NEW YORK (Reuters Health) – For patients with advanced HIV disease –either AIDS or a CD4 count below 200 — initial antiretroviral regimens based on efavirenz or ritonavir-boosted lopinavir are both effective. However, other components of the regimens are associated with differences in efficacy and toxicity, a South African study shows.

Dr. Michael A. Polis, with the National Institutes of Health in Bethesda, Maryland and members of the Phidisa trial note in their report in the November 15 issue of the Journal of Infectious Diseases that the initial treatment of HIV is important in resource-limited settings, “because individuals present for treatment with advanced disease and the available regimens are limited.”

To determine the effect of different initial antiretroviral regimens in that situation, the team first randomized 1771 participants with CD4 counts less than 200 cells/microliter or frank AIDS to treatment with either efavirenz or lopinavir/ritonavir. They were then further randomized to receive additionally either zidovudine and didanosine or stavudine and lamivudine — thus creating four treatment arms.

Over a median follow-up period of 2 years the hazard ratio for the occurrence of AIDS or death was 1.04 for participants assigned to efavirenz versus lopinavir/ritonavir, according to the report. For the groups assigned to zidovudine and didanosine compared with stavudine and lamivudine, the corresponding hazard ratio was 1:15.

HIV levels were lower and CD4 counts were higher with stavudine and lamivudine than zidovudine and didanosine. However, discontinuations because of toxicity were highest with stavudine (12%) than with other treatments (<5%). “In summary, our findings show that either efavirenz or lopinavir/ritonavir can be used as components of first-line antiretroviral therapy,” the researchers conclude. “In this setting, regimens containing zidovudine and didanosine should be monitored for slower virologic response and more modest immunologic enhancement, and regimens containing stavudine and lamivudine should be monitored for higher rates of toxicities.” The authors of an accompanying editorial, titled “Rescue of Severely Immunocompromised HIV-Positive Persons,” say that the fact that many HIV patients enter care late is a major public health issue throughout the world. After discussing some of the finer points of the Phidisa findings, they conclude: “Let us hope that this will be the first in a series of research projects that further improve the body of evidence regarding how to best manage HIV infection in a resource-constrained environment.” Reference:
A Randomized Factorial Trial Comparing 4 Treatment Regimens in Treatment‐Naive HIV‐Infected Persons with AIDS and/or a CD4 Cell Count <200 Cells/μL in South Africa

JID 2010:202.