August 15, 2006
Timothy Sterling and colleagues conducted a retrospective study that combined data from two clinics, the Johns Hopkins HIV Clinic in Baltimore, Md., and the Comprehensive Care Center in Nashville, Tenn., to determine whether HIV regimens that included efavirenz (EFV, Sustiva, Stocrin) or a ritonavir (RTV, Norvir)-boosted protease inhibitor (PI) regimen differed in terms of the number of AIDS-defining events or death rates.1
Included in the study were those patients who started their first highly active antiretroviral therapy (HAART) regimen between June 1, 1998 to April 1, 2005. HAART in this study was defined as two nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) plus either efavirenz or a ritonavir-boosted PI. Patients receiving only ritonavir or ritonavir and saquinavir (SQV, Fortovase, Invirase) were excluded. Patients had to have been in care for at least 90 days and had to have had more than 30 days of a HAART regimen. HIV disease progression was defined as a new AIDS-defining event or death. Durable virologic suppression was defined as two successive viral load values over 400 copies/mL.
Analyses were performed using a multivariable Cox proportional hazards model, log rank for Kaplan-Meier survival analyses, Wilcoxon rank-sum test for analysis of continuous variables, and Chi square and Fisher's exact test for analysis of categorical variables.
Nine hundred twenty-nine patients (650 on efavirenz and 279 on a boosted PI) were included in the study. The demographic data that was presented indicated that 57% were from the Johns Hopkins HIV Clinic and 43% from the Nashville clinic; 27% were female, 61% black, and 28% were injection drug users. The median baseline CD4+ cell count and viral load were 148 cells/mm3 (13%) and 53,588 copies/mL, respectively. The median treatment duration was 54 weeks and the median follow-up was 83 weeks. Durable virologic suppression in the entire cohort was 48%, in the efavirenz arm it was 52% and in the boosted-PI arm it was 36% (P < .001). Those on efavirenz-containing regimens had slightly, but significantly, higher median baseline CD4+ cell counts (160 versus 123), lower viral loads (51,000 versus 72,391), and significantly longer duration of treatment (69 versus 36 weeks) and follow-up (104 versus 54 weeks). There were a total of 116 deaths and 86 AIDS-defining events. There was no significant difference in events between efavirenz and boosted-PI regimens.
Predictors of disease progression regardless of regimen included those patients who initiated treatment with a baseline CD4+ cell count of less than 200; a CD4% of less than 13%, even if the CD4+ cell count was more than 350; injection drug use; and treatment duration. A baseline viral load of more than 100,000 copies/mL or a CD4+ cell count between 200 to 350 or more than 350 was not associated with greater disease progression.
This study concluded that there is no difference in disease progression between efavirenz or boosted-PI regimens when controlling for confounding variables. However, this study had its limitations -- namely that the median treatment duration and follow-up were short and significantly different between the arms. Thus, the findings could be different if both regimens had the same treatment duration and a longer follow-up. In addition, we were not told whether there was a difference between different boosted-PI regimens or the NRTIs that were used with respect to either treatment response or survival.