A randomized, controlled study evaluating an induction treatment strategy in which enfuvirtide was added to an oral, highly active antiretroviral therapy regimen in treatment-experienced patients: the INTENSE study (original) (raw)
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AIDS Research and Therapy, 2014
Background: Treatments in patients with multidrug resistance often involve the use of multiple agents with partial antiviral activity and overlapping metabolic toxicities. Enfuvirtide is therefore a welcome addition to the antiretroviral management of patients with multiclass resistant virus, given the low risk of systemic toxicities and novel mechanism of action relative to existing drug classes. The aim of this study was to evaluate the effectiveness of ENF plus optimized background regimen (OBR) in a Mexican cohort of highly HIV-1 ARV-experienced patients. Methods: Prospective cohort of treatment-experienced HIV-1-infected adults with virological failure who started therapy with an ENF-containing regimen. The effectiveness of ENF treatment was evaluated with percentages of undetectable HIV-1 RNA viral load after 24 and 48 weeks of treatment, and changes in CD4+ cell counts.
Antimicrobial Agents and Chemotherapy, 2008
Enfuvirtide is the first fusion and entry inhibitor approved for use for the treatment of human immunodeficiency virus (HIV) type 1 infection and as such represents a novel class of agents. For the population of patients experienced with three antiretroviral classes, enfuvirtide provides an additional option for treatment. This prospective, open-label, 24-week, single-arm trial assessed the efficacy and safety of enfuvirtide (90 mg injected subcutaneously twice daily) in combination with darunavir-ritonavir (600/100 mg administered orally twice daily) in triple-antiretroviral-class-experienced adults failing their current regimen. The primary efficacy endpoint was the proportion of participants with plasma HIV RNA loads of <50 copies/ml. Other virological and immunological measures were also evaluated, as were the effects of the baseline viral coreceptor tropism and darunavir phenotype sensitivity scores on the outcomes. At week 24, 60.3%, 72.5%, and 84.0% of 131 participants ach...
Canadian Consensus Recommendations for the Optimal Use of Enfuvirtide in HIV/AIDS Patients
The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie médicale / AMMI Canada, 2006
An eight-member group consisting of Canadian infectious disease and immunology specialists and a family physician with significant experience in HIV management was convened to update existing recommendations, specifically intended for use by Canadian HIV-treating physicians, on the appropriate use of enfuvirtide in HIV/AIDS patients with resistance to other antiretroviral drugs. Evidence from the literature and expert opinions of the group members formed the basis of the guidelines. Comments on the draft guidelines were obtained from other physicians across Canada with HIV expertise. The final guidelines represent the group's consensus agreement. The recommendations were developed to guide physicians in optimal practices in patient selection for enfuvirtide treatment and subsequent patient management. The issues considered include positive predictors of response to enfuvirtide, stage of disease, optimization of the background regimen, early indicators of enfuvirtide response, an...
Revista clínica española, 2007
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. 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 (consid...
Clinical Infectious Diseases, 2009
Background. Among patients with multidrug-resistant human immunodeficiency virus type 1 (HIV-1) infection, salvage regimens including enfuvirtide have demonstrated sustained efficacy. Because of reluctance to use subcutaneous injections, raltegravir may be an alternative to replace enfuvirtide within a suppressive regimen. We conducted a prospective, randomized, open-label trial to compare the antiviral efficacy and safety of a switch to raltegravir with the efficacy and safety of continuing enfuvirtide. Methods. A total of 170 patients with multidrug-resistant HIV-1 infection and plasma HIV-1 RNA levels !400 copies/mL who were receiving enfuvirtide-based regimens were randomized 1:1 to maintain enfuvirtide or to switch to raltegravir. The primary efficacy end point was the cumulative proportion of patients with virologic failure, defined as a confirmed plasma HIV-1 RNA level у400 copies/mL, over 24 weeks. The secondary end points mainly involved safety. Results. The switch to raltegravir was non-inferior to the maintenance of enfuvirtide, with virologic failure rates of 1.2% in both treatment arms in the intention-to-treat analysis (; 95% confidence interval, Ϫ6.7 d p 0.01% to 6.8) and 1.2% and 0%, respectively, in the on-treatment analysis (; 95% confidence interval, Ϫ5.6 d p 1.22% to 8.1). At week 24, 88%-89% of patients in both arms had plasma HIV-1 RNA levels !50 copies/mL. No significant CD4 cell count changes occurred in either arm. Grade 3-4 adverse events and laboratory abnormalities were uncommon and were not different between the treatment arms. Conclusion. A switch to raltegravir was safe, well tolerated, and virologically non-inferior to the maintenance of enfuvirtide in patients infected with multidrug-resistant HIV-1 infection who were receiving suppressive antiretroviral therapy. Clinical trials registration. NCT00454337. Enfuvirtide, the first human immunodeficiency virus type 1 (HIV-1) fusion inhibitor, has demonstrated sus
Enfuvirtide antiretroviral therapy in HIV-1 infection
Therapeutics and Clinical Risk Management, 2008
It has been over 25 years since the fi rst diagnosis of what would be known as AIDS. Although great strides in anti-HIV therapeutics have been made, there is still a great need for antiretrovirals that are effective against drug-resistant HIV. Enfuvirtide (ENF) is the fi rst of a new class of fusion inhibitors to be approved by the US Food and Drug Administration for use in combination with other antiretroviral agents among HIV-1 infected patients with previous treatment experience. The inclusion of enfuvirtide in an optimized antiretroviral background regimen for the treatment of HIV-1 infected (treatment-experienced) patients followed the success of two critical clinical trials (TORO: T20 vs Optimized Regimen Only I and II). Even though injection-site reactions persisted in these trials, improved virological and immunological responses were observed among patients. Challenges associated with ENF treatment include the high cost of the drug, injection-site reactions, determining the optimal time to initiate treatment, and the potential for the selection of drug resistant mutants and viral evolution. ENF is a promising novel treatment for HIV infected individuals whose choices for effective treatment are limited by previous treatment and resistance. Understanding the implications of viral fi tness and evolution in the presence of ENF treatment is crucial in determining effective and safe treatment regimens, particularly among treatment-experienced patients.
