September 15, 2003
This study looked at a large cohort of 1,119 antiretroviral-naive patients who started HAART therapy. These patients were from the U.S. (HOPS) or The Netherlands (ATHENA) and started treatment between 1999 and 2002.
Five commonly used drugs were compared:
The effectiveness of each medication as part of an initial regimen was determined by looking at the time it took for patients' HIV-RNA (viral load) to fall below 500 copies/mL and then also by noting these same patients' subsequent time to failure as defined by two consecutive HIV-RNA levels greater than 500 copies/mL.
The statistical methods used included a proportional hazards model adjusted for age, sex, risk group, country, previous NRTI use (one or two NRTIs), calendar year, baseline HIV-1 RNA and baseline CD4 cell counts.
In this cohort study, patients who were started on nevirapine or efavirenz were more likely to have higher CD4 cell counts and lower viral loads. This finding limits the strength of some of the findings below.
This study showed that patients commencing therapy with nevirapine, efavirenz or lopinavir/ritonavir were more likely than nelfinavir to achieve HIV-RNA levels lower than 500 copies. (The risk ratio compared to nelfinavir was 1.7, 1.8 and 1.7, respectively.)
Those on nevirapine and efavirenz were less likely to experience viral rebound above 500 copies, as compared to those on nelfinavir and indinavir/ritonavir. (The risk ratio compared to nelfinavir for nevirapine was 0.46, and for efavirenz it was 0.38.) Those on lopinavir/ritonavir had a trend towards a lower risk of viral rebound, but the small sample size limited analysis.
The conclusion of this study was that HAART regimens containing efavirenz, nevirapine and lopinavir/ritonavir appeared to be more effective in antiretroviral-naive patients than nelfinavir. This real-world observational study matches well with the multiple studies that have shown the superior outcomes of NNRTI-based therapy (efavirenz and nevirapine) compared to nelfinavir-based therapy.
The recent DHHS HIV treatment guidelines also reflect previous research demonstrating the inferior results of unboosted protease inhibitors for the treatment of HIV infection.
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