A comparison of the long-term durability of nevirapine, efavirenz and lopinavir in routine clinical practice in Europe: a EuroSIDA study

Abstract

ObjectivesThe 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. MethodsPatients 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 o500 HIV-1 RNA copies/mL. Durability was measured as discontinuation rate or development/worsening of clinical markers. ResultsA 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 5 0.43) or lopinavir (P 5 0.13). Compared with the nevirapine group, those on efavirenz had a 48% (P 5 0.0002) and those on lopinavir a 63% (Po0.0001) lower risk of discontinuation because of treatment failure and a 31% (P 5 0.01) and 66% (Po.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 5 0.003), but there was no significant difference in this variable between those on nevirapine and those on efavirenz (P 5 0.39). ConclusionsThe 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. [5][6][7]. 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 ritonavirboosted protease inhibitor, such as lopinavir [8,9]. 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 [10][11][12][13][14], 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 discontinuat...

Nevirapine-Based Regimens in HIV-Infected Antiretroviral-Naive Patients: Systematic Review and Meta-Analysis of Randomized Controlled Trials

“…On the other hand, a prospective, observational trial involving more than 20 000 patients showed a lower incidence of death and AIDS-defining illness, as well as lower risk of virologic failure at 12 months for efavirenz compared with nevirapine [39]. Results obtained in routine clinical practice in Europe also showed that patients starting efavirenz had a 48% lower risk of discontinuation due to treatment failure compared with the nevirapine group (however, in this trial about 60% of patients were treatment-experienced) [40]. …”

Enhanced Eryptosis Following Exposure to Lopinavir

“…The concentrations required for the effect are well in the range of plasma concentrations determined in patients under lopinavir treatment [61]. The observed eryptosis and hemolysis may thus well explain the anemia following lopinavir treatment [14].…”

“…Side effects of lopinavir treatment include anemia [14]. Lopinavir may induce proteotoxic stress [15,16], trigger oxidative stress [16], and suppress NF-κB activity [17].…”

Antiretroviral therapy in Indian setting: When & what to start with, when & what to switch to?

“…An non nucleoside reverse transcriptase inhibitor (NNRTI) based regimen is preferred over protease inhibitors (PI/r) based regimens considering similar potency, convenience, lesser expense and lower prevalence of primary resistance in the population53–55. Efavirenz (EFV) is preferred over nevirapine (NVP) when concomitant use of rifampicin is indicated, patients preference for once daily (lower pill burden) regimen and if pre-therapy CD4 count is >250/mm 3 and >400/mm 3 in women and men respectively56–60.…”