Effect of Lopinavir/ritonavir (Kaletra) Monotherapy on Symptoms and Quality of Life

The standard-of-care for treatment of HIV consists of a combination of at least 3 antiretroviral drugs from 2 classes -- typically 2 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) plus either a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a protease inhibitor (PI).

However, other therapeutic strategies could be beneficial given the long-term toxicities and quality of life issues associated with taking multiple antiretroviral drugs for many years. One such approach is monotherapy using only a ritonavir-boosted PI.

Quality of Life

Kaletra Tablet

In the prospective, open label MONARK pilot study, antiretroviral-naive patients were randomly assigned to receive either lopinavir/ritonavir (Kaletra) monotherapy or a standard regimen consisting of lopinavir/ritonavir plus zidovudine/lamivudine (AZT/3TC; Combivir).

As previously reported, lopinavir/ritonavir monotherapy demonstrated a lower rate of virological suppression compared with triple combination therapy at 48 weeks. At the XVII International AIDS Conference last month in Mexico City, researchers reported that while patients who achieved HIV RNA < 50 copies/mL at week 48 maintained viral suppression through week 96, low-level viremia appeared to increase the risk of developing drug resistance.

In the current study, published in a recent issue of Antiviral Therapy, researchers presented data from the MONARK trial concerning quality of life (QOL) and patient-reported symptoms.

Information on symptoms was collected at baseline and at weeks 4, 12, 24, and 48 using a list of 22 symptoms. QOL was assessed at baseline, week 24, and week 48 using the 6-domain World Health Organization QOL short form questionnaire for HIV-infected individuals, including an evaluation of global health perception.

Results

• Patients treated with standard triple-drug therapy reported significantly more symptoms over 48 weeks of treatment than patients treated with lopinavir/ritonavir monotherapy (incidence rate ratio P = 0.001 and P = 0.0004 for the total number of symptoms and the number of symptoms causing discomfort, respectively).

• No baseline differences and no significant changes were observed in the 6 QOL scores.

• The percentage of patients with a positive perception of their global health status increased significantly in the monotherapy arm from 32% at baseline to 67% at week 48 (P < 0.0001).

According to the study authors, "These results suggest that the number of self-reported symptoms could be used as a treatment-sensitive measure of patients' well-being in clinical trials."

NSERM U912 Economic Et Social Sciences, Health Systems Et Societies, Marseilles, France.

Maintenance Monotherapy and Lipoatrophy

In a related brief report in the July 15, 2008 Journal of Infectious Diseases, researchers described the outcome of another lopinavir/ritonavir monotherapy study.

Unlike MONARK, this trial used an induction-maintenance strategy. All antiretroviral-naive participants started on a standard regimen of zidovudine/lamivudine plus either lopinavir/ritonavir (n = 104) or efavirenz (Sustiva)(n = 51). In the lopinavir/ritonavir arm, patients who had 3 consecutive monthly HIV RNA measurements < 50 copies/mL dropped the NRTIs and continued on lopinavir/ritonavir monotherapy.

Results

• In a previous-failure=failure analysis, 48% of patients in the lopinavir/ritonavir group and 61% in the efavirenz group maintained HIV RNA < 50 copies/mL through week 96 (P = 0.17).

• In a non-completion=failure analysis, 60% and 63%, respectively maintained HIV RNA < 50 copies/mL at week 96 (P = 0.73).

• Significant sparing of peripheral lipoatrophy (fat loss) was noted in the lopinavir/ritonavir simplification arm.

In conclusion, the authors wrote, "This study has provided important information for future studies using treatment simplified to lopinavir/ritonavir monotherapy."

Division of Infectious Diseases, University of Ottawa at the Ottawa Hospital, Ottawa, Ontario, Canada; McGill University Health Center, Montreal, Quebec, Canada; Abbott Laboratories, Abbott Park, IL; Body Positive, Inc., Phoenix, AZ; Southwest Infectious Disease Associates, Dallas, TX; Hospital La Paz, Madrid, Spain.

9/12/08

References

B Spire, F Marcellin, I Cohen-Codar, and others. Effect of lopinavir/ritonavir monotherapy on quality of life and self-reported symptoms among antiretroviral-naive patients: results of the MONARK trial. Antiviral Therapy 13(4): 591-599. 2008.

DW Cameron, BA da Silva, JR Arribas, and others. A 96-week comparison of lopinavir-ritonavir combination therapy followed by lopinavir-ritonavir monotherapy versus efavirenz combination therapy. Journal of Infectious Diseases 198(2): 234-240. July 15, 2008. (Abstract).