96-week results of a dual therapy with darunavir/ritonavir plus rilpivirine once a day vs triple therapy in patients with suppressed viraemia: virological success and non-HIV related morbidity evaluation

Abstract Background The discovery of antibiotics in the mid-twentieth century marked a major transition in tuberculosis (TB) treatment and control. There are few studies describing the duration of TB disease and its treatment from the pre-chemotherapy era and little data on how these treatments changed in response to the development of effective antibiotics. The goal of this research is to understand how inpatient treatment for high incidence populations, the First Nations peoples of Saskatchewan, Canada, changed in response to increasing availability of antibiotics effective against TB. We expected that as treatment regimens transitioned from convalescence-only to triple antibiotic therapy, the length of inpatient treatment would shorten. Methods Analyses were performed on records of sanatoria admissions and discharges occurring between 1933 and 1959 in Saskatchewan, Canada. Year of antibiotic discovery was taken as a proxy for treatment regimen: no chemotherapy (pre-1944), mono-therapy (Streptomycin, 1944–1946), dual-therapy (Streptomycin and PAS, 1946–1952), and triple-therapy (Streptomycin, PAS, and INH 1952-). A pooled linear regression of log-transformed length of first admission as predicted by year of admission was modeled to assess the relationship between admission length and year of admission, corrected for clinical and demographic variables. Results First admission length increased 19% in the triple-therapy era as compared to the pre-chemotherapy era, from 316 days (10.4 months) to 377 days (12.4 months). After the discovery of INH (1952), we find statistically significant increases in the proportion of successfully completed therapies (0.55 versus 0.60, p = 0.035), but also in patients who left hospital against medical advice (0.19 versus 0.29, p < 0.0001), indicating that as hospitalizations lengthened, more patients chose to discharge without the sanction of their physician. The readmission rate increased from 10 to 50% of all admissions while the province-level TB-specific death rate fell from 63.1 per 10,000 in 1933 to 4.7 per 10,000 in 1958. Conclusion Counterintuitively, we find that the length of first admissions increased with the discovery of TB-treating antibiotics. Increasing admission volume and readmission rate indicate an intensification of inpatient TB treatment during this era. These analyses provide a novel estimate of the effect of changing treatment policy on sanatorium admissions in this population.

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Single Inhaler Triple Therapy (FF/UMEC/VI) Versus FF/VI and UMEC/VI in Patients with COPD: Subgroup Analysis of the China Cohort in the IMPACT Trial

10.21203/rs.2.18023/v1 ◽

2019 ◽

Author(s):

Jinping Zheng ◽

Nanshan Zhong ◽

Changzheng Wang ◽

Li Ping Wei ◽

Xiang Dong Zhou ◽

...

Keyword(s):

Triple Therapy ◽

Dual Therapy ◽

Multicenter Trial ◽

Forced Expiratory Volume ◽

Phase Iii ◽

Chronic Obstructive ◽

Severe Exacerbation ◽

Double Blind ◽

Treatment Difference ◽

The Impact

Abstract Background In the Phase III InforMing the PAthway of COPD Treatment (IMPACT) trial, fluticasone furoate [FF]/umeclidinium [UMEC]/vilanterol [VI] single-inhaler triple therapy resulted in lower rates of moderate/severe exacerbations than dual therapy with FF/VI or UMEC/VI in patients with symptomatic chronic obstructive pulmonary disease (COPD) and a history of exacerbations. Here we present the result in the subpopulation of patients enrolled in China. Methods The IMPACT trial was a 52-week, randomized, double-blind, parallel-group, multicenter trial. Patients (≥40 years of age) with COPD and ≥1 moderate/severe exacerbations in the prior year were randomized 2:2:1 to once-daily FF/UMEC/VI 100/62.5/25 µg, FF/VI 100/25 µg, or UMEC/VI 62.5/25 µg administered via the Ellipta inhaler. Endpoints, assessed in the overall intent-to-treat (ITT) population and in patients from China, included annual rates of exacerbations, time-to-first on-treatment moderate/severe exacerbation, and change from baseline in trough forced expiratory volume in 1 second (FEV1) at Week 52. Results Of the 10,355 patients randomized, 535 (5.2%) were from China. In the China cohort, the rate of on-treatment moderate/severe exacerbations was 0.81 per year with FF/UMEC/VI versus 0.96 with FF/VI (rate ratio [RR]: 0.84; 95% confidence interval [CI]: 0.64, 1.11; p=0.227) and 0.80 with UMEC/VI (RR: 1.02; 95% CI: 0.72, 1.44; p=0.929). Hazard ratio for time-to-first moderate/severe exacerbation was 0.84 (95% CI: 0.63, 1.11; p=0.218) for FF/UMEC/VI versus FF/VI, and 0.89 (95% CI: 0.62, 1.27; p=0.516) for FF/UMEC/VI versus UMEC/VI. Improvements in mean change from baseline in trough FEV1 were observed for FF/UMEC/VI versus FF/VI (treatment difference 137 mL; 95% CI: 86, 188; p<0.001) and FF/UMEC/VI versus UMEC/VI (treatment difference 63 mL; 95% CI: 0, 125; p=0.0.050) in China. Health status was also improved with FF/UMEC/VI versus both dual therapies. Broadly, these results were in the same direction as those seen in the overall ITT population. No new safety signals were identified. Conclusions In the China cohort of the IMPACT trial, single-inhaler triple therapy with FF/UMEC/VI versus dual therapy with FF/VI or UMEC/VI reduced the rate and risk of exacerbations, and improved lung function and quality of life similar to the overall ITT population. Trial registration: NCT02164513 (GSK study number CTT116855).