Journal of Clinical Virology, 2009
Background: Raltegravir is a potential treatment option for virologically suppressed HIV-1 infected patients on enfuvirtide with injection site reactions. Objectives: To characterize safety and efficacy of an enfuvirtide to raltegravir switch including changes in T-cells, quality of life, and residual viremia. Study design: In patients with viral load <50 copies/mL and injection site reactions, enfuvirtide was switched to raltegravir without additional changes to the antiretroviral regimen. Virologic failure was defined as a viral load >1000 copies/mL or two consecutive viral load measurements between 50 and 1000 copies/mL (low-level viremia). Over the 24 week study, we compared changes in T-cells, injection site reactions, quality of life, and residual viremia, as measured through the single-copy assay which can detect plasma virus down to a single copy, using paired t-tests. Results: Fourteen patients with a median CD4+ T-cell count of 420 cells/L were enrolled. After the switch, two patients experienced virologic failure due to confirmed low-level viremia. However, both patients subsequently were re-suppressed, one without any changes to his regimen. There was no change in CD4+ T-cell count. Injection site reactions resolved. However, there was little reported change in quality of life. The baseline median level of residual viremia was 6 copies/mL and did not change after the switch to raltegravir. Conclusions: A switch to raltegravir in virologically suppressed patients on enfuvirtide is effective in maintaining immunologic and virologic control at 24 weeks but did not result in a change in residual viremia. (P.M. Grant). raltegravir. 5,6 In patients on older antiretroviral regimens, over 80% with a viral load <50 copies/mL as measured by the standard ultra-sensitive assay have detectable virus on the single-copy assay, a highly sensitive assay which quantifies persistent viremia in plasma down to a single copy. 7 However, relatively little is known regarding residual viremia in patients on newer antiretroviral agents such as enfuvirtide and raltegravir.
HIV Clinical Trials, 2001
To compare in a real clinical setting the largely unknown midterm clinical effectiveness of two protease inhibitor (PI)-based highly active antiretroviral therapy (HAART) regimens with different potency and tolerability profiles in naïve patients. Method: This study was a multicenter, open-label, randomized trial in naïve patients with less than 400 CD4+ cell count/µL, regardless of viral load. Treatment arms were hard gel capsule saquinavir (HGC-SQV)-based HAART (Arm A), with an expected more favorable tolerability profile, and indinavir (IDV)-based HAART (Arm B), with more potent virologic activity. While viroimmunological surrogate markers and World Health Organization (WHO) grade III toxicity (secondary endpoints) were regularly monitored, primary endpoints of the study were clinical and defined as any AIDS-defining event, AIDS-related death, WHO grade IV toxicity, drop outs, and protocol violations. Results: 262 consecutive patients were enrolled in the study from in 24 different Italian clinical centers (132, Arm A; 130, Arm B). After 24 months of follow-up, patients who were enrolled in Arm B showed a significantly higher rate of virological success (75% had viremia below 500 copies/mL, CI = 12.9%, in the on-treatment analysis) and immunological gain (mean CD4+ cell count increase of 274 CD4+ cells/µL, SD = 234) when compared to patients enrolled in arm A (57%, CI = 15.5% and 223 CD4+ cells/µL, SD = 192; p = .0353 and .026, respectively). Despite the significant difference observed in surrogate markers, the number of total primary endpoints did not differ in the two groups (55 out of 132 in Arm A vs. 58 out of 130 personyears in Arm B; p = .86). Conclusion: Our results suggest that, after 24 months of follow-up in a real clinical setting, a PI-based HAART induces significant clinical benefits in naïve patients even in the absence of a complete suppression of viral replication. However, the long-term clinical impact of the possible accumulation of viral mutations in the presence of low-grade viral replication remains to be elucidated.