Single-Tablet Regimens in HIV Therapy

Astuti, Noemi; Maggiolo, Franco

doi:10.1007/s40121-014-0024-z

Cited by 53 publications

(50 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In view of this, the use of single doses has been highly recommended to achieve positive outcomes in HIV patients 24. One of the main outcomes linked to high adherence is clinical outcomes 34. Both CD4 and viral counts are affected by the degree of medication adherence 33.…”

Section: Discussionmentioning

confidence: 99%

Simplification of HAART therapy on ambulatory HIV patients in Malaysia: a randomized controlled trial

Velvanathan

Islahudin

Sim

et al. 2016

Pharm Pract (Granada)

View full text Add to dashboard Cite

Objective:Evaluate the impact of fixed-dose combination (FDC) containing emtricitabine (FTC), tenofovir (TDF), and efavirenz (EFV) versus a free-dose combination (FRC) of the same three drugs on clinical outcomes, adherence and quality of life in Malaysian outpatients with HIV.Methods:HIV patients (n=120) on highly active antiretroviral therapy (HAART) in the infectious disease clinic of Hospital Sungai Buloh were randomized to either FDC (n=60) or FRC (n=60). Morisky scores, health-related quality of life scores and clinical outcomes such as CD4 count and viral load were assessed in both groups at baseline and six months.Result:Patients on FDC (108 SD=1.1) had a significantly higher CD4 count increase compared to the FRC group (746.1 SD=36.3 vs 799.8 SD=33.8) (p <0.001). The viral load profile was unchanged and remained undetectable in both groups. The quality of life EQ-5D scores showed a positive correlation with CD4 counts in the FDC group (ρ=0.301, p=0.019) at six months. On the other hand, quality of life EQ-VAS scores was significantly associated with medication adherence in the FDC group at six months (ρ=0.749, p=0.05). However, no significant changes or associations were observed in the FRC group.Conclusion:Management of HAART using an FDC demonstrated a positive clinical outcome, adherence and quality of life within six months in local HIV patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Simplification of HAART therapy on ambulatory HIV patients in Malaysia: a randomized controlled trial

Velvanathan

Islahudin

Sim

et al. 2016

Pharm Pract (Granada)

View full text Add to dashboard Cite

show abstract

“…Single-tablet regimens (STRs) represent a significant advance in the management of HIV infection through simplifying ART, limiting the impact of therapy on daily life, and improving patient adherence to all components of their antiretroviral regimen [3]. …”

Section: Introductionmentioning

confidence: 99%

Real-World Assessment of Renal and Bone Safety among Patients with HIV Infection Exposed to Tenofovir Disoproxil Fumarate-Containing Single-Tablet Regimens

et al. 2016

View full text Add to dashboard Cite

ObjectivesTenofovir disoproxil fumarate (TDF)-containing antiretroviral regimens have been associated with an increased incidence of renal and bone adverse outcomes. Here, we estimated the real-world incidence of renal and bone adverse outcomes among patients with HIV infection receiving different TDF-containing single-tablet regimens (STRs).MethodsThis cohort study used US health insurance data spanning the years 2008–2014. We identified HIV-infected patients aged ≥18 years (all HIV patients) and those with ≥6 months of continuous enrollment prior to initiating efavirenz/emtricitabine/TDF (EFV/FTC/TDF), rilpivirine/FTC/TDF (RPV/FTC/TDF) or elvitegravir/cobicistat/FTC/TDF (EVG/COBI/FTC/TDF). Renal adverse outcomes were identified using renal International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes. Bone adverse outcomes were identified using ICD-9-CM diagnosis codes for fracture. Incidence rates (IRs) and associated 95% confidence intervals (CIs) were estimated assuming a Poisson distribution, and outcomes between STRs were compared using IR ratios (IRRs) and IR differences (IRDs).ResultsWe identified 9876 and 10,383 eligible patients for the renal and fracture analyses, respectively. Observed IRs for renal adverse outcomes were 9.7, 10.5, 13.6, and 18.0 per 1000 person-years among those receiving EFV/FTC/TDF, RPV/FTC/TDF, or EVG/COBI/FTC/TDF, or all HIV patients, respectively. Corresponding values for IRs of fracture were 3.4, 3.6, 7.2, and 4.4 per 1000 person-years, respectively. Renal adverse outcomes with EFV/FTC/TDF were significantly less frequent than with EVG/COBI/FTC/TDF (IRD −3.96; 95% CI: −7.31, −1.06). No IRR differences were identified for the renal analysis. Fractures with EFV/FTC/TDF were significantly less frequent than with EVG/COBI/FTC/TDF (IRR 0.47; 95% CI: 0.27, 0.81 and IRD −3.85; 95% CI: −5.02, −2.78).ConclusionsIn this large real-world database, observed IRs for renal adverse outcomes with TDF-containing STRs were lower or similar to those for all HIV patients, with the lowest IRs observed among patients receiving EFV/FTC/TDF. Compared with all HIV patients, the observed IR for fracture was higher with EVG/COBI/FTC/TDF, comparable with RPV/FTC/TDF, and lower with EFV/FTC/TDF.

