Results from two new studies indicate that Kaletra plus Isentress may be as safe and effective as standard treatment regimens for people with HIV. One study was conducted in treatment-experienced patients and the other in people who had not previously taken antiretrovirals.

The results were presented this week at the 6th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention (IAS 2011).

Standard antiretroviral therapy includes two nucleoside reverse transcriptase inhibitors (NRTIs) plus at least one additional antiretroviral from a different class.  However, some people are unable to tolerate therapies containing NRTIs.

“Patients intolerant of an NRTI-containing regimen can be safely switched to the NRTI-sparing regimen of [Kaletra plus Isentress] and still retain comparable virologic suppression. It offers another effective and potentially well-tolerated regimen for our patient population,” said Dr. Igho Ofotokun, a researcher from Emory University and lead author of the study in treatment experienced patients.

“I think that the field will have to continue conducting nucleoside-sparing studies for our patients that are intolerant to [NRTIs],” agreed Dr. Vi Bowman, a researcher from the University of California, San Diego and lead author of the study in previously untreated patients.

“Although we’re not quite there in terms of having an excellent nucleoside-sparing regimen to offer our antiretroviral-naive patients, the results of [these studies] show that there are promising outlooks for the future,” she added.

Both researchers noted that the results would need to be confirmed in larger clinical trials.

Results from previous studies have indicated that long-term NRTI use may be linked to a variety of conditions in people with HIV, including premature aging, heart disease, and dementia. In addition, some people cannot take NRTIs due to side effects, allergic reactions, or other conditions.

Such toxic effects observed in HIV-positive individuals taking NRTIs have led scientists to search for alternative, non-NRTI based antiretroviral therapies, also known as NRTI-sparing regimens.

The first study included 60 treatment-experienced HIV-positive adults on standard NRTI-based antiretroviral therapy who had undetectable viral loads (amount of HIV in the blood). At the start of the study, 40 participants were randomly assigned to switch to Kaletra (lopinavir/ritonavir) plus Isentress (raltegravir), while the rest of the participants continued with their original regimen. Kaletra is a protease inhibitor, and Isentress is an integrase inhibitor.

Results showed that after 48 weeks, 92 percent of participants who switched to Kaletra plus Isentress had successfully maintained undetectable viral loads, compared to 88 percent of participants on traditional NRTI-based antiretroviral therapy.

In addition, participants in both treatment groups had similar average CD4 cell counts after 48 weeks: 535 cells per microliter in the Kaletra/Isentress group versus 574 cells per microliter in the standard NRTI-based therapy group. The difference was not large enough to be considered significant.

The researchers noted that three patients in the Kaletra/Isentress group switched regimens (one due to side effects) versus zero patients on traditional therapy. Results also showed that patients in the Kaletra/Isentress group had significantly higher levels of cholesterol and triglycerides after 48 weeks than participants in the NRTI-based therapy group.

The most common side effects in the Kaletra/Isentress group were diarrhea (25 percent of participants), flatulence (10 percent), nausea (10 percent), insomnia (10 percent), rash (10 percent), decreased libido (10 percent), and cough (10 percent).

The most common side effects in the traditional antiretroviral therapy group were muscle pain (25 percent of participants), joint pain (15 percent), abdominal pain (10 percent), and insomnia (10 percent).

There were no significant differences in bone mineral density, kidney function, or total body fat distribution between the two groups.

The second study included 51 HIV-positive adults who had not previously taken antiretrovirals. Half of the participants were randomly assigned to receive Isentress plus Kaletra and the rest to take Atripla (efavirenz/emtricitabine/tenofovir), the most commonly prescribed first-line regimen for people with HIV.

Results showed that after four weeks, 54 percent of participants taking Isentress and Kaletra had successfully achieved undetectable viral loads compared to 12 percent of participants taking Atripla. By week 48, there was no significant difference between the groups: 86 percent of participants in the Kaletra/Isentress group had undetectable viral loads compared to 88 percent of participants in the Atripla group.

The average change in CD4 cell counts by week 48 was also similar between the groups: an increase of 194 cells per microliter in the Kaletra/Isentress group versus 166 cells per microliter in the Atripla group. The difference was not considered significant.

The researchers also observed no significant differences in safety and tolerability among the two regimens. Participants in the Atripla group reported more nervous system-related side effects and rash, while participants in the Kaletra/Isentress group reported more gastrointestinal side effects.

For more information, please see the abstracts for the studies in treatment-experienced and treatment-naive participants on the IAS 2011 conference website.