Multiple-tablet Regimen Research Articles

Increase in Single-Tablet Regimen Use and Associated Improvements in Adherence-Related Outcomes in HIV-Infected Women

The use of single-tablet antiretroviral therapy (ART) regimens and its implications on adherence among HIV-infected women have not been well described. Participants were enrolled in the Women's Interagency HIV Study, a longitudinal study of HIV infection in US women. We examined semiannual trends in single-tablet regimen use and ART adherence, defined as self-reported 95% adherence in the past 6 months, during 2006-2013. In a nested cohort study, we assessed the comparative effectiveness of a single-tablet versus a multiple-tablet regimen with respect to adherence, virologic suppression, quality of life, and AIDS-defining events, using propensity score matching to account for demographic, behavioral, and clinical confounders. We also examined these outcomes in a subset of women switching from a multiple- to single-tablet regimen using a case-crossover design. We included 15,523 person-visits, representing 1727 women (53% black, 29% Hispanic, 25% IDU, median age 47). Use of single-tablet regimens among ART users increased from 7% in 2006% to 27% in 2013; adherence increased from 78% to 85% during the same period (both P < 0.001). Single-tablet regimen use was significantly associated with increased adherence (adjusted risk ratio: 1.05; 95% confidence interval: 1.03 to 1.08) and virologic suppression (risk ratio: 1.06; 95% confidence interval: 1.01 to 1.11), while associations with improved quality of life and fewer AIDS-defining events did not achieve statistical significance. Similar findings were observed among the subset of switchers. Single-tablet regimen use was associated with increased adherence and virologic suppression. Despite this, 15% of women prescribed ART were still not optimally adherent; additional interventions are needed to maximize therapeutic benefits.

Switching From Twice-Daily Raltegravir Plus Tenofovir Disoproxil Fumarate/Emtricitabine to Once-Daily Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate in Virologically Suppressed, HIV-1–Infected Subjects: 48 Weeks Data

Background: Pill burden, dosing frequency, and concerns about safety and toler-ability are important obstacles to maintaining adequate medication adherence. Ralte-gravir (RAL) is indicated for twice-daily dosing and when taken with emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF), it becomes a twice-daily multiple-tablet regimen. Elvitegravir (EVG)/cobicistat (COBI)/FTC/TDF, STB, is the first approved once-a-day integrase strand transfer inhibitor (INSTI) containing single-tablet regimen that combines EVG, an INSTI, and COBI, a novel pharmacoenhancer, with the preferred nucleos(t)ide backbone of FTC/TDF. Methods: This was a 48-week prospective, single-arm open-label study of the switch to STB in virologically sup-pressed HIV-1–infected adult patients on FTC/TDF and twice-daily RAL for at least 6 months. Objectives were to evaluate the tolerability and safety of a regimen simpli-fication to once-a-day STB, while maintaining viral suppression through 48 weeks. Results: Forty-eight individuals in the United States were enrolled. The median age was 44 years, 96% were male, and 83% were White. The median time on RAL + FTC/TDF treatment prior to enrollment was 34 months. Ninety-six percent of participants cited regimen simplification as the reason to enroll in the switch study. At base-line, the median CD4 count was 714 cell/µL and estimated glomerular filtration rate (eGFR) was 105 mL/min. At week 48, all assessed study participants remained viro-logically suppressed to the lower limit of quantification (HIV-1 RNA<50 copies/mL) and maintained high CD4 cell count (median, 751 cells/mL) and stable eGFR (median, 100.5 mL/min). STB was well tolerated with no discontinuations, no study drug–related serious adverse events, and no study drug–related grade 3/4 adverse events. Conclusions: All participants switching to 1 tablet once-a-day STB from a twice-daily RAL + FTC/TDF regimen remained virologically suppressed. STB was well tolerated. Switching to STB may be a viable option for virologically suppressed patients wanting to simplify from a twice-daily RAL-containing regimen.

