ICAAC: Pilot study shows dual protease inhibitor regimen as safe and effective as traditional two class HIV therapy

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A dual protease inhibitor regimen consisting of ritonavir-boosted lopinavir (Kaletra) with saquinavir is as effective and safe as a traditional regimen consisting of a protease inhibitor and two nucleoside analogues, according to a small pilot study presented as a poster to the 45th Interscience Conference on Antimicrobial Agents and Chemotherapy in Washington DC last month.

It is thought that some of the metabolic complications seen in HIV-positive patients taking antiretroviral therapy are due to an interaction between different classes of anti-HIV drugs - for example, fat loss caused by nucleoside analogues may be exacerbated if protease inhibitors are used alongside NRTIs, particularly stavudine (d4T). Most HIV treatment regimens currently consist of at least three drugs from two different classes of antiretroviral drugs.

Investigators designed a 48 week study to determine the efficacy, safety and metabolic toxicities associated with two regimens containing Kaletra (lopinavir boosted by ritonavir) in HIV-positive patients who had never taken anti-HIV drugs before.

Glossary

nucleoside

A precursor to a building block of DNA or RNA. Nucleosides must be chemically changed into nucleotides before they can be used to make DNA or RNA. 

boosting agent

Booster drugs are used to ‘boost’ the effects of protease inhibitors and some other antiretrovirals. Adding a small dose of a booster drug to an antiretroviral makes the liver break down the primary drug more slowly, which means that it stays in the body for longer times or at higher levels. Without the boosting agent, the prescribed dose of the primary drug would be ineffective.

metabolism

The physical and chemical reactions that produce energy for the body. Metabolism also refers to the breakdown of drugs or other substances within the body, which may occur during digestion or elimination.

triglycerides

A blood fat (lipid). High levels are associated with atherosclerosis and are a risk factor for heart disease.

 

cholesterol

A waxy substance, mostly made by the body and used to produce steroid hormones. High levels can be associated with atherosclerosis. There are two main types of cholesterol: low-density lipoprotein (LDL) or ‘bad’ cholesterol (which may put people at risk for heart disease and other serious conditions), and high-density lipoprotein (HDL) or ‘good’ cholesterol (which helps get rid of LDL).

The study involved 30 patients who were randomised to either take a regimen which only included drugs from the protease inhibitor class (Kaletra and hard gel saquinavir) or a more traditional antiretroviral regimen which included Kaletra and two nucleoside analogues, AZT and 3TC.

Median baseline viral load was 177,000 copies/ml and median baseline CD4 cell count was 175 cells/mm3. A total of eight patients withdrew from the study, three in the dual protease inhibitor arm (one because of side-effects) and five in the nucleoside analogue arm (three because of side-effects).

In the on-treatment analysis (which only included patients who completed the study), by week 48, comparable numbers of patients in both arms of the study (77% dual protease inhibitor and 78% nucleoside analogue) had a viral load below 50 copies/ml. In the more rigorous intent-to-treat analysis, which included all patients enrolled at baseline, 63% of patients in the dual protease inhibitor arm had a viral load below 50 copies/ml compared to 50% of patients randomised to take two nucleoside analogues.

Mean increase in CD4 cell count was +141 cells/mm3 in the Kaletra/saquinavir group and +187 cells/mm3 in the dual class group.

One patient in each arm of the study experienced an increase in their total cholesterol above 300mg/dl or their triglycerides above 750mg/dl, and the mean increases in total cholesterol (+60mg/dl) and triglycerides (+85mg/dl in the dual PI group, +64mg/dl in the NRTI group) were similar between the two groups. In addition, two patients in each arm reported moderate-to-severe physical side-effects including nausea, vomiting or diarrhoea.

“Anti-HIV activity of a dual boosted-protease inhibitor regimen was comparable to a standard regimen”, conclude the investigators, who add “additional controlled studies of appropriate nucleoside analogue-sparing regimens for long-term metabolic toxicities are warranted.”

The study involved investigators from the manufacturers of Kaletra, Abbott Laboratories.

References

Cameron DW et al. Comparative safety and anti-HIV activity of a dual protease inhibitor regimen versus a nucleoside-containing regimen. 45th Interscience Conference on Antimicrobial Agents and Chemotherapy, abstract H-523, Washington DC, 2005.