show abstract

“…T he availability of efficacious and well-tolerated antiretroviral agents and their coformulation into a single-tablet regimen (STR) for convenient dosing have transformed the treatment landscape and rendered HIV into a manageable disease (1). Indeed, several STRs have been approved for HIV treatment, including efavirenz (EFV)-emtricitabine (FTC)-tenofovir disoproxil fumarate (TDF), rilpivirine (RPV)-FTC-TDF, elvitegravir (EVG)-cobicistat (COBI)-FTC-TDF, and, recently, abacavir (ABC)-dolutegravir (DTG)-lamivudine (3TC).…”

mentioning

confidence: 99%

Pharmacokinetics and Safety of Tenofovir Alafenamide in HIV-Uninfected Subjects with Severe Renal Impairment

Custodio

Fordyce

Garner

et al. 2016

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Tenofovir alafenamide (TAF) is an oral prodrug of tenofovir (TFV) that has greater stability in plasma than TFV disoproxil fumarate (TDF) and circulates as intact TAF, resulting in the direct and higher lymphatic loading of and exposure to TFV diphosphate, the active moiety. Unlike TFV, TAF is minimally eliminated in urine. The pharmacokinetics (PK) of TAF and TFV in HIVuninfected subjects with severe renal impairment and matched healthy controls were evaluated. Subjects with severe renal impairment (RI; estimated glomerular filtration rate [eGFR], 15 to 29 ml/min) and controls (eGFR, >90 ml/min) matched for age, gender, and body mass index received a single dose of TAF at 25 mg. Blood and urine samples for TAF and TFV PK determinations were collected over 7 days postdosing, and subjects were followed up at 14 days. A total of 14 renally impaired subjects and 13 control subjects enrolled and completed the study. The TAF maximum observed concentration in plasma (C max ) and the area under the concentration-versus-time curve (AUC) extrapolated to infinite time (AUC inf ) were 79% and 92% higher, respectively, in subjects with severe RI than the controls, primarily due to higher absorption. The TFV C max and AUC inf were 2.8-fold and 5.7-fold higher, respectively, in subjects with severe RI than the controls. In subjects with severe RI, TAF at 25 mg provided a TFV AUC 10 to 40% lower than that from historical TDF-based TFV exposures in subjects with normal renal function. There were no discontinuations due to adverse events. In subjects with severe RI receiving TAF at 25 mg, TAF exposures were higher than those for the controls; these differences are unlikely to be clinically meaningful. TFV exposures were higher than those for the controls but lower than the exposures in nonrenally impaired subjects on TDF-based regimens.T he availability of efficacious and well-tolerated antiretroviral agents and their coformulation into a single-tablet regimen (STR) for convenient dosing have transformed the treatment landscape and rendered HIV into a manageable disease (1). Indeed, several STRs have been approved for HIV treatment, including efavirenz (EFV)-emtricitabine (FTC)-tenofovir disoproxil fumarate (TDF), rilpivirine (RPV)-FTC-TDF, elvitegravir (EVG)-cobicistat (COBI)-FTC-TDF, and, recently, abacavir (ABC)-dolutegravir (DTG)-lamivudine (3TC). Although STRs have been beneficial to a large number of HIV-infected patients, their use in special populations, such as those with end-organ dysfunction, has been limited due to the inability to alter the dose and the discordance in the doses of the various components with the different routes of elimination needed. Specifically, one or more components of the STRs mentioned above are predominantly if not exclusively renally eliminated [i.e., the nucleos(t)ide reverse transcriptase inhibitors TDF, FTC, and 3TC], necessitating dose reductions in patients with certain levels of renal impairment that is incompatible with fixed-dose-strength STR dosage forms. Therefore, patients with m...

show abstract

Single-Tablet Regimens in HIV Therapy

Cited by 53 publications

References 50 publications

Simplification of HAART therapy on ambulatory HIV patients in Malaysia: a randomized controlled trial

Simplification of HAART therapy on ambulatory HIV patients in Malaysia: a randomized controlled trial

Real-World Assessment of Renal and Bone Safety among Patients with HIV Infection Exposed to Tenofovir Disoproxil Fumarate-Containing Single-Tablet Regimens

Pharmacokinetics and Safety of Tenofovir Alafenamide in HIV-Uninfected Subjects with Severe Renal Impairment

Contact Info

Product

Resources

About