A Phase IV Study to Assess the Impact of the Change of Antiretroviral Treatment From Dual Therapy to Triple Therapy on Inflammation in Patients With HIV Infection

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).

Download Full-text

Scaling up access to antiretroviral treatment for HIV infection: the impact of decentralization of healthcare delivery in Cameroon

AIDS ◽

10.1097/01.aids.0000366078.45451.46 ◽

2010 ◽

Vol 24 (Suppl 1) ◽

pp. S5-S15 ◽

Cited By ~ 53

Author(s):

Sylvie Boyer ◽

Fred Eboko ◽

Mamadou Camara ◽

Claude Abé ◽

Mathias Eric Owona Nguini ◽

...

Keyword(s):

Hiv Infection ◽

Antiretroviral Treatment ◽

Healthcare Delivery ◽

Scaling Up ◽

The Impact

Download Full-text

Early Triple Therapy vs Mono or Dual Therapy for Children With Perinatal HIV Infection

JAMA ◽

10.1001/jama.295.6.626-b ◽

2006 ◽

Vol 295 (6) ◽

pp. 623 ◽

Cited By ~ 5

Keyword(s):

Hiv Infection ◽

Triple Therapy ◽

Dual Therapy ◽

Perinatal Hiv

Download Full-text

S09.2: The impact of HIV infection and HIV antiretroviral treatment on the placenta and fetal development

American Journal of Reproductive Immunology ◽

10.1111/aji.45_13417 ◽

2021 ◽

Vol 85 (S1) ◽

pp. 37-37

Keyword(s):

Hiv Infection ◽

Fetal Development ◽

Antiretroviral Treatment ◽

The Impact

Download Full-text

Looking back at paediatric HIV treatment in South Africa. My, how we have grown!

Southern African Journal of HIV Medicine ◽

10.4102/sajhivmed.v22i1.1283 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Leon J. Levin ◽

Juliet L. Horak ◽

James Nuttall

Keyword(s):

South Africa ◽

Triple Therapy ◽

Antiretroviral Treatment ◽

Dual Therapy ◽

Hiv Treatment ◽

Hiv Patients ◽

Paediatric Hiv ◽

Paediatric Patients ◽

Life Saving ◽

Looking Back

Antiretroviral treatment has undergone major changes in the last 20 years, from monotherapy, to dual therapy and finally to triple therapy. Lately, more focus has been placed on better, more well-tolerated combinations and formulations. As in most other disciplines in medicine, the development of paediatric HIV dosages and formulations always tends to lag behind adult research. Twenty years ago, it could take several years before data were available to enable the use of life-saving antiretrovirals in children. Paediatricians, being ever resourceful, were not prepared to let their paediatric patients suffer despite the lack of data or formulations and so made a plan. This article describes some of the trials and tribulations that we went through trying to make sure that our paediatric HIV patients not only survived but thrived. Clinicians treating paediatric patients today have it so much easier because of what our colleagues and their patients went through in those early days.

Download Full-text

Comparable viral decay with initial dolutegravir plus lamivudine versus dolutegravir-based triple therapy

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkz190 ◽

2019 ◽

Vol 74 (8) ◽

pp. 2365-2369 ◽

Cited By ~ 3

Author(s):

Jason Gillman ◽

Patrick Janulis ◽

Roy Gulick ◽

Carole L Wallis ◽

Baiba Berzins ◽

...

Keyword(s):

Drug Therapy ◽

Decay Rate ◽

Triple Therapy ◽

Therapy Group ◽

Dual Therapy ◽

Baseline Viral Load ◽

Linear Mixed Effect Model ◽

Mixed Effect ◽

The Mean ◽

The Impact

Abstract Objectives To expand understanding of the virological potency of initial dolutegravir plus lamivudine dual therapy (dolutegravir/lamivudine), we compared the viral decay seen in the pilot ACTG A5353 study with the decay observed with dolutegravir plus two NRTIs in the SPRING-1 and SINGLE studies, while also exploring the impact of baseline viral load (VL). Methods Change in VL from baseline was calculated for timepoints shared by A5353 (n = 120, including 37 participants with pretreatment VL >100000 copies/mL), SPRING-1 (n = 51) and SINGLE (n = 417). The 95% CIs of change from baseline were determined for each observed week, using the mean log10-transformed VL, and compared between the dolutegravir/lamivudine and triple therapy groups using the Wilcoxon Rank Sum test for non-inferiority (δ = 0.5). To assess the impact of baseline VL on viral decay, we examined a bi-exponential non-linear mixed-effect model. Results The mean VL change from baseline to week 24 was −2.9 log10 copies/mL for dolutegravir/lamivudine versus −3.0 log10 copies/mL for dolutegravir-based three-drug therapy (P < 0.001). In the decay model, baseline VL >100000 copies/mL was associated with a slower initial decay rate (d1). A faster initial decay rate was seen with dolutegravir/lamivudine, which was partially offset when baseline VL was >100000 copies/mL as indicated by a significant interaction between baseline VL and drug therapy group. The secondary decay rate (d2) was not significantly different from zero, with no significant associations. Conclusions Viral decay with dolutegravir/lamivudine was comparable to viral decay with dolutegravir-based triple therapy, even in individuals with higher pretreatment VL (>100000 copies/mL).

Download Full-text