HIV-positive individuals with very low CD4 cells starting therapy for the first time may be more likely to keep their viral loads undetectable and to remain on treatment using a regimen containing Sustiva (efavirenz) versus Kaletra (lopinavir/ritonavir), according to a new Mexican study reported at the XVII International AIDS Conference in Mexico City.

Although a large clinical trial conducted in the United States (ACTG 5142) concluded that Sustiva and Kaletra are roughly similar in terms of effectiveness and treatment discontinuation rates because of side effects, it had enrolled patients with relatively high CD4 counts. In Mexico and other low- and middle-income countries—and about 25 percent of HIV-positive people in the United States—many HIV-positive people are not diagnosed with the infection and started on treatment until they are sick with an AIDS-related complication and have a very low CD4 cell count. In turn, presenting study author Juan Sierra-Madero, MD, of the National Institute of Medical Sciences in Mexico City, explained that it is essential to determine which antiretrovirals are the most likely to succeed in patients with advanced HIV disease.

To explore possible differences between Sustiva and Kaletra—two leading first-line treatment options throughout the world—Dr. Sierra-Madero and his colleagues conducted a clinical trial involving 189 patients with very low CD4 counts starting HIV treatment for the first time. Ninety-five of the patients received Sustiva plus Combivir (zidovudine/lamivudine) and 94 received Kaletra plus Combivir.

The average CD4 count in the Sustiva group, at the start of the study, was 64 cells. In the Kaletra group, the average pre-treatment CD4 count was 52 cells. Nearly half of all patients enrolled in the study had CD4s below 50 before starting their assigned regimen.

After nearly a year (48 weeks) of treatment, 71 percent of patients in the Sustiva group were still on treatment, compared with 58 percent of those originally allotted to take Kaletra. This difference was statistically significant, meaning it was too great to have occurred by chance.

Sierra-Madero reported that virologic failure—failing to push viral load to undetectable levels, or experiencing viral load rebounds—and side effects were both to blame for the higher discontinuation rates in the Kaletra group.

Patients receiving Sustiva plus Combivir were also much more likely to have undetectable viral loads by the end of the study. Approximately 70 percent of those in the Sustiva group had undetectable viral loads (below 50 copies) after 48 weeks, compared with 53 percent of those in the Kaletra group. This difference was also statistically significant. 

Dr. Sierra-Madero's group noted that the virologic benefit in favor of Sustiva was only noted among those with CD4s below 50. The percentages of patients with undetectable viral loads starting treatment with more than 50 CD4 cells were not statistically significant between the two groups after 48 weeks.

While the study was designed to show that one regimen was not inferior to the other, the overall significant difference between the two groups allowed Sierra-Madero and his fellow study authors to conclude that Sustiva is superior to Kaletra in those starting HIV treatment with very low CD4 cell counts.  

As has been seen in other studies, rates of central nervous system side effects were higher among those in the Sustiva group, whereas those taking Kalera were more likely to experience increases in triglycerides.

Sierra-Madero noted that the study is limited by its small sample size and its single-country focus. However, he also suggested that the data are strong enough to help guide treatment decisions for patients with advanced HIV infection.