Effectiveness of Once-Daily ART vs a Triple-Tablet Regimen
Effectiveness of Once-Daily ART vs a Triple-Tablet Regimen
Background: To assess the impact on virological outcomes of a switch from branded single-tablet regimen (STR) including tenofovir, efavirenz, and emtricitabine (STR-TEE) to generic triple-tablet regimen (TTR), including tenofovir, efavirenz, and lamivudine (TTR-TEL), which was implemented on April 1, 2011 to obtain economic savings.
Methods and Findings: From the Capital Region of Denmark (covering two-thirds of the Danish HIV patients), we included combination antiretroviral therapy (cART)–naive patients who administered STR-TEE from April 1, 2010 to March 31, 2011 (n = 111) or TTR-TEL from April 1, 2011 to March 31, 2012 (n = 56) and cART-experienced HIV patients who were on STR-TEE from April 1, 2010 (n = 356) or were switched from STR-TEE to TTR-TEL after April 1, 2011 (n = 512). We estimated the fraction with detectable HIV-RNA, development of the 184V/I resistance mutations, and time to switch of cART. Approximately 96.2% of cART-experienced patients on STR-TEE were shifted to TTR-TEL after April 1, 2011. For the naive STR-TEE and TTR-TEL patients, the fractions with detectable HIV-RNA at week 48 were 7.0% and 8.3% and for the cART experienced 4.0% and 4.4%, respectively. The 184V/I resistance mutation was detected in 1 cART-experienced patient on TTR-TEL with virological failure. The risk of switch to a new cART regimen was slightly increased in the cART-experienced population (difference in 1-year risk: 1.5%; 95% confidence interval: −2.4% to 5.4%).
Conclusions: In settings comparable with the Danish health care system, the estimated economic savings from a switch from STR-TEE to TTR-TEL can be realized with negligible short-term risk of adverse outcomes.
Most modern combination antiretroviral therapies (cARTs) include 3 drugs from at least 2 drug classes and therefore the regimens often are triple-tablet regimens (TTR). Good adherence to cART is among the key determinants of successful HIV treatment and is essential to minimize virological failure and emergence of drug resistance. Reducing the pill burden by combining different drugs into fewer pills in fixed-dose combinations has been widely introduced into clinical practice to address this problem. Of importance, fixed-dose combinations reduce the potential for selective noncompliance and thus decrease the risk of development of virological resistance. Tenofovir, efavirenz, and emtricitabine have proved to be an efficient first-line cART regimen. The first once-daily single-tablet regimen (STR) including tenofovir, efavirenz, and emtricitabin (STR-TEE) (Atripla; Gilead Sciences Inc, Foster City, CA, and Bristol-Myers Squibb, New York City, NY), was approved in the US in 2006. Despite the fact that STR-TEE is not licensed in Europe for use in cART-naive patients, it is included in international recommendations and Danish national guidelines for initial cART.
In a mathematical simulation, Walensky et al recently demonstrated that a switch from STR to TTR in the United States would initially yield annual savings of $920 million. The saving may however be a tradeoff in terms of a potential risk of decreased adherence, which may lead to virological failure and poor outcome. However, few clinical data support the effectiveness of STR versus TTR.
To obtain economic savings, HIV-infected patients in the Capital Region of Denmark in treatment with STR-TEE were switched from April 1, 2011 to a cheaper TTR including tenofovir, efavirenz, and lamivudine (TTR-TEL) and also cART-naive patients eligible for STR-TEE were started on TTR-TEL. We aimed to estimate the impact of the switch to TTR-TEL on antiretroviral effectiveness.
Abstract and Introduction
Abstract
Background: To assess the impact on virological outcomes of a switch from branded single-tablet regimen (STR) including tenofovir, efavirenz, and emtricitabine (STR-TEE) to generic triple-tablet regimen (TTR), including tenofovir, efavirenz, and lamivudine (TTR-TEL), which was implemented on April 1, 2011 to obtain economic savings.
Methods and Findings: From the Capital Region of Denmark (covering two-thirds of the Danish HIV patients), we included combination antiretroviral therapy (cART)–naive patients who administered STR-TEE from April 1, 2010 to March 31, 2011 (n = 111) or TTR-TEL from April 1, 2011 to March 31, 2012 (n = 56) and cART-experienced HIV patients who were on STR-TEE from April 1, 2010 (n = 356) or were switched from STR-TEE to TTR-TEL after April 1, 2011 (n = 512). We estimated the fraction with detectable HIV-RNA, development of the 184V/I resistance mutations, and time to switch of cART. Approximately 96.2% of cART-experienced patients on STR-TEE were shifted to TTR-TEL after April 1, 2011. For the naive STR-TEE and TTR-TEL patients, the fractions with detectable HIV-RNA at week 48 were 7.0% and 8.3% and for the cART experienced 4.0% and 4.4%, respectively. The 184V/I resistance mutation was detected in 1 cART-experienced patient on TTR-TEL with virological failure. The risk of switch to a new cART regimen was slightly increased in the cART-experienced population (difference in 1-year risk: 1.5%; 95% confidence interval: −2.4% to 5.4%).
Conclusions: In settings comparable with the Danish health care system, the estimated economic savings from a switch from STR-TEE to TTR-TEL can be realized with negligible short-term risk of adverse outcomes.
Introduction
Most modern combination antiretroviral therapies (cARTs) include 3 drugs from at least 2 drug classes and therefore the regimens often are triple-tablet regimens (TTR). Good adherence to cART is among the key determinants of successful HIV treatment and is essential to minimize virological failure and emergence of drug resistance. Reducing the pill burden by combining different drugs into fewer pills in fixed-dose combinations has been widely introduced into clinical practice to address this problem. Of importance, fixed-dose combinations reduce the potential for selective noncompliance and thus decrease the risk of development of virological resistance. Tenofovir, efavirenz, and emtricitabine have proved to be an efficient first-line cART regimen. The first once-daily single-tablet regimen (STR) including tenofovir, efavirenz, and emtricitabin (STR-TEE) (Atripla; Gilead Sciences Inc, Foster City, CA, and Bristol-Myers Squibb, New York City, NY), was approved in the US in 2006. Despite the fact that STR-TEE is not licensed in Europe for use in cART-naive patients, it is included in international recommendations and Danish national guidelines for initial cART.
In a mathematical simulation, Walensky et al recently demonstrated that a switch from STR to TTR in the United States would initially yield annual savings of $920 million. The saving may however be a tradeoff in terms of a potential risk of decreased adherence, which may lead to virological failure and poor outcome. However, few clinical data support the effectiveness of STR versus TTR.
To obtain economic savings, HIV-infected patients in the Capital Region of Denmark in treatment with STR-TEE were switched from April 1, 2011 to a cheaper TTR including tenofovir, efavirenz, and lamivudine (TTR-TEL) and also cART-naive patients eligible for STR-TEE were started on TTR-TEL. We aimed to estimate the impact of the switch to TTR-TEL on antiretroviral effectiveness.