Long-term Durability of Nevirapine, Efavirenz and Lopinavir
Objectives The durability of combination antiretroviral therapy (cART) regimens can be measured as time to discontinuation because of toxicity or treatment failure, development of clinical disease or serious long-term adverse events. The aim of this analysis was to compare the durability of nevirapine, efavirenz and lopinavir regimens based on these measures.
Methods Patients starting a nevirapine, efavirenz or lopinavir-based cART regimen for the first time after 1 January 2000 were included in the analysis. Follow-up started ≥3 months after initiation of treatment if viral load was <500 HIV-1 RNA copies/mL. Durability was measured as discontinuation rate or development/worsening of clinical markers.
Results A total of 603 patients (21%) started nevirapine-based cART, 1465 (51%) efavirenz, and 818 (28%) lopinavir. After adjustment there was no significant difference in the risk of discontinuation for any reason between the groups on nevirapine and efavirenz (P=0.43) or lopinavir (P=0.13). Compared with the nevirapine group, those on efavirenz had a 48% (P=0.0002) and those on lopinavir a 63% (P<0.0001) lower risk of discontinuation because of treatment failure and a 31% (P=0.01) and 66% (P<.0001) higher risk, respectively, of discontinuation because of toxicities or patient/physician choice. There were no significant differences in the incidence of non-AIDS-related events, worsening anaemia, severe weight loss, increased aspartate aminotransferase (AST)/alanine aminotransferase (ALT) levels or increased total cholesterol. Compared with patients on nevirapine, those on lopinavir had an 80% higher incidence of high-density lipoprotein (HDL) cholesterol decreasing below 0.9 mmol/L (P=0.003), but there was no significant difference in this variable between those on nevirapine and those on efavirenz (P=0.39).
Conclusions The long-term durability of nevirapine-based cART, based on risk of all-cause discontinuation and development of long-term adverse events, was comparable to that of efavirenz or lopinavir, in patients in routine clinical practice across Europe who initially tolerated and virologically responded to their regimen.
Choosing an antiretroviral treatment regimen for patients requires consideration of a number of factors, including comorbidities, likely adherence, convenience, adverse events and the potential for drug interactions with other treatments. Adverse effects have been reported with all antiretrovirals and are one of the most common reasons for discontinuation of treatment. Some adverse events, such as gastrointestinal problems and hypersensitivity, occur rapidly, within the first few months of starting treatment, while other adverse events, such as cardiovascular disease and pancreatitis, can take much longer to develop. Such long-term adverse events can influence the durability of a regimen.
Combination antiretroviral therapy (cART) regimens most often include a nonnucleoside reverse transcriptase inhibitor, such as efavirenz or nevirapine, or a ritonavir-boosted protease inhibitor, such as lopinavir. cART regimens with durability as well as virological efficacy are required in order to achieve long-term virological suppression and to maintain CD4 cell counts at a level that significantly reduces the risk of morbidity and mortality. Many cohort studies have compared the short-term and long-term efficacies of different cART regimens, but less is known about the durability of different regimens, particularly in patients who have started a cART regimen more recently. If a regimen is virologically effective, durability can then be measured as the time to discontinuation of the regimen because of treatment failure or toxicity, or the rate at which changes occur in potential markers of toxicity, such as liver transaminases and cholesterol.
The aim of the study was therefore to compare the long-term durability of nevirapine-based cART regimens with those of efavirenz- or lopinavir-based cART regimens based on the time to discontinuation and the development of any serious clinical adverse events once virological suppression had been achieved and after at least 3 months on the drug to exclude discontinuations because of early-onset potentially treatment-limiting toxicities that each of the three drugs may cause.
Abstract and Introduction
Abstract
Objectives The durability of combination antiretroviral therapy (cART) regimens can be measured as time to discontinuation because of toxicity or treatment failure, development of clinical disease or serious long-term adverse events. The aim of this analysis was to compare the durability of nevirapine, efavirenz and lopinavir regimens based on these measures.
Methods Patients starting a nevirapine, efavirenz or lopinavir-based cART regimen for the first time after 1 January 2000 were included in the analysis. Follow-up started ≥3 months after initiation of treatment if viral load was <500 HIV-1 RNA copies/mL. Durability was measured as discontinuation rate or development/worsening of clinical markers.
Results A total of 603 patients (21%) started nevirapine-based cART, 1465 (51%) efavirenz, and 818 (28%) lopinavir. After adjustment there was no significant difference in the risk of discontinuation for any reason between the groups on nevirapine and efavirenz (P=0.43) or lopinavir (P=0.13). Compared with the nevirapine group, those on efavirenz had a 48% (P=0.0002) and those on lopinavir a 63% (P<0.0001) lower risk of discontinuation because of treatment failure and a 31% (P=0.01) and 66% (P<.0001) higher risk, respectively, of discontinuation because of toxicities or patient/physician choice. There were no significant differences in the incidence of non-AIDS-related events, worsening anaemia, severe weight loss, increased aspartate aminotransferase (AST)/alanine aminotransferase (ALT) levels or increased total cholesterol. Compared with patients on nevirapine, those on lopinavir had an 80% higher incidence of high-density lipoprotein (HDL) cholesterol decreasing below 0.9 mmol/L (P=0.003), but there was no significant difference in this variable between those on nevirapine and those on efavirenz (P=0.39).
Conclusions The long-term durability of nevirapine-based cART, based on risk of all-cause discontinuation and development of long-term adverse events, was comparable to that of efavirenz or lopinavir, in patients in routine clinical practice across Europe who initially tolerated and virologically responded to their regimen.
Introduction
Choosing an antiretroviral treatment regimen for patients requires consideration of a number of factors, including comorbidities, likely adherence, convenience, adverse events and the potential for drug interactions with other treatments. Adverse effects have been reported with all antiretrovirals and are one of the most common reasons for discontinuation of treatment. Some adverse events, such as gastrointestinal problems and hypersensitivity, occur rapidly, within the first few months of starting treatment, while other adverse events, such as cardiovascular disease and pancreatitis, can take much longer to develop. Such long-term adverse events can influence the durability of a regimen.
Combination antiretroviral therapy (cART) regimens most often include a nonnucleoside reverse transcriptase inhibitor, such as efavirenz or nevirapine, or a ritonavir-boosted protease inhibitor, such as lopinavir. cART regimens with durability as well as virological efficacy are required in order to achieve long-term virological suppression and to maintain CD4 cell counts at a level that significantly reduces the risk of morbidity and mortality. Many cohort studies have compared the short-term and long-term efficacies of different cART regimens, but less is known about the durability of different regimens, particularly in patients who have started a cART regimen more recently. If a regimen is virologically effective, durability can then be measured as the time to discontinuation of the regimen because of treatment failure or toxicity, or the rate at which changes occur in potential markers of toxicity, such as liver transaminases and cholesterol.
The aim of the study was therefore to compare the long-term durability of nevirapine-based cART regimens with those of efavirenz- or lopinavir-based cART regimens based on the time to discontinuation and the development of any serious clinical adverse events once virological suppression had been achieved and after at least 3 months on the drug to exclude discontinuations because of early-onset potentially treatment-limiting toxicities that each of the three drugs may cause.
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