All-oral direct-acting antiviral therapy against hepatitis C virus (HCV) in human immunodeficiency virus/HCV-coinfected subjects in real-world practice: Madrid coinfection registry findings.

We evaluated treatment outcomes in a prospective registry of human immunodeficiency virus/hepatitis C virus (HCV)-coinfected patients treated with interferon-free direct-acting antiviral agent-based therapy in hospitals from the region of Madrid between November 2014 and August 2016. We assessed sustained viral response at 12 weeks after completion of treatment and used multivariable logistic regression to identify predictors of treatment failure. We evaluated 2,369 patients, of whom 59.5% did not have cirrhosis, 33.9% had compensated cirrhosis, and 6.6% had decompensated cirrhosis. The predominant HCV genotypes were 1a (40.9%), 4 (22.4%), 1b (15.1%), and 3 (15.0%). Treatment regimens included sofosbuvir (SOF)/ledipasvir (61.9%), SOF plus daclatasvir (14.6%), dasabuvir plus ombitasvir/paritaprevir/ritonavir (13.2%), and other regimens (10.3%). Ribavirin was used in 30.6% of patients. Less than 1% of patients discontinued therapy owing to adverse events. The frequency of sustained viral response by intention-to-treat analysis was 92.0% (95% confidence interval, 90.9%-93.1%) overall, 93.8% (92.4%-95.0%) for no cirrhosis, 91.0% (88.8%-92.9%) for compensated cirrhosis, and 80.8% (73.7%-86.6%) for decompensated cirrhosis. The factors associated with treatment failure were male sex (adjusted odds ratio, 1.75; 95% confidence interval, 1.14-2.69), Centers for Diseases Control and Prevention category C (adjusted odds ratio, 1.65; 95% confidence interval, 1.12-2.41), a baseline cluster of differentiation 4-positive (CD4+) T-cell count <200/mm3 (adjusted odds ratio, 2.30; 95% confidence interval, 1.35-3.92), an HCV RNA load ≥800,000 IU/mL (adjusted odds ratio, 1.63; 95% confidence interval, 1.14-2.36), compensated cirrhosis (adjusted odds ratio, 1.35; 95% confidence interval, 0.96-1.89), decompensated cirrhosis (adjusted odds ratio, 2.92; 95% confidence interval, 1.76-4.87), and the use of SOF plus simeprevir, SOF plus ribavirin, and simeprevir plus daclatasvir. CONCLUSION: In this large real-world study, direct-acting antiviral agent-based therapy was safe and highly effective in coinfected patients; predictors of failure included gender, human immunodeficiency virus-related immunosuppression, HCV RNA load, severity of liver disease, and the use of suboptimal direct-acting antiviral agent-based regimens. (Hepatology 2018;68:32-47).

[Factors predicting the failure of interruption of highly active antiretroviral treatment (HAART) in HIV-infected patients]. / Factores que predicen el fracaso de las interrupciones del tratamiento antirretroviral (TAR) en los pacientes con infección por el VIH.

INTRODUCTION: Treatment interruptions may be an alternative to HAART in the management of chronically infected HIV-patients. We designed this study in an attempt to assess the predictability of this strategy. METHODS: We recruited HIV-infected patients whose treatment had been suspended. Interruption was due to the patient's own decision, or toxicity, or because the patient had started the treatment with more than 350 CD41 cells/microL (immunologic criteria). RESULTS: Forty-one consecutive patients were included, with a median follow-up of 13 months. Failure was associated with the reason for interruption (p 5 0.0063). Failure occurred in 14.3% of those who interrupted treatment due to immunological criteria and in 40% of those who interrupted treatment due to their own decision or toxicity. The reasons for interruption were: toxicity in 11 patients (26.8%), personal decision in 9 (21.9%) and immunological criteria in 21 (51.2%). In the univariate analysis, the nadir CD41 cell count < 350 cél./microL [OR 16 (p = 0.054)] was statistically significant in the patients who stopped treatment due to immunological criteria, while treatment with protease inhibitors [OR 14 (p = 0.032)] was statistically significant in the remaining patients. In the multivariable analysis only nadir CD41 < 350 cél./microL was independently related with failure. CONCLUSIONS: Failure was related to interruption criteria and was greater in patients who stopped due their own decision or toxicity. When interruption was due to immunological criteria, the factor predicting failure was nadir CD41 cell count < 350 cél./microL. In the remaining patients, none of the variables was related to failure.

Factores que predicen el fracaso de las interrupciones del tratamiento antirretroviral (TAR) en los pacientes con infección por el VIH / Factors predicting the failure of interruption of highly active antiretroviral treatment (HAART) in HIV-infected patients