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A COMPARATIVE EVALUATION OF THE EFFICACY OF TRIPLE DRUG THERAPY WITH DUAL DRUG THERAPY IN COPD PATIENTS

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2018v10i4.24529 ◽

2018 ◽

Vol 10 (4) ◽

pp. 105

Author(s):

Pathan Amanulla Khan ◽

A. Sujala ◽

B.b. Sarah Nousheen ◽

Ayesha Farhath Fatima ◽

Hibba Tul Ala ◽

...

Keyword(s):

Drug Therapy ◽

Combination Therapy ◽

Triple Therapy ◽

Drug Combination ◽

Dual Therapy ◽

Drug Combination Therapy ◽

Copd Patients ◽

Number Of Patients ◽

Dual Drug

Objective: The present study was conducted with the objective of analyzing the efficacy of triple-drug combination therapy (formoterol, ciclesonide, tiotropium) by comparing it with double drug combination therapy (formoterol, budesonide).Methods: A prospective observational study was conducted. Sixty patients were enrolled, and divided into two groups of thirty each; one group was treated with the double-drug and the other with a triple drug combination. FEV1 and FVC pre-and post-treatment in either group were assessed spirometrically. Score ranges of 0-10, 11-20 and 21-30 were allotted to mild, moderate and severe categories and results were analyzed statistically.Results: Of the 60 patients recruited, 61-70 y olds constituted the majority (35%) of the population. Males (63.3%) were more in number compared to females (36.6%). Twenty-three of thirty-eight men smoked (60.5%); there were no female smokers. Common symptoms included cough (93.3%), dyspnoea (85%), fever (45%) and haemoptysis (15%). Hypertension accounted for 70% of patient comorbidities, followed by diabetes (60%) and cardiovascular diseases (40%). Three months after treatment with triple therapy, a significant increase in the differences of means of both FEV1 (14.27) and FVC (14.90) values was observed. Further analysis based on score ranges demonstrated that triple therapy administration markedly reduced the number of patients suffering from severe COPD.Conclusion: Our comparative analysis indicated that triple therapy was more effective in improving lung function, enhancing patients’ quality of life (evidenced from score ranges) thereby reducing mortality. While much is known about the greater effectiveness of triple over dual therapy, researchers to formulate the most effective triple therapy are in progress.

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Genital Human Immunodeficiency Virus–1 RNA and DNA Shedding in Virologically Suppressed Individuals Switching From Triple- to Dual- or Monotherapy: Pooled Results From 2 Randomized, Controlled Trials

Clinical Infectious Diseases ◽

10.1093/cid/ciz511 ◽

2019 ◽

Vol 70 (9) ◽

pp. 1973-1979

Author(s):

Laurent Hocqueloux ◽

Camélia Gubavu ◽

Thierry Prazuck ◽

Barbara De Dieuleveult ◽

Jérôme Guinard ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Clinical Trials ◽

Triple Therapy ◽

Dual Therapy ◽

Pooled Analysis ◽

Similar Proportion ◽

Hiv Rna ◽

Immunodeficiency Virus ◽

Lower Drug ◽

Genital Shedding

Abstract Background Increasingly, people living with human immunodeficiency virus (HIV) benefit from lower drug regimens (LDRs). Exploring viral genital shedding during LDRs is crucial to ensure their safety. Methods We pooled genital sub-studies from 2 clinical trials in this area. Patients were randomized 1:1 to continue abacavir/lamivudine/dolutegravir or switch to dolutegravir (MONCAY trial), or to continue tenofovir/emtricitabine + a third agent or switch to tenofovir/emtricitabine (TRULIGHT trial). Participants whose plasma HIV-RNA remained <50 copies/mL had sperm or cervicovaginal lavage collected between Weeks 24 and 48. HIV-RNA and HIV-DNA were amplified by ultrasensitive polymerase chain reaction. The main objective was to measure the proportion of participants who had no detectable HIV in genital fluids, both according to each strategy and then in an aggregated analysis (LDR versus triple therapies). Results There were 64 participants (35 males, 29 females) included: 16 received dual therapies and 16 received triple therapies in TRULIGHT; and 16 received monotherapies and 16 received triple therapies in MONCAY. In TRULIGHT, 13/15 (87%) of evaluable participants on dual therapy had no detectable HIV in their genital fluid, versus 14/15 (93%) under triple therapy (P = 1.0). In MONCAY, these figures were 12/15 (80%) on monotherapy versus 13/16 (81%) on triple therapy (P = 1.0). In the pooled analysis, a similar proportion of participants in the LDR and triple therapy groups had no detectable HIV: 25/30 (83%) and 27/31 (87%), respectively (P = .73). Conclusions There was no evidence of increased HIV-RNA and/or -DNA shedding in the genital fluids of people who maintained undetectable plasma HIV-RNA during LDRs. Clinical Trials Registration NCT02302547 and NCT02596334

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