Adherence to single-tablet versus multiple-tablet regimens in the treatment of HIV infection—A questionnaire-based survey on patients satisfaction

AimThe aim of the study was to assess the degree of adherence and patient satisfaction with the antiretroviral treatment they are receiving relative to treatment efficacy. BackgroundAntiretroviral treatment in patients with HIV infection is long-term and requires systematic medication intake. Simplified treatment regimens may considerably improve adherence. Materials and methodsThe analysis was performed on the basis of a voluntary questionnaire filled in by 95 patients with HIV infection receiving antiretroviral treatment. The patients responded to questions about how often and why they omitted their medication doses, questions about side effects, convenience of using their current regimen, fatigue with the necessity of taking medication, and changes in well-being after treatment commencement. Patients treated with a simplified single-tablet daily treatment regimen (TDF/FTC/EFV or RPV) (Group 1) were compared with the remaining group of patients (Group 2). The results of the survey were analysed in relation to the treatment efficacy assessed on the basis of HIV viral load. ResultsSignificantly more cases of omitting medication dose due to forgetting were observed in Group 2 than in Group 1 (53% vs 22.6%, p<0.005). No significant differences were observed between the two groups of patients in terms of how common or how troublesome side effects were during treatment. The convenience of medication use was rated high by a significantly greater percentage of patients in Group 1 (p<0.005). Fatigue with the necessity to take medication was reported less commonly and subjective improvement in well-being after treatment was reported more often in Group 1. Detectable levels of HIV viral load were more common in Group 2 (p<0.05). ConclusionThe efficacy of antiretroviral treatment largely depends on the degree of patient adherence. The study has confirmed greater acceptance of the simplified single-tablet treatment regimen among the patients, which was associated with the greater ease of regularly taking medication and with higher quality of life. In the group of patients receiving multiple-tablet regimens, suboptimal suppression of HIV replication was observed more often, which may negatively affect remote treatment outcomes. Patients treated for HIV infection highly rate the convenience of simplified single-tablet regimens, which is associated with improved adherence and improved quality of life. The use of simplified single-tablet regimens may improve treatment efficacy.

Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate Single-Tablet Regimen (Stribild®): A Review of Its Use in the Management of HIV-1 Infection in Adults

A new single-tablet, fixed-dose formulation consisting of elvitegravir, an HIV-1 integrase strand transfer inhibitor (INSTI); cobicistat, a pharmacokinetic enhancer; emtricitabine, a nucleoside reverse transcriptase inhibitor; and tenofovir disoproxil fumarate (tenofovir DF), a nucleotide reverse transcriptase inhibitor (elvitegravir/cobicistat/emtricitabine/tenofovir DF 150 mg/150 mg/200 mg/300 mg; Stribild®) is available in some countries for the once-daily treatment of HIV-1 infection in antiretroviral therapy-naïve adults. Elvitegravir/cobicistat/emtricitabine/tenofovir DF is the first INSTI-based single-tablet regimen available for the complete initial treatment of adults with HIV-1 infection. In two large, randomized, double-blind, phase III trials, once-daily treatment with elvitegravir/cobicistat/emtricitabine/tenofovir DF was effective in reducing plasma HIV-1 RNA levels to <50 copies/mL at the week 48 assessment and showed virological efficacy noninferior to that of the efavirenz/emtricitabine/tenofovir DF single-tablet regimen or a once-daily regimen of atazanavir plus ritonavir (ritonavir-boosted atazanavir) plus the fixed-dose combination of emtricitabine/tenofovir DF. Elvitegravir/cobicistat/emtricitabine/tenofovir DF also showed durable efficacy in terms of achieving sustained suppression of HIV-1 RNA levels to <50 copies/mL for up to 144 weeks in both of the phase III trials. Elvitegravir/cobicistat/emtricitabine/tenofovir DF is an important addition to the group of simplified once-daily single-tablet regimens currently available for the effective treatment of HIV-1 infection in antiretroviral therapy-naïve patients and is among the preferred regimens recommended for use as initial treatment. It offers advantages over more complex multiple-tablet regimens that may impair treatment adherence, which is fundamental to the successful management of HIV-1 infection.

