First-line antiretroviral therapy is just as effective in routine clinical care as in randomised controlled trials, investigators report in the online edition of the Journal of Acquired Immune Deficiency Syndromes.
The researchers compared virological and clinical outcomes between patients in AIDS Clinical Trial Group (ACTG) trials and individuals being monitored in the international Antiretroviral Therapy Cohort Collaboration (ART-CC).
“Our finding that ART regimen differences in the ACTG clinical trials correlated with the routine care setting of ART-CC suggests the generalizability of the results and provides an important link between clinical trials and their applicability to a broader patient population,” comment the authors.
Randomised controlled trials are the cornerstone of evidence-based medicine, and their results help shape HIV treatment guidelines.
However, such studies have stringent inclusion criteria. Moreover, patients enrolled in studies receive more intensive monitoring and support than that available in routine care. There is therefore some concern that the often-impressive results seen in randomised controlled trials may not be translated to general clinical settings.
Because of these reservations, investigators compared outcomes between patients who started several treatment regimens when enrolled in two large ACTG studies and those achieved by individuals taking the same combinations of drugs in the ART-CC.
“To our knowledge,” write the authors, “this is the first large-scale regimen level comparison of contemporary ART regimens among patients receiving treatment through clinical trials v. routine care.”
The ACTG trials included in the analysis were the 5095 study, which compared first-line therapy consisting of abacavir, AZT, 3TC against efavirenz, AZT, 3TC, and the 5142 study, which compared regimens based on efavirenz with those based on lopinavir/ritonavir.
The proportion of patients in these studies achieving an undetectable viral load at weeks 24 and 48 were compared to outcomes seen in the ART-CC study. The investigators also compared rates of progression to AIDS and the risk of mortality.
Baseline characteristics between the ACTG and ART-CC patients were broadly comparable. However, individuals followed in routine care were somewhat more likely than those in clinical trials to be women.
Adjusted analysis showed that patients in the 5095 study who received efavirenz had approximately half the risk of virological failure compared to those who received abacavir (OR = 5.3; 95% CI, 0.36-0.79). Efavirenz has the same level of superiority over abacavir in routine care (OR = 0.46; 95% CI, 0.37-0.57).
Regimens based on efavirenz or lopinavir/ritonavir were also found to have the same level of virological efficacy in clinical trials as in clinical practice (adjusted 48-week risk of failure, 0.97; 95% CI, 0.71-1.00 vs. 0.87; 95% CI, 0.45-1.69).
The clinical outcomes seen in clinical trials were also broadly comparable to those achieved in routine care.
Patients receiving efavirenz had lower rates of AIDS and death in both the 5095 trial and the ART-CC (OR = 0.60; 95% CI, 0.26-1.41 vs. 0.73; 95% CI, 0.54-0.99).
Rates of AIDS and death were similar for efavirenz and lopinavir/ritonavir in the ACTG study and routine clinical care (OR = 0.95; 95% CI, 0.40-2.30 vs. 0.88; 95% CI, 0.73-1.06).
Restricting analysis to the risk of death after 48 weeks also showed that regimens had similar efficacy in randomised studies and routine care.
“Among patients initiating antiretroviral therapy for HIV infection,” write the investigators, “differences in virologic and clinical effectiveness between ART regimens compared in the ACTG 5095 and ACTG 5142 were similar to observed differences when comparing identical regimens administered in routine care in the ART Cohort Collaboration.”
They conclude, “we believe our study provides pivotal new evidence demonstrating the comparative effectiveness of antiretroviral treatments evaluated in clinical trials and large cohort studies; this research will help inform ART treatment decisions for HIV-infected patients in routine clinical care.”
Mugavero, M et al. Comparative effectiveness of initial antiretroviral therapy regimens: ACTG 5095 and 5142 Clinical Trials relative to ART-CC Cohort Study. J Acquir Immune Defic Syndr, online edition, doi: 10.1097/QAI.0b013e318230372e (click here for the free abstract).