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How Do Different Treatment Strategies Compare?

A comprehensive review of prospective clinical trials and an analysis of a large clinical cohort provide estimates of the effectiveness of various antiretroviral regimens.

Current treatment guidelines by the USPHS and International AIDS Society-USA list multiple combination regimens among the treatment options for HIV-infected patients. These 2 studies -- one a systematic overview of multiple clinical trials and the other a large observational cohort of patients receiving various regimens -- offer important insights into the relative strengths of different treatment strategies.

Bartlett and colleagues searched MEDLINE and reviewed package-insert data and proceedings of the major HIV conferences for all triple-combination therapy clinical trials published or presented between July 1994 and February 2000. Studies were included for review if they had at least 30 antiretroviral-naive treatment subjects. Twenty-three trials involving 3257 patients satisfied the inclusion criteria. The mean baseline viral load and CD4 count of participants were 49,329 copies/ml and 375 cells/mm³, respectively. At week 24, 64% of patients had viral loads less than 400 copies/ml and 54% had less than 50 copies/ml. Although few significant differences were found among PI-, NNRTI-, or triple-NRTI based regimens, the treatment strategies that involved the lowest pill burden were associated with an increased likelihood of virologic suppression. Of note, when efavirenz-containing regimens were excluded from the analysis, patients receiving NNRTI-based therapies achieved viral loads less than 50 copies/ml at a rate of only 38%.

Lucas and colleagues reviewed the effectiveness of NRTI-based regimens combined with a single PI, ritonavir/saquinavir (RTV/SQV), or efavirenz in an urban clinic from February 1996 to May 2000. Patients were included in the analysis if they were starting a regimen consisting of at least 3 antiretroviral drugs (including at least 1 new NRTI) and were PI- and NNRTI-naive. Those who used hard-gel saquinavir were excluded from the analysis. Data were extracted from the Johns Hopkins observational clinical database, which collects information on patients at 6-month intervals.

Data on 545 patients were included; 416 received a single PI, 68 received RTV/SQV (both agents dosed at 400 mg twice daily), and 61 received efavirenz. At baseline, a higher proportion of the efavirenz group was antiretroviral naive compared with the other groups, and the RTV/SQV group had a higher viral load and a lower CD4-cell count than the single-PI group. By intent-to-treat analysis, 72% of the efavirenz group achieved virologic suppression, compared with 49% of the PI and 51% of the RTV/SQV groups, a significant difference. After adjusting for multiple factors by logistic regression modeling, efavirenz therapy was still significantly associated with virologic suppression (odds ratio, 2.7; 95% confidence interval, 1.1-6.7). There was no difference among the 3 groups in time to virologic rebound among patients who initially achieved a viral load less than 400 copies/ml.

The major potential limitation of the Johns Hopkins study is that the patients were not randomized to different treatment strategies and thus may have differed in important ways unaccounted for in the statistical analyses. In addition, because efavirenz-treated patients were generally started on therapy later in the study period compared with patients receiving other regimens, it is possible that increased expertise in prescribing and monitoring antiretroviral therapy accounted for some advantages of this drug. A limitation of both studies is that neither included the most recently approved drug in the PI class -- lopinavir/ritonavir -- which in prospective studies appears to be more effective than the PIs used here. Despite these limitations, the results of these 2 studies provide further support for the excellent virologic efficacy of efavirenz-containing regimens.

— Paul E. Sax, MD

Dr. Sax is Research Notes Editor of ACC.

Published in Journal Watch HIV/AIDS Clinical Care November 1, 2001

Citation(s):

Bartlett JA et al. Overview of the effectiveness of triple combination therapy in antiretroviral-naive HIV-1 infected adults. AIDS 2001 Jul 27; 15:1369-77.

• Medline abstract (Free)

Lucas GM et al. Comparison of initial combination antiretroviral therapy with a single protease inhibitor, ritonavir and saquinavir, or efavirenz. AIDS 2001 Sep 7; 15:1679-86.

• Medline abstract (Free)

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