Cost‐effectiveness evaluation of initial HAART regimens for managing HIV‐infected patients according to real clinical practice

We evaluated the single‐tablet regimen (STR) versus multiple‐tablet regimen (MTR) strategies through an incremental cost‐effectiveness analysis in a large cohort of patients starting their first HAART. Adult HIV‐1‐naïve patients, followed at the San Raffaele Hospital, starting their first‐line regimen from June 2008 to April 2012, were included in the analysis. First‐line HAART regimens more frequently used (&gt;10%) were grouped into two classes as follows: a) single‐tablet regimen (STR) of TDF + FTC + EFV; b) multiple‐tablet regimen (MTR) including TDF + FTC + EFV, TDF + FTC + ATV/r, TDF + FTC + DRV/r TDF + FTC + LPV/r. The incremental cost‐effectiveness analysis was carried out by means of a Markov model calculating quality of life and costs for each patient, according to the given regimen (including any subsequent switch if occurred), through 1‐year cycles. The outcome measure was quality‐adjusted life‐years (QALYs). Data were analysed from the point of view of the Lombardy Regional Health Service (RHS): HAART, hospitalisations, visits, examinations and other concomitant non‐HAART drugs costs were evaluated, price variations included. 474 naïve patients: 90% males, mean age 42.2 years, mean baseline HIV‐RNA 4.50 log10copies/ml and CD4+ count of 310 cells/µL with a mean follow‐up of 28 months. Patients starting with an STR treatment were less frequently HCVAb positive (4% vs 11%, P=0.040), had higher mean CD4+ values [351 vs 297, P=0.004] as compared to MTR patients. The mean year cost/patient was €9,213 (range: €6,574.71–€33,570.00) with a mean per patient QALYs of 0.986 (range: 0.878–0.999) among STR patients; the mean year cost/patient was €14,277 (range: €5,908.89–€82,310.30) with a mean QALY of 0.933 (0.830–0.976) among MTR patients. STR dominates (i.e. is more effective and less costly) compared to MTR. (Fig. 1) At multivariable analysis, after adjustment for age, gender, HCVAb status, HIV risk factor, baseline CD4+ and HIV‐RNA, the cost‐effectiveness ratio was significantly lower among patients starting an STR treatment as compared to a MTR regimen (adjusted mean: €12,096 vs. €16,106; P=0.0001). The incremental cost‐effectiveness ratio (ICER) values comparing the two treatment strategies reported in the table. Starting with a first‐line STR regimen compared to multiple‐tablet regimens resulted cost‐effective showing lower costs and better efficacy as measured by QALYs.Incremental Cost Effectiveness Ratio of HAART Regimens.image

A single tablet regimen is associated with higher adherence and viral suppression than multiple tablet regimens in HIV+ homeless and marginally housed people

Although, single-tablet regimen (STR) efavirenz, emtricibine, and tenofovir disoproxil fumarate (EFV/FTC/TDF) may be appealing in HIV-infected persons who are at high risk for nonadherence, the degree to which this simplified formulation affects adherence is not known. The virologic effectiveness of this STR in a potentially nonadherent population remains a concern, given the rapid selection of drug resistance seen with these drugs. We performed a prospective observational study assessing adherence and virologic response to EFV/FTC/TDF STR among a cohort of homeless and marginally housed individuals. We compared adherence and viral suppression to historical controls followed in the same cohort. Adherence was higher in EFV/FTC/TDF STR regimen compared to non-one-pill-once-daily therapy (P = 0.006) after controlling for multiple confounders. Viral suppression (HIV RNA <50 copies/ml) was greater in EFV/ FTC/TDF STR than non-one-pill-once-daily regimens (69.2 versus 46.5%; P = 0.02), but there was no difference in viral suppression after controlling for adherence. Once-daily EFV/TNF/FTC STR appears to be a reasonable option for individuals with multiple barriers to adherence. Randomized clinical trials addressing various therapeutic strategies for this patient population are needed.