Real world reassurance about a misperception
By Dean L. Winslow, MD, FACP, FIDSA, Chief, Division of AIDS Medicine, Santa Clara Valley Medical Center; Clinical Professor, Stanford University, School of Medicine. Dr. Winslow serves as a consultant for Siemens Diagnostics, and is on the speaker's bureau for Boehringer-Ingelheim and GSK.
Synopsis: From January 1996 until May 2007 all patients in the Swiss HIV Cohort initiating their first combination antiretroviral therapy (cART) regimen, who had baseline CD4+ T-cell counts and HIV RNA levels, were included in the analysis. Of the patients, 2590 (78.7%) initiated a non-boosted protease inhibitor (PI) regimen, 452 (13.7%) initiated a nnRTI regimen, and 251 (7.6%) initiated a ritonavir-boosted PI regimen. CD4+ recovery was similar across all three groups.
Source: Khanna N, et al. CD4+ T cell count recovery in HIV type 1-infected patients is independent of class of antiretroviral therapy. Clin Infect Dis. 2008;47:1093-1101.
Patients enrolled in the Swiss HIV cohort study, initiating their first cART regimen between 1996 and early 2007, who had baseline and follow up CD4+ count and HIV RNA data available, were included in the analysis. Baseline characteristics of the patients across the three treatment groups were comparable, with the exception of lower baseline CD4 counts (168/uL) in the boosted PI group vs. 201/uL in the non-boosted PI group and 220/uL in the nnRTI group. Using a primary endpoint of absolute increase in CD4 count from baseline in the three groups, the data were analyzed using a Cox proportional hazards model.
Baseline determinants of CD4 count changes, which were found to be statistically significant after adjusted analysis, included age, prior antiretroviral treatment, HCV infection, baseline HIV RNA level, and prior AZT therapy (all negatively associated with response), and baseline CD4 count (positively associated with response). In the non-boosted PI group, CD4 increased from a median 210 to 520 cells/uL at 48 months, from a median 220 to 475 cells/uL in the nnRTI group, and from 168 to 511 in the boosted PI group. The increase in CD4 count of the three groups was not statistically significantly different. A statistically significant decrease in HIV RNA was achieved in all treatment groups after six months. HIV RNA levels decreased more rapidly in the nnRTI and boosted PI groups than in the non-boosted PI group. Virologic failure occurred in 28.7% of patients treated with non-boosted PI regimens and less frequently in the other two groups (nnRTI 11.1% and boosted PI 10.0%).
Some (but not all) studies comparing ART regimens in treatment-naïve patients have found smaller increases in CD4 counts in patient treated with nnRTI-based ART. This concern has, in some circles, become almost a matter of dogma, despite the fact that four large studies comparing nnRTI and PI-based cART found comparable CD4 responses.1-4 While this study is limited by the factors inherent to all observational cohort studies, the numbers are robust, and should reassure clinicians that in the "real world" setting there is no inherent immunological advantage of boosted PI over nnRTI regimens. Another common misperception of HIV-treating physicians is that PI regimens have superior virologic efficacy to nnRTI regimens in patients with high baseline viral loads. Similarly, this is not supported by clinical trial data.
- AVANTI and INCAS Study Groups. Highly active antiretroviral therapy including protease inhibitors does not confer a unique CD4 cell benefit. AIDS. 2000; 14:1383-1388.
- Podzamczer D, et al. A randomized clinical trial comparing nelfinavir or nevirapine associated to zidovudine/lamivudine in HIV-infected naïve patients (the Combine Study). Antivir Ther. 2002;7:81-90.
- Friedl AC, et al. Response to first protease inhibitor- and efavirenz-containing antiretroviral combination therapy. The Swiss HIV Cohort Study. AIDS. 2001;15:1793-1800.
- MacArthur RD, et al. A comparison of three highly active antiretroviral treatment strategies consisting of non-nucleoside reverse transcriptase inhibitors, protease inhibitors, or both in the presence of nucleoside reverse transcriptase inhibitors as initial therapy (CPCRA 058 FIRST Study): a long-term randomized trial. Lancet. 2006;368:2125-2135.