INTRODUCCIÓN. La interrupción del tratamiento puede ser una alternativa terapéutica al tratamiento antirretroviral en el manejo de la infección crónica por el virus de la inmunodeficiencia humana. Para estudiar esta opción, se ha diseñado un estudio de predicibilidad. MÉTODOS. Se incluyeron a pacientes que pararon el tratamiento por abandono de la medicación, toxicidad o por haber iniciado el tratamiento con una cifra de CD4+ > 350 cél./ml (criterio inmunológico).RESULTADOS. Se seleccionaron de forma prospectiva41 pacientes y la mediana de seguimiento fue de 13 meses. El fracaso se relacionó con el criterio de suspensión(p = 0,0063). En aquellos que abandonaron el tratamiento por criterio inmunológico el fracaso fue del 14,3% y en los que pararon por toxicidad o por abandono, el 40%. Las causas que motivaron la suspensión fueron: 11 (26,8%) por toxicidad; 9 (21,9%) por abandono y 21 (51,2%) por criterio inmunológico. Aunque en el análisis univariado, en el grupo que paró el tratamiento por “criterio inmunológico” la variable CD4+ nadir inferior a 350 cél./ml (odds ratio[OR] 16; p = 0,054) fue estadísticamente significativa, y en los otros pacientes lo fue el tratamiento con inhibidores de proteasa (OR 14; p = 0,032), en el análisis multivariable sólo CD4+ nadir inferior a 350 cél./ml se asoció de forma independiente con el fracaso. CONCLUSIONES. El fracaso se relacionó con el criterio de suspensión, y fue mayor cuando se suspendió por toxicidad o por abandono. El factor que predijo el fracaso en los pacientes que pararon por “criterio inmunológico ”fue una cifra de CD4+ nadir inferior a 350 cél./ml. En el otro grupo de pacientes, ninguna variable se relacionó con el fracaso (AU)

INTRODUCTION. Treatment interruptions may be an alternative to HAART in the management of chronically infected HIV-patients. We designed this study in an attempt to assess the predictability of this strategy. METHODS. We recruited HIV-infected patients whose treatment had been suspended. Interruption was due to the patient’s own decision, or toxicity, or because the patient had started the treatment with more than 350 CD4+ cells/mL (immunologic criteria).RESULTS. Forty-one consecutive patients were included, with a median follow-up of 13 months. Failure was associated with the reason for interruption (p = 0.0063).Failure occurred in 14.3% of those who interrupted treatment due to immunological criteria and in 40% of those who interrupted treatment due to their own decision or toxicity. The reasons for interruption were: toxicity in 11 patients (26.8%), personal decision in 9 (21.9%) and immunological criteria in 21 (51.2%). In the univariate analysis, the nadir CD4+ cell count < 350 cél./mL[OR 16 (p = 0.054)] was statistically significant in the patients who stopped treatment due to immunological criteria, while treatment with protease inhibitors [OR14 (p = 0.032)] was statistically significant in there maining patients. In the multivariable analysis only nadir CD4+ < 350 cél./mL was independently related with failure. CONCLUSIONS. Failure was related to interruption criteria and was greater in patients who stopped due their own decision or toxicity. When interruption was due to immunological criteria, the factor predicting failure was nadir CD4+ cell count < 350 cél./mL. In the remaining patients, none of the variables was related to failure (AU)

Treatment-limiting toxicities associated withnucleoside analogue reverse transcriptase inhibitor therapy: A prospective, observational study.

BACKGROUND: The Recover Study is an ongoing, prospective study designed 10 to assess toxicity associated with the use of nucleoside analogue reverse transcriptase inhibitors (NRTIs) (stavudine, zidovudine, lamivudine, didanosine, abacavir) in HIV-1-infected patients receiving highly active antiretroviral therapy (HAART) in routine clinical practice. This project is being conducted at 120 HIV units at teaching hospitals across Spain. OBJECTIVE: The aim of this study was to identify the most common treatment-limiting 10 moderate to severe clinical and laboratory adverse effects (AEs), and the individual NRTIs involved in the development of these effects, in HIV-1-infected patients receiving HAART who discontinued use of an NRTI in the Recover Study. METHODS: Patients eligible for participation in the Recover Study are aged10 ≥18 years; have virologically documented HIV-1 infection; have sustained viral suppression (viral load <200 cells/mL or stable, heavily experienced [ie, have received ≥3 antiretroviral regimens] patients with viral load <5000 cells/mL) for ≥6 months; are receiving HAART; are undergoing active follow-up; and have developed 2:1 NRTI-associated AE that, in the opinion of a study investigator and under the conditions of routine clinical practice, justified discontinuation of treatment with the offending drug (principal AE/offending NRTI). The present study included patients recruited for the Recover Study between September 2002 and May 2003. RESULTS: A total of 1391 patients were enrolled (966 men, 425 women; mean 1 age, 42 years [range, 18-67 years]). Five hundred six patients (36.4%) had been diagnosed with AIDS. The mean duration of treatment with the offending NRTI was 74 months (range, 6-156 months). Seven hundred nine patients (51.0%) were receiving fourth-line (or more) therapy. Eight hundred twenty-one patients (59.0%) were receiving nonnucleoside analogues, and 552 patients (39.7%), protease inhibitors, as components of their HAART regimens. The NRTIs with the highest discontinuation rates were stavudine (914 patients [65.7%]) and zidovudine (177 [12.7%]). The most frequent NRTI-related AEs were lipoatrophy (550 patients [39.5%]) and peripheral neuropathy (170 [12.2%]). Lipoatrophy was most commonly associated with stavudine (480/550 cases [87.3%]); periph eral neuropathy, with stavudine and didanosine (107/170 [62.9%] and 48/170 [28.2%] cases, respectively); and anemia, with zidovudine (70/77 cases [90.9%]). CONCLUSIONS: The results of this study in patients with HIV-1 recruited in the10 Recover Study and undergoing HAART suggest that long-term treatment with NRTIs is associated with AEs (lipoatrophy, peripheral neuropathy, and lipodystrophy), with morphologic disorders (lipoatrophy, lipodystrophy) being the most common AEs leading to discontinuation. Minimizing these AEs by switching to an NRTI not associated with these AEs (eg, tenofovir) would contribute to adherence and hence efficacy of long-term HAART.