of the AMSP, microbiological baselines, antimicrobial consumption and consensus on AMS activities were evaluated at the diagnosis and early implementation periods of the AMSP. RESULTS: Following implementation, hospitals doubled their score of resources and processes available for the AMS program from 6.75 to 13.75. The prevalence of extended spectrum beta-lactamase producing enterobacteria was 50-60% while Pseudomonas aeruginosa averaged 69% resistance to carbapenems. The defined daily dose (DDD) of ceftriaxone was 13.63, vancomycin 7.35 and meropenem 6.73 in average. Hospitals A and C decreased the use of antimicrobials (30-50%). DISCUSSION: The implementation of the AMSP in the three hospitals was achieved through diverse strategies designed by multidisciplinary teams, which in addition to its articulation, reduce the consumption of broad spectrum antimicrobials at an early stage.

Programas de optimización del uso de antimicrobianos en Perú: un acuerdo sobre lo fundamental / Antimicrobial Stewardship programs in Peru: a fundamental agreement

Resumen Introducción: La resistencia a los antimicrobianos (RAM) es una amenaza para la salud pública mundial. Los programas de optimización del uso de antimicrobianos (PROAs) son programas que promueven su adecuado uso, mejoran los resultados clínicos, económicos y contribuyen a contener la RAM. Objetivos: Evaluar las fases de diagnóstico e implementación temprana de los PROAs en tres hospitales de alta complejidad pertenecientes al Sistema de Seguridad Social del Perú. Materiales y Métodos: Estudio multicéntrico, cuasi experimental. La estructuración de los programas, las líneas de base microbiológicas, el consumo de antimicrobianos y los consensos fueron evaluadas durante los períodos de diagnóstico inicial y durante la implementación temprana de los PROAs. Resultados: Con posterioridad a la implementación, los hospitales duplicaron la puntuación de recursos disponibles para los programas (6,75 vs 13,75). La prevalencia de enterobacterias portadoras de β-lactamasas de espectro extendido era de 50-60%, mientras que la resistencia a carbapenémicos en Pseudomonas aeruginosa promedió el 69%. La dosis diaria definida de ceftriaxona fue de 13,63, de 7,35 para vancomicina y 6,73 para meropenem en promedio. Los hospitales A y C disminuyeron el uso de antimicrobianos en 30 a 50%. Discusión: A través de estrategias diseñadas por equipos multidisciplinarios para implementar los PROAs, se logró disminuir tempranamente el consumo de antimicrobianos de amplio espectro.

Background. Antimicrobial resistance (AMR) is a global threat to public health. Antibiotic stewardship programs (AMSP) promote the proper use of antimicrobials, improve clinical and economic outcomes, and helps containing the AMR. Aim: To evaluate the diagnostic phase of the AMS programs and early implementation of AMS at three high complexity hospitals that belong to the social security system in Peru. Methods: A quasi-experimental multicenter study was implemented. The construction of the AMSP, microbiological baselines, antimicrobial consumption and consensus on AMS activities were evaluated at the diagnosis and early implementation periods of the AMSP. Results: Following implementation, hospitals doubled their score of resources and processes available for the AMS program from 6.75 to 13.75. The prevalence of extended spectrum beta-lactamase producing enterobacteria was 50-60% while Pseudomonas aeruginosa averaged 69% resistance to carbapenems. The defined daily dose (DDD) of ceftriaxone was 13.63, vancomycin 7.35 and meropenem 6.73 in average. Hospitals A and C decreased the use of antimicrobials (30-50%). Discussion: The implementation of the AMSP in the three hospitals was achieved through diverse strategies designed by multidisciplinary teams, which in addition to its articulation, reduce the consumption of broad spectrum antimicrobials at an early stage.

Sustained antiretroviral effect of raltegravir after 96 weeks of combination therapy in treatment-naive patients with HIV-1 infection.

