teaser
Christopher W James
PharmD
Clinical Pharmacy Specialist
HIV Community Program
Christiana Care Health Services
Susan Szabo
MD
Medical Director
HIV Community Program
Christiana Care Health Services
Wilmington, DE
USA
E:[email protected]
Currently available antiretroviral regimens are highly effective in suppressing viral load in patients with human immunodeficiency virus (HIV) infection. However, adherence poses barriers to maximal and durable virological suppression in many patients. Once-daily antiretro‑viral regimens are thought to surmount some of these barriers, by enhancing convenience and adherence. Ten antiretroviral agents or fixed-dose combination products are approved for once-daily administration by the Food and Drug Administration (FDA). Tenofovir/lamivudine/efavirenz is recommended as a preferred regimen by the United States Department of Health and Human Services treatment guidelines for adults and adolescents.(1) Lamivudine and efavirenz possess low genetic barriers to antiretroviral resistance.(2) However, when combined with tenofovir, stavudine or zidovudine in clinical trials, treatment failures with this combination are rare.(3,4) In this article, we evaluated immunological and virological outcomes, as well as the emergence of resistance, in patients receiving once-daily antiretroviral therapy consisting of tenofovir, lamivudine and efavirenz.
Methods
A chart review of patients who initiated tenofovir, lamivudine and efavirenz from 09/01/2001 to 05/04/2004 was conducted.
Results
Forty patients were identified during the study period, with a median follow-up of 582 days. Baseline characteristics for the study population are listed in Table 1. Of note, 24 patients (60%) received prior antiretroviral therapy. However, at the time of initiation of the study regimen, 17 patients (70.8%) had undetectable viral loads (<400 copies/ml).
[[HPE28_table1_77]]
Initial virological suppression (HIV RNA PCR <400 copies/ml) was achieved in 80% of patients (32/40). However, virological failure after initial suppression occurred in 75% of patients (24/32) at a median of 269 days (28–786 days). Resistance testing was attempted on 24 specimens (see Table 2).Of note, resistance to tenofovir, lamivudine or efavirenz was demonstrated in 50% of the specimens. Figure 1 illustrates that resistance occurred more frequently in patients with low baseline CD4+ counts (<100 cells/mm(3)). Interestingly, a significant number of specimens were unable to be quantified for resistance testing. For these patients, this likely reflects spurious HIV viraemia due to the use of plasma preparation tubes for sample collection during the study period.(5)
[[HPE28_table2_77]]
[[HPE28_fig1_78]]
At last follow-up, median CD4+ count and median HIV RNA PCR was 263 cells/mm(3) (10–808 cells/mm(3)) and 683 copies/ml (50–433,870 copies/ml), respectively. There were 18 treatment failures, resulting in abacavir intensification (eight patients), complete regimen change (six patients) or treatment discontinuation (four patients).
Discussion
Tenofovir, lamivudine and efavirenz offer a convenient regimen for the treatment of HIV infection. Clinical trials with this regimen (or emtricitabine in lieu of lamivudine) have demonstrated potency and durability in treatment-naive patients.(3,4) Although 60% of our patients received prior antiretroviral therapy, the majority of these were fully virologically suppressed at the time of initiation with tenofovir, lamivudine and efavirenz, thus indicating the absence of baseline treatment resistance. Our data indicate that resistance develops frequently (50% of patients) and relatively rapidly (median 269 days). This discrepancy may be related to more stringent selection criteria utilised in clinical trials, whereas adherence may pose a greater barrier for some individuals in the clinical setting. Suboptimal adherence and treatment interruptions may jeopardise the antiviral susceptibility of combinations with low genetic barriers to resistance, such as the regimen studied here. We further observed an increased rate of resistance for each component of this regimen in patients with low baseline CD4+ counts (<100 cells/mm(3)).
Therefore caution should be exercised when prescribing antiretroviral regimens with low genetic barriers to resistance, especially in patients with advanced HIV infection.
References
- Panel on Clinical Practices for Treatment of HIV Infection. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Washington, DC: Department of Health and Human Services; 2005. Available from: http://www.aidsinfo.nih.gov
- Luber AD. Genetic barriers to resistance and impact on clinical response. eJIAS: eJournal of the International AIDS Society Medscape General Medicine 2005;7(3):69. Available from: http://www.medscape.com
- Gallant JE, Staszewski S, Pozniak AL, et al. Efficacy and safety of tenofovir DF vs. stavudine in combination therapy in antiretroviral naïve patients: a 3-year randomized trial. JAMA 2004;292:191-201.
- Gallant JE, DeJesus E, Arribas JR, et al. Tenofovir DF, emtricitabine, and efavirenz vs. zidovudine,lamivudine, and efavirenz for HIV.N Engl J Med 2006;354:251-60.
- Stosor V, Palella FJ Jr, Berzins B,et al. Transient viremia in HIV-infected patients and use of plasma preparation tubes. Clin Infect Dis 2005;41:1671-4.