OBJECTIVES: The purpose of this study was to evaluate the safety and efficacy of raltegravir vs efavirenz-based antiretroviral therapy after 96 weeks in treatment-naive patients with HIV-1 infection. METHODS: Multicenter, double-blind, randomized study of raltegravir (100, 200, 400, or 600 mg twice a day) vs efavirenz (600 mg every day), both with tenofovir/lamivudine (TDF/3TC), for 48 weeks, after which raltegravir arms were combined and all dosed at 400 mg twice a day. Eligible patients had HIV-1 RNA > or =5000 copies per milliliter and CD4 T cells > or =100 cells per microliter. RESULTS: One hundred ninety-eight patients were randomized and treated; 160 received raltegravir and 38 received efavirenz. At week 96, 84% of patients in both groups achieved HIV-1 RNA <400 copies per milliliter; 83% in the raltegravir group and 84% in the efavirenz group achieved <50 copies per milliliter (noncompleter = failure). Both groups showed similar increases in CD4 T cells (221 vs 232 cells/uL, respectively). An additional 2 patients (1 in each group) met the protocol definition of virologic failure between weeks 48 and 96; no known resistance mutations were observed in the raltegravir recipient; the efavirenz recipient had nucleoside reverse transcriptase inhibitor and nonnucleoside reverse transcriptase inhibitor resistance mutations. Investigator reported drug-related clinical adverse events (AEs) were less frequent with raltegravir (51%) than efavirenz (74%). Drug-related AEs occurring in >10% of patients in either group were nausea in both groups and dizziness and headache in the efavirenz group. Laboratory AEs remained infrequent. Raltegravir had no adverse effect on total or low-density lipoprotein cholesterol or on triglycerides. Neuropsychiatric AEs remained less frequent with raltegravir (34%) than efavirenz (58%). There were no drug-related serious AEs in patients receiving raltegravir. CONCLUSIONS: In antiretroviral therapy-naive patients, raltegravir with TDF/3TC had potent antiretroviral activity, which was similar to efavirenz/TDF/3TC and was sustained to week 96. Raltegravir was generally well tolerated; drug-related AEs were less frequent in patients treated with raltegravir compared with efavirenz.

Rapid and durable antiretroviral effect of the HIV-1 Integrase inhibitor raltegravir as part of combination therapy in treatment-naive patients with HIV-1 infection: results of a 48-week controlled study.

BACKGROUND: Raltegravir is an HIV-1 integrase strand-transfer inhibitor with potent in vitro activity. This study explored the antiretroviral activity and safety of raltegravir in treatment-naive patients with plasma HIV-1 RNA levels > or = 5000 copies/mL and CD4 T-cell counts > or = 100 cells/mm. METHODS: Multicenter, double-blind, randomized, controlled study of raltegravir at doses of 100, 200, 400, and 600 mg twice daily versus efavirenz at a dose of 600 mg/d, all in combination with tenofovir at a dose of 300 mg/d and lamivudine at a dose of 300 mg/d (clinicaltrials.gov identifier: NCT00100048). RESULTS: In the 198 patients treated (160 on raltegravir and 38 on efavirenz), the mean HIV-1 RNA level ranged from 4.6 to 4.8 log10 copies/mL at baseline. At weeks 2, 4, and 8, the proportion of patients achieving an HIV-1 RNA level <50 copies/mL was greater in each of the raltegravir treatment groups than in the efavirenz group. By week 24, all treatment groups appeared similar, with plasma HIV-1 RNA levels <400 copies/mL in 85% to 98% of patients and <50 copies/mL in 85% to 95% of patients. These reductions were maintained through week 48 in 85% to 98% of patients and in 83% to 88% of patients, respectively. Five (3%) patients on raltegravir and 1 (3%) on efavirenz experienced virologic failure before week 48. Drug-related clinical adverse events were less common with raltegravir than with efavirenz. After 24 and 48 weeks of treatment, raltegravir did not result in increased serum levels of total cholesterol, low-density lipoprotein cholesterol, or triglycerides. CONCLUSIONS: Raltegravir at all doses studied was generally well tolerated in combination with tenofovir and lamivudine. Raltegravir exhibited potent and durable antiretroviral activity similar to that of efavirenz at 24 and 48 weeks but achieved HIV-1 RNA levels below detection at a more rapid rate.